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x
II.A. CRIMEAN-CONGO HEMORRHAGIC FEVER ................... 55
II.B. OMSK HEMORRHAGIC FEVER
KYASANUR FOREST DISEASE ...................................... 57
ASCARIASIS ............................................................................................ 59
ASPERGILLOSIS ..................................................................................... 62
BABESIOSIS ............................................................................................ 65
BALANTIDIASIS ..................................................................................... 68
BARTONELLOSIS ................................................................................... 70
BLASTOMYCOSIS .................................................................................. 73
BOTULISM AND INTESTINAL BOTULISM ......................................... 75
BRUCELLOSIS ........................................................................................ 82
BURULI ULCER ...................................................................................... 85
CAMPYLOBACTER ENTERITIS ............................................................ 88
CANDIDIASIS ......................................................................................... 91
CAPILLARIASIS ...................................................................................... 94
I. CAPILLARIASIS DUE TO CAPILLARIA PHILIPPINENSIS ....... 94
II. CAPILLARIASIS DUE TO CAPILLARIA HEPATICA ................. 95
III. PULMONARY CAPILLARIASIS ................................................... 96
CAT-SCRATCH DISEASE ....................................................................... 98
CHANCROID .......................................................................................... 100
CHICKENPOX/HERPES ZOSTER ......................................................... 102
CHLAMYDIAL INFECTIONS ................................................................. 108
GENITAL INFECTIONS, CHLAMYDIAL ............................................. 109
URETHRITIS, NONGONOCOCCAL AND NONSPECIFIC ................. 112
CHOLERA AND OTHER VIBRIOSES .................................................... 113
I. VIBRIO CHOLERAE SEROGROUPS O1 AND O139 ............... 113
II. VIBRIO CHOLERAE SEROGROUPS
OTHER THAN O1 AND O139 ............................................... 122
III. VIBRIO PARAHAEMOLYTICUS ENTERITIS ............................ 124
IV. INFECTION WITH VIBRIO VULNIFICUS ................................ 125
V. INFECTION WITH OTHER VIBRIOS ........................................ 127
CHROMOMYCOSIS ............................................................................... 128
CLONORCHIASIS .................................................................................. 130
OPISTHORCHIASIS ........................................................................... 131
COCCIDIOIDOMYCOSIS .................................................................... 133
CONJUNCTIVITIS/KERATITIS ............................................................. 136
I. ACUTE BACTERIAL CONJUNCTIVITIS .................................... 136
II. KERATOCONJUNCTIVITIS, ADENOVIRAL .............................. 138
III. ADENOVIRAL HEMORRHAGIC CONJUNCTIVITIS ................. 140
ENTEROVIRAL HEMORRHAGIC CONJUNCTIVITIS ........... 140
IV. CHLAMYDIAL CONJUNCTIVITIS .............................................. 142
COXSACKIEVIRUS DISEASES ............................................................... 146
I.A. ENTEROVIRAL VESICULAR PHARYNGITIS ............................. 146
I.B. ENTEROVIRAL VESICULAR STOMATITIS WITH EXANTHEM .. 146
xi
I.C. ENTEROVIRAL LYMPHONODULAR PHARYNGITIS ............... 146
II. COXSACKIEVIRUS CARDITIS .................................................... 148
CRYPTOCOCCOSIS ............................................................................. 150
CRYPTOSPORIDIOSIS .......................................................................... 152
DIARRHEA CAUSED BY CYCLOSPORA ........................................ 154
CYTOMEGALOVIRUS INFECTIONS ................................................... 156
CYTOMEGALOVIRUS DISEASE ...................................................... 156
CONGENITAL CYTOMEGALOVIRUS INFECTION ....................... 156
DENGUE FEVER ................................................................................... 160
DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK
SYNDROME ...................................................................................... 164
DERMATOPHYTOSIS ........................................................................... 167
I. TINEA BARBAE AND TINEA CAPITIS ..................................... 167
II. TINEA CRURIS AND TINEA CORPORIS ................................. 169
III. TINEA PEDIS .............................................................................. 171
IV. TINEA UNGUIUM ...................................................................... 173
DIARRHEA, ACUTE .............................................................................. 175
DIARRHEA CAUSED BY ESCHERICHIA COLI .................................. 176
I. ENTEROHEMORRHAGIC STRAINS ......................................... 176
II. ENTEROTOXIGENIC STRAINS ................................................ 180
III. ENTEROINVASIVE STRAINS .................................................... 182
IV. ENTEROPATHOGENIC STRAINS ............................................. 183
V. ENTEROAGGREGATIVE E. COLI ............................................. 186
VI. DIFFUSE-ADHERENCE E. COLI ................................................ 187
DIPHTHERIA ......................................................................................... 188
DIPHYLLOBOTHRIASIS ....................................................................... 193
DRACUNCULIASIS ............................................................................... 195
EBOLA-MARBURG VIRAL DISEASES .................................................. 198
ECHINOCOCCOSIS .............................................................................. 201
I. DUE TO ECHINOCOCCUS GRANULOSUS ............................. 201
II. DUE TO ECHINOCOCCUS MULTILOCULARIS ...................... 204
III. DUE TO ECHINOCOCCUS VOGELI ........................................ 205
EHRLICHIOSIS ...................................................................................... 206
ENCEPHALOPATHY, SUBACUTE SPONGIFORM ............................. 209
I. CREUTZFELDT-JAKOB DISEASE .............................................. 209
II. KURU .......................................................................................... 212
ENTEROBIASIS ..................................................................................... 213
ERYTHEMA INFECTIOSUM/HUMAN PARVOVIRUS INFECTION ...... 216
EXANTHEMA SUBITUM ...................................................................... 219
FASCIOLIASIS ....................................................................................... 222
FASCIOLOPSIASIS ................................................................................ 224
FILARIASIS ............................................................................................ 226
DIROFILARIASIS ............................................................................... 230
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OTHER NEMATODES PRODUCING MICROFILARIAE IN
HUMANS ....................................................................................... 231
FOODBORNE INTOXICATIONS ........................................................ 232
I. STAPHYLOCOCCAL FOOD INTOXICATION ......................... 233
II. CLOSTRIDIUM PERFRINGENS FOOD INTOXICATION ...... 235
III. BACILLUS CEREUS FOOD INTOXICATION .......................... 237
IV. SCOMBROID FISH POISONING .............................................. 238
V. CIGUATERA FISH POISONING ................................................ 239
VI. PARALYTIC SHELLFISH POISONING ...................................... 240
VII. NEUROTOXIC SHELLFISH POISONING ................................. 240
VIII. DIARRHETIC SHELLFISH POISONING .................................... 241
IX. AMNESIC SHELLFISH POISONING .......................................... 241
X. PUFFER FISH POISONING (TETRODOTOXIN) ..................... 242
XI. AZASPIRACID POISONING (AZP) ............................................ 242
GASTRITIS CAUSED BY HELICOBACTER PYLORI .......................... 243
GASTROENTERITIS, ACUTE VIRAL ................................................... 246
I. ROTAVIRAL ENTERITIS ............................................................ 246
II. EPIDEMIC VIRAL GASTROENTEROPATHY ........................... 249
GIARDIASIS ........................................................................................... 252
GONOCOCCAL INFECTIONS ............................................................. 255
I. GONOCOCCAL INFECTION .................................................... 255
II. GONOCOCCAL CONJUNCTIVITIS (NEONATORUM) .......... 259
GRANULOMA INGUINALE ................................................................. 261
HANTAVIRAL DISEASES ...................................................................... 263
I. HEMORRHAGIC FEVER WITH RENAL SYNDROME ............. 263
II. HANTAVIRUS PULMONARY SYNDROME .............................. 266
HENDRA AND NIPAH VIRAL DISEASES ........................................... 269
HEPATITIS, VIRAL ............................................................................... 271
I. VIRAL HEPATITIS A .................................................................. 271
II. VIRAL HEPATITIS B .................................................................. 276
III. VIRAL HEPATITIS C .................................................................. 285
IV. DELTA HEPATITIS ..................................................................... 287
V. VIRAL HEPATITIS E .................................................................... 289
HERPES SIMPLEX AND ANOGENITAL HERPESVIRAL INFECTIONS ..... 292
MENINGOENCEPHALITIS DUE TO CERCOPITHECINE HERPES
VIRUS 1 .......................................................................................... 295
HISTOPLASMOSIS ................................................................................ 297
I. INFECTION BY HISTOPLASMA CAPSULATUM ..................... 297
II. HISTOPLASMOSIS DUBOISII .................................................... 300
HOOKWORM DISEASE ....................................................................... 301
HYMENOLEPIASIS ................................................................................. 304
I. DUE TO HYMENOLEPIS NANA .............................................. 304
II. DUE TO HYMENOLEPIS DIMINUTA ....................................... 305
III. DIPYLIDIASIS .............................................................................. 306
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INFLUENZA .......................................................................................... 307
KAWASAKI SYNDROME ...................................................................... 313
LASSA FEVER ........................................................................................ 316
LEGIONELLOSIS AND NONPNEUMONIC LEGIONELLOSIS ............. 319
LEISHMANIASIS .................................................................................... 322
I. CUTANEOUS AND MUCOSAL ................................................. 322
II. VISCERAL ..................................................................................... 325
LEPROSY ................................................................................................ 329
LEPTOSPIROSIS ..................................................................................... 334
LISTERIOSIS ........................................................................................... 338
LOIASIS ................................................................................................. 342
LYME DISEASE ..................................................................................... 345
LYMPHOCYTIC CHORIOMENINGITIS .............................................. 350
LYMPHOGRANULOMA VENEREUM .................................................. 352
MALARIA ................................................................................................ 354
MALIGNANT NEOPLASMS ASSOCIATED WITH INFECTIOUS AGENTS . 371
I. HEPATOCELLULAR CARCINOMA ............................................. 371
II. BURKITT LYMPHOMA .............................................................. 372
III. NASOPHARYNGEAL CARCINOMA ......................................... 373
IV. MALIGNANCIES POSSIBLY RELATED TO EBV ....................... 374
IV.A. HODGKIN DISEASE ........................................................... 374
IV.B. NON-HODGKIN LYMPHOMAS ........................................ 375
V. KAPOSI SARCOMA .................................................................... 375
VI. LYMPHATIC TISSUE MALIGNANCY ....................................... 377
VII. CERVICAL CANCER .................................................................. 377
MEASLES ............................................................................................... 379
MELIOIDOSIS ....................................................................................... 386
GLANDERS ......................................................................................... 388
MENINGITIS ......................................................................................... 389
I. VIRAL MENINGITIS ................................................................... 389
II. BACTERIAL MENINGITIS ......................................................... 391
II.A. MENINGOCOCCAL INFECTION ..................................... 391
II.B. HEMOPHILUS MENINGITIS ............................................ 398
II.C. PNEUMOCOCCAL MENINGITIS ..................................... 400
II.D. NEONATAL MENINGITIS ................................................ 402
MOLLUSCUM CONTAGIOSUM .......................................................... 404
MONONUCLEOSIS, INFECTIOUS ...................................................... 406
MUMPS .................................................................................................. 409
MYALGIA, EPIDEMIC .......................................................................... 413
MYCETOMA: ACTINOMYCETOMA AND EUMYCETOMA .............. 415
NAEGLERIASIS AND ACANTHAMEBIASIS ........................................ 417
NOCARDIOSIS ...................................................................................... 420
ONCHOCERCIASIS .............................................................................. 422
xiv
ORF VIRUS DISEASE ............................................................................ 426
PARACOCCIDIOIDOMYCOSIS ........................................................... 428
PARAGONIMIASIS ................................................................................ 430
PEDICULOSIS AND PHTHIRIASIS ....................................................... 433
PERTUSSIS AND PARAPERTUSSIS ...................................................... 436
PINTA .................................................................................................... 442
PLAGUE ................................................................................................. 444
PNEUMONIA ........................................................................................ 451
I. PNEUMOCOCCAL ..................................................................... 451
II. MYCOPLASMAL ......................................................................... 455
III. PNEUMOCYSTIS ........................................................................ 457
IV. CHLAMYDIAL ............................................................................ 459
IV.A. DUE TO CHLAMYDIA TRACHOMATIS ......................... 459
IV.B. DUE TO CHLAMYDIA PNEUMONIAE ........................... 460
OTHER PNEUMONIAS .................................................................... 462
POLIOMYELITIS, ACUTE .................................................................... 463
PSITTACOSIS ........................................................................................ 470
Q FEVER ................................................................................................ 473
RABIES ................................................................................................... 477
RAT-BITE FEVER .................................................................................. 486
I. STREPTOBACILLOSIS ................................................................ 486
II. SPIRILLOSIS ................................................................................ 487
RELAPSING FEVER ............................................................................... 488
RESPIRATORY DISEASE, ACUTE VIRAL ............................................ 492
I. ACUTE VIRAL RHINITISTHE COMMON COLD ................. 493
II. ACUTE FEBRILE RESPIRATORY DISEASE ............................... 494
RICKETTSIOSES, TICK-BORNE .......................................................... 498
I. ROCKY MOUNTAIN SPOTTED FEVER ................................... 498
II. BOUTONNEUSE FEVER ............................................................ 500
III. AFRICAN TICK BITE FEVER .................................................... 501
IV. QUEENSLAND TICK TYPHUS .................................................. 501
V. NORTH ASIAN TICK FEVER .................................................... 502
VI. RICKETTSIALPOX ..................................................................... 502
RUBELLA AND CONGENITAL RUBELLA ........................................... 503
SALMONELLOSIS .................................................................................. 508
SCABIES ................................................................................................. 513
SCHISTOSOMIASIS ................................................................................ 516
SEVERE ACUTE RESPIRATORY SYNDROME ..................................... 520
SHIGELLOSIS .......................................................................................... 527
SMALLPOX ............................................................................................. 532
VACCINIA ......................................................................................... 534
MONKEYPOX .................................................................................... 535
SPOROTRICHOSIS ................................................................................. 537
STAPHYLOCOCCAL DISEASES ............................................................ 539
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I. IN THE COMMUNITY ................................................................ 539
II. IN HOSPITAL NURSERIES ........................................................ 542
III. ON HOSPITAL MEDICAL AND SURGICAL WARDS .............. 545
IV. TOXIC SHOCK SYNDROME .................................................... 547
STREPTOCOCCAL DISEASES CAUSED BY GROUP A
(BETA HEMOLYTIC) STREPTOCOCCI ...................................... 549
GROUP B STREPTOCOCCAL SEPSIS OF THE NEWBORN ......... 555
DENTAL CARIES OF EARLY CHILDHOOD ................................... 557
STRONGYLOIDIASIS ........................................................................... 558
SYPHILIS ............................................................................................... 561
I. SYPHILIS ..................................................................................... 561
II. NONVENEREAL ENDEMIC SYPHILIS ...................................... 566
TENIASIS ............................................................................................... 568
ASIAN TENIASIS ............................................................................... 571
TETANUS .............................................................................................. 572
TETANUS NEONATORUM .................................................................. 577
TOXOCARIASIS ..................................................................................... 579
GNATHOSTOMIASIS ........................................................................ 581
CUTANEOUS LARVA MIGRANS ..................................................... 582
TOXOPLASMOSIS ................................................................................ 583
CONGENITAL TOXOPLASMOSIS .................................................... 583
TRACHOMA .......................................................................................... 587
TRENCH FEVER ..................................................................................... 590
TRICHINELLOSIS ................................................................................. 592
TRICHOMONIASIS ............................................................................... 595
TRICHURIASIS ...................................................................................... 597
TRYPANOSOMIASIS ............................................................................ 599
I. AFRICAN .................................................................................... 599
II. AMERICAN ................................................................................. 603
TUBERCULOSIS .................................................................................... 607
DISEASES DUE TO OTHER MYCOBACTERIA .............................. 618
TULAREMIA .......................................................................................... 620
TYPHOID FEVER AND PARATYPHOID FEVER ................................ 624
TYPHUS FEVER .................................................................................... 630
I. EPIDEMIC LOUSE-BORNE ........................................................ 630
II. ENDEMIC FLEA-BORNE ............................................................ 633
III. SCRUB TYPHUS ......................................................................... 634
WARTS, VIRAL ..................................................................................... 637
YAWS .................................................................................................... 640
YELLOW FEVER .................................................................................... 643
YERSINIOSIS ......................................................................................... 648
ZYGOMYCOSIS .................................................................................... 652
MUCORMYCOSIS .............................................................................. 652
ENTOMOPHTHORAMYCOSIS ......................................................... 654
xvi
ABBREVIATIONS .................................................................................. 655
EXPLANATION OF TERMS ................................................................. 660
TABLE: IMMUNIZATION SCHEDULES .............................................. 672
xvii
FOREWORD
xviii
community. I thank them for their work. I also want to thank the many
men and women who work silently behind the scenes and on occasion
have given their lives to contain the threat of infectious disease.
Finally, I would be remiss in not acknowledging the death during work
on this edition of long-time CCDM editor, Dr. Abram S. Benenson, who
died December 15, 2003, at his home in Lenox MA. A renowned scientist,
research doctor, and professor, Dr. Benenson was editor of CCDM for 28
years, for the 11th16th editions. Dr. Benenson set a high standard of
excellence for CCDM and APHA will always be grateful for his outstanding
contributions to the health of the nation and the world, and to the
scientific knowledge base of the profession.
xix
FOREWORD
LEE Jong-wook
Director-General
World Health Organization
xx
PREFACE TO THE EIGHTEENTH EDITION
Communicable diseases kill, maim and surprise. Far from having been
conquered, they have resurged dramatically in recent years. The microbial
agents that cause them are dynamic, resilient, and well adapted to exploit
opportunities for change and spread. Their public health significance in
terms of human suffering, deaths, and disability is compounded by the
considerable toll they take on economic growth and development. For
many important diseases, control is problematic either because of the lack
of effective vaccines and therapeutic drugs, or because existing drugs are
being rendered ineffective as antimicrobial resistance spreads.
Communicable diseases kill more than 14 million people each year,
mainly in the developing world. In these countries, approximately 46% of
all deaths are due to communicable diseases, and 90% of these deaths are
attributed to acute diarrhoeal and respiratory infections of children, AIDS,
tuberculosis, malaria, and measles.
Other diseases, that rarely kill, maim millions. Large populations living
in remote areas of the developing world are at risk of disabling diseases,
such as poliomyelitis, leprosy, lymphatic filariasis, and onchocerciasis. For
these diseases, the toll of suffering and permanent disability is com-
pounded by a double economic burden. The huge number of permanently
disabled persons reduces the work force and further undermines the
financial security of already impoverished families and communities, who
already take on the onus of care and economic support.
Communicable diseases also deliver surprises, whether in the form of
new diseases or well-known diseases behaving in new ways. As the
emergence of severe acute respiratory syndrome (SARS) so clearly dem-
onstrated, every country is vulnerable, and the economic consequences,
exaggerated by public fear of the unknown, can be felt around the world.
When severe and poorly understood diseases such as SARS and Ebola
emerge, they often take their heaviest toll on health care workers and can
jeopardize the capacity of health systems to cope. This situation is likely to
be repeated when the next new disease emerges, when the next inevitable
influenza pandemic occurs, or following the deliberate release of a
pathogen with deliberate intent to harm.
For all these reasons, concern about the impact of communicable
diseases has increased, with some encouraging results. Lack of access to
effective vaccines and drugs has been a long-standing problem in the
developing world. Major new initiatives, including the Global Fund to
Fight AIDS, Tuberculosis and Malaria, the Global Alliance for Vaccines and
Immunization, and the Roll Back Malaria and Stop TB partnerships, have
formed to attack the main communicable diseases that kill and are
delivering badly needed drugs and vaccines. The concern of international
xxi
community is also evident in time-limited drives to eradicate or eliminate
polio, leprosy, lymphatic filariasis, onchocerciasis and other diseases that
maim. While microbial agents will always deliver surprises, the shock of
SARS has encouraged a number of countries to give infrastructures for
protecting public health much higher priority. All health care will benefit.
This 18th edition of the Control of Communicable Diseases Manual
(CCDM18) provides guidance to countries as they give higher priority to
the communicable disease threat, and is yet another tool in our collective
efforts to protect world populations from communicable diseases
whether rare and exotic or all too common. It has been a privilege to work
with the worlds experts in communicable disease control as CCDM18 has
been updated, and to broaden this edition by adding considerations for
developing countries. It was with great sadness, in mid-January of this
year, just as the editorial review was completed, that we learned of the
death of one of our long time colleagues and fellow editorial board
member, Dr Robert E. Shope. Bob Shope was certainly the worlds
authority on arboviruses, and shared his knowledge with all who asked,
including CCDM18 where his final touches to the chapter on arboviruses
are yet another memorial to his life and friendship.
xxii
USERS GUIDE TO CCDM18
xxiii
humans; or from an infected person to animals, including arthro-
pods.
8. Susceptibility (including immunity) provides information on
human or animal populations at risk of infection, or that are
resistant to either infection or disease. Information on subsequent
immunity consecutive to infection is also given.
9. Methods of control are described under the following headings:
A. Preventive measures: for individuals and groups.
B. Control of patient, contacts and the immediate environ-
ment: measures designed to prevent further spread of the disease
from infected persons, and specific best current treatment to
minimize the period of communicability and to reduce morbidity
and mortality.
Recommendations for isolation of patients depend first on
universal precautions with specific measures cited mainly
from CDC and WHO guidelines available on the worldwide
web.
CCDM18 is not intended to be a therapeutic guide. However,
current clinical management is presented in section 9B7 of
each disease. Specific dosages and clinical management are
indicated primarily for those diseases where delay in instituting
therapy might jeopardize the patients life.
Some of the licensed drugs needed for treatment of rare or
exotic diseases are available at no cost from WHO, and those
which are not licensed may, at times, be available from CDC as
Investigational New Drugs (IND).
Details, including telephone numbers and e-mail addresses are
entered in section 9B7 for those diseases where such drugs or
biologics may be available.
C. Epidemic measures: describes those procedures of an emer-
gency character designed to limit the spread of a communicable
disease that has developed widely in a group or community, or
within an area, state or nation.
D. Disaster implications: given a disaster, indicates the likelihood
that the disease might constitute a major problem if preventive
actions are not initiated.
E. International measures: outlines those interventions designed
xxiv
to protect populations against the known risk of infection from
international sources. The WHO Collaborating Centres, the CDC,
and other operational institutions can provide national authorities
with the services following: laboratory diagnosis, consultation,
analysis of information, production and distribution of standard
and reference materials and reagents, training, organization of
collaborative research, and provision of further information on
specific diseases. WHO can be approached directly for further
details about these Centres, listed at www.who.int/WHOCC_Net/
for WHO Collaborating Centres dealing specifically with commu-
nicable diseases and http://whocc.who.int/ database for all other
WHO Collaborating Centres. Outbreaks can be electronically
reported 24 hours a day by e-mail at [email protected].
F. Measures in case of deliberate use of biological agents to
cause harm (formerly bioterrorism measures): for selected
diseases, this new section provides information and guidelines for
public health workers who may be confronted with a threatened
or actual act of deliberate use with a specific infectious disease
agent.
The relevant telephone numbers are:
(0041) 22 791 2111 for WHO
(001) 770 488 7100/ 404 639 3311/ 404 639 2888 for CDC.
The relevant websites are:
http://www.who.int/csr/delibepidemics for WHO
http://www.cdc.gov/
Outbreaks can be electronically reported 24 hours a day:
[email protected]
[email protected]
To update CCDM17, a literature review was done to identify
publications during the preceding five-year period for each
disease in that edition. These publications were provided to the
primary reviewer for use in updating the chapter for CCDM18
(2004); additional chapters were added on Buruli ulcer and on
Severe Acute Respiratory Syndrome (SARS). The name of each
primary reviewer is provided in square brackets at the end of
each disease entry. Some diseases did not undergo major updat-
ing for the 18th edition and show no primary reviewer.
xxv
REPORTING OF COMMUNICABLE DISEASES
Reporting of some communicable diseases is required within countries
and in some instances internationally to WHO. Reporting can take the
form of either a case report or an outbreak report.
1. Case reports: Case reporting provides diagnosis, age, sex and
date of onset for each person with the disease. Sometimes it
includes identifying information such as the name and address of
the person with the disease. Additional information such as
treatment provided and its duration are required for certain case
reports.
xxvi
new sources for reporting information on infectious diseases. WHO will
formally consult its Member States and constituents on the proposed
revisions during 2004 with a target for adoption of the Revised Regulations
in 2005. The key proposals in the revision are to:
Require the establishment of defined core capacities in surveil-
lance and response to public health emergencies.
Require the international reporting of public health emergen-
cies of international concern as defined by decision-tree anal-
ysis under the Regulations.
Link reporting to specific response actions recommended by
WHO and tailored to the epidemiology of the reported event.
Enhance communication and collaboration during such emer-
gencies through a network of national focal points for the
International Health Regulations.
xxvii
undue frequency or severity, in order to stimulate control measures or
acquire essential epidemiological data. Examples of diseases in this class
are scrub typhus, schistosomiasis and fasciolopsiasis.
xxviii
Verify the diagnosis
Initial notification of an outbreak is often made by a health worker who
must collect as detailed a history as possible from the initial cases. A
tentative differential diagnosis may be made, for example food poisoning
or cholera, that enables the investigator to anticipate the diagnostic
specimens required and the kind of equipment to be used during the
investigation. The laboratory that will analyse the specimens should be
alerted at this stage. If initial cases have died, the extent and need for
autopsies should be considered. For surveillance and control purposes,
investigators must agree on a common surveillance case definition (this
may not always correspond to the clinical case definition).
Confirm the existence of an outbreak
Some diseases, although long endemic in an area, remain unrecognized;
new cases may come to light, for instance, when new treatments attract
patients who previously relied on traditional medicines. Such false
outbreaks must be excluded through attempts at determining the previ-
ous incidence or prevalence of the disease.
An outbreak can be demonstrated on a graph of incidence over time and
by a map of geographical extension. For endemic diseases, an outbreak is
said to have begun when incidence rises above the normally expected
level. For diseases showing a cyclical or seasonal variation, the average
incidence rates over particular weeks or months of previous years, or
average high or low levels over a period of years, may be used as baselines.
Identify affected persons and their characteristics
Record case histories
Information about each confirmed or suspected case must be
recorded to obtain a complete understanding of the outbreak.
Usually this information includes name, age, sex, occupation, place
of residence, recent movements, details of symptoms (including
dates and time of onset) and dates of previous immunization against
childhood or other diseases. Other details will vary with the
differential diagnosis. If the incubation period is known, informa-
tion on possible source contacts may be sought. This information is
best recorded on specially prepared record forms called line lists.
The logistics of form duplication, data entry and verification must
be worked out in relation to reporting (See Reporting).
Identify additional cases
Initial notification of an outbreak may come from a clinic or
hospital; enquiries in health centres, dispensaries and villages in the
area may reveal other cases, sometimes with a range of additional
symptoms.
xxix
Define and investigate population at risk
The population at risk of infection must be identified; this provides the
denominator required and ensures that remaining cases can be identified.
Overall or specific attack rates (age-specific village-specific) can then be
calculated. These calculations may lead to new hypotheses requiring
further investigation and development of study designs. In addition the
population at risk may require laboratory investigation (e.g. rate of nasal
meningococcal carriage in the population). Microbiological typing and
susceptibility to antibiotics can then be used to develop appropriate
control measures.
Formulate a hypothesis as to source and spread of the outbreak
Determine why the outbreak occurred when it did and what set the
stage for its occurrence. Whenever possible the relevant conditions before
the outbreak should be determined. For foodborne outbreaks it is neces-
sary to determine source, vehicle, predisposing circumstances and portal
of entry. If transmission is widespread this may prove difficult. All links in
the process must be considered: i) disease-causing agent in the population
and its characteristics; ii) existence of a reservoir; iii) mode of exit from
this reservoir or source; iv) mode of transmission to the next host; v) mode
of entry; vi) susceptibility of the host.
Contain the outbreak
The key to effective containment of an outbreak is a coordinated
investigation and response involving health workers including clinicians,
epidemiologists, microbiologists, health educators and the public health
authority. The best way to ensure coordination may be to establish an
outbreak containment committee early in the outbreak.
Manage cases
Health workers, including clinicians, must assume responsibility for
treatment of diagnosed cases. In outbreaks of meningitis, plague or
cholera, emergency accommodation may have to be found and additional
staff may require rapid essential training. Outbreaks of diseases such as
sleeping sickness and cholera may require special treatment and recourse
to drugs not normally available. The investigative team must estimate
requirements and obtain supplies urgently. Outbreaks such as poliomyeli-
tis may leave in their wake patients with an immediate need for physio-
therapy and rehabilitation; timely organization of these services will lessen
the impact of the outbreak.
Implement control measures to prevent spread
After the epidemiological characteristics of the outbreak have been
better understood, it is possible to implement control measures to prevent
further spread of the infectious agent. However, from the very beginning
xxx
of the investigation the investigative team must attempt to limit the spread
and the occurrence of new cases.
Many communicable diseases can be prevented by chemoprophylaxis
or vaccination. Immediate isolation of affected persons can prevent
spread, and measures to prevent movement in or out of the affected area
may be considered. Universal precautions in patient care are essential.
Whatever the urgency of the control measures they must also be explained
to the community at risk. Population willingness to report new cases,
attend vaccination campaigns, improve standards of hygiene or other such
activities is critical for successful containment.
If supplies of vaccine or drugs are limited, it may be necessary to identify
the groups at highest risk initial for control measures. Once these urgent
measures have been put in place, it is necessary to initiate more perma-
nent ones such as health education, improved water supply, vector
control or improved food hygiene. It may be necessary to develop and
implement long-term plans for continued vaccination after an initial
campaign.
Conduct ongoing disease surveillance
During the acute phase of an outbreak it may be necessary to
keep persons at risk (e.g. contacts) under surveillance for disease
onset. After the outbreak has initially been controlled, continued
community surveillance may be needed in order to identify addi-
tional cases and to complete containment. Sources of information
for surveillance include: i) notifications of illness by health workers,
community chiefs, employers, school teachers, heads of families; ii)
certification of deaths by medical authorities; iii) data from other
sources such as public health laboratories, entomological and
veterinary services. It may be necessary to maintain estimates of the
immune status of the population when immunization is part of
control activities, by relating the amount of vaccine used to the
estimated number of persons at risk, including newborns.
Prepare a report
A report should be prepared at intervals during containment if
possible, and after the outbreak has been fully contained. Reports
may be: i) a popular account for the general public so that they
understand the nature of the outbreak and what is required of them
to prevent spread or recurrence; ii) an account for planners in the
Ministry of Health/local authority so as to ensure that the necessary
administrative steps are taken to prevent recurrence: iii) a scientific
report for publication in a medical journal or epidermiological
bulletin (reports of recent outbreaks are valuable aids when
teaching staff about outbreak control).
xxxi
Undertake experimental verification of agent and mode of
transmission
The verification of hypotheses about an outbreak may at times require
experimental evidence of biological feasibility. For example, it may be
necessary to show that sliced foodstuffs can be contaminated by an
infected slicing machine if this has not been proven during the outbreak
investigation. Such verification requires more laboratory facilities than are
available in the field, and is often not completed until long after the
outbreak has been contained.
xxxii
considers that deliberate use of biological agents to cause harm is a real
threat and that it can occur at any time; however, such risk analysis is not
generally considered a public health function.
According to national intelligence and defence services, there is evi-
dence that national and international networks have engineered biological
agents for use as weapons, in some instances with suggestions of attempts
to increase pathogenicity and to develop delivery mechanisms for their
deliberate use. Infection of humans may be a one-time occurrence, or may
be repeated over a period of time after the initial occurrence. The agent
used will determine whether there is a risk of person-to-person transmis-
sion after the initial and subsequent attacks; information on this risk is
covered in more detail under specific disease agents. Incubation period,
period of communicability and susceptibility are agent-specific.
Prevention of the deliberate use of biological agents presupposes
accurate and up-to-date intelligence about terrorists and their activities.
The agents may be manufactured using equipment necessary for the
routine manufacture of drugs and vaccines, and the possibility of dual use
of these facilities adds to the complexity of prevention. This has led some
analysts to regard a strong public health infrastructure, with rapid and
effective detection and response mechanisms for naturally occurring
infectious diseases of outbreak potential, as the only reasonable means of
responding to the threat of deliberately caused outbreaks of infectious
disease.
PREPAREDNESS FOR DELIBERATELY CAUSED OUTBREAKS
OF INFECTIOUS DISEASE
Routine national and global surveillance systems for naturally occurring
outbreak-prone and emerging infectious diseases enhance the capacity to
detect, and respond to, deliberately caused infectious diseases because the
public health detection and response mechanisms are the same. Adequate
background information on the natural behaviour of infectious diseases
will facilitate recognition of an unusual event and help determine whether
suspicions of a deliberate use should be investigated.
Preparedness for deliberate use also requires mechanisms that can be
immediately called into action to enhance communication and collabora-
tion among the public health authorities, the intelligence community, law
enforcement agencies and national defence systems as need may arise.
Preparedness should draw on existing plans for responding to large-scale
natural disasters, such as earthquakes or industrial or transportation
accidents, in which health care facilities are required to deal with a surge
of casualties and emergency admissions.
Most health workers will have little or no experience in managing illness
arising from several of the potential infectious agents; training in clinical
recognition and initial management may therefore be needed for first
xxxiii
responders. This training should include methods for infection control,
safe handling of diagnostic specimens and body fluids, and decontamina-
tion procedures. One of the most difficult issues for the public health
system is to decide whether preparedness should include stockpiling of
drugs, vaccines and equipment.
CONTROL
One of the routine criteria to be considered for outbreak assessment
under the revised International Health Regulations is suspected acci-
dental or deliberate release. The global outbreak alert and response
network (GOARN), facilitated by WHO, supports operational implemen-
tation of the International Health Regulations and will be called into
action immediately in case of deliberate use, in order to contribute to a
coordinated international response. Outbreaks of international impor-
tance, whether naturally occurring or thought to have been deliberately
caused, should be reported electronically by national governments to
[email protected]
Further information at WHO:
004122792531
http://www.who.int/csr/delibepidemics
xxxiv
ACQUIRED IMMUNODEFICIENCY
SYNDROME ICD-9 042-044, 279.5; ICD-10 B20-B24
(HIV infection, AIDS)
1. IdentificationAcquired Immunodeficiency syndrome (AIDS) is a
term first used by epidemiologists concerned about the emergence in
1981 of a cluster of diseases associated with loss of cellular immunity in
adults who had no obvious reason for presenting such immune deficien-
cies. AIDS was subsequently shown to be the late clinical stage of infection
with the human immunodeficiency virus (HIV). Within several weeks to
several months after infection with HIV, many persons develop an acute
self-limited mononucleosis-like illness lasting for a week or two. They may
then be free of clinical signs or symptoms for months or years before other
clinical manifestations develop. The severity of subsequent HIV-related
opportunistic infections or cancers is, in general, directly correlated with
the degree of immune system dysfunction.
More than a dozen opportunistic infections and several cancers were
considered to be sufficiently specific indicators of the underlying immu-
nodeficiency for inclusion in the initial (1982) case definition of AIDS. If
diagnosed by standard histological and/or culture techniques, these dis-
eases were accepted as meeting the surveillance definition of AIDS cases,
provided other known causes of immunodeficiency were ruled out.
This definition was broadened in 1987 to include additional indicator
diseases and to accept some of the indicator diseases as a presumptive
diagnosis if laboratory tests showed evidence of HIV infection. In 1993, a
revised surveillance definition of AIDS included additional indicator dis-
eases. In addition, all HIV-infected persons with a CD4 cell count of
under 200/mm3 or a CD4 T-lymphocyte percentage of total lymphocytes
under 14%, regardless of clinical status, are regarded as AIDS cases. The
1993 definition continues to be generally accepted for clinical use in most
industrialized countries; but it is often not used by developing countries,
which lack adequate laboratory facilities for CD4 cell counts or for the
histological or culture diagnosis of the surrogate indicator diseases.
The history of WHO AIDS surveillance started with a provisional clinical
case definition without serological confirmation and progressed to a
revised definition formulated in Bangui, Central African Republic in 1994.
Many countries now report new HIV infections rather than new AIDS
cases. The revised African AIDS case definition incorporates HIV serolog-
ical testing, if available, and includes a few indicator diseases (tuberculosis,
pneumococcal disease and non-typhoid salmonellosis, which are not
diseases of high virulence) as diagnostic in seropositive individuals.
Bacterial pneumonia is one of the commonest presentations. The
clinical manifestations of HIV infection in infants and young children
overlap with failure to thrive, inherited immunodeficiencies and other
1
2 / ACQUIRED IMMUNODEFICIENCY SYNDROME
10 / ACTINOMYCOSIS
12 / AMOEBIASIS
16 / ANGIOSTRONGYLIASIS
9. Methods of control
A. Preventive measures:
ABDOMINAL
ANGIOSTRONGYLIASIS ICD-9 128.8
INTESTINAL
ANGIOSTRONGYLIASIS ICD-10 B81.3
Since 1967, a syndrome similar to appendicitis has been recognized in
Costa Rica, predominantly among children under 13, with abdominal pain
and tenderness in the right iliac fossa and flank, fever, anorexia, vomiting,
abdominal rigidity, a tumour-like mass in the right lower quadrant and pain
on rectal examination. Leukocytosis is generally between 20 000 and
30 000/mm3 (SI units: 20 30 109/L), with eosinophils ranging from 11%
to 61%. On surgery, yellow granulations are found in the subserosa of the
intestinal wall, and eggs and larvae of Parastrongylus (Angiostrongylus)
in lymph nodes, intestinal wall and omentum; adult worms are found in
the small arteries, generally in the ileocaecal area. Human infections are
also known from Central and South America and the USA.
The reservoir of this parasite is a rodent (the cotton rat, Sigmodon
hispidus); slugs are the usual intermediate hosts. In the rodent host, adults
live in the mesenteric arteries of the ileocoecal area, and eggs are carried
into the intestinal wall. On embryonation, first-stage larvae migrate to the
lumen, are excreted in the feces and ingested by a slug, where they
develop to third stage, which is infective for rats and people. Infective
larvae are found in slug slime (mucus) left on soil or other surfaces. When
tiny slugs (or perhaps the slime) are ingested by people, infective larvae
penetrate the gut wall, maturing in the lymphatic nodes and vessels. Adult
worms migrate to the mesenteric arterioles of the ileocoecal region where
oviposition occurs. In people, most of the eggs and larvae degenerate and
cause a granulomatous reaction. There is no specific treatment; surgical
intervention is sometimes necessary.
[L. Savioli]
ANISAKIASIS / 19
ANISAKIASIS ICD-9 127.1; ICD-10 B81.0
1. IdentificationA parasitic disease of the human GI tract usually
manifested by cramping abdominal pain and vomiting, acquired through
ingestion of uncooked or undertreated marine fish containing larval
ascaridoid nematodes. The motile larvae burrow into the stomach wall
producing acute ulceration with nausea, vomiting and epigastric pain,
sometimes with hematemesis. They may migrate upwards and attach in
the oropharynx, causing cough. In the small intestine, they cause eosino-
philic abscesses, and the symptoms may mimic appendicitis or regional
enteritis. At times they perforate into the peritoneal cavity; rarely they
involve the large bowel.
Diagnosis is made by recognition of the 2-cm-long larvae invading the
oropharynx or by visualizing the larvae through gastroscopic examination
or in surgically removed tissue. Serological tests are under development.
9. Methods of control
20 / ANISAKIASIS
A. Preventive measures:
1) Avoid ingestion of inadequately cooked marine fish. Heating
to 60C (140F) for 10 minutes, blast-freezing to 35C
(31F) or below for 15 hours or freezing by regular means
at 23C (9.4F) for at least 7 days kills the larvae. The
latter control method is used with success in the Nether-
lands. Irradiation effectively kills the parasite.
2) Cleaning (evisceration) of fish as soon as possible after they
are caught reduces the number of larvae penetrating into
the muscles from the mesenteries.
3) Candling (exposure to a light source) for fishery products
where parasites can be visualized.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Not ordinarily justifiable,
Class 5 (see Reporting). A case or cases recognized in an
area not previously known to be involved or where control
measures are in effect must be reported.
2) Isolation: Not applicable.
3) Concurrent disinfection: Not applicable.
4) Quarantine: Not applicable.
5) Immmunization of contacts: Not applicable.
6) Investigation of contacts and source of infection: Examina-
tion of others possibly exposed at the same time may be
productive.
7) Specific treatment: Gastroscopic removal of larval abscesses;
excision of lesions.
C. Epidemic measures: None.
D. Disaster implications: None.
E. International measures: None.
[D. Engels]
ANTHRAX / 21
ANTHRAX ICD-9 022; ICD-10 A22
(Malignant pustule, Malignant oedema, Woolsorter disease,
Ragpicker disease)
1. IdentificationAn acute bacterial disease that usually affects the
skin, but may rarely involve the oropharynx, mediastinum or intestinal
tract. In cutaneous anthrax, itching of exposed skin surface occurs first,
followed by a lesion that becomes papular, then vesicular and in 2 6 days
develops into a depressed black eschar. Moderate to severe and very
extensive oedema usually surrounds the eschar, sometimes with small
secondary vesicles. Pain is unusual and, if present, is due to oedema or
secondary infection. The head, forearms and hands are common sites of
infection. The lesion has been confused with human Orf (see Orf virus
disease). Obstructive airway disease due to associated oedema may
complicate cutaneous anthrax of the face or neck. Untreated infections
may spread to regional lymph nodes and the bloodstream with over-
whelming septicaemia. The meninges can become involved. Untreated
cutaneous anthrax has a case-fatality rate between 5% and 20%; with
effective treatment, few deaths occur. The lesion evolves through typical
local changes even after the initiation of antibiotherapy.
Initial symptoms of inhalation anthrax are mild and nonspecific and may
include fever, malaise and mild cough or chest pain; acute symptoms of
respiratory distress, X-ray evidence of mediastinal widening, fever and
shock follow in 35 days, with death shortly thereafter. Intestinal anthrax
is rare and more difficult to recognize; it tends to occur in explosive food
poisoning outbreaks where abdominal distress is followed by fever, signs
of septicaemia and death in typical cases. An oropharyngeal form of
primary disease has been described.
Laboratory confirmation is through demonstration of the causative
organism in blood, lesions or discharges by direct polychrome methylene
blue (MFadyean)-stained smears or by culture, rarely by inoculation of
mice, guinea pigs or rabbits. Rapid identification of the organism through
immunodiagnostic testing, ELISA and PCR may be available in certain
reference laboratories.
2. Causative agentBacillus anthracis, a Gram-positive, encapsu-
lated, spore forming, nonmotile rod (specifically the anthrax spores of
B. anthracis are the infectious agent; vegetative B. anthracis rarely
establish disease.)
3. OccurrencePrimarily a disease of herbivores; humans and carni-
vores are incidental hosts. In most industrialized countries, anthrax is an
infrequent and sporadic human infection; it is an occupational hazard
primarily of workers who process hides, hair (especially from goats), bone
and bone products and wool; and of veterinarians and agriculture and
wildlife workers who handle infected animals. Human anthrax is endemic
in the agricultural regions of the world where anthrax in animals is
22 / ANTHRAX
common, such as Africa and Asia, south and central America, southern and
eastern Europe. New areas of infection in livestock may develop through
introduction of animal feed containing contaminated bone meal. Environ-
mental events such as floods may provoke epizootics. Anthrax has been
deliberately used to cause harm; as such, it could present in epidemiolog-
ically unusual circumstances.
4. ReservoirAnimals (normally herbivores, both livestock and wild-
life) shed the bacilli in terminal hemorrhages or blood at death. On
exposure to the air, vegetative cells sporulate and the B. anthracis spores,
which resist adverse environmental conditions and disinfection, may
remain viable in contaminated soil for years. Dormant anthrax spores may
be passively redistributed in the soil and adjacent vegetation through the
action of water, wind and other environmental forces. Scavengers feeding
on infected carcases may also disperse anthrax spores beyond the site of
death, either through blood and viscera adhering to their fur or feathers or
through excretion of viable anthrax spores in fecal matter. Dried or
otherwise processed skins and hides of infected animals may harbour
spores for years and are the fomites by which the disease is spread
worldwide.
5. Mode of transmissionContact with tissues of animals (cattle,
sheep, goats, horses, pigs and others) dying of the disease; possibly also
through biting flies that have partially fed on such animals; contact with
contaminated hair, wool, hides or products made from them (e.g. drums,
brushes, rugs); or contact with soil associated with infected animals or
with contaminated bone meal used in gardening. Inhalation anthrax
results from inhalation of spores in risky industrial processessuch as
tanning hides and processing wool or bonewith aerosols of B. anthracis
spores in an enclosed, poorly-ventilated area. Intestinal and oropharyngeal
anthrax may arise from ingestion of contaminated undercooked meat;
there is no evidence that milk from infected animals transmits anthrax.
The disease spreads among grazing animals through contaminated soil and
feed; and among omnivorous and carnivorous animals through contami-
nated meat, bone meal or other feeds derived from infected carcases.
Accidental infections may occur among laboratory workers.
In 1979, 66 persons were documented to have died of anthrax and 11
infected persons were known to have survived in an outbreak of largely
inhalation anthrax in Yekaterinburg (Sverdlovsk), the Russian Federation;
numerous other cases are presumed to have occurred. Investigations
disclosed that the cases occurred as the result of a plume emanating from
a biological research institute and led to the conclusion that the outbreak
had resulted from an accidental aerosol related to biological warfare
studies.
6. Incubation periodFrom 1 to 7 days, although incubation periods
up to 60 days are possible. In the Sverdlovsk outbreak, incubation periods
extended up to 43 days.
ANTHRAX / 23
7. Period of communicabilityPerson-to-person transmission is
rare. Articles and soil contaminated with spores may remain infective for
several years.
8. SusceptibilityThere is some evidence of inapparent infection
among people in frequent contact with the infectious agent; second
attacks can occur, but reports are rare.
9. Methods of control
A. Preventive measures:
ARENAVIRAL HEMORRHAGIC FEVERS IN THE WESTERN HEMISPHERE / 27
ARENAVIRAL HEMORRHAGIC
FEVERS IN THE WESTERN
HEMISPHERE ICD-9 078.7;
ICD-10 A96
JUNIN (ARGENTINIAN)
HEMORRHAGIC FEVER ICD-10 A96.0
MACHUPO (BOLIVIAN)
HEMORRHAGIC FEVER ICD-10 A96.1
GUANARITO (VENEZUELAN)
HEMORRHAGIC FEVER ICD-10 A96.8
SABIA (BRAZILIAN)
HEMORRHAGIC FEVER ICD-10 A96.8
1. IdentificationAcute febrile viral illnesses; duration is 715 days.
Onset is gradual with malaise, headache, retroorbital pain, conjunctival
injection, sustained fever and sweats, followed by prostration. There may
be petechiae and ecchymoses, accompanied by erythema of the face, neck
and upper thorax. An enanthem with petechiae on the soft palate is
frequent. Severe infections result in epistaxis, hematemesis, melaena,
hematuria and gingival hemorrhage. Encephalopathies, intention tremors
and depressed deep tendon reflexes are frequent. Bradycardia and hypo-
tension with clinical shock are common findings, and leukopenia and
thrombocytopenia are characteristic. Moderate albuminuria is present,
with cellular and granular casts and vacuolated epithelial cells in the urine.
Case-fatality rates range from 15% to 30% in untreated individuals.
Diagnosis is made through virus isolation or antigen detection in blood
or organs; by PCR, or serologically by IgM capture ELISA; or through the
detection of neutralizing antibody or rises in the titre thereof by ELISA or
IFA. Laboratory studies for virus isolation and neutralizing antibody tests
require BSL-4.
2. Infectious agentsAmong the 18 known New World arenaviruses
belonging to the Tacaribe complex, 4 have been associated with hemor-
rhagic fever in humans: Junn for the Argentine disease; the closely related
Machupo virus for the Bolivian; Guanarito virus for the Venezuelan; and
the Sabia virus for the Brazilian. These viruses are related to the Old World
arenaviruses that include the agents of Lassa fever and lymphocytic
choriomeningitis. A further virus, Whitewater Arroyo Virus, has been
found in rodents in North America.
3. OccurrenceArgentine hemorrhagic fever was first described
among corn harvesters in Argentina in 1955. Since then, the number of
cases reported from the endemic areas of the Argentine pampa has ranged
from 100 to 4000 per year, with an estimated cumulative total of 30 000
28 / ARENAVIRAL HEMORRHAGIC FEVERS IN THE WESTERN HEMISPHERE
symptomatic cases. The region at risk has been expanding northwards and
now potentially affects a population of 5 million. Disease occurs seasonally
from late February to October, predominantly in males, 63% in the age
group 20 49.
A similar disease, Bolivian hemorrhagic fever, caused by the related
virus, occurs sporadically or in epidemics in small villages of rural
northeastern Bolivia. In JulySeptember 1994, there were 9 cases with 7
deaths.
In 1989, an outbreak of severe hemorrhagic illness occurred in the
municipality of Guanarito, Venezuela; 104 cases with 26 deaths occurred
between May 1990 and March 1991 among rural residents in Guanarito
and neighboring areas. To date, about 200 confirmed cases have been
reported. Although the virus continued circulating in the rodent popula-
tion, there was an unexplained drop in human cases between 1992 and
2002 (one outbreak with 18 cases).
Sabia virus caused a fatal illness with hemorrhage and jaundice in Brazil
in 1990, a laboratory infection in Brazil in 1992 and a laboratory infection
treated with ribavirin in the USA in 1994.
4. ReservoirIn Argentina, wild rodents of the pampas (Calomys
musculinus and Calomys laucha) are the hosts for Junn virus. In Bolivia,
Calomys callosus is the reservoir animal. Cane rats (Zygodontomys
brevicauda) were shown to be the main reservoir of Guanarito virus. The
reservoir of Sabia virus is not known, although a rodent host is presumed.
5. Mode of transmissionTransmission to humans occurs primarily
by inhalation of small particle aerosols from rodent excreta containing
virus, from saliva or from rodents disrupted by mechanical harvesters.
Viruses deposited in the environment may also be infective when second-
ary aerosols are generated by farming and grain processing, when in-
gested, or by contact with cuts or abrasions. While uncommon, person-
to-person transmission of Machupo virus has been documented in health
care and family settings. Fatal scalpel accidents during necropsy as well as
laboratory infections without further person-to-person transmission have
been described.
6. Incubation periodUsually 714 days (in extreme cases 521
days).
7. Period of communicabilityRarely transmitted directly from
person to person, although this has occurred in both Argentine and
Bolivian diseases.
8. SusceptibilityAll ages appear to be susceptible, but protective
immunity of unknown duration follows infection. Subclinical infections
occur.
9. Methods of control
ARENAVIRAL HEMORRHAGIC FEVERS IN THE WESTERN HEMISPHERE /
29
A. Preventive measures: Specific rodent control in houses has
been successful in Bolivia. In Argentina, human contact most
commonly occurs in the fields, and rodent dispersion makes
control more difficult. An effective live attenuated Junn vaccine
has been administered to more than 150 000 persons in Argen-
tina. In experimental animals, this vaccine is effective against
Machupo but not Guanarito virus; it is still not known whether it
provides effective cross-protection in humans.
30 / ARTHROPOD-BORNE VIRAL DISEASES
ARTHROPOD-BORNE VIRAL
DISEASES
(Arboviral Diseases)
Introduction
Virus family,
genus, group Name of virus Vector Disease in humans Where found
TOGAVIRIDAE
Alphavirus *Barmah Forest Mosquito Fever, arthralgia, rash Australia
*Chikungunya Mosquito Fever, arthralgia, rash Africa, SE Asia, Philippines
(hemorrhage rare)
*Eastern equine encephalomyelitis Mosquito Encephalitis Americas
*Mayaro (Uruma) Mosquito Fever, arthralgia, rash S America
*Onyong-nyong Mosquito Fever, arthralgia, rash Africa
*Ross River Mosquito Fever, arthralgia, rash Australia, S Pacific
Semliki Forest Mosquito Encephalitis Africa
*Sindbis (Ockelbo, Babanki) Mosquito Fever, arthralgia, rash Africa, India, SE Asia, Europe,
Philippines, Australia,
Russian Federation
*Venezuelan equine encephalomyelitis Mosquito Fever, encephalitis Americas
*Western equine encephalomyelitis Mosquito Fever, encephalitis Americas
FLAVIVIRIDAE
Flavivirus *Banzi Mosquito Fever Africa
Bussuquara Mosquito Fever, arthralgia S America
*Dengue 1, 2, 3 and 4 Mosquito Fever, hemorrhage, rash Throughout tropics
Edge Hill Mosquito Fever, arthralgia Australia
Ilheus Mosquito Fever, encephalitis Central & S America
*Japanese encephalitis Mosquito Encephalitis, fever Asia, Pacific islands,
northern Australia
Kokobera Mosquito Fever, arthralgia Australia
Koutango Fever, rash Africa
*Kunjin Mosquito Fever, encephalitis Australia, Sarawak
ARTHROPOD-BORNE VIRAL DISEASES
* Asterisked groups and viruses are discussed in the text. See index for page numbers.
/ 31
DISEASES IN HUMANS CAUSED BY ARTHROPOD-BORNE VIRUSES 32 /
Virus family,
genus, group Name of virus Vector Disease in humans Where found
FLAVIVIRIDAE
Flavivirus (cont). *Louping ill Tick Encephalitis United Kingdom, western Eu-
rope
*Murray Valley encephalitis Mosquito Encephalitis Australia, N. Guinea
Negishi Unknown Encephalitis Japan
*Omsk hemorrhagic fever Tick Hemorrhage, fever Russian Federation
*Powassan Tick Encephalitis Canada, Russian Federation, USA
Rocio Mosquito Encephalitis Brazil
Sepik Mosquito Fever Papua New Guinea
*Spondweni Mosquito Fever Africa
*St. Louis encephalitis Mosquito Encephalitis, hepatitis Americas
*Tick-borne encephalitis Tick Encephalitis, paralysis Europe
*European subtype Tick Encephalitis, paralysis Europe
*Far Eastern subtype Tick Encephalitis Europe, Asia
Usutu Mosquito Fever, rash Africa, Europe
Wesselsbron Mosquito Fever Africa, SE Asia
ARTHROPOD-BORNE VIRAL DISEASES
*West Nile Mosquito Fever, encephalitis, rash Africa, North America, Indian
subcontinent, Middle East,
former Soviet Union, Europe
*Yellow fever Mosquito Hemorrhagic fever Africa, S & Central America
*Zika Mosquito Fever Africa, SE Asia
BUNYAVIRIDAE
Bunyavirus
*Group C
Apeu Mosquito Fever S America
Caraparu Mosquito Fever S and Central America
*Asterisked groups and viruses are discussed in the text. See index for page numbers.
BUNYAVIRIDAE
Bunyavirus (cont.) Itaqui Mosquito Fever S America
Madrid Mosquito Fever Panama
Marituba Mosquito Fever S America
Murutucu Mosquito Fever S America
Nepuyo Mosquito Fever S and Central America
Oriboca Mosquito Fever S America
Ossa Mosquito Fever Panama
Restan Mosquito Fever Trinidad, Suriname
Bunyamwera group *Bunyamwera Mosquito Fever, rash Africa
Germiston Mosquito Fever, rash Africa
Ilesha Unknown Fever, rash, hemorrhage Africa
Tensaw Mosquito Encephalitis N America
Bwamba group *Bwamba Mosquito Fever, rash Africa
California group *California encephalitis Mosquito Encephalitis USA
Guaroa Mosquito Fever S America, Panama
*Jamestown Canyon Mosquito Encephalitis USA, Canada
*LaCrosse Mosquito Encephalitis USA
*Snowshoe hare Mosquito Encephalitis Canada, China, Russian
Federation, USA
Tahyna (Lumbo) Mosquito Fever Africa, Asia, Europe
Trivittatus Mosquito Fever N America
Guama group Catu Mosquito Fever S America
Guama Mosquito Fever S America
Simbu group *Oropouche Midges Fever, meningitis S America, Panama
(Culicoides)
Phlebovirus
(*Sandfly fever group) Candiru Unknown Fever S. America
Chagres Phlebotomine Fever Central America
ARTHROPOD-BORNE VIRAL DISEASES
*Asterisked groups and viruses are discussed in the text. See index for page numbers.
/ 33
DISEASES IN HUMANS CAUSED BY ARTHROPOD-BORNE VIRUSES 34 /
Virus family,
genus, group Name of virus Vector Disease in humans Where found
*Colorado tick fever Colorado tick fever Tick Fever Canada, USA
RHABDOVIRIDAE
Ungrouped Orungo Mosquito Fever Africa
Vesicular stomatitis group *Vesicular stomatitis, Indiana & New Phlebotomine Fever, encephalitis Americas
Jersey
Vesicular stomatitis, Alagoas Phlebotomine Fever S America
*Chandipura Mosquito Fever Africa, India
ORTHOMYXOVIRIDAE *Thogoto Tick Meningitis Africa, Europe
NOT CLASSIFIED *Quaranfil Tick Fever Africa, Arabia
*Asterisked groups and viruses are discussed in the text. See index for page numbers.
36 / ARTHROPOD-BORNE VIRAL ARTHRITIS AND RASH
ARTHROPOD-BORNE VIRAL
ARTHRITIS AND RASH ICD-9 066.3; ICD-10 B33.1
(Polyarthritis and rash, Ross River fever, Epidemic polyarthritis)
ARTHROPOD-BORNE VIRAL ENCEPHALITIDES / 39
ARTHROPOD-BORNE VIRAL
ENCEPHALITIDES
I. MOSQUITO-BORNE VIRAL
ENCEPHALITIDES ICD-9 062
JAPANESE ENCEPHALITIS ICD-10 A83.0
WESTERN EQUINE ENCEPHALITIS ICD-10 A83.1
EASTERN EQUINE ENCEPHALITIS ICD-10 A83.2
ST. LOUIS ENCEPHALITIS ICD-10 A83.3
MURRAY VALLEY ENCEPHALITIS
(AUSTRALIAN ENCEPHALITIS) ICD-10 A83.4
LACROSSE ENCEPHALITIS ICD-10 A83.5
CALIFORNIA ENCEPHALITIS ICD-10 A83.5
ROCIO ENCEPHALITIS ICD-10 A83.6
JAMESTOWN CANYON
ENCEPHALITIS ICD-10 A83.8
1. IdentificationA group of acute inflammatory viral diseases of
short duration involving parts of the brain, spinal cord and meninges. Signs
and symptoms of these diseases are similar but vary in severity and rate of
progress. Most infections are asymptomatic; mild cases often occur as
febrile headache or aseptic meningitis. Severe infections are usually
marked by acute onset, headache, high fever, meningeal signs, stupor,
disorientation, coma, tremors, occasional convulsions (especially in in-
fants) and spastic (rarely flaccid) paralysis. Case-fatality rates range from
0.3% to 60%, rates for Japanese encephalitis (JE), Murray Valley (MV) and
eastern equine encephalomyelitis (EEE) are among the highest. Neurolog-
ical sequelae occur with variable frequency depending on age and
infecting agent; they tend to be most severe in infants infected with JE,
western equine encephalomyelitis (WEE) and EEE viruses. Mild leukocy-
tosis is usual; leukocytes in the CSF, predominantly lymphocytes, range
from 50 to 500/mm3 (SI units: 50 to 500 x 106/L) and may be 1000/mm3
or greater (SI units: 1000 x 106/L or greater) in infants infected with EEE
virus. The elderly are at greatest risk of encephalitis with St. Louis
encephalitis (SLE) or EEE virus infection, while children under 15 are at
greatest risk from LaCrosse virus infection and may develop seizures.
These diseases require differentiation from tick-borne encephalitides
(see below); encephalitic and nonparalytic poliomyelitis; rabies; mumps
meningoencephalitis; lymphocytic choriomeningitis; aseptic meningitis
due to enteroviruses; herpes encephalitis; postvaccinal or postinfection
encephalitides; and bacterial, mycoplasmal, protozoal, leptospiral and
mycotic meningitides or encephalitides. Venezuelan equine encephalomy-
elitis, Rift Valley fever and West Nile viruses primarily produce fever (see
40 / ARTHROPOD-BORNE VIRAL ENCEPHALITIDES
C. Epidemic measures:
9. Methods of control
A. Preventive measures:
46 / ARTHROPOD-BORNE VIRAL FEVERS
I. MOSQUITO-BORNE AND
CULICOIDES-BORNE VIRAL
FEVERS:
(Yellow fever and dengue are presented separately.)
I.A. VENEZUELAN EQUINE
ENCEPHALOMYELITIS VIRUS
DISEASE ICD-9 066.2; ICD-10 A92.2
(Venezuelan equine encephalitis, Venezuelan equine fever)
1. IdentificationClinical manifestations of this viral infection are
influenza-like, with abrupt onset of severe headache, chills, fever, myalgia,
retroorbital pain, nausea and vomiting. Conjunctival and pharyngeal
congestion are the only physical signs. Most infections are relatively mild,
with symptoms lasting 35 days. Some cases may have a diphasic fever
course; after a few days of fever, particularly in children, CNS involvement
may range from somnolence to frank encephalitis with disorientation,
convulsions, paralysis, coma and death.
Presumptive diagnosis is based on clinical and epidemiological grounds (expo-
sure in an area where an equine epizootic is in progress) and confirmed by virus
isolation, rise in antibody titres, detection of specific IgM or DNA. Virus can be
isolated in cell culture or in newborn mice from blood and nasopharyngeal
washings during the first 72 hours of symptoms; acute and convalescent sera
drawn 10 days apart can show rising antibody titres. Laboratory infections may
occur in the absence of proper containment facilities.
2. Infectious agentVenezuelan equine encephalomyelitis (VEE) vi-
rus, an alphavirus (Togaviridae, Alphavirus), with enzootic subtypes and
epizootic varieties of subtype 1.
3. OccurrenceEndemic in northern South America, Trinidad and
central America. The disease appears as epizootics, mainly in northern and
western South America; and in 1971 spread temporarily into the southern
part of the USA.
4. ReservoirEnzootic subtypes of VEE are maintained in a rodent-
mosquito cycle. Epizootic varieties of subtype 1 are believed to arise
periodically from enzootic VEE 1D viruses in northern South America.
During outbreaks, epizootic VEE virus is transmitted in a cycle involving
horses, which serve as the major source of virus, to mosquitoes, which in
turn infect humans. Humans also develop sufficient viraemia to serve as
hosts in a human-mosquito-human transmission cycle.
5. Mode of transmissionBite of an infected mosquito. VEE viruses have
been isolated from Culex (Melanoconion), Aedes, Mansonia, Psorophora,
ARTHROPOD-BORNE VIRAL FEVERS / 47
Haemagogus, Sabethes, Deinocerites and Anopheles mosquitoes, Simulium and
possibly ceratopogonid gnats. Infection by aerosol transmission is common;
primarily in laboratories; there is no evidence of horses-to-humans transmission.
6. Incubation periodUsually 2 6 days; can be as short as 1 day.
7. Period of communicabilityInfected humans and horses are
infectious for mosquitoes for up to 72 hours; infected mosquitoes
probably transmit virus throughout life.
8. SusceptibilityGeneral. Mild infections and subsequent immunity
occur frequently in endemic areas. Children are at greatest risk for
developing CNS infection.
9. Methods of control
A. Preventive measures:
C. Epidemic measures:
C. Epidemic measures:
ARTHROPOD-BORNE VIRAL HEMORRHAGIC FEVERS / 55
ARTHROPOD-BORNE VIRAL
HEMORRHAGIC FEVERS
I. MOSQUITO-BORNE DISEASES
(Dengue hemorrhagic fever and yellow fever are presented
separately.)
II. TICK-BORNE DISEASES
II.A. CRIMEAN-CONGO
HEMORRHAGIC FEVER ICD-9 065.0; ICD-10 A98.0
(Central Asian hemorrhagic fever)
1. IdentificationA viral disease with sudden onset of fever, malaise,
weakness, irritability, headache, severe pain in limbs and loins and marked
anorexia. Vomiting, abdominal pain and diarrhea occur occasionally. Flush
on face and chest and conjunctival injection develop early. hemorrhagic
enanthem of soft palate, uvula and pharynx, and a fine petechial rash
spreading from the chest and abdomen to the rest of the body are
generally associated with the disease, sometimes with large purpuric
areas.
There may be bleeding from gums, nose, lungs, uterus and intestine, but
only in serious or fatal cases does this occur in large amounts, often
associated with severe liver damage. Hematuria and albuminuria are
common but usually not massive. Fever is constantly elevated for 512
days or may be biphasic; it falls rapidly by lysis. Convalescence is
prolonged. Other findings are leukopenia, with lymphopenia more
marked than neutropenia. Thrombocytopenia is common. The reported
case-fatality rate ranges from 2% to 50%. In the Russian Federation, an
estimated 5 infections occur for each hemorrhagic case.
Diagnosis is through isolation of virus from blood (inoculation of cell
cultures or suckling mice) or PCR. Serological diagnosis is by ELISA,
reverse passive HI, IFA, CF, immunodiffusion or plaque-reduction neutral-
ization test. Specific IgM may be present during the acute phase; conva-
lescent sera often have low neutralization antibody titres.
2. Infectious agentThe Crimean-Congo hemorrhagic fever virus
(Bunyaviridae, Nairovirus).
3. OccurrenceObserved in the steppes of western Crimea and in
the Rostov and Astrakhan regions of the Russian Federation, as well as in
Afghanistan, Albania, Bosnia and Herzegovina, Bulgaria, western China,
the Islamic Republic of Iran, Iraq, Kazakhstan, Pakistan, South Africa,
Turkey, Uzbekistan, the Arabian Peninsula and sub-Saharan Africa. Most
patients are animal husbandry workers or medical personnel. Seasonal
occurrence in the Russian Federation is from June to September, the
period of vector activity.
56 / ARTHROPOD-BORNE VIRAL HEMORRHAGIC FEVERS
ARTHROPOD-BORNE VIRAL
HEMORRHAGIC FEVERS
II.B. OMSK HEMORRHAGIC
FEVER ICD-9 065.1; ICD-10 A98.1
KYASANUR FOREST
DISEASE ICD-9 065.2; ICD-10 A98.2
1. IdentificationThese two viral diseases have marked similarities:
Onset is sudden with chills, headache, fever, pain in lower back and limbs
and severe prostration, often associated with conjunctivitis, diarrhea and
vomiting by the 3rd or 4th day. A papulovesicular eruption on the soft
palate, cervical lymphadenopathy and conjunctival suffusion are usually
present. Confusion and encephalopathic symptoms may occur in patients
with Kyasanur Forest disease (KFD); often there is a biphasic course of
illness and fever, and the CNS abnormalities develop after an afebrile
period of 12 weeks.
Severe cases are associated with hemorrhages but with no cutaneous
rash. Bleeding occurs from gums, nose, GI tract, uterus and lungs (rarely
from the kidneys), sometimes for many days and, when severe, results in
shock and death; shock may also occur without manifest hemorrhage. The
febrile period ranges from 5 days to 2 weeks, at times with a secondary rise
in the third week. Estimated case-fatality rate is from 1% to 10%.
Leukopenia and thrombocytopenia are marked. Convalescence tends to
be slow and prolonged.
Diagnosis is made through isolation of virus from blood in suckling mice
or cell cultures (virus may be present up to 10 days following onset) or
through serological tests.
2. Infectious agentsThe Omsk hemorrhagic fever (OHF) and KFD
viruses are closely related; they belong to the tick-borne encephalitis-
louping ill complex of flaviviruses and are similar antigenically to the other
viruses in the complex.
3. OccurrenceIn the Kyasanur Forest of the Shimoga and Kanara
districts of Karnataka, India, principally in young adult males exposed
in the forest during the dry season, from November to June. In 1983,
there were 1155 cases with 150 deaths, the largest epidemic of KFD
ever reported. OHF occurs in the forest steppe regions of western
Siberia, within the Omsk, Novosibirsk, Kurgan and Tjumen regions.
The Novosibirsk district reported 2 to 41 cases per year between 1989
and 1998, mostly in muskrat trappers. Seasonal occurrence in each area
coincides with vector activity. Laboratory infections are common with
both viruses.
58 / ARTHROPOD-BORNE VIRAL HEMORRHAGIC FEVERS
ASCARIASIS / 59
ASCARIASIS ICD-9 127.0; ICD-10 B77
(Roundworm infection, Ascaridiasis)
1. IdentificationA helminthic infection of the small intestine gen-
erally associated with few or no overt clinical symptoms. Live worms,
passed in stools or occasionally from the mouth, anus, or nose, are often
the first recognized sign of infection. Some patients have pulmonary
manifestations (pneumonitis, Loffler syndrome) caused by larval migration
(mainly during reinfections) and characterized by wheezing, cough, fever,
eosinophilia and pulmonary infiltration. Heavy parasite burdens may
aggravate nutritional deficiency and, if chronic, may affect work and
school performance. Serious complications, sometimes fatal, include
bowel obstruction by a bolus of worms, particularly in children; or
obstruction of bile duct, pancreatic duct or appendix by one or more adult
worms. Reports of ascaris pancreatitis are increasing.
Diagnosis is made by identifying eggs in feces, or adult worms passed
from the anus, mouth or nose. Intestinal worms may be visualized by
radiological and sonographic techniques; pulmonary involvement may be
confirmed by identifying ascarid larvae in sputum or gastric washings.
2. Infectious agentAscaris lumbricoides, the large intestinal round-
worm of humans. A. suum, a similar parasite of pigs, rarely, if ever,
develops to maturity in humans, although it may cause larva migrans.
3. OccurrenceCommon and worldwide, with greatest frequency in
moist tropical countries where prevalence often exceeds 50%. Prevalence and
intensity of infection are usually highest in children between 3 and 8 years.
4. ReservoirHumans; ascarid eggs in soil.
5. Mode of transmissionIngestion of infective eggs from soil
contaminated with human feces or from uncooked produce contaminated
with soil containing infective eggs, but not directly from person to person
or from fresh feces. Transmission occurs mainly in the vicinity of the
home, where children, in the absence of sanitary facilities, fecally pollute
the area; heavy infections in children are frequently the result of ingesting
soil (pica). Contaminated soil may be carried long distances on feet or
footwear into houses and conveyances; transmission of infection by dust
is also possible.
Eggs reach the soil in the feces, then undergo development (embryo-
nation); at summer temperatures they become infective after 23 weeks
and may remain infective for several months or years in favorable soil.
Ingested embryonated eggs hatch in the intestinal lumen; the larvae
penetrate the gut wall and reach the lungs via the circulatory system.
Larvae grow and develop in the lungs, pass into the alveoli 9 10 days after
infection, ascend the trachea and are swallowed to reach the small
intestine 14 20 days after infection, where they grow to maturity, mate
60 / ASCARIASIS
and begin laying eggs 45 60 days after initial ingestion of the embryonated
eggs. Eggs passed by gravid females are discharged in feces.
6. Incubation periodThe life cycle requires 4 8 weeks to be
completed.
7. Period of communicabilityAs long as mature fertilized female
worms live in the intestine. Usual life span of adult worms is 12 months;
maximum may reach 24 months. The female worm can produce more
than 200 000 eggs a day. Under favorable conditions, embryonated eggs
can remain viable in soil for years.
8. SusceptibilitySusceptibility is general.
9. Methods of control
A. Preventive measures:
62 / ASPERGILLOSIS
BABESIOSIS / 65
BABESIOSIS ICD-9 088.8; ICD-10 B60.0
1. IdentificationA potentially severe and sometimes fatal disease
caused by infection with a protozoan parasite of red blood cells. Clinical
syndrome may include fever, chills, myalgia, fatigue and jaundice second-
ary to a hemolytic anaemia that may last from several days to a few months.
Seroprevalence studies indicate that most infections are asymptomatic. In
some cases, symptomless parasitaemia may last months or even years. Dual
infection with Borrelia burgdorferi, causal agent of Lyme disease, may
increase the severity of both diseases.
Diagnosis is through identification of the parasite within red blood cells
on a thick or thin blood film. Demonstration of specific antibodies by
serological analysis (IFA babesial DNA [PCR]) or isolation in appropriate
laboratory animals provides supportive evidence for the diagnosis. Differ-
entiation from Plasmodium falciparum may be difficult in patients who
have been in malarious areas or who may have acquired infection by blood
transfusion; if diagnosis is uncertain, manage as if it were a case of malaria
and send thick and thin blood films to an appropriate reference laboratory.
2. Infectious agentsSeveral species are known to cause disease in
humans. Babesia microti is the most common in the eastern and
midwestern USA, while Babesia isolate type WA1 parasites are most
common on the western coast. B. divergens is the most common species
in Europe.
3. OccurrenceWorldwide, scattered. In the USA, the geographic
distribution of B. microti infection has increased with the range of the tick
vector, Ixodes scapularis (formerly I. dammini). Babesiosis is endemic on
several eastern coastal islands and in southern Connecticut. Infection has
also been reported from Wisconsin and Minnesota. Babesia isolate type
WA1 and other species have caused human cases reported in California,
Washington and Missouri states in the USA, and in Mexico. In Europe,
human infections caused by B. divergens have been reported from France,
Germany, Ireland, the Russian Federation, Serbia and Montenegro (for-
merly the Federal Republic of Yugoslavia), Spain, Sweden and the United
Kingdom (Scotland). Human infections with less well-characterized spe-
cies have been reported from China (including Taiwan), Egypt, Japan,
Spain (Canary Islands), and South Africa.
4. ReservoirRodents for B. microti and cattle for B. divergens.
Reservoirs for Babesia isolate type WA1 and MO1 (Missouri) are unknown.
5. Mode of transmissionB. microti is transmitted primarily during
summer through the bite of nymphal Ixodes ticks (I. scapularis) that have
fed on infected deer mice (Peromyscus leucopus) and other small
mammals (e.g. voles, Microtus pennsylvanicus). The adult tick is normally
found on deer (which are not infected by the parasite) but may also feed
on other mammalian and avian hosts. The vector of B. divergens in Europe
66 / BABESIOSIS
68 / BALANTIDIASIS
A. Preventive measures:
70 / BARTONELLOSIS
9. Methods of control
A. Preventive measures:
BLASTOMYCOSIS / 73
BLASTOMYCOSIS ICD-9 116.0; ICD-10 B40
(North American blastomycosis, Gilchrist disease)
1. IdentificationA granulomatous mycosis, primarily of the lungs,
skin, bone and/or genitourinary tract with hematogenous dissemination.
Pulmonary blastomycosis may be acute or chronic. Acute infection is
rarely recognized but presents with the sudden onset of fever, cough and
a pulmonary infiltrate on chest X-ray. The acute disease resolves sponta-
neously after 13 weeks of illness. During or after the resolution of
pneumonia, some patients exhibit extrapulmonary infection. More com-
monly, there is an indolent onset that evolves into chronic disease.
Cough and chest ache may be mild or absent so that patients may
present with infection already spread to other sites, particularly the skin,
less often to bone, prostate or epididymis. Cutaneous lesions begin as
erythematous papules that become verrucous, crusted or ulcerated and
spread slowly. Most commonly, cutaneous lesions are located on the face
and distal extremities. Weight loss, weakness and low-grade fever are often
present; pulmonary lesions may cavitate. Untreated disseminated or
chronic pulmonary blastomycosis eventually progresses to death.
Direct microscopic examination of unstained smears of sputum and
lesional material shows characteristic broad-based budding forms of the
fungus, often dumbbell-shaped, which can be isolated through culture.
Serological tests are not useful. There is no commercially available skin
test.
2. Infectious agentBlastomyces dermatitidis (teleomorph, Ajello-
myces dermatitidis), a dimorphic fungus that grows as a yeast in tissue
and in enriched culture media at 37C (98.6F), and as a mould at room
temperature (25C/77F).
3. OccurrenceUncommon. Occurs sporadically in Africa (Demo-
cratic republic of the Congo, South Africa, the United Republic of
Tanzania), Canada, India, Israel, Saudi Arabia, central and southeastern
USA. Rare in children; more frequent in males than females. Disease in
dogs is frequent; it has also been reported in cats, a horse, a captive African
lion and a sea lion.
4. ReservoirMoist soil, particularly wooded areas along waterways
and undisturbed places, e.g. under porches or sheds.
5. Mode of transmissionConidia, typical of the mould or sapro-
phytic growth form, inhaled in spore-laden dust.
6. Incubation periodIndefinite; probably weeks to months. For
symptomatic infections, median is 45 days.
7. Period of communicabilityNo direct person-to-person or ani-
mal-to-person transmission.
74 / BLASTOMYCOSIS
BOTULISM / 75
BOTULISM
INTESTINAL BOTULISM
FORMERLY INFANT
BOTULISM ICD-9 005.1; ICD-10 A05.1
1. IdentificationHuman botulism is a serious but relatively rare
intoxication caused by potent preformed toxins produced by Clostridium
botulinum. Of the 7 recognized types of Clostridium botulinum, types A,
B, E, rarely F and possibly G cause human botulism.
There are 3 forms of botulism: foodborne (the classic form), wound, and
intestinal (infant and adult) botulism. The site of toxin production differs
for each form but all share the flaccid paralysis that results from botulinum
neurotoxin. The name intestinal botulism is now used instead of infant
botulism.
Foodborne botulism is a severe intoxication resulting from ingestion of
preformed toxin present in contaminated food. The characteristic early
symptoms and signs are marked fatigue, weakness and vertigo, usually
followed by blurred vision, dry mouth, and difficulty in swallowing and
speaking. Vomiting, diarrhea, constipation and abdominal swelling may
occur. Neurological symptoms always descend through the body: shoul-
ders are first affected, then upper arms, lower arms, thighs, calves, etc.
Paralysis of breathing muscles can cause loss of breathing and death unless
assistance with breathing (mechanical ventilation) is provided. There is no
fever and no loss of consciousness. Similar symptoms usually appear in
individuals who shared the same food. Most cases recover, if diagnosed
and treated promptly, including early administration of antitoxin and
intensive respiratory care. The case-fatality rate in the USA is 5%10%.
Recovery may take months.
Intestinal (infant) botulism is rare; it affects children below 1 and
(rarely) adults with altered GI anatomy and microflora. Ingested spores
germinate and produce bacteria that reproduce in the gut and release
toxin. In most adults and children over 6 months, germination would not
happen because natural defences prevent germination and growth of
Clostridium botulinum. Clinical symptoms in infants include constipa-
tion, loss of appetite, weakness, an altered cry, and a striking loss of head
control. Infant botulism has in some cases been associated with ingestion
of honey contaminated with botulism spores, and mothers are warned not
to feed raw honey to their infants.
Infant botulism ranges from mild illness with gradual onset to sudden
infant death; some studies suggest that it may cause an estimated 5% of
cases of sudden infant death syndrome (SIDS). The case fatality rate of
hospitalized cases is less than 1%; it is much higher without access to
hospitals with paediatric intensive care units.
Wound botulism, a rare disease, occurs when spores get into an open
76 / BOTULISM
of spores for infants include foods and dust. Honey, fed on occasion to
infants, can contain C. botulinum spores.
6. Incubation periodNeurological symptoms of foodborne botu-
lism usually appear within 1236 hours, sometimes several days after
eating contaminated food. The shorter the incubation period, the more
severe the disease and the higher the case-fatality rate. The incubation
period of intestinal botulism in infants is unknown, since the precise time
of ingestion often cannot be determined.
7. Period of communicabilityDespite excretion of C. botulinum
toxin and organisms at high levels (about 106 organisms/gram) in the feces
of intestinal botulism patients weeks to months after onset of illness, no
instance of secondary person-to-person transmission has been docu-
mented. Foodborne botulism patients typically excrete the toxin for
shorter periods.
8. SusceptibilitySusceptibility is general. Almost all patients hospi-
talized with intestinal botulism are between 2 weeks and 1 year old; 94%
are less than 6 months; the median age at onset was 13 weeks. Adults with
special bowel problems leading to unusual GI flora (or with a flora
unintentionally altered by antibiotic treatment for other purposes) may be
susceptible to intestinal botulism.
9. Methods of control
82 / BRUCELLOSIS
BURULI ULCER / 85
BURULI ULCER ICD-9 031.1; ICD-10 A31.1
1. IdentificationClassically, Buruli ulcer presents as a chronic
essentially painless skin ulcer with undermined edges and a necrotic
whitish or yellowish base (cotton wool appearance). Most lesions are
located on the extremities and occur among children living near wetlands
in rural tropical environments. Buruli ulcer often starts as a painless nodule
or a papule, which eventually ulcerates; other presentations, such as
plaques and indurated oedematous lesions, represent a rapidly dissemi-
nated form that does not pass through a nodular stage. Bones and joints
may be affected by direct spread from an overlying cutaneous lesion of
Buruli ulcer or through the blood stream; osteomyelitis due to Mycobac-
terium ulcerans is being reported with increasing frequency. Long-
neglected or poorly managed patients usually present with scars
sometimes hypertrophic or keloid, with partially healed areas or disabling
contractures, especially for lesions that cross joints. Marjolin ulcers
(squamous cell carcinoma) may develop in unstable or chronic non-
pigmented scars.
In experienced hands and in endemic areas, diagnosis can usually be
made on clinical grounds. Smears and biopsy specimens can be sent to the
laboratory for confirmation by the Ziehl-Neelsen stain for acid-fast bacilli,
culture, PCR and histopathology. Histopathological features of active
disease include the contiguous coagulation necrosis of subcutaneous fat
and demonstration of acid-fast bacilli. The differential diagnosis of
M. ulcerans disease includes the following: minor infections: insect bites
and a variety of dermatological conditions; nodules: cysts, lipomas, boils,
onchocercomas, lymphadenitis and mycoses; plaques: leprosy, cellulitis,
mycoses and psoriasis; oedematous forms: cellulitis, elephantiasis, actino-
mycosis; ulcers: tropical phagedenic ulcer, leishmaniasis, neurogenic
ulcer, yaws, squamous cell carcinoma, pyoderma gangrenosum, noma.
88 / CAMPYLOBACTER ENTERITIS
CAMPYLOBACTER
ENTERITIS ICD-9 008.4; ICD-10 A04.5
(Vibrionic enteritis)
1. IdentificationAn acute zoonotic bacterial enteric disease of
variable severity characterized by diarrhea (frequently with bloody stools),
abdominal pain, malaise, fever, nausea and/or vomiting. Symptoms usually
occur 25 days after exposure and may persist for a week. Prolonged
illness and/or relapses may occur in adults. Gross or occult blood with
mucus and WBCs is often present in liquid stools. Less common forms
include a typhoid-like syndrome, febrile convulsions, meningeal syn-
drome; rarely, post-infectious complications include reactive arthritis,
febrile convulsions or Guillain-Barre syndrome. Cases may mimic acute
appendicitis or inflammatory bowel disease. Many infections are asymp-
tomatic and occasionally self-limited.
Diagnosis is based on isolation of the organisms from stools using
selective media, reduced oxygen tension and incubation at 43C
(109.4F). Visualization of motile and curved, spiral or S-shaped rods
similar to those of Vibrio cholerae by stool phase contrast or darkfield
microscopy can provide rapid presumptive evidence for Campylobacter
enteritis.
2. Infectious agentsCampylobacter jejuni and, less commonly,
C. coli are the usual causes of Campylobacter diarrhea in humans. At
least 20 biotypes and serotypes occur; their identification may be
helpful for epidemiological purposes. Other Campylobacter organ-
isms, including C. larii and C. fetus subsp. fetus, have been associated
with diarrhea in normal hosts; standard culture methods may not detect
C. fetus.
3. OccurrenceThese organisms are an important cause of diar-
rheal illness in all age groups, causing 5%14% of diarrhea worldwide.
They are an important cause of travellers diarrhea. In industrialized
countries; children under 5 and young adults have the highest inci-
dence of illness. Persons who are immunocompromised show an
increased risk for infection and recurrences, more severe symptoms
and a greater likelihood of being chronic carriers. In developing
countries, illness is confined largely to children under 2, especially
infants. Common-source outbreaks have occurred, most often associ-
ated with foods, especially undercooked poultry, unpasteurized milk
and nonchlorinated water. The largest numbers of sporadic cases in
temperate areas occur in the warmer months.
4. ReservoirAnimals, most frequently poultry and cattle. Puppies,
kittens, other pets, swine, sheep, rodents and birds may also be sources
of human infection. Most raw poultry meat is contaminated with
C. jejuni.
CAMPYLOBACTER ENTERITIS / 89
5. Mode of transmissionIngestion of the organisms in under-
cooked meat, contaminated food and water, or raw milk; from contact
with infected pets (especially puppies and kittens), farm animals or
infected infants. Contamination of milk usually occurs from intestinal
carrier cattle; people and food can be contaminated from poultry,
especially from common cutting boards. The infective dose is often low.
Person-to-person transmission with C. jejuni appears uncommon.
6. Incubation periodUsually 2 to 5 days, with a range of 110 days,
depending on dose ingested.
7. Period of communicabilityThroughout the course of infection;
usually several days to several weeks. Individuals not treated with antibi-
otics may excrete organisms for 27 weeks. The temporary carrier state is
probably of little epidemiological importance, except for infants and
others who are incontinent of stool. Chronic infection of poultry and other
animals constitutes the primary source of infection.
8. SusceptibilityImmune mechanisms are not well understood, but
lasting immunity to serologically related strains follows infection. In
developing countries, most people develop immunity in the first 2 years of
life.
9. Methods of control
A. Preventive measures:
1) Control and prevention measures at all stages of the food-
chain, from agricultural production on the farm to process-
ing, manufacturing and preparation of foods in both commer-
cial establishments and the domestic environment.
2) Pasteurize all milk and chlorinate or boil water supplies. Use
irradiated foods or thoroughly cook all animal foodstuffs,
particularly poultry. Avoid common cutting boards and re-
contamination from uncooked foods within the kitchen after
cooking is completed.
3) Reduce incidence of Campylobacter on farms through spe-
cific interventions. Comprehensive control programs and
hygienic measures (change of boots and clothes; thorough
cleaning and disinfection) to prevent spread of organisms in
poultry and animal farms. Good slaughtering and handling
practices will reduce contamination of carcases and meat
products. Further reduction of contamination through freez-
ing poultry.
4) Recognize, prevent and control Campylobacter infections
among domestic animals and pets. Puppies and kittens with
diarrhea are possible sources of infection; erythromycin may
be used to treat their infections, reducing risk of transmission
to children. Stress handwashing after animal contact.
90 / CAMPYLOBACTER ENTERITIS
CANDIDIASIS / 91
CANDIDIASIS ICD-9 112; ICD-10 B37
(Moniliasis, Thrush, Candidosis)
1. IdentificationA mycosis usually confined to the superficial layers
of skin or mucous membranes, presenting clinically as oral thrush,
intertrigo, vulvovaginitis, paronychia or onychomycosis. Ulcers or
pseudomembranes may form in the oesophagus, stomach or intestine.
Candidemia commonly arises from intravascular catheters and may pro-
duce lesions in many organs: oesophagus, CNS, kidneys, vagina, spleen,
endocardium, liver, eyes, meninges, respiratory and urinary tracts and
native cardiac valves (or around prosthetic cardiac valves).
Diagnosis requires both laboratory and clinical evidence of candidiasis.
The single most valuable laboratory test is microscopic demonstration of
pseudohyphae and/or yeast cells in infected tissue or body fluids. Culture
confirmation is important, but isolation from sputum, bronchial washings,
stool, urine, mucosal surfaces, skin or wounds is not proof of a causal
relationship to the disease. Severe or recurrent oropharyngeal infection in
an adult with no obvious underlying cause should suggest the possibility
of HIV infection.
2. Infectious agentsCandida albicans, C. tropicalis, C. dubliniensis
and occasionally other species of Candida. Candida (Torulopsis) glabrata is
distinguished from other causes of candidiasis by lack of pseudohyphae
formation in tissue.
3. OccurrenceWorldwide. C. albicans is often part of the normal
human flora.
4. ReservoirHumans.
5. Mode of transmissionContact with secretions or excretions of
mouth, skin, vagina and feces, from patients or carriers; by passage from
mother to neonate during childbirth; and by endogenous spread.
6. Incubation periodVariable, 25 days for thrush in infants.
7. Period of communicabilityPresumably while lesions are
present.
8. SusceptibilityThe frequent isolation of Candida species from
sputum, throat, feces and urine in the absence of clinical evidence of
infection suggests a low level of pathogenicity or widespread immu-
nity. Oral thrush is a common, usually benign condition during the first
few weeks of life. Clinical disease occurs when host defences are low.
Local factors contributing to superficial candidiasis include interdigital
intertrigo and paronychia on hands with excessive water exposure
(e.g. cannery and laundry workers) and intertrigo in moist skinfolds of
obese individuals. Repeated clinical skin or mucosal eruptions are
common.
92 / CANDIDIASIS
94 / CAPILLARIASIS
CAPILLARIASIS
Three types of nematodes of the superfamily Trichuroidea, genus
Capillaria, produce disease in humans.
III. PULMONARY
CAPILLARIASIS ICD-9 128.8; ICD-10 B 83.8
A pulmonary disease manifested by fever, cough and asthmatic breath-
ing, caused by Capillaria aerophila (Thominx aerophila), a nematode
parasite of cats, dogs and other carnivorous mammals. Pneumonitis may
be severe; heavy infections may be fatal. The worms live in tunnels in the
CAPILLARIASIS / 97
epithelial lining of the trachea, bronchi and bronchioles; fertilized eggs are
sloughed into the air passages, coughed up, swallowed and discharged
from the body in the feces. In the soil, larvae develop in the eggs and
remain infective for a year or longer. Infection is acquired mainly by
children, through ingestion of infective eggs in soil or in soil-contaminated
food or water. Eggs may appear in the sputum in 4 weeks; symptoms may
appear earlier or later. Human cases have been recorded from the Islamic
Republic of Iran, Morocco and the former Soviet Union; animal infection
has been reported in North and South America, Europe, Asia and Australia.
[D. Engels]
98 / CAT-SCRATCH DISEASE
Control of
Communicable
Diseases Manual
David L. Heymann, MD, Editor
Eighteenth Edition 2004
ii
EDITOR
David L. Heymann, MD
World Health Organization
20 Avenue Appia, 1211 Geneva, SWITZERLAND
ASSOCIATE EDITOR
Michel C. Thuriaux, MD
World Health Organization
20 Avenue Appia, 1211 Geneva, SWITZERLAND
EDITORIAL BOARD
Georges C. Benjamin, MD, FACP
Executive Director
American Public Health Association
800 I Street NW, Washington DC 20001-3710, USA
John Bennett, MD
Head, Clinical Mycology Section
LCI, National Institute for Allergies and Infectious Diseases
National Institutes of Health
Clinical Center Room 11C304
9000 Rockville Pike, Bethesda MD 20892, USA
Johan Giesecke, MD
Professor, Infectious Disease Epidemiology
Karolinska Institute SE-171 77 Stockholm, SWEDEN
Marc Girard, MD
Director General
Fondation Merieux, 17 rue Bourgelat, 69002 Lyon, FRANCE
Donato Greco, MD
Director, National Epidemiology Centre
Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, ITALY
Scott B. Halstead, MD
Preventive Medicine and Biostatistics
Uniformed Services University of Health Sciences
5824 Edson Lane N., Bethesda MD 20852, USA
James M. Hughes, MD
Director, National Center for Infectious Diseases
Centers for Disease Control and Prevention
1600 Clifton Road NE, Mailstop C12, Atlanta GA 30333, USA
iii
Jacob John, MD
formerly Professor and Head, Department of Microbiology
Christian Medical College Hospital, Vellore Tamilnadu 632004, INDIA
Omar A. Khan, MD, MMS
Chair, Publications Board
American Public Health Association
800 I Street NW, Washington DC 20001-3710, USA
Ann Marie Kimball, MD, MPH
Professor, Epidemiology and Health Services/Director
Asia Pacific Emerging Infections Network
School of Public Health and Community Medicine
University of Washington
Box 354809, Seattle WA 98195, USA
Mary Ann Lansang, MD, MMSc
Executive Director, The INCLEN Trust
Section E, 5/F Ramon Magsaysay Center
1680 Roxas Boulevard, Malate, Manila 1004, THE PHILIPPINES
Angus Nicoll, MD
Director, PHLS Communicable Disease Surveillance Centre
61 Colindale Avenue, London NW9 5EQ, UNITED KINGDOM
Christophe Paquet, MD, MPH
Departement international et tropical
Institut de Veille Sanitaire
12 rue de Val dOsne, 94415 Saint Maurice, FRANCE
Aileen Plant, MD
Professor of International Health
Centre for International Health, Division of Health Sciences
Curtin University of Technology
GPO U1987, Perth WA, 6845, AUSTRALIA
Stanley A. Plotkin, MD
Emeritus Professor
University of Pennsylvania/Wistar Institute
4650 Wismer Road, Doylestown PA 18901, USA
Guenael Rodier, MD
Communicable Disease Surveillance & Response
World Health Organization
20 Avenue Appia, 1211 Geneva, SWITZERLAND
Bijan Sadrizadeh, MD
Senior Adviser to the Minister of Health
Ministry of Health and Medical Education
310 Hafez Avenue, Tehran, ISLAMIC REPUBLIC OF IRAN
iv
Robert E. Shope, MD
Professor of Pathology
University of Texas Medical Branch
301 University Blvd., Galveston, TX 77555, USA
Ron St. John, MD
Director General
Centre for Emergency Preparedness & Response
Health Canada, 100 Colonnade, Ottawa ON K1A 0K9, CANADA
Yasuhiro Suzuki, MD, PhD
Secretary of Health
Tochigi Prefecture, 1-1-20 Hanawada Utsunomiya, 320-8501 JAPAN
Pat Troop, MD, CBE, FFPH, FRCP
Chief Executive Officer
Health Protection Agency, 11th Floor, The Adelphi
1-11 John Adam Street, London WC2N 6HT, UNITED KINGDOM
Karl A. Western, MD, DTPH
Assistant Director for International Research
Director, Office of Global Affairs
National Institute for Allergies and Infectious Diseases
Room 2021, 6610 Rockledge Drive, Bethesda, MD 20892-6613, USA
Eng Kiong Yeoh, JP
Secretary for Health Welfare & Food
Health, Welfare, and Food Bureau, Government Secretariat
19/F Murray Building Garden Road Central, Hong Kong, CHINA
v
George Deepe, MD
Director, Infectious Diseases
University of Cincinnati
MSB 7163 POB 670560, Cincinatti, OH 45277-0560, USA
David W. Denning, MBBS
School of Medicine, University of Manchester and Wythenshawe
Hospital
Southmoor Road, Manchester M23NPL, UNITED KINGDOM
Don C. Dragon, PhD
Chemical and Biological Defence Station
Defence Research and Development Canada
Suffield, POB 4000 Station Main, Medicine Hat AB, T1A8K6, CANADA
Ramon Diaz Garcia, MD
Director, Department of Microbiology
Professor of Medical Microbiology.School of Medicine
University of Navarra, Pamplona, SPAIN
J. Stephen Dumler, MD
Director, Medical Microbiology, Dept of Pathology
The Johns Hopkins Medical Institutions
600 N. Wolfe Street, Baltimore, MD 21287, USA
Roderick Hay, MD
Professor (Medicine and Health Sciences)
Room G28A, Queens University Belfast, Whitla Medical Building
University Road Belfast BT71NN
Northern Ireland, UNITED KINGDOM
Dagmar Hulnska, PhD
Head, National Reference for Borreliosis
Department of Electron Microscopy, Epidemiology and Microbiology
National Institute of Public Health
Srobarova 48, Prague 10042, CZECH REPUBLIC
Jon Iredell, MD, PhD
Centre for Infectious Diseases and Microbiology
University of Sydney, Westmead Hospital, Sydney 2145, AUSTRALIA
Edward L. Kaplan
Professor, Department of Pediatrics
MMC 296, University of Minnesota Medical School
Room #820-2 Mayo Bldg.,
420 Delaware St SE, Minneapolis MN 55455 USA
Frans van Knapen
Chairman, Department of Public Health and Food Safety
Veterinary Medicine, Urecht University, THE NETHERLANDS
vi
John Mackenzie, MD
Department of Microbiology and Parasitology
School of Molecular and Microbial Sciences
The University of Queensland, Brisbane 4072, AUSTRALIA
Paul Martin, MD
Laboratoire des Listeria
Institut Pasteur, 28 rue du Dr Roux, 75724 Paris, FRANCE
Didier Raoult, MD
Directeur, Laboratoire des Bartonelloses
Universite de la Mediterranee
58 Boulevard Charles Livon, 12384 Marseille, FRANCE
Eduardo Salazar-Lindo, MD,
Professor, Department of Pediatrics
Cayetano Heredia University, Lima, PERU
Roberto Salvatella Agrelo, MD
National Adviser/Regional Chagas Disease Focal Point
PAHO/WHO Offices, Av Brasil 2697, CP 11300
Montevideo, URUGUAY
Luiz Carlos Severo, MD, PhD
Associate Professor of Internal Medicine/
Head, Laboratory of Mycology, School of Medicine
Federal University, Rio Grande do Sul, BRAZIL
Anders Sjostedt, MD
Professor, Department of Clinical Bacteriology
Ume University
SE-901 85, Ume, SWEDEN
F. Waldvogel, MD
Professor and Physician-in-chief, Medical Services 2
Hopital cantonal universitaire de Geneve, SWITZERLAND
David H. Walker, MD
Professor and Chairman, Department of Pathology
Executive Director, Center for Biodefense and Emerging Infectious
Diseases
University of Texas Medical Branch,
301 University Boulevard, Keiller Bldg, Galveston, TX 77555-0609, USA
Hiroshi Yanagawa, MD, FFPH,
President, Saitama Prefectural University
820 Sannomiya, Koshigaya-shi, Saitama-ken 343 8540, JAPAN
vii
Centers for Disease Control and Prevention
1600 Clifton Road NE, Mailstop C12, Atlanta, GA 30333, USA
Larry Anderson, MD Patricia Griffin, MD
C. Ben Beard, PhD Thomas Ksiazek, MD, DVM
Richard Besser, MD James Maguire, MD, MPH
Anna Bowen, MD, MPH Eric Mintz, MD, MPH
Chris Braden, MD Lyle Petersen, MD, MPH
Inger Damon, MD, MPH Pierre Rollin, MD
Amy Dechet, MD Nancy Rosenstein, MD
Amy Dubois, MD Jeremy Sobel, MD, MPH
Mark Eberhard, PhD Robert Tauxe, MD, MPH
Alicia Fry, MD Cynthia Whitney, MD, MPH
Kenneth Gage, PhD
viii
Susan E. Robertson, MD, MPH Nahoko Shindo, MD, PhD
Cathy Roth, PhD Klaus Stohr, DVM, PhD
Lorenzo Savioli, MD, MSc Hajime Toyofuku, DVM, VPH
Allan Schapira, MD, DSc Julie Symons
Jorgen Schlundt, DVM, PhD Jos Vandelaer, MD, MPH
ix
100 / CHANCROID
102 / CHICKENPOX/HERPES ZOSTER
108 / CHLAMYDIAL INFECTIONS
CHLAMYDIAL INFECTIONS
As laboratory techniques improve, chlamydial organisms are increas-
ingly implicated as causes of human disease. Chlamydiae are obligate
intracellular bacteria that differ from viruses and rickettsiae but, like the
latter, are sensitive to broad-spectrum antimicrobials. Those that cause
human disease are classified into 3 species:
1) Chlamydia psittaci, the etiologic agent of psittacosis (q.v.);
2) C. trachomatis, including serotypes that cause trachoma (q.v.),
genital infections (see below), chlamydial conjunctivitis (q.v.) and infant
pneumonia (q.v.), and other serotypes that cause lymphogranuloma
venereum (q.v.); and
3) C. pneumoniae, the cause of respiratory disease including pneumo-
nia (q.v.) and implicated in coronary artery disease.
Chlamydiae are increasingly recognized as important pathogens respon-
sible for several sexually transmitted infections, with infant eye and lung
infections consequent to maternal genital infection.
GENITAL INFECTIONS,
CHLAMYDIAL ICD-9 099.8; ICD-10 A56
1. IdentificationSexually transmitted genital infection is mani-
fested in males primarily as a urethritis, and in females as a cervical
infection. Clinical manifestations of urethritis are often difficult to distin-
guish from gonorrhoea and include moderate or scanty mucopurulent
discharges, urethral itching, and burning on urination. Asymptomatic
infection may be found in 1%25% of sexually active men. Possible
complications or sequelae of male urethral infections include epididymitis,
infertility and Reiter syndrome. In homosexual men, receptive anorectal
intercourse may result in chlamydial proctitis.
In the female, the clinical manifestations may be similar to those of
gonorrhoea and may present as a mucopurulent endocervical discharge,
with oedema, erythema and easily induced endocervical bleeding caused
by inflammation of the endocervical columnar epithelium. Up to 70% of
sexually active women with chlamydial infections are asymptomatic.
Complications and sequelae include salpingitis with subsequent risk of
infertility, ectopic pregnancy or chronic pelvic pain. Asymptomatic
chronic infections of endometrium and fallopian tubes may lead to the
same outcome. Less frequent manifestations include Bartholinitis, urethral
syndrome with dysuria and pyuria, perihepatitis (Fitz-Hugh-Curtis syn-
drome) and proctitis. Infection during pregnancy may result in premature
rupture of membranes and preterm delivery, and conjunctival and pneu-
monic infection of the newborn. Endocervical chlamydial infection has
been associated with increased risk of acquiring HIV infection.
Chlamydial infections may be acquired concurrently with gonorrhoea
and persist after gonorrhoea has been treated successfully. Because
gonococcal and chlamydial cervicitis are often difficult to distinguish
CHLAMYDIAL INFECTIONS / 109
clinically, treatment for both organisms is recommended when one is
suspected.
Diagnosis of nongonococcal urethritis (NGU) or cervicitis is usually
based on the failure to demonstrate Neisseria gonorrhoeae by smear and
culture; chlamydial etiology is confirmed by examination of intraurethral
or endocervical swab material by direct IF test with monoclonal antibody,
EIA, DNA probe, nucleic acid amplification test (NAAT) or cell culture.
NAATs can be used with urine specimens. The intracellular organisms are
less readily recoverable from the discharge itself. For other agents, see
Urethritis, nongonococcal.
2. Infectious agentChlamydia trachomatis, immunotypes D through
K, has been identified in approximately 35%50% of cases of nongonococcal
urethritis in the USA.
3. OccurrenceCommon worldwide; recognition has increased
steadily in the last two decades.
4. ReservoirHumans.
5. Mode of transmissionSexual intercourse.
6. Incubation periodPoorly defined, probably 714 days or longer.
7. Period of communicabilityUnknown. Relapses are probably
common.
8. SusceptibilitySusceptibility is general. No acquired immunity
has been demonstrated; cellular immunity is immunotype-specific.
9. Methods of control
A. Preventive measures:
URETHRITIS, NONGONOCOCCAL
AND NONSPECIFIC ICD-9 099.4; ICD-10 N34.1
(NGU, NSU)
While chlamydiae are the most frequently isolated causal agents in cases
of non-gonococcal urethritis, other agents are involved in a significant
number of cases. Ureaplasma urealyticum is considered the causal agent
in approximately 10%20% of NGU cases and Mycoplasma genitalium has
been implicated in some studies. Herpesvirus simplex type 2 is rarely
implicated; Trichomonas vaginalis, though rarely implicated, has been
shown to be a significant cause of urethritis in some high prevalence
settings. If laboratory facilities for demonstration of chlamydia are not
available, all cases of NGU (together with their sexual partners) are best
managed as though their infections were due to chlamydia, especially
since many chlamydia-negative cases also respond to antibiotherapy.
[F. Ndowa]
GENITAL INFECTIONS, CHLAMYDIAL / 109
GENITAL INFECTIONS,
CHLAMYDIAL ICD-9 099.8; ICD-10 A56
1. IdentificationSexually transmitted genital infection is mani-
fested in males primarily as a urethritis, and in females as a cervical
infection. Clinical manifestations of urethritis are often difficult to distin-
guish from gonorrhoea and include moderate or scanty mucopurulent
discharges, urethral itching, and burning on urination. Asymptomatic
infection may be found in 1%25% of sexually active men. Possible
complications or sequelae of male urethral infections include epididymitis,
infertility and Reiter syndrome. In homosexual men, receptive anorectal
intercourse may result in chlamydial proctitis.
In the female, the clinical manifestations may be similar to those of
gonorrhoea and may present as a mucopurulent endocervical discharge,
with oedema, erythema and easily induced endocervical bleeding caused
by inflammation of the endocervical columnar epithelium. Up to 70% of
sexually active women with chlamydial infections are asymptomatic.
Complications and sequelae include salpingitis with subsequent risk of
infertility, ectopic pregnancy or chronic pelvic pain. Asymptomatic
chronic infections of endometrium and fallopian tubes may lead to the
same outcome. Less frequent manifestations include Bartholinitis, urethral
syndrome with dysuria and pyuria, perihepatitis (Fitz-Hugh-Curtis syn-
drome) and proctitis. Infection during pregnancy may result in premature
rupture of membranes and preterm delivery, and conjunctival and pneu-
monic infection of the newborn. Endocervical chlamydial infection has
been associated with increased risk of acquiring HIV infection.
Chlamydial infections may be acquired concurrently with gonorrhoea
and persist after gonorrhoea has been treated successfully. Because
gonococcal and chlamydial cervicitis are often difficult to distinguish
clinically, treatment for both organisms is recommended when one is
suspected.
Diagnosis of nongonococcal urethritis (NGU) or cervicitis is usually
based on the failure to demonstrate Neisseria gonorrhoeae by smear and
culture; chlamydial etiology is confirmed by examination of intraurethral
or endocervical swab material by direct IF test with monoclonal antibody,
EIA, DNA probe, nucleic acid amplification test (NAAT) or cell culture.
NAATs can be used with urine specimens. The intracellular organisms are
less readily recoverable from the discharge itself. For other agents, see
Urethritis, nongonococcal.
2. Infectious agentChlamydia trachomatis, immunotypes D through
K, has been identified in approximately 35%50% of cases of nongonococcal
urethritis in the USA.
3. OccurrenceCommon worldwide; recognition has increased
steadily in the last two decades.
4. ReservoirHumans.
110 / GENITAL INFECTIONS, CHLAMYDIAL
112 / URETHRITIS, NONGONOCOCCAL AND NONSPECIFIC
URETHRITIS, NONGONOCOCCAL
AND NONSPECIFIC ICD-9 099.4; ICD-10 N34.1
(NGU, NSU)
While chlamydiae are the most frequently isolated causal agents in cases
of non-gonococcal urethritis, other agents are involved in a significant
number of cases. Ureaplasma urealyticum is considered the causal agent
in approximately 10%20% of NGU cases and Mycoplasma genitalium has
been implicated in some studies. Herpesvirus simplex type 2 is rarely
implicated; Trichomonas vaginalis, though rarely implicated, has been
shown to be a significant cause of urethritis in some high prevalence
settings. If laboratory facilities for demonstration of chlamydia are not
available, all cases of NGU (together with their sexual partners) are best
managed as though their infections were due to chlamydia, especially
since many chlamydia-negative cases also respond to antibiotherapy.
[F. Ndowa]
CHOLERA AND OTHER VIBRIOSES / 113
CHOLERA AND OTHER
VIBRIOSES ICD-9 001; ICD-10 A00
I. VIBRIO CHOLERAE
SEROGROUPS O1 AND O139
1. IdentificationAn acute bacterial enteric disease characterized in
its severe form by sudden onset, profuse painless watery stools (rice-water
stool), nausea and profuse vomiting early in the course of illness. In
untreated cases, rapid dehydration, acidosis, circulatory collapse, hypogly-
caemia in children, and renal failure can rapidly lead to death. In most
cases infection is asymptomatic or causes mild diarrhea, especially with
organisms of the El Tor biotype; asymptomatic carriers can transmit the
infection. In severe dehydrated cases (cholera gravis), death may occur
within a few hours, and the case-fatality rate may exceed 50%. With proper
and timely rehydration, this can be less than 1%.
Diagnosis is confirmed by isolating Vibrio cholerae of the serogroup O1
or O139 from feces. V. cholerae grows well on standard culture media, the
most widely used of which is TCBS agar. The strains are further charac-
terized by O1 and O139 specific antisera. Strains that agglutinate in O1
antisera are further characterized for serotype. If laboratory facilities are
not nearby or immediately available, Cary Blair transport medium can be
used to transport or store a fecal or rectal swab. For clinical purposes, a
quick presumptive diagnosis can be made by darkfield or phase micro-
scopic visualization of the vibrios moving like shooting stars, inhibited
by preservative-free, serotype-specific antiserum. For epidemiological pur-
poses, a presumptive diagnosis can be based on the demonstration of a
significant rise in titre of antitoxic and vibriocidal antibodies. In nonen-
demic areas, organisms isolated from initial suspected cases should be
confirmed in a reference laboratory through appropriate biochemical and
serological reactions and by testing the organisms for cholera toxin
production or for the presence of cholera toxin genes. A one-step dipstick
test for rapid detection of V. cholerae O1 and O139 has been developed
and should soon be available on the market to improve application of
effective public health interventions. In epidemics, once laboratory con-
firmation and antibiotic sensitivity have been established, it becomes
unnecessary to confirm all subsequent cases. Shift should be made to using
primarily the clinical case definition proposed by WHO as follows:
A. Preventive measures:
C. Epidemic measures:
E. International measures:
9. Methods of control
A. Preventive measures:
9. Methods of control
128 / CHROMOMYCOSIS
130 / CLONORCHIASIS
COCCIDIOIDOMYCOSIS / 133
COCCIDIOIDOMYCOSIS ICD-9 114; ICD-10 B38
(Valley fever, San Joaquin fever, Desert fever, Desert
rheumatism, Coccidioidal granuloma)
1. IdentificationA deep mycosis that generally begins as a respira-
tory infection. The primary infection may be entirely asymptomatic or
resemble an acute influenzal illness with fever, chills, cough and (rarely)
pleuritic pain. About 1 in 5 clinically recognized cases (an estimated 5% of
all primary infections) develops erythema nodosum, most common in
Caucasian females and rarest in American males of African origin. Primary
infection may heal completely without detectable sequelae; may leave
fibrosis, a pulmonary nodule that may or may not have calcified areas; may
leave a persistent thin-walled cavity; or most rarely, may progress to the
disseminated form of the disease.
An estimated 1 out of every 1000 cases of symptomatic coccidioidomy-
cosis becomes disseminated. Disseminated coccidioidomycosis is a pro-
gressive, uncommon, frequently fatal granulomatous disease characterized
by lung lesions and abscesses throughout the body, especially in subcuta-
neous tissues, skin, bone and the CNS. Coccidioidal meningitis resembles
tuberculous meningitis but runs a more chronic course.
Diagnosis is made through demonstration of fungus on microscopic
examination or through culture of sputum, pus, urine, CSF or biopsies of
skin lesions or organs. Handling cultures of the mould form is extremely
hazardous and must be carried out in a BSL-2 or BSL-3 facility. A positive
skin test to spherulin appears from 23 days to 3 weeks after onset of
symptoms. Precipitin and CF tests are usually positive within the first 3
months of clinical disease. The precipitin test detects IgM antibody, which
appears 12 weeks after symptoms appear and persists for 3 4 months.
Complement fixation tests detect mostly IgG antibody, which appears 12
months after clinical symptoms start and persists for 6 8 months. Serial
skin and serological tests may be necessary to confirm a recent infection
or indicate dissemination; skin tests are often negative in disseminated
disease, and serological tests may be negative in the immunocompro-
mised.
2. Infectious agentCoccidioides immitis, a dimorphic fungus. It
grows in soil and culture media as a saprophytic mould that reproduces by
arthroconidia; in tissues and under special conditions, the parasitic form
grows as spherical cells (spherules) that reproduce by endospore forma-
tion.
3. OccurrencePrimary infections are common only in arid and
semi-arid areas of the Western Hemisphere: the USA from California to
southern Texas; northern Argentina, Brazil (Nordeste), Colombia, Mexico,
Paraguay, Venezuela and central America. Elsewhere, dusty fomites from
endemic areas can transmit infection; disease has occurred in people who
have merely travelled through endemic areas. The disease affects all ages
134 / COCCIDIOIDOMYCOSIS
and all races. More than half the patients with symptomatic infection are
between 15 and 25; men are affected more frequently than women,
probably because of occupational exposure. Infection is most frequent in
summers following a rainy winter or spring, especially after wind and dust
storms. It is an important disease among migrant workers, archaeologists
and military personnel from nonendemic areas who move into endemic
areas. Since 1991, a marked increase of coccidioidomycosis has been
reported in California.
9. Methods of control
A. Preventive measures:
136 / CONJUNCTIVITIS/KERATITIS
I. ACUTE BACTERIAL
CONJUNCTIVITIS ICD-9 372.0; ICD-10
H10.0-H10.3
(Pinkeye, Sticky eye, Brazilian purpuric fever [ICD-10 A48.4])
1. IdentificationA clinical syndrome beginning with lacrimation,
irritation and hyperaemia of the palpebral and bulbar conjunctivae of one
or both eyes, followed by oedema of eyelids and mucopurulent discharge.
In severe cases, ecchymoses of the bulbar conjunctiva and marginal
infiltration of the cornea with mild photophobia may occur. Nonfatal
(except as noted below), the disease may last from 2 days to 23 weeks;
many patients have no more than hyperaemia of the conjunctivae and
slight exudate for a few days.
Confirmation of clinical diagnosis through microscopic examination of
a stained smear or culture of the discharge is required to differentiate
bacterial from viral or allergic conjunctivitis, or adenovirus/enterovirus
infection. Inclusion conjunctivitis (see below), trachoma and gonococcal
conjunctivitis are described separately.
2. Infectious agentsHaemophilus influenzae biogroup aegyptius
(Koch-Weeks bacillus) and Streptococcus pneumoniae appear to be the
most important; H. influenzae type b, Moraxella and Branhamella spp.,
Neisseria meningitidis and Corynebacterium diphtheriae may also pro-
duce the disease. H. influenzae biogroup aegyptius, gonococci (see
Gonoccocal infections), S. pneumoniae, S. viridans, various Gram-nega-
tive enteric bacilli and, rarely, Pseudomonas aeruginosa may produce the
disease in newborn infants.
3. OccurrenceWidespread and common worldwide, particularly in
warmer climates; frequently epidemic. In North America, infection with
H. influenzae biogroup aegyptius is confined largely to southern rural
areas from Georgia to California, primarily during summer and early
autumn; in North Africa and the Middle East, infections occur as seasonal
epidemics. Infection due to other organisms occurs throughout the world,
often associated with acute viral respiratory disease during cold seasons.
Occasional cases of systemic disease have occurred among children in
several communities in Brazil, 13 weeks after conjunctivitis due to a
unique invasive clone of Haemophilus influenzae biogroup aegyptius.
This severe Brazilian purpuric fever (BPF), had a 70% case-fatality rate
among more than 100 cases recognized over a wide area of Brazil
including 4 states; it may be clinically indistinguishable from meningococ-
caemia. The causal agent has been isolated from conjunctival, pharyngeal
and blood cultures. The disease has been restricted essentially to Brazil; 2
CONJUNCTIVITIS/KERATITIS / 137
cases in Australia were similar clinically, but the organism differed from
the Brazilian strain.
4. ReservoirHumans. Carriers of H. influenzae biogroup aegyptius
and S. pneumoniae are common in many areas during interepidemic
periods.
5. Mode of transmissionContact with discharges from conjuncti-
vae or upper respiratory tracts of infected people; contaminated fingers,
clothing and other articles, including shared eye makeup applicators,
multiple dose eye medications and inadequately sterilized instruments
such as tonometers. Eye gnats or flies may transmit the organisms
mechanically in some areas, but their importance as vectors is undeter-
mined and probably differs from area to area.
6. Incubation periodUsually 24 72 hours.
7. Period of communicabilityDuring the course of active infec-
tion.
8. SusceptibilityChildren under 5 are most often affected; inci-
dence decreases with age. The very young, the debilitated and the aged are
particularly susceptible to staphylococcal infections. Immunity after attack
is low grade and varies with the infectious agent.
9. Methods of control
A. Preventive measures: Personal hygiene, hygienic care and
treatment of affected eyes.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Obligatory report of epidem-
ics; no case report for classic disease, Class 4; for systemic
disease, Class 2 (see Reporting).
2) Isolation: Drainage and secretion precautions. Children
should not attend school during the acute stage.
3) Concurrent disinfection: Of discharges and soiled articles.
Terminal cleaning.
4) Quarantine: Not applicable.
5) Immmunization of contacts: Not applicable.
6) Investigation of contacts and source of infection: Usually not
beneficial for conjunctivitis; but must be undertaken for
Brazilian purpuric fever.
7) Specific treatment: Local application of an ointment or drops
containing a sulfonamide such as sodium sulfacetamide,
gentamicin or combination antibiotics such as polymyxin B
with neomycin or trimethoprim is generally effective. For
BPF, systemic treatment is required; isolates are sensitive to
both ampicillin and chloramphenicol and resistant to tri-
138 / CONJUNCTIVITIS/KERATITIS
C. Epidemic measures:
1) Prompt and adequate treatment of patients and their close
contacts.
2) In areas where insects are suspected of mechanically trans-
mitting infection, measures to prevent access of eye gnats or
flies to eyes of sick and well people.
3) Insect control, according to the suspected vector.
II. KERATOCONJUNCTIVITIS,
ADENOVIRAL ICD-9 077.1; ICD-10 B30.0
(Epidemic keratoconjunctivitis [EKC], Shipyard conjunctivitis,
Shipyard eye)
1. IdentificationAn acute viral disease of the eye, with unilateral or
bilateral inflammation of conjunctivae and oedema of the lids and perior-
bital tissue. Onset is sudden with pain, photophobia, blurred vision and
occasionally low-grade fever, headache, malaise and tender preauricular
lymphadenopathy. Approximately 7 days after onset in about half the
cases, the cornea exhibits several small round subepithelial infiltrates;
these may eventually form punctate erosions that stain with fluorescein.
Duration of acute conjunctivitis is about 2 weeks; it may continue to
evolve, leaving discrete subepithelial opacities that may interfere with
vision for a few weeks. In severe cases permanent scarring may result.
Diagnosis is confirmed by recovery of virus from appropriate cell
cultures inoculated with eye swabs or conjunctival scrapings; virus may be
visualized through FA staining of scrapings or through IEM; viral antigen
may be detected by ELISA testing. Serum neutralization or HAI tests may
identify type-specific titre rises.
2. Infectious agentsTypically, adenovirus types 8, 19 and 37 are
responsible, though other adenovirus types have been involved. Most
severe disease has been found in infections caused by types 8, 5 and 19.
3. OccurrencePresumably worldwide. Both sporadic cases and
large outbreaks have occurred in Asia, Europe, Hawaii and North America.
4. ReservoirHumans.
CONJUNCTIVITIS/KERATITIS / 139
5. Mode of transmissionDirect contact with eye secretions of an
infected person and, indirectly, through contaminated surfaces, instru-
ments or solutions. In industrial plants, epidemics are centered in first-aid
stations and dispensaries where treatment is frequently administered for
minor trauma to the eye; transmission occurs through fingers, instruments
and other contaminated items. Similar outbreaks have originated in eye
clinics and medical offices. Dispensary and clinic personnel acquiring the
disease may act as sources of infection. Family spread is common, with
children typically introducing the infection.
6. Incubation periodBetween 5 and 12 days, but in many instances
this duration is exceeded.
7. Period of communicabilityFrom late in the incubation period
to 14 days after onset. Prolonged viral shedding has been reported.
8. SusceptibilityThere is usually complete type-specific immunity
after adenoviral infections. Trauma, even minor, and eye manipulation
increase the risk of infection.
9. Methods of control
A. Preventive measures:
9. Methods of control
C. Epidemic measures:
1) Organize adequate facilities for the diagnosis and symptom-
atic treatment of cases.
2) Improve standards of hygiene and limit overcrowding wher-
ever possible.
IV. CHLAMYDIAL
CONJUNCTIVITIS ICD-9 077.0; ICD-10 A74.0
(Inclusion conjunctivitis, Paratrachoma, Neonatal inclusion
blennorrhoea, Sticky eye)
(See separate chapter for Trachoma.)
1. IdentificationIn the newborn, an acute conjunctivitis with pu-
rulent discharge, usually recognized within 512 days after birth. The
acute stage usually subsides spontaneously in a few weeks; inflammation
of the eye may persist for more than a year if untreated, with mild scarring
of the conjunctivae and infiltration of the cornea (micropannus). Chlamydial
CONJUNCTIVITIS/KERATITIS / 143
pneumonia (see Pneumonia, chlamydial) occurs in some infants with concur-
rent nasopharyngeal infection. Gonococcal infection must be ruled out.
In children and adults, an acute follicular conjunctivitis is seen typically
with preauricular lymphadenopathy on the involved side, hyperaemia,
infiltration and a slight mucopurulent discharge, often with superficial
corneal involvement. In adults, there may be a chronic phase with scant
discharge and symptoms that sometimes persist for more than a year if
untreated. The agent may cause symptomatic infection of the urethral
epithelium in men and women and the cervix in women, with or without
associated conjunctivitis.
Laboratory methods to assist diagnosis include isolation in cell culture,
antigen detection using IF staining of direct smears, EIA methods, DNA probe.
2. Infectious agentsChlamydia trachomatis of serovars D through
K. Feline strains of C. psittaci have caused acute follicular keratoconjunc-
tivitis in humans.
3. OccurrenceSporadic cases of conjunctivitis are reported world-
wide among sexually active adults. Neonatal conjunctivitis due to
C. trachomatis is common and occurs in 15%35% of newborns exposed
to maternal infection. Among adults with genital chlamydial infection, 1 in
300 develops chlamydial eye disease.
4. ReservoirHumans for C. trachomatis; cats for C. psittaci.
5. Mode of transmissionGenerally transmitted during sexual inter-
course; the genital discharges of infected people are infectious. In the
newborn, conjunctivitis is usually acquired by direct contact with infec-
tious secretions during transit through the birth canal. In utero infection
may also occur. The eyes of adults become infected by the transmission of
genital secretions to the eye, usually by the fingers. Older children may
acquire conjunctivitis from infected newborns or other household mem-
bers; they should be assessed for sexual abuse as appropriate. Outbreaks
reported among swimmers in nonchlorinated pools have not been con-
firmed by culture and may be due to adenoviruses or other known causes
of swimming pool conjunctivitis.
6. Incubation periodIn newborns, 512 days, ranging from 3 days
to 6 weeks; adults 6 19 days.
7. Period of communicabilityWhile genital or ocular infection
persists; carriage on mucous membranes has been observed as long as 2
years after birth.
8. SusceptibilityThere is no evidence of resistance to reinfection,
although the severity of the disease may be decreased.
9. Methods of control
A. Preventive measures:
144 / CONJUNCTIVITIS/KERATITIS
[S. Resnikoff]
146 / COXSACKIEVIRUS DISEASES
COXSACKIEVIRUS
DISEASES ICD-9 074; ICD-10 B34.1
The coxsackieviruses, members of the enterovirus group of the family
Picornaviridae, are the causal agents of a group of diseases discussed here, as
well as epidemic myalgia, enteroviral hemorrhagic conjunctivitis and menin-
gitis (see under individual disease listings) and coxsackievirus carditis (see
below). They cause disseminated disease in newborns; there is evidence
suggesting their involvement in the etiology of juvenile onset insulin-depen-
dent diabetes.
4. ReservoirHumans.
II. COXSACKIEVIRUS
CARDITIS ICD-9 074.2; ICD-10 B33.2
(Viral carditis, Enteroviral carditis)
1. IdentificationAn acute or subacute viral myocarditis or pericar-
ditis occurring (occasionally with other manifestations) as a manifestation
of infection with enteroviruses, especially group B coxsackievirus.
The myocardium is affected, particularly in neonates, in whom fever and
lethargy may be followed rapidly by heart failure with pallor, cyanosis,
COXSACKIEVIRUS DISEASES / 149
dyspnoea, tachycardia and enlargement of heart and liver. Heart failure
may be progressive and fatal, or recovery may take place over a few weeks;
some cases run a relapsing course over months and may show residual
heart damage. In young adults, pericarditis is the more common manifes-
tation, with acute chest pain, disturbance of heart rate, and often
dyspnoea. It may mimic myocardial infarction but is frequently associated
with pulmonary or pleural manifestations (pleurodynia). The disease may
be associated with aseptic meningitis, hepatitis, orchitis, pancreatitis,
pneumonia, hand, foot and mouth disease, rash or epidemic myalgia (see
Myalgia, epidemic).
Serological studies or virus isolation from feces usually help diagnosis,
but such results are inconclusive; a significant rise in specific antibody
titres is diagnostic. Virus is rarely isolated from pericardial fluid, myocar-
dial biopsy or postmortem heart tissue; such an isolation provides a
definitive diagnosis.
2. Infectious agentsGroup B coxsackievirus (types 15); occasion-
ally group A coxsackievirus (types 1, 4, 9, 16, 23) and other enteroviruses.
3. OccurrenceAn uncommon disease, mainly sporadic, but in-
creased during epidemics of group B coxsackievirus infection. Institu-
tional outbreaks, with high case-fatality rates in newborns, have been
described in maternity units.
4., 5., 6., 7., 8. and 9. ReservoirMode of transmission, Incuba-
tion period, Period of communicability, Susceptibility and Methods
of controlSee Epidemic myalgia.
[D. Lavanchy]
150 / CRYPTOCOCCOSIS
152 / CRYPTOSPORIDIOSIS
A. Preventive measures:
DIARRHEA CAUSED BY
CYCLOSPORA ICD-10 A07.8
This diarrheal disease is caused by Cyclospora cayetanensis, a sporu-
lating coccidian protozoon infecting the upper small bowel. The clinical
CRYPTOSPORIDIOSIS / 155
syndrome consists of watery diarrhea, nausea, anorexia, abdominal
cramps, fatigue and weight loss; fever is rare. The median incubation
period is about 1 week. Diarrhea in the immunocompetent can be
prolonged but is self-limited; mean duration of organism shedding was 23
days in Peruvian children. In the immunocompromised, diarrhea lasted for
months in some patients. It has also been associated with diarrhea in
travellers to Asia, the Caribbean, Mexico and Peru.
Diagnosis is made by identification in the stools of the 8 10 micrometer
size oocysts, about twice the size of Cryptosporidium parvum in wet
mount under phase contrast microscopy. A modified acid-fast stain or
modified safranin technique can be used. Organisms autofluoresce under
ultraviolet illumination.
Cyclospora is endemic in many developing countries. Transmission can
be food- or waterborne and occurs either through drinking or swimming
in contaminated water or through consumption of contaminated fresh
fruits and vegetables. Cyclospora oocysts in freshly excreted stool are not
infectious. They require days to weeks outside the host to sporulate and
become infectious. C. cayetanensis was responsible for multiple food-
borne outbreaks in North America linked to various types of fresh produce
imported from developing countries. Raspberries, basil and lettuce are
among the incriminated vehicles.
Produce should be washed thoroughly before it is eaten, although this
practice does not eliminate the risk of cyclosporiasis. Cyclospora is
resistant to chlorination.
Cyclosporiasis can be treated with a 7-day course of oral trimethoprim-
sulfamethoxazole (for adults, 160 mg trimethoprim plus 800 mg sulfame-
thoxazole twice daily; for children, 5 mg/kg trimethoprim plus 25 mg/kg
sulfamethoxazole twice daily). In patients who are not treated, illness can
be protracted, with remitting and relapsing symptoms. Treatment regi-
mens for patients who cannot tolerate sulfa drugs have not been identified.
Health care providers should consider the diagnosis of Cyclospora
infection in persons with prolonged diarrheal illness and request stool
specimens so that specific tests for this parasite can be made. In
jurisdictions where formal reporting mechanisms are not yet established,
clinicians and laboratory workers who identify cases of cyclosporiasis are
encouraged to inform the appropriate health departments.
[L. Savioli]
156 / CYTOMEGALOVIRUS INFECTIONS
CYTOMEGALOVIRUS
INFECTIONS
CYTOMEGALOVIRUS
DISEASE ICD-9 078.5; ICD-10 B25
CONGENITAL
CYTOMEGALOVIRUS
INFECTION ICD-9 771.1; ICD-10 P35.1
1. IdentificationWhile infection with cytomegalovirus (CMV) is
common, it often passes undiagnosed as a febrile illness without specific
characteristics. Serious manifestations of infection vary depending on the
age and immunocompetence of the individual at the time of infection.
The most severe form of the disease develops in 5%10% of infants
infected in utero. These show signs and symptoms of severe generalized
infection, especially involving the CNS and liver. Lethargy, convulsions,
jaundice, petechiae, purpura, hepatosplenomegaly, chorioretinitis, intra-
cerebral calcifications and pulmonary infiltrates may occur. Survivors
show mental retardation, microcephaly, motor disabilities, hearing loss
and evidence of chronic liver disease. Death may occur in utero; the
neonatal case-fatality rate is high for severely affected infants. Neonatal
CMV infection occurs in 0.3%1% of births, making it one of the most
common congenital infections; 90%95% of these intrauterine infections
are inapparent but 15%25% of these infants eventually manifest some
degree of neurosensory disability. Fetal infection may occur during either
primary or reactivated maternal infections; primary infections carry a
much higher risk for symptomatic disease and sequelae. Seronegative
newborns who receive blood transfusions from seropositive donors may
also develop severe disease.
Infection acquired later in life is generally inapparent but may cause a
syndrome clinically and hematologically similar to Epstein-Barr virus
mononucleosis, distinguishable by virological or serological tests and the
absence of heterophile antibodies. CMV causes up to 10% of all cases of
mononucleosis seen among university students and hospitalized adults
aged 2534. It is the most common cause of mononucleosis following
transfusion to nonimmune individuals; many posttransfusion infections are
clinically inapparent. Disseminated infection, with pneumonitis, retinitis,
GI tract disorders (gastritis, enteritis, colitis) and hepatitis, occurs in
immunodeficient and immunosuppressed patientsthis is a serious man-
ifestation of AIDS.
CMV is also the most common cause of posttransplant infection, both
for solid organ and bone marrow transplants; in the former, this is
particularly so with a seronegative recipient and a seropositive (carrier)
donor, whereas reactivation is a common cause of disease after bone
marrow transplant. In both cases, serious disease occurs in about 1 of 4
cases.
Optimal diagnosis in the newborn is through virus isolation or PCR,
CYTOMEGALOVIRUS INFECTIONS / 157
usually from urine. Positive tests for IgM antibodies to CMV are also
helpful. Diagnosis of CMV disease in the adult is made difficult by the high
frequency of asymptomatic and relapsing infections. Multiple diagnostic
modalities should be used if possible. Virus isolation, CMV antigen
detection (which can be done within 24 hours) and CMV DNA detection
by PCR or in situ hybridization can be used to demonstrate virus in organs,
blood, respiratory secretions or urine. Serological studies should be done
to demonstrate the presence of CMV specific IgM antibody or a 4-fold rise
in antibody titre. Interpretation of the results requires knowledge of the
patients clinical and epidemiological background.
2. Infectious agentHuman (beta) herpesvirus 5 (human CMV), a
member of the subfamily Betaherpesvirus of the family Herpesviridae;
includes 4 major genotypes and many strains, although there often is
cross-antigenicity among genotypes and strains.
3. OccurrenceWorldwide. In the USA, intrauterine infection occurs
in 0.5%1% of pregnancies, usually as the result of a primary infection. In
Europe, intrauterine infection is slightly less common. The situation in
developing countries is not well described, but infection generally occurs
early in life and most intrauterine infections are due to reactivation or
reinfection of maternal infection. Serum antibody prevalence in young
adults varies from 40% in highly industrialized countries to almost 100% in
some developing countries; it is higher in women than in men and is
inversely related to socioeconomic status within the USA; in the United
Kingdom, antibody prevalence is related to race rather than social class. In
various population groups, 8% 60% of infants begin shedding virus in the
urine during their first year of life as a result of infection acquired from the
mothers cervix or breastmilk.
4. ReservoirHumans are the only known reservoir of human CMV;
strains found in many animal species are not infectious for humans.
5. Mode of transmissionIntimate exposure through mucosal con-
tact with infectious tissues, secretions and excretions. CMV is excreted in
urine, saliva, breastmilk, cervical secretions and semen during primary and
reactivated infections. Persistent excretion may occur in infected new-
borns and immunosuppressed individuals. The fetus may be infected in
utero from either a primary or reactivated maternal infection; serious fetal
infection with manifest disease at birth occurs most commonly during a
mothers primary infection, but infection (usually without disease) may
develop even when maternal antibodies existed prior to conception.
Postnatal infection occurs more commonly in infants born to mothers
shedding CMV in cervical secretions at delivery; thus, transmission of the
virus from the infected cervix at delivery is a common means of neonatal
infection. Virus can be transmitted to infants through infected breastmilk,
an important source of infection but not of disease, except when milk
from a surrogate mother is given to seronegative infants. Viraemia may be
158 / CYTOMEGALOVIRUS INFECTIONS
A. Preventive measures:
160 / DENGUE FEVER
sion. Patients are infective for mosquitoes from shortly before the febrile
period to the end thereof, usually 35 days. The mosquito becomes
infective 812 days after the viraemic blood-meal and remains so for life.
8. SusceptibilitySusceptibility in humans is universal, but children
usually have a milder disease than adults. Recovery from infection with
one serotype provides lifelong homologous immunity but only short-term
protection against other serotypes and may exacerbate disease upon
subsequent infections (see Dengue hemorrhagic fever).
9. Methods of control
A. Preventive measures:
164 / DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK SYNDROME (DHF/DSS)
DERMATOPHYTOSIS / 167
DERMATOPHYTOSIS ICD-9 110; ICD-10 B35
(Tinea, Ringworm, Dermatomycosis, Epidermophytosis,
Trichophytosis, Microsporosis)
Dermatophytosis and tinea are general terms, essentially synonymous,
applied to fungal infection of keratinized areas of the body (hair, skin and
nails). Various genera and species of fungi known collectively as the
dermatophytes are causative agents. The dermatophytoses are subdivided
according to the site of infection.
A. Preventive measures:
1) Educate the public, especially parents, to the danger of
acquiring infection from infected individuals as well as from
dogs, cats and other animals.
2) In the presence of epidemics or in hyperendemic areas
where non-Trichophyton species are prevalent, survey heads
of young children by UV light (Wood lamp) before school
entry.
DIARRHEA, ACUTE / 175
DIARRHEA, ACUTE ICD-9 001-009; ICD-10 A09
[O. Fontaine]
176 / DIARRHEA, E. COLI
DIARRHEA CAUSED BY
ESCHERICHIA COLI ICD-9 008.0;
ICD-10 A04.0-A04.4
I. DIARRHEA CAUSED BY
ENTEROHEMORRHAGIC
STRAINS ICD-9 008.0; ICD-10 A04.3
(EHEC, Shiga toxin producing E. coli [STEC], E. coli O157:H7,
Verotoxin producing E. coli) [VTEC]
1. IdentificationThis category of diarrhea-causing E. coli was rec-
ognized in 1982 when an outbreak of hemorrhagic colitis occurred in the
USA and was shown to be due to an unusual serotype, E. coli O157:H7, not
previously incriminated as an enteric pathogen. The diarrhea may range
from mild and nonbloody to stools that are virtually all blood. Lack of fever
in most patients can help to differentiate this infection from that due to
other enteric pathogens. The most severe clinical manifestation of EHEC
infection is the hemolytic uraemic syndrome (HUS) (sometimes diagnosed
as thrombotic thrombocytopenic purpura (TTP) in adults). About 8% of
persons with E. coli O157:H7 diarrhea progress to this syndrome. Rates are
likely to vary for other serotypes. EHEC elaborate potent cytotoxins called
Shiga toxins 1 and 2 (also called verocytotoxins and previously called
Shiga-like toxins). Shiga toxin 1 is identical to the toxin elaborated by
Shigella dysenteriae 1; HUS is also a complication of S. dysenteriae 1
infection. The structural genes for the toxins are found on chromosomally-
encoded phages. Most EHEC strains have a chromosomal pathogenicity
island containing multiple virulence genes, including those encoding
proteins that cause attaching and effacing lesions.
In North America most strains of the most common EHEC serotype,
O157:H7, can be identified in stool cultures on sorbitol-MacConkey media
by their inability to ferment sorbitol. Because most other EHEC strains
ferment sorbitol, other techniques must be used, among which are
demonstrating the ability to elaborate Shiga toxins (a commercial assay is
available), or the use of DNA probes that identify the toxin genes. All EHEC
strains should sent to the state health department laboratory for serotyping
to monitor the frequency of various serotypes and to help detect out-
DIARRHEA, E. COLI / 177
breaks. In addition, E. coli O157:H7 strains are subtyped by pulsed-field gel
electrophoresis to help detect outbreaks.
2. Infectious agentThe main EHEC serotype in North America is
E. coli O157:H7; this serotype is thought to cause over 90% of cases of
diarrhea-associated HUS. The other most common serogroups in the
United States are O26, O111, O103, O45, and O121.
3. OccurrenceThese infections are an important problem in North
America, Europe, Japan, the southern cone of South America and southern
Africa. Their importance in the rest of the world is less well established.
4. ReservoirCattle are the most important reservoir of EHEC; hu-
mans may also serve as a reservoir for person-to-person transmission.
Other animals, including deer, may also carry EHEC.
5. Mode of transmissionMainly through ingestion of food contam-
inated with ruminant feces. Serious outbreaks, including cases of hemor-
rhagic colitis, HUS, and some deaths have occurred in the USA from beef
(usually as inadequately cooked hamburgers), produce (including melons,
lettuce, coleslaw, apple cider, and alfalfa sprouts), and unpasteurized dairy
milk. Direct person-to-person transmission occurs in families, child care
centers and custodial institutions. Waterborne transmission occurs both
from contaminated drinking water and from recreational waters.
6. Incubation periodRelatively long, 210 days, with a median of
3 4 days.
7. Period of communicabilityThe duration of excretion of the
pathogen is typically 1 week or less in adults but 3 weeks in one-third of
children. Prolonged carriage is uncommon.
8. SusceptibilityThe infectious dose is very low. Little is known
about differences in susceptibility and immunity, but infections occur in
persons of all ages. Children under 5 years old are most frequently
diagnosed with infection and are at greatest risk of developing HUS. The
elderly also appear to be at increased risk of complications.
9. Methods of control
C. Epidemic measures:
A. Preventive measures:
1) For general measures for prevention of fecal-oral spread of
infection, see Typhoid fever, 9A.
2) For adult travellers going for short periods of time to high-risk
areas where it is not easy to obtain safe food or water, the use
of prophylactic bismuth subsalicylate (2 tablets 4 times a day)
or antibiotics (norfloxacin, 400 mg daily) may be considered;
however each regimen is associated with health risks of its
own. A much preferable approach is to initiate very early
treatment, beginning with the onset of diarrhea, e.g. after the
second or third loose stool (See section 9B7.)
V. DIARRHEA CAUSED BY
ENTEROAGGREGATIVE
E. COLI ICD-9 008.0; ICD-10 A04.4
(EAggEC)
188 / DIPHTHERIA
A. Preventive measures:
DIPHYLLOBOTHRIASIS / 193
DIPHYLLOBOTHRIASIS ICD-9 123.4; ICD-10 B70.0
(Dibothriocephaliasis, Broad or fish tapeworm infection)
1. IdentificationAn intestinal tapeworm infection of long duration;
symptoms commonly are trivial or absent. A few patients in whom the
worms are attached to the jejunum rather than to the ileum develop
vitamin B12 deficiency anaemia. Massive infections may be associated with
diarrhea, obstruction of the bile duct or intestine, and toxic symptoms.
Identification of eggs or segments (proglottids) of the worm in feces
confirms the diagnosis.
2. Infectious agentsDiphyllobothrium latum (Dibothriocephalus
latus), D. pacificum, D. dendriticum, D. ursi, D. dalliae and D. kle-
banovskii, all cestodes.
3. OccurrenceThe disease occurs in lake regions in the northern
hemisphere, and subarctic, temperate and tropical zones where eating raw
or partly cooked freshwater fish is popular. Prevalence increases with age.
In North America, endemic foci have been found among Eskimos in Alaska
and Canada. Infections in the USA are sporadic and usually come from
eating uncooked fish from Alaska or, less commonly, from midwestern or
Canadian lakes. Japan and Peru report cases of D. pacificum infection
among consumers of marine (but not freshwater) fish.
4. ReservoirHumans; mainly infected hosts discharging eggs in
feces; reservoir hosts other than people include dogs, bears and other fish
eating mammals.
5. Mode of transmissionHumans acquire the infection by eating
raw or inadequately cooked fish. Eggs in mature segments of the worm are
discharged in feces into bodies of fresh water, where they mature and
hatch; ciliated embryos (coracidium) infect the first intermediate host
(copepods of the genera Cyclops and Diaptomus) and become procercoid
larvae. Susceptible species of freshwater fish (pike, perch, turbot, salmon)
ingest infected copepods and become second intermediate hosts, in
which the worms transform into the plerocercoid (larval) stage, which is
infective for people and fish eating mammals, e.g. fox, mink, bear, cat,
dog, pig, walrus and seal. The egg-to-egg cycle takes at least 11 weeks.
6. Incubation periodFrom 3 to 6 weeks between ingestion and
passage of eggs in the stool.
7. Period of communicabilityNo direct person-to-person transmis-
sion. Humans and other definitive hosts disseminate eggs into the envi-
ronment as long as worms remain in the intestine, sometimes for many
years.
8. SusceptibilityPeople are universally susceptible. No apparent
resistance follows infection.
194 / DIPHYLLOBOTHRIASIS
9. Methods of control
A. Preventive measures: Thorough heating of freshwater fish
(56C/133F for 5 minutes), freezing for 24 hours at 18C
(0F), or irradiation.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Official report not ordinarily
justifiable, Class 5 (see Reporting). Report indicated if a
commercial source is implicated.
2) Isolation: Not applicable.
3) Concurrent disinfection: Sanitary disposal of feces.
4) Quarantine: Not applicable.
5) Immmunization of contacts: Not applicable.
6) Investigation of contacts and source of infection: Not usually
justified.
7) Specific treatment: Praziquantel or niclosamide are the drugs
of choice.
C. Epidemic measures: None.
D. Disaster implications: None.
E. International measures: None.
[L. Savioli]
DRACUNCULIASIS / 195
DRACUNCULIASIS ICD-9 125.7; ICD-10 B72
(Guinea worm disease, Dracontiasis)
1. IdentificationAn infection of the subcutaneous and deeper tis-
sues by a large nematode. A blister appears, usually on a lower extremity
(especially the foot) when the gravid 60 100 cm long adult female worm
is ready to discharge its larvae. Burning and itching of the skin in the area
of the lesion and frequently fever, nausea, vomiting, diarrhea, dyspnoea,
generalized urticaria and eosinophilia may accompany or precede vesicle
formation. After the vesicle ruptures, the worm discharges larvae when-
ever the infected part is immersed in fresh water. The prognosis is good
unless bacterial infection of the lesion occurs; such secondary infections
may produce arthritis, synovitis, ankylosis and contractures of the involved
limb and may be life-threatening. Tetanus infections may occur via the site
of the lesion.
Diagnosis is made by visual recognition of the adult worm protruding
from a skin lesion or by microscopic identification of larvae.
2. Infectious agentDracunculus medinensis, a nematode.
3. OccurrenceIn Africa (13 countries south of the Sahara). Local
prevalence varies greatly. In some locales, nearly all inhabitants are
infected, in others, few, mainly young adults.
4. ReservoirHumans; there are no other known animal reservoirs.
5. Mode of transmissionLarvae discharged by the female worm
into stagnant fresh water are ingested by minute crustacean copepods
(Cyclops spp). In about 2 weeks, the larvae develop into the infective
stage. People swallow the infected copepods in drinking water from
infested step wells and ponds. The larvae are liberated in the stomach,
cross the duodenal wall, migrate through the viscera and become adults.
The female, after mating, grows and develops to full maturity, then
migrates to the subcutaneous tissues (most frequently of the legs).
6. Incubation periodAbout 12 months.
7. Period of communicabilityFrom rupture of vesicle until larvae
have been completely evacuated from the uterus of the gravid worm,
usually 23 weeks. In water, the larvae are infective for the copepods for
about 5 days. After ingestion by copepods, the larvae become infective for
people after 1214 days at temperatures above 25C (77F), and remain
infective in the copepods for about 3 weeks, the life span of an infected
copepod. No direct person-to-person transmision.
8. SusceptibilitySusceptibility is universal. No acquired immunity;
multiple and repeated infections may occur in the same person.
9. Methods of control/eradicationThe provision of safe, filtered
196 / DRACUNCULIASIS
drinking water and health education of the populations at risk could lead
to eradication of the disease. Foci of disease formerly present in some parts
of the Middle East and the Indian subcontinent have been eliminated in
this manner.
A. Preventive measures:
198 / EBOLA-MARBURG VIRAL DISEASES
EBOLA-MARBURG VIRAL
DISEASES ICD-9 078.8; ICD-10 A98.4, A98.3
(African hemorrhagic fever, Ebola virus hemorrhagic fever,
Marburg virus hemorrhagic fever)
1. IdentificationSevere acute viral illnesses, usually with sudden
onset of fever, malaise, myalgia and headache, followed by pharyngitis,
vomiting, diarrhea and maculopapular rash. In severe and fatal forms, the
hemorrhagic diathesis is often accompanied by hepatic damage, renal
failure, CNS involvement and terminal shock with multiorgan dysfunction.
Laboratory findings usually show lymphopenia, severe thrombocytopenia
and transaminase elevation (AST greater than ALT), sometimes with
hyperamylasaemia, elevated creatinine and blood urea nitrogen levels
during the final renal failure phase. Case-fatality rates for Ebola infections
in Africa have ranged from 50% to nearly 90%; 25% 80% of reported cases
of Marburg virus infection have been fatal.
Diagnosis is usually through a combination of assays detecting antigen
or RNA and antibody IgM or IgG. RT-PCR or ELISA antigen detection can
be used on blood, serum or organ homogenates (the presence of IgM
antibody suggests recent infection). Virus isolation attempts in cell culture
or suckling mice must be undertaken in a BSL-4 laboratory. ELISA is used
for specific IgM and IgG antibody detection in serum (the presence of IgM
antibody suggesting recent infection). Virus may sometimes be visualized
in liver, spleen, skin and other tissue sections by EM. Postmortem
diagnosis through immunohistochemical examination of formalin-fixed
skin biopsy or autopsy specimens is possible. IFA tests for antibodies have
often been misleading, particularly in serological surveys for past infec-
tion. Laboratory studies represent an extreme biohazard and should be
carried out only where protection against infection of the staff and
community is available (BSL-4 containment).
2. Infectious agentsVirions are 80 nanometers in diameter and 970
(Ebola) or 790 nanometers (Marburg) in length, and are respectively
members of Ebolavirus and Marburgvirus genus in the family Filoviridae.
Pleomorphic virions with branched, circular or coiled shapes are frequent
on electron microscopy preparation and may reach micrometers in length.
The Ebola and Marburg viruses are antigenically distinct. In the Republic
of Congo, Cote dIvoire, the Democratic Republic of the Congo (formerly
Zaire), Gabon, Sudan and Uganda, 3 different subtypes of Ebolavirus
(Cote dIvoire, Sudan and Zaire) have been associated with human disease.
A 4th Ebola subtype, Reston, causes fatal hemorrhagic disease in nonhu-
man primates originated from the Philippines in Asia; few human infec-
tions have been documented and those were clinically asymptomatic.
3. OccurrenceEbola disease was first recognized in 1976 in the
western Equatoria province of the Sudan and 800 kilometers away in Zaire
(now Democratic Republic of the Congo); more than 600 cases were
EBOLA-MARBURG VIRAL DISEASES / 199
identified in rural hospitals and villages; the case-fatality rate for these
nearly simultaneous outbreaks was respectively about 55% and about 90%.
A second outbreak occurred in the same area in Sudan in 1979. A new
subtype of Ebola virus was recovered from one person probably infected
while dissecting an infected chimpanzee in Cote-dIvoire in 1994. In 1995,
a major Ebola outbreak with 315 cases and 244 deaths was centered on
Kikwit (Democratic Republic of the Congo, formerly Zaire). Between the
end of 1994 and the third trimester of 1996 three outbreaks reported in
Gabon resulted in 150 cases and 98 deaths. A fatal secondary infection
occurred in a nurse in South Africa.
Between August 2000 and January 2001 an epidemic (425 cases, 224
deaths) occurred in northern Uganda. From October 2001 to April 2003,
several outbreaks were reported in Gabon and the Republic of Congo with
a total of 278 cases and 235 deaths; high numbers of deaths were reported
among wild animals in the region, particularly non-human primates.
Antibodies have been found in residents of other areas of sub-Saharan
Africa; their relation to the Ebola virus is unknown. End 2003, an outbreak
in the Republic of Congo, with high case-fatality and thought to be related
to contact with non-human primates, was rapidly controlled. In 2004 the
Russian Federation and the USA reported 2 laboratory infections (1 fatal).
Ebolavirus, Reston subtype, have been isolated from cynomolgus
monkeys (Macaca fascicularis) imported in 1989, 1990 and 1996 to the
USA and in 1992 to Italy from the same export facility Philippines; many
of these monkeys died. In Reston, 4 animal handlers with daily exposure
to these monkeys in 1989 developed specific antibodies.
Marburg disease has been recognized on 5 occasions: in 1967, in
Germany and what was then the Federal Republic of Yugoslavia, 31
humans (7 fatalities) were infected following exposure to African green
monkeys (Cercopithecus aethiops) imported from Uganda; in 1975, the
fatal index case of 3 cases diagnosed in South Africa had been infected in
Zimbabwe; in 1980, 2 linked cases, 1 of which fatal, were confirmed in
Kenya; in 1987, a fatal case occurred in Kenya. From 1998 to 2000, in the
Democratic Republic of the Congo, at least 12 cases were confirmed
among more than 145 suspected cases (case-fatality rate 80%) of Marburg
viral hemorrhagic fever.
ECHINOCOCCOSIS / 201
ECHINOCOCCOSIS ICD-9 122; ICD-10 B67
The larval stage (hydatid or cystic) of species of Echinococcus produces
disease in humans and other animals; disease characteristics depend upon
the infecting species. Cysts usually develop in the liver but also in other
viscera, nervous tissue or bone. They can be: a) unilocular or cystic, b)
multilocular or alveolar, c) polycystic.
I. ECHINOCOCCOSIS DUE TO
ECHINOCOCCUS
GRANULOSUS ICD-9 122.4; ICD-10 B67.0-B67.4
(Cystic or unilocular echinococcosis, Cystic hydatid disease)
1. IdentificationLarval stages of the tapeworm Echinococcus
granulosus, the most common Echinococcus, cause cystic echinococcosis
or hydatid disease. Hydatid cysts enlarge slowly and require several years
for development. Developed cysts range from 115 cm in diameter, but
may be larger. Infections may be asymptomatic until cysts cause notice-
able mass effect; signs and symptoms will vary according to location, cyst
size, cyst type and numbers. Ruptured or leaking cysts can cause severe
anaphylactoid reactions and may release protoscolices that can produce
secondary echinococcosis. Cysts are typically spherical, thick-walled and
unilocular, most frequently found in the liver and lungs, although they may
occur in other organs.
Clinical diagnosis is based on signs and symptoms compatible with a
slowly growing tumour, a history of residence in an endemic area, along
with association with canines. Differential diagnoses include malignancies,
amoebic abscesses, congenital cysts and tuberculosis. Radiography, com-
puterized tomography and sonography along with serological testing are
useful for laboratory diagnosis. WHO has developed a classification of
ultrasound images on cystic echinococcosis for diagnostic and prognostic
purposes and determination of the type of intervention required (see
Treatment 9B7). Definitive diagnosis in seronegative patients, however,
requires microscopic identification from specimens obtained at surgery or
by percutaneous aspiration; the potential risks of this (anaphylaxis,
spillage) can be avoided by ultrasound guidance and anthelmintic cover-
age. Species identification is based on finding thick laminated cyst walls
and protoscolices as well as on the structure and measurements of
protoscolex hooks.
2. Infectious agentEchinococcus granulosus, a small tapeworm of
dogs and other canids.
3. OccurrenceAll continents except Antarctica; depends on close
association of humans and infected dogs. Especially common in grazing
countries where dogs consume viscera containing cysts. Transmission has
been eliminated in Iceland and greatly reduced in Tasmania (Australia),
202 / ECHINOCOCCOSIS
A. Preventive measures:
1) Educate those at risk on avoidance of exposure to dog feces.
Emphasize basic hygiene practices such as handwashing,
washing fruits and vegetables and control of contacts with
infected dogs.
2) Interrupt transmission from intermediate to definitive hosts
by preventing access of dogs to potentially contaminated
(uncooked) viscera through supervision of livestock slaugh-
tering and safe disposal of infected viscera.
3) Incinerate or deeply bury infected organs from intermediate
hosts.
4) Periodically treat high-risk dogs; reduce dog populations to
the occupational need for them. Eliminate ownerless dogs
whenever possible and encourage responsible dog owner-
ship.
5) Field and laboratory personnel must observe strict safety
precautions to avoid ingestion of tapeworm eggs.
206 / EHRLICHIOSES
ENCEPHALOPATHY, SUBACUTE SPONGIFORM / 209
ENCEPHALOPATHY, SUBACUTE
SPONGIFORM ICD-9 046; ICD-10 A81
(Slow virus infections of the CNS)
A group of subacute degenerative diseases of the brain caused by
unconventional filterable infectious agents, with very long incubation
periods and no demonstrable inflammatory or immune response. The
infectious agents are thought to be unique proteins replicating by an as yet
unknown mechanism; the term prion may be an appropriate name and is
generally accepted. Humans evidence 4 prion diseases: Creutzfeldt-Jakob
disease (CJD), Gerstmann-Staussler-Scheinker syndrome (GSS), kuru, fatal
familial insomnia; and animals 5: scrapie in sheep and goats, transmissible
mink encephalopathy, chronic wasting disease of North American mule
deer and elk, feline spongiform encephalopathy affecting domestic cats
and bovine spongiform encephalopathy (BSE or mad cow disease).
During the late 1990s, a new form of Creutzfeldt-Jakob disease, variant CJD
(vCJD) emerged and has been linked causally to bovine spongiform
encephalopathy.
I. CREUTZFELDT-JAKOB
DISEASE ICD-9 046; ICD-10 A81.0
(Jakob-Creutzfeldt syndrome, Subacute spongiform
encephalopathy)
1. IdentificationCJD has 4 different categories: sporadic (sCJD)
accounting for 80%90% of cases, iatrogenic CJD associated with medical
use of infected pituitary-derived hormones and dura mater, familial CJD
and the recently described vCJD. Subacute onset with confusion, progres-
sive dementia and variable ataxia in patients aged 14 to over 80, almost all
(more than 95%) 35 or older. Myoclonic jerks appear later, together with
a variable spectrum of other neurological signs. Characteristically, routine
laboratory studies and the CSF cell count are normal and there is no fever.
Typical periodic high-voltage complexes are present in the electroenceph-
alogram (EEG) in about 70% of cases and the CSF 14-3-3 protein is elevated
in about 90%. The EEG is non-specific and the CSF 14-3-3 is not elevated
in vCJD. Disease progresses rapidly; death usually occurs within 312
months (median 4 months, mean 7 months). Pathological changes are
restricted to the CNS. About 10% of cases are associated with one of
several mutations in the gene on chromosome 20 that encodes for prion
protein (PrP), but only about one-third have a family history of CJD. One
familial form of human prion disease, GSS, is characterised neuropatho-
logically by many multicentric plaques and differs from CJD by an
extended duration of illness and early ataxia.
CJD must be differentiated from other forms of dementia (especially
Alzheimer disease), other infections (including encephalitis), toxic and
metabolic encephalopathies and, occasionally, tumours.
Reports from the United Kingdom over the past 15 years have described
210 / ENCEPHALOPATHY, SUBACUTE SPONGIFORM
over 130 000 BSE cases in domestic cattle. Concern that BSE might
transmit to humans through consumption of beef products led to large-
scale epidemiological and laboratory studies of BSE and CJD. In 1996 these
studies suggested that a new form of CJD, designated variant CJD (vCJD),
had occurred in the United Kingdom. This condition differs in several
ways from conventional or sporadic CJD (sCJD). vCJD occurs in a younger
age group (mean age at death 29, range 1573) than sCJD and its clinical
course is longer (mean 14 months vs. 7 months). The typical EEG changes
of sCJD are not seen in vCJD, but the MRI scan in vCJD shows high signal
in the posterior thalamus in about 90% of cases. By 2003 over 130 cases of
vCJD had been identified in the United Kingdom and a few cases have
been identified in other countries including Canada (1), France (6), Ireland
(1), Italy (1) and the USA (1). The cases in Canada, Italy and the USA had
a history of residence in the United Kingdom, where they may have been
exposed to BSE. All tested cases of vCJD to date have been homozygous for
methionine at codon 129 of the PrP gene. Laboratory transmission studies
show that the infectious agent in vCJD is likely to be that of BSE.
Diagnosis of all forms of CJD is based on clinical features together with
investigations, including EEG, CSF 14-3-3 assay and neuro-imaging. Brain
biopsy and, in vCJD, tonsil biopsy can provide antemortem diagnosis, but
these are invasive procedures and a definite diagnosis depends on
postmortem examination of brain tissue.
2. Infectious agentCJD is believed to be caused by a self-replicating
host-encoded protein or prion protein. This is transmissible in the
laboratory to many species, including wild and transgenic mice and
non-human primates.
3. OccurrencesCJD has been reported worldwide. The annual mor-
tality rate for sCJD approaches or exceeds 1 per million, with familial
clusters reported from Chile, Israel and Slovakia. The highest age-specific
average mortality rate (more than 5 cases/million) occurs in the 6579 age
group. Over 130 cases of vCJD have been reported, mainly from the
United Kingdom.
4. ReservoirHuman cases constitute the only known reservoir for
sCJD. The reservoir for vCJD is believed to be BSE-infected cattle.
5. Mode of transmissionThe mode of transmission for conven-
tional or sporadic CJD (sCJD) is unknown; de novo spontaneous genera-
tion of the self-replicating protein has been hypothesized. Iatrogenic cases
include 170 cases following human pituitary hormone therapy, 136
following human dura mater grafts, 3 linked to corneal grafts, and 6 linked
to neurosurgical instruments. In all these cases it is presumed that
infection from a case or cases of sCJD was inadvertently transmitted to
another person in the course of medical/surgical treatment. The mecha-
nism of transmission of BSE to humans has not been established, but the
favored hypothesis is that humans are infected through dietary consump-
ENCEPHALOPATHY, SUBACUTE SPONGIFORM / 211
tion of the BSE agent, probably beginning in the 1980s and now thought
to have ended because of changes in animal feeding and slaughtering
practices.
6. Incubation periodIatrogenic cases: 15 months to over 30 years;
the route of exposure influences incubation period: 15120 months with
direct CNS exposure, 4.530 years with peripheral exposure (human
pituitary hormones given by injection). Incubation period unknown in
naturally occurring sCJD and vCJD.
7. Period of communicabilityInfection present in lymphoid tis-
sues from early in the incubation period. The level of infectivity in the CNS
rises late in the incubation period and high levels of infectivity occur in the
CNS throughout symptomatic illness. In vCJD higher levels of infectivity
are present in lymphoid tissues during clinical illness (and probably during
incubation) than in sCJD. There is evidence that blood may be infective in
some forms of experimental prion disease.
8. SusceptibilityMutations of the PrP gene are associated with
familial forms of human prion disease, with an autosomal pattern of
inheritance. Polymorphic regions of the PrP gene influence susceptibility
to infection and incubation period in animal species, including sheep and
mice. In human disease, the genotype at codon 129 of the PrP gene
influences susceptibility to sCJD (70% methionine homozygous), vCJD
(100% methionine homozygous) and iatrogenic CJD (an excess of homozy-
gotes for either valine or methionine).
9. Methods of control
ENTEROBIASIS / 213
ENTEROBIASIS ICD-9 127.4; ICD-10 B80
(Pinworm infection, Oxyuriasis)
1. IdentificationA common intestinal helminthic infection that is
often asymptomatic. There may be perianal itching, disturbed sleep,
irritability and sometimes secondary infection of the scratched skin. Other
clinical manifestations include vulvovaginitis, salpingitis, and pelvic and
liver granulomata. Appendicitis and enuresis have rarely been reported as
possible associated conditions.
Diagnosis is made by applying transparent adhesive tape (tape swab or
pinworm paddle) to the perianal region and examining the tape or paddle
microscopically for eggs; the material is best obtained in the morning
before bathing or passage of stools. Examination should be repeated 3 or
more times before accepting a negative result. Eggs are sometimes found
on microscopic stool and urine examination. Female worms may be found
in feces and in the perianal region during rectal or vaginal examinations.
2. Infectious agentEnterobius vermicularis, an intestinal nema-
tode.
3. OccurrenceWorldwide, affecting all socioeconomic classes, with
high rates in some areas. It is the most common worm infection in North
America and other countries of temperate climate; prevalence is highest in
school-age children (in some groups near 50%), followed by preschoolers,
and is lowest in adults except for mothers of infected children. Infection
often occurs in more than one family member. Prevalence is often high in
domiciliary institutions.
4. ReservoirHumans. Pinworms of other animals are not transmis-
sible to people.
5. Mode of transmissionDirect transfer of infective eggs by hand
from anus to mouth of the same or another person, or indirectly through
clothing, bedding, food or other articles contaminated with parasite eggs.
Dustborne infection is possible in heavily contaminated households and
institutions. Eggs become infective within a few hours after being
deposited at the anus by migrating gravid females; eggs survive less than 2
weeks outside the host. Larvae from ingested eggs hatch in the small
intestine; young worms mature in the caecum and upper portions of the
colon. Gravid worms usually migrate actively from the rectum and may
enter adjacent orifices.
6. Incubation periodThe life cycle requires 2 6 weeks. Symptom-
atic disease with high worm burdens results from successive reinfections
occurring within months after initial exposure.
7. Period of communicabilityAs long as gravid females discharge
eggs on perianal skin. Eggs remain infective in an indoor environment for
about 2 weeks.
214 / ENTEROBIASIS
A. Preventive measures:
216 / ERYTHEMA INFECTIOSUM HUMAN PARVOVIRUS INFECTION
ERYTHEMA INFECTIOSUM
HUMAN PARVOVIRUS
INFECTION ICD-9 057.0; ICD-10 B08.3
(Fifth Disease)
1. IdentificationErythema infectiosum is a mild, usually nonfebrile,
viral disease with an erythematous eruption that occurs sporadically or in
epidemics, especially among children. Characteristic is a striking erythema
of the cheeks (slapped face appearance) frequently associated with a
lace-like rash on the trunk and extremities that fades but may recur for 13
weeks or longer on exposure to sunlight or heat (e.g. bathing). Mild
constitutional symptoms may precede onset of rash. In adults, the rash is
often atypical or absent, but arthralgias or arthritis lasting days to months
or even years may occur; 25% or more of infections may be asymptomatic.
Differentiation from rubella, scarlet fever and erythema multiforme often
necessary.
Severe complications of infection with the causal virus are unusual, but
persons with anaemia that requires increased red cell production (e.g.
sickle cell disease) may develop transient aplastic crisis, often in the
absence of a preceding rash. Intrauterine infection in the first half of
pregnancy has resulted in fetal anaemia with hydrops fetalis and fetal
death in less than 10% of such infections. Immunosuppressed people may
develop severe, chronic anaemia. Several diseases (e.g. rheumatoid arthri-
tis, systemic vasculitis, fulminant hepatitis and myocarditis) have been
reported to occur in association with erythema infectiosum, but no causal
link has been established.
Diagnosis, usually on clinical and epidemiological grounds; can be
confirmed by detection of specific IgM antibodies against parvovirus B19
(B19), or by a rise in B19 IgG antibodies. IgM titres begin to decline 30 60
days after the onset of symptoms. Diagnosis of B19 infection can also be
made by detecting viral antigens of DNA. PCR for B19 DNA is the most
sensitive of these tests and will often be positive during the first month of
an acute infection and in some persons for prolonged periods.
2. Infectious agentHuman parvovirus B19, a 2025-nanometer
DNA virus belonging to the family Parvoviridae. The virus replicates
primarily in erythroid precursor cells.
3. OccurrenceWorldwide. Common in children; both sporadic and
epidemic. In temperate zones, epidemics tend to occur in winter and
spring, with a periodicity of 37 years in a given community.
4. ReservoirHumans.
5. Mode of transmissionPrimarily through contact with infected
respiratory secretions; also, from mother to fetus, and parenterally through
transfusion of blood and blood products. B19 is resistant to inactivation by
various methods, including heating to 80C (176F) for 72 hours.
ERYTHEMA INFECTIOSUM HUMAN PARVOVIRUS INFECTION / 217
6. Incubation periodVariable; 4 20 days to development of rash or
symptoms of aplastic crisis.
7. Period of communicabilityIn people with rash illness alone,
greatest before onset of rash and probably not communicable thereafter.
People with aplastic crisis are infectious up to 1 week after onset of
symptoms, immunosuppressed people with chronic infection and severe
anaemia for months to years.
8. SusceptibilityUniversal susceptibility in persons with blood
group P antigen, the receptor for B19 erythroid cells; protection appears
to be conferred with development of B19 antibodies. Attack rates among
susceptibles can be high: 50% in household contacts, and 10% 60% in the
day care or school setting over a 2 6 month outbreak period. In the USA,
50% 80% of adults have serological evidence of past infection depending
on age and location.
9. Methods of control
A. Preventive measures:
EXANTHEMA SUBITUM / 219
EXANTHEMA SUBITUM ICD-9 057.8; ICD-10 B08.2
(Sixth disease, Roseola infantum)
1. IdentificationExanthema subitum is an acute, febrile rash illness
of viral etiology, that occurs usually in children under 4 but is most
common before 2. It is one manifestation of illnesses caused by human
herpesvirus-6B (HHV-6B). A fever, sometimes as high as 41C (106F),
appears suddenly and lasts 35 days. A maculopapular rash on the trunk
and later on the remainder of the body ordinarily follows lysis of the fever,
and the rash usually fades rapidly. Symptoms are generally mild, but febrile
seizures have been reported.
The spectrum of clinical illness in children includes high fever without
rash, inflamed tympanic membranes and, rarely, meningoencephalitis,
recurrent seizures or fulminant hepatitis. In immunocompetent adults, a
mononucleosis-like syndrome has been described, and in immunocompro-
mised hosts, pneumonitis has been noted. HHV-6 also causes asymptom-
atic and latent infection. Differentiation from similar vaccine-preventable
exanthems (e.g. measles, rubella) is often necessary.
Diagnosis can be confirmed by testing of paired sera for antibodies to
HHV-6 by IFA or by isolation of HHV-6. Practical IgM tests are not available;
an IgM response is usually not detectable until at least 5 days following the
onset of symptoms. Detection of HHV-6 DNA in blood by PCR in the
absence of concurrent IgG antibody shows promise as a future practical
method for rapid diagnosis.
2. Infectious agentHuman herpesvirus-6 (subfamily, betaherpesvi-
rus, genus Roseolovirus) is the most common cause of exanthema
subitum. HHV-6 can be divided into HHV-6A and HHV-6B by using
monoclonal techniques. Most HHV-6 infections in humans are now known
to be caused by HHV-6B. Cases of exanthema subitum due to human
herpesvirus 7 also occur.
3. OccurrenceWorldwide. In Hong Kong (China), Japan, the United
Kingdom and USA, where the seroepidemiology of HHV-6 has been best
described, incidence peaks in 6 12 month olds, with 65%100% sero-
prevalence by age 2 years. Seroprevalence in childbearing women ranges
from 80%100% in most of the world, although rates as low as 20% have
been observed in Morocco and 49% in Malaysia. Distinct outbreaks of
exanthema subitum or HHV-6 are rarely recognized; a seasonal predilec-
tion (late winter, early spring) has been described only in Japan.
4. ReservoirHumans appear to be the main reservoir of infection.
5. Mode of transmissionIn children, the rapid acquisition of early
childhood infection that follows the waning of maternal antibodies and the
high prevalence of HHV-6 viral DNA in salivary glands of adults suggest
that salivary contact with caregivers and parents is the most likely mode of
infection. However, in one USA study, the age specific infection rate
220 / EXANTHEMA SUBITUM
increased when there was more than one sibling in the household, which
suggests that children may also be important reservoirs for transmission.
Renal and hepatic transplants from HHV-6-infected donors can cause
primary infection in seronegative transplant recipients.
6. Incubation periodTen days, with a usual range of 515 days.
Onset of illness is usually 2 4 weeks after transplantation in susceptible
transplant recipients.
7. Period of communicabilityIn acute infection, unknown. Fol-
lowing acute infection, the virus may establish latency in lymph nodes,
kidney, liver, salivary glands and in monocytes. The duration of potential
communicability from these latent infections is unknown but may be
lifelong.
8. SusceptibilitySusceptibility is general. Infection rates in infants
under 6 months are low but increase rapidly thereafter, which suggests
that temporary protection is conferred by transplacentally acquired ma-
ternal antibodies. Second cases of exanthema subitum are rare. Latent
infection appears to be established in most persons but is of uncertain
clinical significance, notably in persons who are immunosuppressed,
among whom primary disease may be more severe and symptoms last
longer.
9. Methods of controlEffective measures are not available.
A. Preventive measures:
222 / FASCIOLIASIS
224 / FASCIOLOPSIASIS
A. Preventive measures:
FASCIOLOPSIASIS / 225
1) Educate the population at risk in endemic areas on the mode
of transmission and life cycle of the parasite.
2) Treat night soil to destroy eggs.
3) Bar swine from contaminating areas where water plants are
growing; do not feed water plants to pigs.
4) Dry suspected plants, or if plants are to be eaten fresh, dip
them in boiling water for a few seconds; both methods kill
metacercariae.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: In selected endemic areas;
in most countries, not a reportable disease, Class 3 (see
Reporting).
2) Isolation: Not applicable.
3) Concurrent disinfection: Safe disposal of feces.
4) Quarantine: Not applicable.
5) Immmunization of contacts: Not applicable.
6) Investigation of contacts and source of infection: In the
individual case, of little value. A community problem (see
9C).
7) Specific treatment: Praziquantel is the drug of choice.
C. Epidemic measures: Identify aquatic plants that harbour
encysted metacercariae and are eaten fresh, identify infected
snail species living in water with such plants and prevent
contamination of water with human and pig feces.
D. Disaster implications: None.
E. International measures: None.
[D. Engels]
226 / FILARIASIS
FILARIASIS DUE TO
WUCHERERIA
BANCROFTI ICD-9 125.0; ICD-10 B74.0
(Bancroftian filariasis)
FILARIASIS DUE TO BRUGIA
MALAYI ICD-9 125.1; ICD-10 B74.1
(Malayan filariasis, Brugian filariasis)
FILARIASIS DUE TO BRUGIA
TIMORI ICD-9 125.6; ICD-10 B74.2
(Timorean filariasis )
1. IdentificationBancroftian filariasis is an infection with the nem-
atode Wuchereria bancrofti, which normally resides in the lymphatics in
infected people. Female worms produce microfilariae that reach the
bloodstream 6 12 months after infection. Two biologically different forms
occur: in one, the microfilariae circulate in the peripheral blood at night
(nocturnal periodicity) with greatest concentrations between 10 pm and 2
am; in the other, microfilariae circulate continuously in the peripheral
blood, but occur in greater concentration in the daytime (diurnal). The
latter form is endemic in the South Pacific and in small rural foci in
southeastern Asia where the principal vectors are day-biting Aedes mos-
quitoes.
Clinical manifestations in regions of endemic filariasis include: a)
asymptomatic and parasitologically negative form; b) asymptomatic micro-
filaraemia; c) filarial fevers manifested by high fever, acute recurrent
lymphadenitis and retrograde lymphangitis with or without microfilarae-
mia; d) lymphostasis associated with chronic signs, including hydrocoele,
chyluria, lymphoedema and elephantiasis of the limbs, breasts and geni-
talia, with low-level or undetectable microfilaraemia; and e) tropical
pulmonary eosinophilic syndrome, manifested by paroxysmal nocturnal
asthma, chronic interstitial lung disease, recurrent low-grade fever, pro-
found eosinophilia and degenerating microfilariae in lung tissues but not in
the bloodstream (occult filariasis).
Brugian and Timorean filariasis are caused by the nematodes Brugia
malayi and B. timori respectively. The nocturnally periodic form of
B. malayi occurs in rural populations living in open rice-growing areas
throughout much of southeastern Asia. The subperiodic form infects
humans, monkeys and wild and domestic carnivores in the forests of
Malaysia and Indonesia. Clinical manifestations are similar to those of
FILARIASIS / 227
Bancroftian filariasis, except that the recurrent acute attacks of adenitis
and retrograde lymphangitis associated with fever are more severe, while
chyluria is uncommon and elephantiasis is usually confined to the distal
extremities, most frequently to the legs below the knees. Hydrocele and
breast lymphoedema are rarely if ever seen.
Brugia timori infections have been described on Timor (now Timor-
Leste) and on southeastern islands of Indonesia. Clinical manifestations are
comparable to those seen in B. malayi infections.
Microfilariae are best detected during periods of maximal microfilarae-
mia. Live microfilariae can be seen under low power in a drop of
peripheral blood (finger prick) on a slide or in hemolysed blood in a
counting chamber. Giemsa-stained thick and thin smears permit species
identification. Microfilariae may be concentrated by filtration of anticoag-
ulated blood through a Nuclepore filter (25 micrometer pore size), in a
Swinnex adapter, by the Knott technique (centrifugal sedimentation of 2
ml of anticoagulated blood mixed with 10 ml of 2% formalin), or by the
Quantitative Buffy Coat (QBC) acridine orange/microhematocrit tube
technique. More sensitive techniques to detect circulating filarial antigen
of W. bancrofti by ELISA or immunochromatic test cards have recently
become available commercially. The adult worms in nests can be diag-
nosed on ultrasound by the filarial dance sign.
2. Infectious agentsWuchereria bancrofti, Brugia malayi and
B. timori; long threadlike worms.
3. OccurrenceW. bancrofti, the most commonly prevalent of the 3
parasites responsible for 90% of the lymphatic filariases, is endemic in
most of the warm humid regions of the world, including Latin America
(scattered foci in Brazil, Costa Rica, the Dominican Republic, French
Guyana, Guyana, Haiti, and Suriname), Africa, Asia and the Pacific islands.
It is common in those urban areas where conditions favor breeding of
vector mosquitoes. In general, nocturnal subperiodicity in Wuchereria-
infected areas of the Pacific is found West of 140E longitude, and diurnal
subperiodicity East of 180E longitude. B. malayi is endemic in rural
southwestern India, southeastern Asia, central and northern coastal areas
of China and the Republic of Korea. B. timori occurs in Timor-Leste and
on the rural islands of Flores, Alor and Roti in southeastern Indonesia.
4. ReservoirHumans with microfilariae in the blood for W. ban-
crofti, periodic B. malayi and B. timori. In Malaysia, southern Thailand,
the Philippines and Indonesia, cats, civets (Viverra tangalunga) and
nonhuman primates serve as reservoirs for subperiodic B. malayi but
zoonotic transmission is not of much significance.
5. Mode of transmissionBite of a mosquito harbouring infective
larvae. W. bancrofti is transmitted by many species, the most important
being Culex quinquefasciatus, Anopheles gambiae, An. funestus, Aedes
polynesiensis, Ae. scapularis and Ae. pseudoscutellaris. B. malayi is
228 / FILARIASIS
[G. Biswas]
232 / FOODBORNE INTOXICATIONS
FOODBORNE INTOXICATIONS
(Food poisoning)
I. STAPHYLOCOCCAL FOOD
INTOXICATION ICD-9 005.0; ICD-10 A05.0
1. IdentificationAn intoxication (not an infection) of abrupt and
sometimes violent onset, with severe nausea, cramps, vomiting and
prostration, often accompanied by diarrhea and sometimes with subnor-
mal temperature and lowered blood pressure. Deaths are rare; illness
commonly lasts only a day or two, but can take longer in severe cases; in
rare cases, the intensity of symptoms may require hospitalization and
surgical exploration. Diagnosis is easier when a group of cases presents
the characteristic acute, predominantly upper GI symptoms and the short
interval between eating a common food item and the onset of symptoms
(usually within 4 hours).
Differential diagnosis includes other recognized forms of food poisoning
as well as chemical poisons.
In the outbreak setting, recovery of large numbers of staphylococci (105
organisms or more/gram of food) on routine culture media, or detection of
enterotoxin from an epidemiologically implicated food item confirms the
diagnosis. Absence of staphylococci on culture from heated food does not
rule out the diagnosis; a Gram stain of the food may disclose the organisms
that have been heat killed. It may be possible to identify enterotoxin or
thermonuclease in the food in the absence of viable organisms. Isolation of
organisms of the same phage type from stools or vomitus of 2 or more ill
persons confirms the diagnosis. Recovery of large numbers of enterotoxin-
producing staphylococci from stool or vomitus from a single person
supports the diagnosis. Phage typing and enterotoxin tests may help
epidemiological investigations but are not routinely available or indicated;
in outbreak settings, pulsed field gel electrophoresis may be more useful
in subtyping strains.
2. Toxic agentSeveral enterotoxins of Staphylococcus aureus, sta-
ble at boiling temperature, even by thermal process. Staphylococci
multiply in food and produce the toxins at levels of water activity too low
for the growth of many competing bacteria.
3. OccurrenceWidespread and relatively frequent; one of the prin-
cipal acute food intoxications worldwide. About 25% of people are
carriers of this pathogen.
4. ReservoirHumans in most instances; occasionally cows with
infected udders, as well as dogs and fowl.
5. Mode of transmissionIngestion of a food product containing
staphylococcal enterotoxin, particularly those foods that come in contact
with food handlers hands, either without subsequent cooking or with
234 / FOODBORNE INTOXICATIONS
A. Preventive measures:
C. Epidemic measures:
FOODBORNE INTOXICATIONS / 235
1) Through quick review of reported cases, determine time
and place of exposure and population at risk; obtain a
complete listing of the foods served and embargo, under
refrigeration, all foods still available. The prominent clinical
features, coupled with an estimate of the incubation period,
provide useful leads to the most probable causal agent.
Collect specimens of feces and vomitus for laboratory
examination; alert the laboratory to suspected causal agents.
Conduct an epidemiological investigation including inter-
views of ill and well persons to determine the association of
illness with consumption of a given food. Compare attack
rates for specific food items eaten and not eaten; the
implicated food item(s) will usually have the greatest differ-
ence in attack rates and most of the sick will remember
having eaten the contaminated food.
2) Inquire about the origin of incriminated food and the
manner of its preparation and storage before serving. Look
for possible sources of contamination and periods of inad-
equate refrigeration and heating that would permit growth
of staphylococci. Submit leftover suspected foods promptly
for laboratory examination; failure to isolate staphylococci
does not exclude the presence of the heat-resistant entero-
toxin if the food has been heated.
3) Search for food handlers with skin infections, particularly of
the hands. Culture all purulent lesions and collect nasal
swabs from all foodhandlers. Antibiograms and/or phage
typing of representative strains of enterotoxin producing
staphylococci isolated from foods and food handlers and
from patient vomitus or feces may be helpful.
D. Disaster implications: A potential hazard in situations involv-
ing mass feeding and lack of refrigeration facilities, including
feeding during air travel.
E. International measures: WHO Collaborating Centres.
A. Preventive measures:
V. CIGUATERA FISH
POISONING ICD-9 988.0; ICD-10 T61.0
This was first reported in Japan in 1978, and thereafter worldwide. The
causative toxins, dinophysistoxin-1 (DTX1), dinophysistoxin-2 (DTX2),
dinophysistoxin-3 (DTX3), okadaic acid (OA), 7-O-acylDTX2 (acylDTX2),
and 7-O-acylOA (acylOA) have been isolated. Illness results from eating
mussels, scallops, or clams that have fed on Dinophysis fortii or Dinophy-
sis acuminata. Symptoms include diarrhea, nausea, vomiting, and abdom-
inal pain.
In scallops, the distribution of toxins was localized in the hepatopan-
creas (midgut gland), the elimination of which renders scallops safe to eat.
Ordinary cooking such as boiling in water or steaming cannot reduce OAs
in this gland because of their chemical stability and lipophilic properties.
Methods of detection of PSP in shellfish include mouse bioassay, ELISA and
liquid chromatography-mass spectrometry. The USA has established action
level for DSP at 0.2 ppm okadaic acid (OA) plus 35-methyl okadaic acid
(DXT1).
GASTRITIS CAUSED BY HELICOBACTER PYLORI / 243
GASTRITIS CAUSED BY
HELICOBACTER PYLORI ICD-9 535; ICD-10 B96.8
1. IdentificationA bacterial infection causing chronic gastritis, pri-
marily in the antrum of the stomach, and duodenal ulcer disease. Infection
with Helicobacter pylori is epidemiologically associated with gastric
adenocarcinoma. The key pathophysiological event in H. pylori infection
is initiation and continuance of an inflammatory response. Development of
atrophy and metaplasia of the gastric mucosa are strongly associated with
H. pylori infection. Oxidative and nitrosative stress in combination with
inflamation plays an important role in gastric carcinogenesis.
Diagnosis may be made from a gastric biopsy specimen through the use
of culture, histology or the detection of H. pylori urease using commer-
cially available kits. The organism requires nutrient media for growth, such
as Brain-Heart Infusion Agar with added horse blood. Selective media have
been developed to prevent contaminating growth when culturing gastric
biopsy material. Cultures should be incubated at 37C (98.6F) in mi-
croaerophilic conditions for 48 72 hours. Specific urea-based breath tests
may also be used and are based on the organisms extremely high urease
activity. The presence of specific serum antibodies can also be measured,
most commonly by ELISA.
2. Infectious agentHelicobacter pylori is a Gram-negative, S and
U spirally shaped bacillus, catalase-, oxidase- and urease-positive. Many
different Helicobacter species have been identified in other animals;
H. cinaedi and H. fennelliae have been associated with diarrhea in men
who have sex with men.
3. OccurrenceH. pylori has an estimated rate of infection of over
one-half of the world population. It could reach up to 70% in developing
countries and up to 20%30% in industrialized countries. Only a minority
of those infected develop duodenal ulcer disease. Although individuals
infected with the organism often have histological evidence of gastritis,
the vast majority are asymptomatic. Most H. pylori infections occur in
children and atrophy of the gastric mucosa progresses during ageing.
Cross-sectional serological studies demonstrate increasing prevalence with
increasing age. Low socioeconomic status, especially in childhood, is
associated with infection.
4. ReservoirMainly humans, though recently H. pylori has been
found in other primates. Most infected persons are asymptomatic, and
without treatment infection is often lifelong. Isolation of H. pylori from
nongastric sites such as oral secretions and stool has been reported but is
infrequent.
5. Mode of transmissionNot clearly established, but infection is
almost certainly a result of ingesting organisms. Transmission is presumed
244 / GASTRITIS CAUSED BY HELICOBACTER PYLORI
A. Preventive measures:
246 / GASTROENTERITIS, ACUTE VIRAL
GASTROENTERITIS, ACUTE
VIRAL ICD-9 008.6; ICD-10 A08
Viral gastroenteritis presents as an endemic or epidemic illness in
infants, children and adults. Several viruses (rotaviruses, enteric adenovi-
ruses, astroviruses and caliciviruses including Norwalk-like viruses) infect
children in their early years and cause a diarrheal illness that may be severe
enough to produce dehydration. Viral agents such as Norwalk-like viruses
are also common causes of epidemics of gastroenteritis among children
and adults. The epidemiology, natural history and clinical expression of
enteric viral infections are best understood for type A rotavirus in infants
and Norwalk agent in adults.
A. Preventive measures
252 / GIARDIASIS
A. Preventive measures:
GONOCOCCAL INFECTIONS / 255
GONOCOCCAL INFECTIONS ICD-9 098; ICD-10 A54
Urethritis, epididymitis, proctitis, cervicitis, Bartholinitis, pelvic inflam-
matory disease (salpingitis and/or endometritis) and pharyngitis of adults;
vulvovaginitis of children; and conjunctivitis of the newborn and adults are
localized inflammatory conditions caused by Neisseria gonorrhoeae.
Gonococcal bacteraemia results in the arthritis-dermatitis syndrome, oc-
casionally associated with endocarditis or meningitis. Other complications
include perihepatitis and the neonatal amniotic infection syndrome.
Clinically similar infections of the same genital structures may be caused
by Chlamydia trachomatis and other infectious agents. Simultaneous
infections are not uncommon.
A. Preventive measures:
II. GONOCOCCAL
CONJUNCTIVITIS
(NEONATORUM) ICD-9 098.4; ICD-10 A54.3
(Gonorrhoeal ophthalmia neonatorum)
1. IdentificationAcute redness and swelling of conjunctiva in one
or both eyes, with mucopurulent or purulent discharge in which gono-
cocci are identifiable by microscopic and culture methods. Corneal ulcer,
perforation and blindness may occur if specific treatment is not given
promptly.
Gonococcal ophthalmia neonatorum is only one of several acute
inflammatory conditions of the eye or the conjunctiva occurring within
the first 3 weeks of life, collectively known as ophthalmia neonatorum.
The gonococcus is the most serious but not the most frequent infectious
agent. The commonest infectious cause is Chlamydia trachomatis, which
produces inclusion conjunctivitis that tends to be less acute than gono-
coccal conjunctivitis and usually appears 514 days after birth (see
Conjunctivitis, chlamydial). Any purulent neonatal conjunctivitis should
be considered gonococcal until proven otherwise.
2. Infectious agentNeisseria gonorrhoeae, the gonococcus.
3. OccurrenceVaries widely according to prevalence of maternal
infections and availability of measures to prevent eye infections in the
newborn at delivery; it is infrequent where infant eye prophylaxis is
adequate. The disease continues to be an important cause of blindness
throughout the world.
4. ReservoirInfection of the maternal cervix.
5. Mode of transmissionContact with the infected birth canal
during childbirth.
6. Incubation periodUsually 15 days.
7. Period of communicabilityWhile discharge persists if untreat-
ed; for 24 hours following initiation of specific treatment.
8. Susceptibility and resistanceSusceptibility is general.
9. Methods of control
260 / GONOCOCCAL INFECTIONS
A. Preventive measures:
1) Prevent maternal infection (see section I, 9A and Syphilis,
9A). Diagnose gonorrhoea in pregnant women and treat the
woman and her sexual partners. Routine culture of the cervix
and rectum for gonococci should be considered prenatally,
especially in the third trimester where infection is prevalent.
2) Use an established effective preparation for protection of
babies eyes at birth; instillation of 1% silver nitrate aqueous
solution stored in individual wax capsules remains the agent
most widely used. Erythromycin (0.5%) and tetracycline (1%)
ophthalmic ointments are also effective. A study carried out
in Kenya found that the incidence of ophthalmia neonatorum
in infants treated with a 2.5% ophthalmic solution of povi-
done-iodine was significantly lower than in those treated with
1% silver nitrate or with 0.5% erythromycin ointment.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Case report is required in
many countries, Class 2 (see Reporting).
2) Isolation: Contact isolation for the first 24 hours after admin-
istration of effective therapy. Hospitalize patients if possible.
Bacterial cure after therapy should be confirmed by culture.
3) Concurrent disinfection: Care in disposal of conjunctival
discharges and contaminated articles.
4) Quarantine: Not applicable.
5) Immunization of contacts: Not applicable; prompt treatment
on diagnosis or clinical suspicion of infection.
6) Investigation of contacts and source of infection: Examina-
tion and treatment of mothers and their sexual partners.
7) Specific treatment: For gonococcal infections when antibi-
otic susceptibility is not known, or for penicillin-resistant
organisms, a single dose of ceftriaxone, 2550 mg/kg (not to
exceed 125 mg) IV or IM, is recommended. Mother and
infant should also be treated for chlamydial infection.
C. Epidemic measures: None.
D. Disaster implications: None.
E. International measures: None.
[S. Resnikoff]
GRANULOMA INGUINALE / 261
GRANULOMA INGUINALE ICD-9 099.2; ICD-10 A.58
(Donovanosis)
1. IdentificationA chronic and progressively destructive, but
poorly communicable bacterial disease of the skin and mucous mem-
branes of the external genitalia, inguinal and anal regions. One or more
indurated nodules or papules lead to a slowly spreading, nontender,
exuberant, granulomatous, ulcerative or cicatricial lesions. The lesions are
characteristically nonfriable beefy red granulomas that extend peripherally
with characteristic rolled edges and eventually form fibrous tissue. Lesions
occur most commonly in warm, moist surfaces such as the folds between
the thighs, the perianal area, the scrotum, or the vulvar labia and vagina.
The genitalia are involved in close to 90% of cases, the inguinal region in
close to 10%, the anal region in 5%10% and distant sites in 1%5%. If
neglected, the process may result in extensive destruction of genital
organs and spread by autoinoculation to other parts of the body.
Laboratory diagnosis is based on demonstration of intracytoplasmic rod
shaped organisms (Donovan bodies) in Wright- or Giemsa-stained smears
of granulation tissue or on histological examination of biopsy specimens;
the presence of large infected mononuclear cells filled with deeply
staining Donovan bodies is pathognomonic. Culture is difficult and
unreliable. PCR and serology are available on a research basis. Haemophi-
lus ducreyi should be excluded by culture on appropriate selective media.
2. Infectious agentKlebsiella granulomatis (Donovania granulo-
matis, Calymmatobacterium granulomatis), a Gram-negative bacillus, is
the presumed causal agent; this is not certain.
3. OccurrenceRare in industrialized countries, but cluster outbreaks
occasionally occur. Endemic in tropical and subtropical areas, such as
central and northern Australia, southern India, Papua New Guinea, Viet
Nam; occasionally in Latin America, the Caribbean islands and central,
eastern and southern Africa. It is more frequently seen among males than
females and among people of lower socioeconomic status; it may occur in
children aged 1 4 years but is predominantly seen at ages 20 40.
4. ReservoirHumans.
5. Mode of transmissionPresumably by direct contact with lesions
during sexual activity, but in various studies only 20% 65% of sexual
partners were infected, thus not quite fulfilling the criteria for sexual
transmission. Donovanosis occurs in sexually inactive individuals and the
very young, suggesting that some cases are transmitted nonsexually.
6. Incubation periodUnknown; probably between 1 and 16 weeks.
7. Period of communicabilityUnknown; probably for the duration
of open lesions on the skin or mucous membranes.
262 / GRANULOMA INGUINALE
HANTAVIRAL DISEASES / 263
HANTAVIRAL DISEASES
Hantaviruses infect rodents worldwide; several species are known to
infect humans with varying severity, with primary impact effect on the
vascular endothelium, resulting in increased vascular permeability, hypo-
tensive shock and hemorrhagic manifestations. Many of these agents have
been isolated from rodents but are not associated with human cases. In
1993, an outbreak of disease caused by a previously unrecognized
hantavirus occurred in the USA; the principal target organ was not the
kidney (the usual target organ in human hantaviral infections) but the
lung. Because they are caused by related causal organisms and have similar
features of epidemiology and pathology (febrile prodrome, thrombocyto-
penia, leukocytosis and capillary leakage), both the renal and the pulmo-
nary syndrome are presented under Hantaviral diseases.
penia and elevated blood urea nitrogen supports the diagnosis. Hantavi-
ruses can be propagated in a limited range of cell cultures and laboratory
rats and mice, mainly for research purposes. Leptospirosis and rickettsio-
ses must be considered in the differential diagnosis.
2. Infectious agentHantaviruses (a genus of the family Bunyaviri-
dae, the only genus without an arthropod vector); 3-segmented RNA
viruses with spherical to oval particles, 95110 nanometers in diameter.
More than 25 antigenically distinguishable viral species exist, each associ-
ated primarily with a single rodent species. Seoul virus is found world-
wide, Puumala virus in Europe, Hantaan virus principally in Asia, less often
in Europe, Dobrava (Belgrade) virus in Serbia and Montenegro (formerly
the Federal Republic of Yugoslavia).
3. OccurrencePrior to World War II, Japanese and Soviet authors
described the disease in Manchuria along the Amur River. In 1951, it was
recognized among United Nations troops in Asia and later in both military
personnel and civiliansthe virus was first isolated from a field rodent
(Apodemus agrarius) in 1977 near the Hantaan river. The disease is
considered a major public health problem in China and the Republic of
Korea. Occurrence is seasonal, most cases occurring in late autumn and
early winter, primarily among rural populations. In the Balkans, a severe
form of the disease due to Dobrava virus affects a few hundred people
annually, with fatality rates at least as high as those in Asia (5%15%). Most
cases there are seen during spring and early summer.
Nephropathia epidemica, due to Puumala virus, is found in most of
Europe, including the Balkans and the Russian Federation West of the Ural
mountains. It is often seen in summer and in the autumn and early winter.
Seasonal occupational and recreational activities probably influence the
risk of exposure, as do climate and other ecological factors of rodent
population densities. Among medical research personnel and animal
handlers in Asia and Europe, the disease has been traced to laboratory rats
infected with Seoul virus, which has been identified in captured urban rats
worldwide, including Argentina, Brazil, Thailand and USA; only in Asia has
it been regularly associated with human disease. The availability of newer
diagnostic techniques has led to increasing recognition of hantaviruses
and hantaviral infections.
4. ReservoirField rodents (Apodemus spp. for Hantaan and Do-
brava-Belgrade viruses in Asia and the Balkans; Clethrionomys spp. for
Puumala in Europe; Rattus spp. for Seoul virus worldwide). Humans are
accidental hosts.
5. Mode of transmissionPresumed aerosol transmission from ro-
dent excreta (aerosol infectivity has been demonstrated experimentally),
though this may not explain all human cases or all forms of inter-rodent
transmission. Virus occurs in urine, feces and saliva of persistently infected
asymptomatic rodents, with maximal virus concentration in the lungs.
HANTAVIRAL DISEASES / 265
Nosocomial transmission of hantaviruses has been documented but is
believed rare.
6. Incubation periodFrom a few days to nearly 2 months, usually
2 4 weeks.
7. Period of communicabilityNot well defined. Person-to-person
transmission is rare.
8. SusceptibilityPersons without serological evidence of past infec-
tion appear to be uniformly susceptible. Inapparent infections occur;
second attacks have not been documented.
9. Methods of control
A. Preventive measures:
1), 2), 3), 4), 5) and 6) Report to local health authority, Isola-
tion, Concurrent disinfection, Quarantine, Immunization of
contacts and Investigation of contacts and source of infec-
tionSee section I, 9B1 through 9B6.
HENDRA AND NIPAH VIRAL DISEASES / 269
HENDRA AND NIPAH VIRAL
DISEASES ICD-9 078.8; ICD-10 B33.8
1. IdentificationThese are newly recognized zoonotic viral dis-
eases named for the locations in Australia and Malaysia where the first
human isolates were confirmed in 1994 and 1999, respectively. Nipah
virus manifests mainly as encephalitis; Hendra virus as a respiratory illness
(2 cases) and as a prolonged and initially mild meningoencephalitis (1
case). The full course and spectrum of these diseases is still unknown;
symptoms range in severity from mild to coma and death and include fever
and headaches, sore throat, dizziness, drowsiness and disorientation.
Pneumonitis was prominent in the initial Hendra cases, one of which was
fatal. Coma usually leads to death in 330 days. The case-fatality rate for
clinical cases is about 50%; subclinical infections occur.
Serological diagnosis is available through detection of IgM and IgG with
an antibody capture ELISA or serum neutralization. Virus isolation from
infected tissues confirms the diagnosis.
2. Infectious agentHendra (formerly called equine morbillivirus)
and Nipah viruses are members of a new genus, Henipaviruses, of the
Paramyxoviridae family.
3. OccurrenceHendra virus caused disease in horses in Queens-
land, Australia. In 1994, 3 human cases followed close contact with sick
horses, the first 2 during the initial outbreak in Hendra, the 3rd occurring
13 months after an initially mild meningitic illness when the virus
reactivated to cause a fatal encephalitis. Nipah virus affected swine in the
pig-farming provinces of Perak, Negeri Sembilan, and Selangor in Malaysia.
The first human case is believed to have occurred in 1996; although the
disease became apparent in late 1998, most cases were identified in the
first months of 1999, with over 100 confirmed deaths as of mid-1999.
During 1999 11 abattoir workers in Singapore developed Nipah virus
infection following contact with pigs imported from Malaysia.
4. ReservoirFruit bats for Hendra virus; virus isolation and serolog-
ical data suggest that Nipah virus may have a similar reservoir. Hendra
virus (in horses) and Nipah virus (domestic swine) cause an acute febrile
illness, which may lead to severe respiratory and CNS involvement and
death. Dogs infected with Nipah virus show a distemper-like manifestation
but their epidemiological role has not been defined. Nipah-seropositive
horses have been identified, but their role is also undetermined. Testing of
other animals is under way; susceptibility testing suggests that cats and
guineapigs can be infected, sometimes with fatal outcomes, mice, rabbits
and rats appear refractory to infection.
5. Mode of transmissionPrimarily through direct contact with
infected horses (Hendra) or swine (Nipah) or contaminated tissues. Oral
and nasal routes are suspected in most cases. There is no evidence for
person-to-person transmission.
270 / HENDRA AND NIPAH VIRAL DISEASES
HEPATITIS, VIRAL / 271
HEPATITIS, VIRAL ICD-9 070; ICD-10 B15-B19
Several distinct infections are grouped as the viral hepatitides; they are
primarily hepatotrophic and have similar clinical presentations, but differ
in etiology and in some epidemiological, immunological, clinical and
pathological characteristics. Their prevention and control vary greatly.
Each will be presented in a separate section.
A. Preventive measures:
C. Epidemic measures:
1) Determine mode of transmission (person-to-person or com-
mon vehicle) through epidemiological investigation; identify
the population exposed. Eliminate common sources of infec-
tion.
2) Effective use of hepatitis A vaccine in community-wide
outbreak situations requires the identification of an appro-
priate target group for immunization, the initiation of immu-
nization early in the course of the outbreak and the rapid
achievement of high (approximately 70% at least) first-dose
vaccine coverage levels. Specific outbreak control measures
must be tailored to the characteristics of hepatitis A epide-
miology and of the existing hepatitis A immunization pro-
gram, if any, in the community. Immunization of older
children who have not previously received vaccine should be
accelerated in communities with ongoing programs of rou-
tine hepatitis A immunization for young children; target
immunization should be undertaken for groups or areas (age
groups, risk groups, census tracts) where local surveillance
and epidemiological data show the highest rates. In outbreak
settings such as day care, hospitals, institutions and schools,
routine use of hepatitis A vaccine is not warranted. These
immunization programs may reduce disease incidence only
in the group(s) targeted.
3) Make special efforts to improve sanitary and hygienic prac-
tices to eliminate fecal contamination of foods and water.
4) Outbreaks in institutions may warrant mass prophylaxis with
hepatitis A vaccine and IG.
stranded RNA that can have a linear or circular conformation. The RNA
does not hybridize with HBV DNA. HDV is unable to infect a cell by itself
and requires co-infection with the HBV to undergo a complete replication
cycle. Synthesis of HDV, in turn, results in temporary suppression of
synthesis of HBV components. HDV is best considered in the new
satellite family of sub-virions, some of which are pathogens of higher
plants. Hepatitis D is the only agent in this family that infects animal
species. Three genotypes of HDV have been identified: Genotype I is the
most prevalent and widespread; genotype II is represented by 2 isolates
from Japan and Taiwan (China); genotype III is reported only in the
Amazon basin, causing severe fulminant hepatitis with microvesicular
steatosis (spongiocytosis).
3. OccurrenceWorldwide, but prevalence varies widely. An esti-
mated 10 million people are infected with hepatitis D virus and its helper
virus HBV. It occurs epidemically or endemically in populations at high
risk of HBV infection, such as where hepatitis B is endemic (highest in
Africa and South America, southern Italy, Romania, parts of the Russian
Federation); among hemophiliacs, injecting drug users and others who
come in frequent contact with blood; in institutions for the developmen-
tally disabled; and to a lesser extent among men who have sex with men.
Severe epidemics have been observed in tropical South America (Brazil,
Colombia, Venezuela), in the Central African Republic and among inject-
ing drug users in the USA. Dramatic changes have occurred in the
epidemiology of HDV in the past years. Since HDV requires a concomitant
HBV infection, the recent decrease in the prevalence of chronic HBsAg
carriers in the general population has led to a rapid decline in both acute
and chronic hepatitis D in the Mediterranean area (Greece, Italy, Spain)
and in many other parts of the world. Better sanitation and social standards
may also have contributed. New foci of high HDV prevalence continue to
appear as in the case of Albania, areas of China, northern India and Japan
(Okinawa).
4. ReservoirHumans. Virus can be transmitted experimentally to
chimpanzees and to woodchucks infected with HBV and woodchuck
hepatitis virus, respectively.
5. Mode of transmissionThought to be similar to that of HBV:
exposure to infected blood and serous body fluids, contaminated needles,
syringes and plasma derivatives such as antihemophilic factor, and through
sexual transmission. Intrafamily contacts with HBsAg carriers are a major
risk factor for the spreading of HDV.
6. Incubation periodApproximately 2 8 weeks.
7. Period of communicabilityBlood is potentially infectious dur-
ing all phases of active delta hepatitis infection. Peak infectivity probably
occurs just prior to onset of acute illness, when particles containing the
HEPATITIS, VIRAL / 289
delta antigen are readily detected in the blood. Following onset, viraemia
probably falls rapidly to low or undetectable levels. HDV has been
transmitted to chimpanzees from the blood of chronically infected pa-
tients in whom particles containing delta antigen could not be detected.
8. SusceptibilityAll people susceptible to HBV infection or who
have chronic HBV can be infected with HDV. Severe disease can occur
even in children.
9. Methods of control
tion of the HEV genome differs substantially from that of other calicivi-
ruses and HEV may eventually be classified in a separate family.
3. OccurrenceHEV is the major causal agent of enterically transmit-
ted non-A, non-B hepatitis worldwide. In recent years, serological tests for
both IgM and IgG anti-HEV have allowed a comprehensive epidemiological
survey of the distribution of HEVthe prevalence of HEV antibodies in
suspected or documented endemic regions was much lower than ex-
pected (3%26%), and it was higher than anticipated (13%) in non-
endemic regions such as the USA. HEV infections account for 50% of
acute sporadic hepatitis in some highly endemic areas. Outbreaks of
hepatitis E and sporadic cases occur over a wide geographic area,
primarily in countries with inadequate environmental sanitation. Out-
breaks often occur as waterborne epidemics, but sporadic cases and
epidemics not clearly related to water have been reported. The highest
rates of clinically evident disease occur in young to middle aged adults;
lower disease rates in younger age groups may be the result of anicteric
and/or subclinical HEV infection. In most industrialized countries, hepati-
tis E cases have been documented only among travellers returning from
HEV endemic areas. Outbreaks have also been reported from Algeria,
Bangladesh, China, Cote dIvoire, Egypt, Ethiopia, Greece, India, Indone-
sia, the Islamic Republic of Iran, Jordan, the Libyan Arab Jamahiryia,
Mexico, Myanmar, Nepal, Nigeria, Pakistan, southern areas of the Russian
Federation, Somalia, eastern Sudan and The Gambia. A large waterborne
outbreak (3682 cases) occurred in 1993 in Uttar Pradesh.
4. ReservoirMan is the natural host for HEV; some non-human
primates, e.g. chimpanzees, cynomolgus monkeys, rhesus monkeys, pig-
tail monkeys, owl monkeys, tamarins and African green monkeys are
reported as susceptible to natural infection with human strains of HEV.
Natural infections have been described in pigs, chicken and cattle,
particularly in highly endemic areas.
5. Mode of transmissionPrimarily by the fecal-oral route; fecally
contaminated drinking-water is the most commonly documented vehicle
of transmission. Person-to-person transmission probably also occurs
through the fecal-oral route, although secondary household cases are
uncommon during outbreaks. Recent studies suggest that hepatitis E may
in fact be a zoonotic infection with coincident areas of high human
infection.
6. Incubation periodThe range is 15 to 64 days; the mean incuba-
tion period has varied from 26 to 42 days in various epidemics.
7. Period of communicabilityNot known. HEV has been detected
in stools 14 days after the onset of jaundice and approximately 4 weeks
after oral ingestion of contaminated food or water; it persists for about 2
weeks.
HEPATITIS, VIRAL / 291
8. SusceptibilityUnknown. Over 50% of HEV infections may be
anicteric; the expression of icterus appears to increase with increasing
age. Women in the third trimester of pregnancy are especially susceptible
to fulminant disease. The occurrence of major epidemics among young
adults in regions where other enteric viruses are highly endemic and most
of the population acquires infection in infancy remains unexplained.
9. Methods of control
A. Preventive measures: Provide educational programs to stress
sanitary disposal of feces and careful handwashing after defeca-
tion and before handling food; follow basic measures to prevent
fecal-oral transmission, as listed under Typhoid fever, 9A. Admin-
istration of immune serum globulin from endemic areas has not
decreased infection rates during epidemics in India; encouraging
advances have occurred in HEV vaccine development.
B. Control of patient, contacts and the immediate environment:
1), 2) and 3) Report to local health authority, Isolation and
Concurrent disinfection: See hepatitis A.
4) Quarantine: Not applicable.
5) Immunization of contacts: No products are available to
prevent hepatitis E. IG prepared from plasma collected in
non- and high-HEV endemic areas were not effective in
preventing clinical disease during hepatitis E outbreaks. A
candidate vaccine using recombinant capsid protein is cur-
rently undergoing phase II/III clinical trials.
6) Investigation of contacts and source of infection: Same as for
hepatitis A.
7) Specific treatment: None.
C. Epidemic measures: Determine mode of transmission through
epidemiological investigation; investigate water supply and iden-
tify populations at increased risk of infection; special efforts to
improve sanitary and hygienic practices in order to eliminate
fecal contamination of foods and water.
D. Disaster implications: A potential problem where there is
mass crowding and inadequate sanitation and water supplies. If
cases occur, increased effort should be exerted to improve
sanitation and the safety of water supplies.
E. International measures: None.
[D. Lavanchy]
292 / HERPES SIMPLEX
ANOGENITAL HERPESVIRAL
INFECTIONS ICD-10 A60
(Alphaherpesviral disease, Herpesvirus hominis, Human
herpesviruses 1 and 2)
1. IdentificationHerpes simplex is a viral infection characterized by
a localized primary lesion, latency and a tendency to localized recurrence.
The two causal agents herpes simplex virus (HSV) types 1 and 2 gen-
erally produce distinct clinical syndromes, depending on the portal of
entry. Either may infect the genital tract or oral mucosa.
Primary infection with HSV-1 may be mild and inapparent and occur in
early childhood. In approximately 10% of primary infections, overt disease
may appear as an illness of varying severity, marked by fever and malaise
lasting a week or more; it may be associated with gingivostomatitis
accompanied by vesicular lesions in the oropharynx, severe keratocon-
junctivitis, a generalized cutaneous eruption complicating chronic ec-
zema, meningoencephalitis or some of the fatal generalized infections in
newborn infants (congenital herpes simplex, ICD-9 771.2, ICD-10 P35.2).
HSV-1 causes about 2% of acute pharyngotonsillitis, usually as a primary
infection.
Reactivation of latent infection commonly results in herpes labialis
(fever blisters, cold sores) manifested, usually on the face or lips, by
superficial clear vesicles on an erythematous base that crust and heal
within days. Reactivation is precipitated by various forms of trauma, fever,
physiological changes or intercurrent disease, and may also involve other
body tissues; it occurs in the presence of circulating antibodies, which are
seldom elevated by reactivation. Severe and extensive spread of infection
may occur in those who are immunodeficient or immunosuppressed.
CNS involvement may appear in association with either primary infec-
tion or recrudescence. HSV-1 is a common cause of meningoencephalitis.
Fever, headache, leukocytosis, meningeal irritation, drowsiness, confu-
sion, stupor, coma and focal neurological signs may occur and are
frequently referable to one or the other temporal region. The condition
may be confused with other intracranial lesions including brain abscess
and tuberculous meningitis. Because antiviral therapy may reduce case-
fatality, diagnostic PCR for DNA of herpes virus in the CSF or biopsy of
cerebral tissue should be considered early in clinically suspected cases.
Genital herpes, usually caused by HSV-2, occurs mainly in adults and is
sexually transmitted. Primary and recurrent infections occur, with or
without symptoms. In women, the principal sites of primary disease are
the cervix and the vulva; recurrent disease generally involves the vulva,
perineal skin, legs and buttocks. In men, lesions appear on the glans penis
or prepuce, and in the anus and rectum of those engaging in anal sex.
Other genital or perineal sites, as well as the mouth, may be involved in
HERPES SIMPLEX / 293
men and women, depending on sexual practices. HSV-2 has been associ-
ated with aseptic meningitis and radiculitis rather than meningoencepha-
litis.
Neonatal infections can be divided into 3 clinical presentations: dissem-
inated infections involving the liver, encephalitides and infections limited
to the skin, eyes or mouth. The first two forms are often lethal. Infections
are most frequently due to HSV-2, but HSV-1 is also common. Risk to the
infant depends on two important maternal factors: stage of pregnancy at
which the mother excretes HSV, and whether the infection is primary or
secondary. Only excretion at the time of delivery is dangerous to the
newborn, with the rare exception of intrauterine infections. Primary
infection in the mother raises the risk of infection from 3% to over 30%,
presumably because maternal immunity confers a degree of protection.
Diagnosis is suggested by characteristic cytological changes (multinu-
cleated giant cells with intranuclear inclusions in tissue scrapings or
biopsy), but confirmed through direct FA tests, isolation of the virus from
oral or genital lesions, or a brain biopsy in cases of encephalitis or again by
demonstration of HSV DNA in lesion or spinal fluid by PCR. A 4-fold titre
rise in paired sera in various serological tests confirms the diagnosis of
primary infection; the presence of herpes-specific IgM is suggestive but
not conclusive evidence of primary infection. Reliable techniques to
differentiate type 1 from type 2 antibody are now available in diagnostic
laboratories; virus isolates can be distinguished readily from one another
by DNA analysis. Type-specific serologic tests are not yet widely available.
2. Infectious agentHerpes simplex virus in the virus family Herpes-
viridae, subfamily Alphaherpesvirinae. HSV types 1 and 2 can be differen-
tiated immunologically (especially when highly specific or monoclonal
antibodies are used) and differ with respect to their growth patterns in cell
culture, embryonated eggs and experimental animals.
3. OccurrenceWorldwide; 50%90% of adults possess circulating
antibodies against HSV-1; initial infection with HSV-1 usually occurs before
the fifth year of life, but more primary infections in adults are now being
reported. HSV-2 infection usually begins with sexual activity and is rare
before adolescence, except in sexually abused children. HSV-2 antibody
occurs in 20%30% of American adults. The prevalence is greater (up to
60%) in lower socioeconomic groups and persons with multiple sexual
partners.
4. ReservoirHumans.
5. Mode of transmissionContact with HSV-1 in the saliva of
carriers is probably the most important mode of spread. Infection on the
hands of health care personnel (e.g. dentists) from patients shedding HSV
results in herpetic whitlow. Transmission of HSV-2 is usually by sexual
contact. Both types 1 and 2 may be transmitted to various sites by
oral-genital, oral-anal or anal-genital contact. Transmission to the neonate
294 / HERPES SIMPLEX
usually occurs via the infected birth canal, less commonly in utero or
postpartum.
6. Incubation periodFrom 212 days.
7. Period of communicabilityHSV can be isolated for 2 weeks and
up to 7 weeks after primary stomatitis or primary genital lesions. Both
primary and recurrent infections may be asymptomatic. After either, HSV
may be shed intermittently from mucosal sites for years and possibly
lifelong, in the presence or absence of clinical manifestations. In recurrent
lesions, infectivity is shorter than after primary infection, and usually the
virus cannot be recovered after 5 days.
8. SusceptibilityHumans are probably universally susceptible.
9. Methods of control
A. Preventive measures:
MENINGOENCEPHALITIS DUE
TO CERCOPITHECINE HERPES
VIRUS 1 ICD-9 054.3; ICD-10 B00.4
(B-virus, Simian B disease)
HSV-1 (occasionally type 2) can cause meningoencephalitis; the picture
is different with B-virus infection, which is a CNS disease caused by
cercopithecine herpesvirus 1, a zoonotic virus closely related to HSV. This
causes an ascending encephalomyelitis seen in veterinarians, laboratory
workers and others in close contact with eastern Hemisphere monkeys or
monkey cell cultures. After an incubation of 3 days to 3 weeks, there is
acute febrile onset with headache, often local vesicular lesions, lympho-
cytic pleocytosis and variable neurological patterns, ending in death in
over 70% of cases, 1 day to 3 weeks after onset of symptoms. Occasional
recoveries have been associated with considerable residual disability; a
few cases, treated with acyclovir, have recovered completely. The virus
causes a natural infection of monkeys analogous to HSV infection in
296 / HERPES SIMPLEX
HISTOPLASMOSIS / 297
HISTOPLASMOSIS ICD-9 115; ICD-10 B39
Two clinically different mycoses are designated as histoplasmosis; the
pathogens that cause them cannot be distinguished morphologically when
grown on culture media as moulds. Detailed information is given for the
infection caused by Histoplasma capsulatum var. capsulatum, and a brief
summary for that caused by H. capsulatum var. duboisii.
I. INFECTION BY HISTOPLASMA
CAPSULATUM ICD-9 115.0; ICD-10 B39.4
(Histoplasmosis capsulati, Histoplasmosis due to H. capsulatum
var. capsulatum, American histoplasmosis)
1. IdentificationA systemic mycosis of varying severity, with the
primary lesion usually in the lungs. While infection is common, overt
clinical disease is not. Five clinical forms are recognized:
1) Asymptomatic; although individuals manifest skin test reac-
tivity to histoplasmin, this reagent is no longer commercially
available.
2) Acute respiratory, which varies from a mild respiratory
illness to temporary incapacity with general malaise, fever,
chills, headache, myalgia, chest pains and nonproductive
cough; occasional erythema multiforme and erythema nodo-
sum. Multiple, small scattered calcifications in the lung, hilar
lymph nodes, spleen and liver may be late findings.
3) Acute disseminated histoplasmosis with debilitating fever, GI
symptoms, evidence of bone marrow suppression, hepato-
splenomegaly, lymphadenopathy and a rapid course, most
frequent in infants and young children and immunocompro-
mised patients including AIDS cases. Without treatment,
usually fatal.
4) Chronic disseminated disease with low-grade intermittent
fever, weight loss, weakness, hepatosplenomegaly, mild he-
matological abnormalities and focal manifestations of disease
(e.g. endocarditis, meningitis, mucosal ulcers of mouth,
larynx, stomach or bowel and Addison disease). Subacute
course progressing over 10 11 months and usually fatal
unless treated.
5) Chronic pulmonary form, clinically and radiologically resem-
bling chronic pulmonary tuberculosis with cavitation; occurs
most often in middle-aged and elderly men with underlying
emphysema, progresses over months or years, with periods
of quiescence and sometimes spontaneous cure.
Clinical diagnosis is confirmed by culture, DNA probe, or
by visualizing the fungus in Giemsa- or Wright-stained smears
of ulcer exudates, bone marrow, sputum or blood; demon-
298 / HISTOPLASMOSIS
HOOKWORM DISEASE / 301
HOOKWORM DISEASE ICD-9 126; ICD-10 B76
(Ancylostomiasis, Uncinariasis, Necatoriasis)
1. IdentificationA common chronic parasitic infection with a vari-
ety of symptoms, usually in proportion to the degree of anemia. In heavy
infections, the bloodletting activity of the nematode leads to iron defi-
ciency and hypochromic, microcytic anemia, the major cause of disability.
Children with heavy long-term infection may have hypoproteinemia and
may be retarded in mental and physical development. Occasionally, severe
acute pulmonary and GI reactions follow exposure to infective larvae.
Death is infrequent and usually can be attributed to other infections. Light
hookworm infections generally produce few or no clinical effects.
Infection is confirmed by finding hookworm eggs in feces; early stool
examinations may be negative until worms mature. Species differentiation
requires microscopic examination of larvae cultured from the feces, or
examination of adult worms expelled by purgation following a vermifuge.
PCR-RFLP techniques allow species differentiation.
2. Infectious agentsAncylostoma duodenale, A. ceylanicum, A.
braziliense, A. caninum and Necator americanus.
3. OccurrenceEndemic in tropical and subtropical countries where
sanitary disposal of human feces is not practised and soil, moisture and
temperature conditions favor development of infective larvae. Also occurs
in temperate climates under similar environmental conditions (e.g. mines).
Both Necator and Ancylostoma occur in many parts of Asia (particu-
larly southeastern Asia), the South Pacific and eastern Africa.
N. americanus is the prevailing species throughout southeastern Asia,
most of tropical Africa and America; A. duodenale prevails in North
Africa, including the Nile Valley, northern India, northern parts of
eastern Asia and the Andean areas of South America. A. ceylanicum
occurs in southeastern Asia but is less common than either
N. americanus or A. duodenale. A. caninum has been described in
Australia as a cause of eosinophilic enteritis syndrome.
swallowed and reach the small intestine where they attach to the
intestinal wall, developing to maturity in 6 7 weeks (3 4 weeks in the
case of A. ceylanicum) and typically producing thousands of eggs per
day. Infection with Ancylostoma may also be acquired by ingesting
infective larvae; possible vertical transmission through breastmilk has
been reported.
A. Preventive measures:
304 / HYMENOLEPIASIS
I. HYMENOLEPIASIS DUE TO
HYMENOLEPIS NANA
(Dwarf tapeworm infection)
1. IdentificationAn intestinal infection with very small tapeworms;
light infections are usually asymptomatic. Massive numbers of worms may
cause enteritis with or without diarrhea, abdominal pain and other vague
symptoms such as pallor, loss of weight and weakness.
Microscope identification of eggs in feces confirms diagnosis.
2. Infectious agentHymenolepis nana (dwarf tapeworm), the only
human tapeworm without an obligatory intermediate host.
3. OccurrenceCosmopolitan; more common in warm than cold, and
in dry than wet climates. Dwarf tapeworm is the most common human
tapeworm in the USA and Latin America; it is common in Australia,
Mediterranean countries, the Near East and India.
4. ReservoirHumans; possibly mice.
5. Mode of transmissionEggs of H. nana are infective when passed
in feces. Infection is acquired through ingestion of eggs in contaminated
food or water; directly from fecally contaminated fingers (autoinfection or
person-to-person transmission); or ingestion of insects bearing larvae that
have developed from eggs ingested by the insect. H. nana eggs, once
ingested, hatch in the intestine, liberating oncospheres that enter mucosal
villi and develop into cysticercoids; these rupture into the lumen and grow
into adult tapeworms. Some H. nana eggs are immediately infectious
when released from the proglottids in the human gut, so autoinfections or
person-to-person transmission can occur. If eggs are ingested by meal-
worms, larval fleas, beetles or other insects, they may develop into
cysticercoids that are infective to humans and rodents when ingested.
6. Incubation periodOnset of symptoms is variable; the develop-
ment of mature worms requires about 2 weeks.
7. Period of communicabilityAs long as eggs are passed in feces.
H. nana infections may persist for years.
8. SusceptibilityUniversal; infection produces resistance to reinfec-
tion. Children are more susceptible than adults; intensive infection occurs
in immunodeficient and malnourished children.
9. Methods of control
A. Preventive measures:
HYMENOLEPIASIS / 305
1) Educate the public in personal hygiene and safe disposal of
feces.
2) Provide and maintain clean toilet facilities.
3) Protect food and water from contamination with human and
rodent feces.
4) Treat to remove sources of infection.
5) Eliminate rodents from home environment.
INFLUENZA / 307
INFLUENZA ICD-9 487; ICD-10 J10, J11
1. IdentificationAn acute viral disease of the respiratory tract
characterized by fever, headache, myalgia, prostration, coryza, sore throat
and cough. Cough is often severe and protracted; other manifestations are
self-limited in most patients, with recovery in 27 days. Recognition is
commonly by epidemiological characteristics (current quick tests lack
sensitivity); only laboratory procedures can reliably identify sporadic
cases. Influenza may be clinically indistinguishable from disease caused by
other respiratory viruses, such as common cold, croup, bronchiolitis, viral
pneumonia and undifferentiated acute respiratory disease. GI tract mani-
festations (nausea, vomiting, diarrhea) are uncommon, but may accom-
pany the respiratory phase in children, and have been reported in up to
25% of children in school outbreaks of influenza B and A (H1N1).
Influenza derives its importance from the rapidity with which epidemics
evolve, the widespread morbidity and the seriousness of complications,
notably viral and bacterial pneumonias. In addition, emergence among
humans of influenza viruses with new surface proteins can cause pandem-
ics ranking as global health emergencies (e.g. 1918, 1957, 1968) with
millions of deaths (c40 million in 1918). Severe illness and death during
annual influenza epidemics occur primarily among the elderly and those
debilitated by chronic cardiac, pulmonary, renal or metabolic disease,
anemia or immunosuppression. The proportion of total deaths associated
with pneumonia and influenza in excess of that expected for the time of
year (excess mortality) varies and depends on the prevalent virus type.
The annual global death toll is estimated to reach up to 1 million. In most
epidemics, 80%90% of deaths occur in persons over 65; in the 1918
pandemic, young adults showed the highest mortality rates. Reye syn-
drome, involving the CNS and liver, is a rare complication following virus
infections in children who have ingested salicylates.
While the epidemiology of influenza is well understood in industrialized
countries, information on influenza in developing countries is minimal.
During the early febrile stage, laboratory confirmation is through
isolation of influenza viruses from pharyngeal or nasal secretions or
washings on cell culture or in embryonated eggs; direct identification of
viral antigens in nasopharyngeal cells and fluids (FA test or ELISA); rapid
diagnostic tests (these differ in the influenza viruses they detect); or viral
RNA amplification. Demonstration of a specific serological response
between acute and convalescent sera may also confirm infection.
2. Infectious agentsThree types of influenza virus are recognized:
A, B and C. Type A includes 15 subtypes of which only 2 (H1and H3) are
associated with widespread epidemics; type B is infrequently associated
with regional or widespread epidemics; type C with sporadic cases and
minor localized outbreaks. The antigenic properties of the 2 relatively
stable internal structural proteins, the nucleoprotein and the matrix
protein, determine virus type.
308 / INFLUENZA
A. Preventive measures:
KAWASAKI SYNDROME / 313
KAWASAKI SYNDROME ICD-9 446.1; ICD-10 M30.3
(Kawasaki disease, Mucocutaneous lymph node syndrome,
Acute febrile mucocutaneous lymph node syndrome)
1. IdentificationAn acute febrile, self-limited, systemic vasculitis of
early childhood, presumably of infectious or toxic origin. Clinically
characterized by a high, spiking fever, unresponsive to antibiotics, associ-
ated with pronounced irritability and mood change; usually solitary and
frequently unilateral nonsuppurative cervical adenopathy; bilateral non-
exudative bulbar conjunctival injection; an enanthem consisting of a
strawberry tongue, injected oropharynx or dry fissured or erythematous
lips; limb changes consisting of oedema, erythema or periungual/general-
ized desquamation; and a generalized polymorphous erythematous exan-
them that can be truncal or perineal and ranges from morbilliform
maculopapular rash to urticarial rash or vasculitic exanthem.
Typically there are 3 phases: 1) acute febrile phase of about 10 days
characterized by high, spiking fever, rash, adenopathy, peripheral ery-
thema or oedema, conjunctivitis and enanthem; 2) subacute phase lasting
about 2 weeks with thrombocytosis, desquamation, and resolution of
fever; 3) lengthy convalescent phase during which clinical signs fade.
The case-fatality rate is 0.1%; half the deaths occur within 2 months of
illness.
There is no pathognomonic laboratory test for Kawasaki syndrome, but
an elevated ESR, C-reactive protein and platelet counts above 450 000/
mm3 (SI units 450 109/L) are common laboratory features.
According to Diagnostic Guidelines of Kawasaki Disease (Japan
Kawasaki Disease Research Committee, 2002), at least 5 of the following
6 principal symptoms should be satisfied, although patients with 4
principal symptoms can be diagnosed when coronary aneurysm or
dilatation is recognized by two-dimensional echocardiography or coronary
angiography: 1) Fever persisting 5 days or more (including cases in whom
the fever has subsided before the 5th day in response to treatment); 2)
bilateral conjunctival congestion; 3) changes of lips and oral cavity:
reddening of lips, strawberry tongue, diffuse injection of oral and pharyn-
geal mucosa, 4) polymorphous exanthema, 5) changes of peripheral
extremities: reddening of palms and soles, indurative oedema in the initial
stage, and membranous desquamation from fingertips in the convalescent
stage, 6) acute nonpurulent cervical lymphadenopathy
2. Infectious agentUnknown. Postulated to be a superantigen
bacterial toxin secreted by Staphylococcus aureus or group A strepto-
cocci, but this has neither been confirmed nor generally accepted.
3. OccurrenceWorldwide; most cases (around 170 000) reported
from Japan, with nationwide epidemics documented in 1979, 1982 and
1986. In the USA, the estimated number of new cases each year is about
2000. Approximately 80% of cases are diagnosed in children under 5, with
314 / KAWASAKI SYNDROME
a peak incidence at 12 years, more in boys than in girls. Cases are more
frequent in the winter and spring. In Japan, where the disease has been
tracked since 1970, peak incidence occurred in 1984 85. Since then, the
incidence rate has been steady, about 140 per 100 000 children under 5.
4. ReservoirUnknown, perhaps humans.
5. Mode of transmissionUnknown; no firm evidence of person-to-
person transmission, even within families. Seasonal variation, limitation to
the pediatric age group and outbreak occurrence in communities are all
consistent with an infectious etiology.
6. Incubation periodUnknown.
7. Period of communicabilityUnknown.
8. Susceptibility and resistanceIn the USA, children, especially
those of Asian ancestry, are most likely to develop the syndrome, but the
majority of cases are reported among Caucasian children and American
children of African origin. Recurrences appear infrequent (3% of reported
patients in Japan).
9. Methods of control
316 / LASSA FEVER
LEGIONELLOSIS / 319
LEGIONELLOSIS ICD-9 482.8; ICD-10 A48.1
(Legionnaire disease; Legionnaire pneumonia)
NONPNEUMONIC
LEGIONELLOSIS ICD-10 A48.2
(Pontiac fever)
1. IdentificationAcute bacterial disease with two distinct clinical
and epidemiological manifestations: Legionnaire disease (ICD-10 A48.1)
and Pontiac fever (ICD-10 A48.2). Both are characterized initially by
anorexia, malaise, myalgia and headache. Within a day, there is usually a
rapidly rising fever associated with chills. Temperatures commonly reach
39C 40.5C (102F105F). Nonproductive cough, abdominal pain and
diarrhea are common. In Legionnaire disease, a chest X-ray may show
patchy or focal areas of consolidation that may progress to bilateral
involvement and ultimately to respiratory failure; the case-fatality rate has
been as high as 39% in hospitalized cases; it is generally higher in those
with compromised immunity.
Pontiac fever has the same initial symptoms as pulmonary legionellosis
(including productive cough) but is not associated with pneumonia or
death; patients recover spontaneously in 25 days without treatment; this
clinical syndrome may represent reaction to inhaled antigen rather than
bacterial invasion.
Diagnosis depends on isolation of the causative organism on special
media, its demonstration by direct IF stain of involved tissue or respiratory
secretions, or detection of antigens of Legionella pneumophila serogroup
1 in urine through radioimmunoassay or through a rise (4-fold or greater)
in IFA titre between acute phase serum and serum drawn 3 6 weeks later.
The use of antigens in one sample of urine as a confirmatory test is under
discussion by the European working Group for Legionella Infections
([email protected]).
2. Infectious agentLegionellae are poorly staining, Gram-negative
bacilli that require cysteine and other nutrients to grow in vitro. Of the 18
serogroups of L. pneumophila currently recognized, L. pneumophila
serogroup 1 is most commonly associated with disease. Related organisms,
including L. micdadei, L. bozemanii, L. longbeachae and L. dumoffii have
been isolated, predominantly from immunosuppressed patients with
pneumonia. In all, 35 species of Legionella with at least 45 serogroups are
currently recognized.
3. OccurrenceThe earliest documented case occurred in 1947; the
earliest documented outbreak in 1957 in Minnesota, USA. Since then, the
disease has been identified throughout North America, as well as in Africa,
Australia, Europe and South America. Although cases occur throughout
the year, both sporadic cases and outbreaks are recognized more com-
monly in summer and autumn. In the few locations studied, antibodies to
320 / LEGIONELLOSIS
322 / LEISHMANIASIS
II. VISCERAL
LEISHMANIASIS ICD-9 085.0; ICD-10 B55.0
(Kala-azar)
1. IdentificationA chronic systemic disease caused by intracellular
326 / LEISHMANIASIS
[P. Desjeux]
LEPROSY / 329
LEPROSY ICD-9 030; ICD-10 A30
(Hansen disease)
1. IdentificationA chronic bacterial disease of the skin, peripheral
nerves and (in lepromatous patients) the upper airway. The clinical
manifestations of the disease vary in a continuous spectrum between 2
polar forms: i) lepromatous (multibacillary) leprosy: symmetrical and
bilateral nodules, papules, macules and diffuse infiltrations, usually numer-
ous and extensive; involvement of the nasal mucosa may lead to crusting,
obstructed breathing and epistaxis; ocular involvement leads to iritis and
keratitis; ii) tuberculoid (paucibacillary) leprosy: skin lesions single or few,
sharply demarcated, anaesthesic or hypoaesthesic; bilateral asymmetrical
involvement of peripheral nerves tends to be severe. Borderline leprosy
has features of both polar forms and is more labile. Indeterminate leprosy
is characterized by hypopigmented maculae with ill-defined borders; if
untreated, it may progress to tuberculoid, borderline or lepromatous
disease.
Case definition (WHO operational definition)
A case of leprosy is a person having one or more of the following, who
has yet to complete a full course of treatment:
334 / LEPTOSPIROSIS
A. Preventive measures:
338 / LISTERIOSIS
9. Methods of control
A. Preventive measures:
342 / LOIASIS
9. Methods of control
A. Preventive measures:
1) Measures directed against the fly larvae are effective but have
not proven practical because the moist, muddy breeding
areas are usually too extensive.
2) Diethyltoluamide or dimethyl phthalate applied to exposed
skin are effective fly repellents.
3) Wear protective clothing (long sleeves and trousers), screen
houses.
4) For temporary residents of endemic areas whose risk of
exposure is high or prolonged, a weekly dose of diethylcar-
bamazine (300 mg) is prophylactic.
[M. Karam]
LYME DISEASE / 345
LYME DISEASE ICD-9 104.8, 088.81;
ICD-10 A69.2, L90.4
(Lyme borreliosis, Tick-borne meningopolyneuritis)
1. IdentificationA tick-borne, spirochaetal, zoonotic disease char-
acterized by a distinctive skin lesion, systemic symptoms and neurological,
rheumatological and cardiac involvement occurring in varying combina-
tions over months to years. Recent reports state that the optic nerve may
be affected because of inflammation or increased intracranial pressure.
Early symptoms are intermittent and changing. The illness typically begins
in the summer; the first manifestation in about 80% of patients is a red
macule or papule that expands slowly in an annular manner, often with
central clearing. This lesion is called erythema migrans (EM; formerly
erythema chronicum migrans). EM may be single or multiple. To be
considered significant for case surveillance purposes, the EM lesion must
reach 5 cm in diameter. With or without EM, early systemic manifestations
may include malaise, fatigue, fever, headache, stiff neck, myalgia, migra-
tory arthralgias and/or lymphadenopathy, all of which may last several
weeks in untreated patients. In middle Europe and Scandinavia skin lesions
called lymphadenosis benigna cutis and acrodermatitis chronica atrophi-
cans are almost exclusively caused by Borrelia afzelii.
Within weeks to months after onset of the EM lesion, neurological
abnormalities such as aseptic meningitis and cranial neuritis may develop
including facial palsy, chorea, cerebellar ataxia, motor or sensory radicu-
loneuritis, myelitis and encephalitis; symptoms fluctuate and may become
chronic. Cardiac abnormalities (including atrioventricular block and,
rarely, acute myopericarditis or cardiomegaly) may occur within weeks
after onset of EM. Weeks to years after onset (mean, 6 months), intermit-
tent episodes of swelling and pain in large joints, especially the knees, may
develop and recur for several years; chronic arthritis may occasionally
result. Treatment-resistant Lyme arthritis is a rare complication that may be
result of cross reactivity between OspA and the human leukocyte function-
associated antigen-1 (hlFA-1) following natural infection with
B. burgdorferi. Similarly, following latent infection, chronic neurological
manifestations may develop and include encephalopathy, polyneuropathy
or leukoencephalitis; the CSF often shows lymphocytic pleocytosis and
elevated protein levels, while the electromyogram is usually abnormal.
Diagnosis is currently based on clinical findings supported by two-stage
serological tests, IFA, ELISA, then Western immunoblot. Serological tests
are poorly standardized and must be interpreted with caution. They are
insensitive during the first weeks of infection and may remain negative in
people treated early with antibiotics. An ELISA for IgM antibodies that uses
a recombinant outer surface protein C (rOspC) is more sensitive for early
diagnosis than whole cell ELISA. VlsE (Vls locus expression site) or C6
recombinant antigens increase the sensitivity of IgG immunoblot. Test
sensitivity increases when patients progress to later stages, but some
346 / LYME DISEASE
A. Preventive measures:
[D. Hulnska]
350 / LYMPHOCYTIC CHORIOMENINGITIS
LYMPHOCYTIC
CHORIOMENINGITIS ICD-9 049.0; ICD-10 A87.2
(LCM, Benign [or serous] lymphocytic meningitis)
1. IdentificationA viral infection of animals, especially mice, trans-
missible to humans, where they produce diverse clinical manifestations.
There may be influenza-like symptoms, with myalgia, retroorbital head-
ache, leukopenia and thrombocytopenia, followed by complete recovery;
in some cases, the illness may begin with meningeal or meningoencepha-
lomyelitic symptoms, or they may appear after a brief remission. Orchitis,
parotitis, arthritis, myocarditis and rash occur occasionally. The acute
course is usually short, very rarely fatal, and even with severe manifesta-
tions (e.g. coma with meningoencephalitis), prognosis for recovery with-
out sequelae is usually good, although convalescence with fatigue and
vasomotor instability may be prolonged. The CSF in cases with neurolog-
ical involvement typically shows a lymphocytic pleocytosis and, at times,
a low glucose level. The primary pathological finding in the rare human
fatality is diffuse meningoencephalitis. Fatal cases of hemorrhagic fever-
like disease have been reported. Transplacental infection of the fetus
leading to hydrocephalus and chorioretinitis occurs and should be tested
for in such cases.
Laboratory diagnostic methods include isolation of virus from blood or
CSF early in the course of illness by intracerebral inoculation of LCM-free
mice (3 to 5 week old) or cell cultures. Specific IgM in serum or CSF as
evidenced by IgM capture ELISA or rising antibody titres by IFA in paired
sera are considered diagnostic. LCM requires differentiation from other
aseptic meningitides and viral encephalitides.
2. Infectious agentLymphocytic choriomeningitis virus, an arenavi-
rus, serologically related to Lassa, Machupo, Junn, Guaranito and Sabia
viruses.
3. OccurrenceNot uncommon in Europe and the Americas; under-
diagnosed. Loci of infection among feral mice often persist over long
periods and results in sporadic clinical disease. Outbreaks have occurred
from exposure to pet hamsters and laboratory animals. Nude mice, now
extensively used in many research laboratories, are susceptible to infec-
tion and may be prolific chronic excreters of virus.
4. ReservoirThe infected house mouse, Mus musculus, is the
natural reservoir; infected females transmit infection to the offspring,
which become asymptomatic persistent viral shedders. Infection also
occurs in mouse and hamster colonies and in transplantable tumour lines.
5. Mode of transmissionVirus excreted in urine, saliva and feces of
infected animals, usually mice. Transmission to humans is probably
through oral or respiratory contact with virus contaminated excreta, food
or dust, or through contamination of skin lesions or cuts. Handling articles
LYMPHOCYTIC CHORIOMENINGITIS / 351
contaminated by naturally infected mice may place individuals at a high
risk of infection.
6. Incubation periodProbably 8 13 days; 1521 days until menin-
geal symptoms appear.
7. Period of communicabilityPerson-to-person transmission not
demonstrated and unlikely.
8. SusceptibilityRecovery from the disease probably indicates im-
munity of long duration. Cell-mediated mechanisms are important, anti-
bodies may play a secondary role.
9. Methods of control
A. Preventive measures: Provide a clean home and place of
work; eliminate mice and dispose of diseased animals. Keep
foods in closed containers. Virological surveillance of commer-
cial rodent breeding establishments, especially those producing
hamsters and mice, is helpful. Ensure that laboratory mice are
not infected and that personnel handling mice follow established
procedures to prevent transmission from infected animals.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Reportable in selected
endemic areas, Class 3 (see Reporting).
2) Isolation: Not applicable
3) Concurrent disinfection: Of discharges from the nose and
throat, urine, feces and articles soiled therewith during acute
febrile period. Terminal cleaning.
4) Quarantine: Not applicable
5) Immunization of contacts: Not applicable
6) Investigation of contacts and source of infection: Search
home and place of employment for presence of house mice
or rodent pets.
7) Specific treatment: None.
C. Epidemic measures: Not applicable.
D. Disaster implications: None.
E. International measures: None.
352 / LYMPHOGRANULOMA VENEREUM
LYMPHOGRANULOMA
VENEREUM ICD-9 099.1; ICD-10 A55
(Lymphogranuloma inguinale, Climatic or tropical bubo, LGV)
1. IdentificationA sexually acquired chlamydial infection beginning
with a small, painless, evanescent erosion, papule, nodule or herpetiform
lesion on the penis or vulva, frequently unnoticed. Regional lymph nodes
undergo suppuration followed by extension of the inflammatory process
to the adjacent tissues. In the male, inguinal buboes are seen that may
become adherent to the skin, fluctuate and result in sinus formation. In the
female, inguinal nodes are less frequently affected and involvement is
mainly of the pelvic nodes with extension to the rectum and rectovaginal
septum; the result is proctitis, stricture of the rectum and fistulae. Proctitis
may result from rectal intercourse; lymphogranuloma venereum is a fairly
common cause of severe proctitis in homosexual men. Elephantiasis of the
genitalia may occur in both men and women. Fever, chills, headache, joint
pains and anorexia are usually present during the bubo formation phase,
probably due to systemic spread of Chlamydia. The disease course is
often long and the disability great, but generally not fatal. Generalized
sepsis with arthritis and meningitis is a rare occurrence.
Diagnosis is made by demonstration of chlamydial organisms by IF, EIA,
DNA probe, PCR, culture of bubo aspirate or by specific micro-IF serologic
test. CF testing is of diagnostic value if there is a 4-fold rise or a single titre
of 1:64 or greater. A negative CF test rules out the diagnosis.
2. Infectious agentChlamydia trachomatis, immunotypes L-1, L-2
and L-3, related to but distinct from the immunotypes causing trachoma
and oculogenital chlamydial infections.
3. OccurrenceWorldwide, especially in tropical and subtropical
areas; more common than ordinarily believed. Endemic in parts of Asia and
Africa. Age incidence corresponds with sexual activity. The disease is less
commonly diagnosed in women, probably due to the frequency of
asymptomatic infections; however, gender differences are not pro-
nounced in countries with high endemicity. All races are affected. In
temperate climates, it is seen predominantly among male homosexuals.
4. ReservoirHumans; often asymptomatic (particularly in females).
5. Mode of transmissionDirect contact with open lesions of
infected people, usually during sexual intercourse.
6. Incubation periodVariable, with a range of 330 days for a
primary lesion; if a bubo is the first manifestation, 10 30 days to several
months.
7. Period of communicabilityVariable, from weeks to years during
presence of active lesions.
LYMPHOGRANULOMA VENEREUM / 353
8. Susceptibility and resistanceSusceptibility is general; status of
natural or acquired resistance is unclear.
9. Methods of control
354 / MALARIA
the oocyst, reach the salivary glands and are infective when injected into
a person, as the insect takes its next blood-meal.
In the susceptible host, sporozoites enter hepatocytes and develop into
exo-erythrocytic schizonts. When these mature, the infected hepatocytes
rupture; asexual parasites reach the bloodstream and invade the erythro-
cytes to grow and multiply cyclically. Most will develop into asexual
forms, from trophozoites to mature blood schizonts that rupture the
erythrocyte within 48 72 hours, to release 8 30 erythrocytic merozoites
(depending on the species) that invade other erythrocytes. At the time of
each cycle, rupture of large numbers of erythrocytic schizonts induces
clinical symptoms. Within infected erythrocytes, some of the merozoites
may develop into male or female forms, gametocytes.
The period between an infective bite and detection of the parasite in a
thick blood smear is the prepatent period, which is typically 6 12 days
for P. falciparum, 8 12 days for P. vivax and P. ovale and 1216 days for
P. malariae. Delayed primary attacks by some P. vivax strains may occur
6 12 months after exposure. Gametocytes usually appear in the blood
stream within 3 days of overt parasitaemia with P. vivax and P. ovale, and
after about 10 days with P. falciparum. In the liver, some sporozoites of
P. vivax and P. ovale become dormant forms (hypnozoites) that remain in
hepatocytes to mature months or years later and produce relapses. This
phenomenon does not occur in falciparum or malariae malaria, and
reappearance of these forms of the disease (recrudescence) is the result of
inadequate treatment or of infection with drug-resistant strains. With
P. malariae, low levels of erythrocytic parasites may persist for many
years, to multiply at some future time to a level that may result again in
clinical illness.
Injection or transfusion of infected blood or use of contaminated
needles and syringes (e.g. injecting drug users) may also transmit malaria.
Congenital transmission occurs rarely. However, pregnant women are
more vulnerable than others to falciparum malaria (and possibly other
Plasmodium species). In areas of intense transmission, P. falciparum may
infect the placenta and cause low birth-weight as well as anemia,
sometimes severe, of the pregnant mother. In low transmission areas,
pregnant women are at high risk of severe malaria, abortion and premature
delivery.
A. Preventive measures:
I. Local community measures
E. International measures:
MALIGNANT NEOPLASMS ASSOCIATED WITH INFECTIOUS AGENTS / 371
MALIGNANT NEOPLASMS
ASSOCIATED WITH
INFECTIOUS AGENTS
Infectious agents are risk factors for several malignancies. Among the
agents implicated in the pathogenesis of various human malignancies,
either directly or indirectly, are parasites, viruses and the bacterium
Helicobacter pylori. The infectious agent is neither necessary nor suffi-
cient cause for all cases of agent-related malignancy; other causes are
involved; cofactors, both external (environmental) and internal (genetic
and physiological at immunological and molecular levels), play important
roles in each of these malignancies, which usually represent the late
outcome of the infection.
Most of the infectious agents implicated in the etiology of tumours are
viruses. A common feature of most virus-related cancers is the persistence
of the virus following infection early in life or the presence of immuno-
suppression: this leads to integration and development of cancer, usually
in a single cell clone (monoclonal tumour). Both DNA and RNA viruses are
involved.
The 4 strongest DNA virus candidates as agents directly or indirectly
involved in the pathogenesis of human malignancies are: (1) hepatitis B
virus (HBV) and hepatitis C virus (HCV); (2) Epstein-Barr virus (EBV); (3)
human papillomaviruses (HPV, mainly types 16 and 18); (4) human
herpesvirus-8 (HHV-8), also called Kaposi sarcoma-associated herpesvirus
(KSHV). The first 3 occur worldwide and produce many more inapparent
than apparent infections; most result in a latent virus state that is subject
to reactivation. Monoclonality of the tumour cells and integration of the
virus into the tumour cell indicate a causal association. The associated
malignancies occur in special host and geographic settings.
Among RNA viruses, retrovirusesincluding human T-cell lympho-
tropic virus (HTLV-1) and human immunodeficiency virus (HIV)are
associated with human T-cell leukaemia/lymphoma. Evidence from serol-
ogy, virology and epidemiology strongly implicates them in the causation
of specific malignancies.
I. HEPATOCELLULAR
CARCINOMA ICD-9 155.0; ICD-10 C22.0
(HCC, Primary liver cancer, Primary hepatocellular carcinoma)
Chronic infection with hepatitis B or C is an important risk factor for
primary hepatocellular cancer (PHC or HCC). Prospective studies have
shown a 100-fold higher risk of hepatocellular cancer in persons chroni-
cally infected with HBV than in noncarriers. Many patients go through
stages of chronic hepatitis and cirrhosis before development of the
tumour.
Periodic screening of carriers of hepatitis B virus (HBV) for alpha-
372 / MALIGNANT NEOPLASMS ASSOCIATED WITH INFECTIOUS AGENTS
[E. K. Yeoh]
III. NASOPHARYNGEAL
CARCINOMA ICD-9 147.9; ICD-10 C11
Nasopharyngeal carcinoma (NPC) is a malignant tumour of the epithelial
cells of the nasopharynx that usually occurs in adults aged 20 40.
Incidence is particularly high (about 10-fold when compared with the
general population) among groups from China (Taiwan and southern
China), even in those who have moved elsewhere. This risk decreases in
subsequent generations after emigration from Asia.
IgA antibody to the EBV viral capsid antigen in both serum and
nasopharyngeal secretions is characteristic of the disease and has been
used in China as a screening test for the tumour. Its appearance may
precede the clinical appearance of nasopharyngeal carcinoma by several
years and its reappearance after treatment heralds recurrence.
The serological and virological evidence relating EBV to NPC is similar
to that for African Burkitt lymphoma (high EBV antibody titres, genome in
tumour cells); this relationship has been found without respect to the
geographical origin of the patient. The tumour occurs worldwide but is
highest in southern China, southeastern Asia, northern and eastern Africa
and the Arctic. Males outnumber females by about 2:1. Chinese with
HLA-2 and SIN-2 antigen profiles have a particularly high risk.
EBV infection occurs early in life in settings where nasopharyngeal
carcinoma is most common, yet the tumour does not appear until age
374 / MALIGNANT NEOPLASMS ASSOCIATED WITH INFECTIOUS AGENTS
[B. Sylla]
[D. Parkin]
MALIGNANT NEOPLASMS ASSOCIATED WITH INFECTIOUS AGENTS / 377
VI. LYMPHATIC TISSUE
MALIGNANCY ICD-9 202;
ICD-10 C84.1, C84.5, C91.4, C91.5
(Adult T-cell leukaemia [ATL], T-cell lymphosarcoma [TLCL],
peripheral T-cell lymphoma [Sezary disease], Hairy cell
leukaemia)
Adult T-cell leukaemia (ATL), a leukaemia/lymphoma of T-cell origin
commonly seen in Japan, is identical to T-cell lymphoma sarcoma-cell
leukaemia (TLCL) seen less commonly in the Caribbean, the Pacific coast
of South America, equatorial Africa and southern USA. These malignancies
primarily involve adults and are associated with human T-cell lymphotro-
phic virus (HTLV-1), a member of the family of retroviruses. The latent
period between infection and the emergence of ATL is 20 30 years.
Infection early in life, primarily through breastmilk, leads to tumour
development in the adult, peaking at about age 50. This suggests the risk
of ATL is lower should infection occur later in life through transfer of
blood or blood products, IV drug use or sexual activity. The same virus
causes tropical spastic paraparesis (also called HTLV-1-associated myelop-
athy in Japan). Adult Japanese and Afro-Caribbeans are at highest risk.
Serological, virological and epidemiological evidence strongly implicate
HTLV-1 in the causation of leukaemia/lymphoma. Control measures are
similar to those for prevention of AIDS (see AIDS, section 9). The
effectiveness of screening donor blood for antibodies against HTLV-1 and
2 has yet to be demonstrated. In the USA, although the low overall virus
prevalence renders transmission from blood donors a rare event, screening
donor units for the virus is now a standard procedure. Cases should be
reported to a tumour registry.
[E. K. Yeoh]
MEASLES / 379
MEASLES ICD-9 055; ICD-10 B05
(Rubeola, Hard measles, Red measles, Morbilli)
1. IdentificationAn acute, highly communicable viral disease with
prodromal fever, conjunctivitis, coryza, cough and small spots with white
or bluish white centers on an erythematous base on the buccal mucosa
(Koplik spots). A characteristic red blotchy rash appears on the third to
seventh day; the rash begins on the face, then becomes generalized, lasts
4 7 days, and sometimes ends in brawny desquamation. Leukopenia is
common. The disease is more severe in infants and adults than in children.
Complications may result from viral replication or bacterial superinfec-
tion, and include otitis media, pneumonia, laryngotracheobronchitis
(croup), diarrhea and encephalitis.
The case-fatality rates in developing countries are estimated to be
3%5%, but are commonly 10%30% in some localities. Acute and delayed
mortality in infants and children have been documented. Measles is a more
severe disease in the very young and in malnourished children, in whom
it may be associated with hemorrhagic rash, protein-losing enteropathy,
otitis media, oral sores, dehydration, diarrhea, blindness and severe skin
infections. Children with clinical or subclinical vitamin A deficiency are at
particularly high risk. In children whose nutrition status is borderline,
measles often precipitates acute kwashiorkor and exacerbates vitamin A
deficiency that may lead to blindness. Subacute sclerosing panencephalitis
(SSPE) develops very rarely (about 1/100 000) several years after infection;
over 50% of SSPE cases had measles diagnosed in the first 2 years of life.
The WHO clinical case-definition reads any person with fever and
maculopapular rash and cough/coryza/conjunctivitis.
Diagnosis is usually on clinical and epidemiological grounds although
laboratory confirmation is preferred. The detection of measles-specific IgM
antibodies, present 3 4 days after rash onset, or a significant rise in
antibody concentrations between acute and convalescent sera confirms
the diagnosis. Techniques used less commonly include identification of
viral antigen in nasopharyngeal mucosal swabs by FA techniques or virus
isolation in cell culture from blood or nasopharyngeal swabs collected
before day 4 of rash, or from urine specimens before day 8 of rash.
2. Infectious agentMeasles virus, a member of the genus Morbilli-
virus of the family Paramyxoviridae.
3. OccurrencePrior to widespread immunization, measles was com-
mon in childhood, so that more than 90% of people had been infected by
age 20; few went through life without becoming infected. In the prevac-
cine era, there was an estimated 100 million cases and 6 million measles
deaths a year. Measles, endemic in large metropolitan communities,
attained epidemic proportions about every second or third year. In smaller
communities and areas, outbreaks tended to be more widely spaced and
somewhat more severe. With longer intervals between outbreaks, as in
380 / MEASLES
A. Preventive measures:
386 / MELIOIDOSIS
MENINGITIS / 389
II. A. MENINGOCOCCAL
INFECTION ICD-9 036; ICD-10 A39
(Meningococcaemia, not meningitis: ICD-10 A39.2-A39.4)
MENINGOCOCCAL
MENINGITIS ICD-9 036.0; ICD-10 A39.0
(Cerebrospinal fever)
1. IdentificationAn acute bacterial disease, characterized by sud-
den onset of fever, intense headache, nausea and often vomiting, stiff neck
and photophobia. A petechial rash with pink macules or occasionally
vesicles may be observed in Europe and North America but rarely in Africa.
Case fatality rates formerly exceeded 50%. Antibiotics, intensive care units
and improved supportive measures have decreased this but it remains high
at 8%15%. In addition, 10%20% of survivors will suffer long-term
sequelae including mental retardation, hearing loss and loss of limb use.
Invasive disease is characterized by one or more clinical syndromes
including bacteraemia, sepsis, or meningitis, the latter being the most
common presentation. Meningococcaemia, or meningococcal sepsis, is
the most severe form of infection with petechial rash, hypotension,
disseminated intravascular coagulation and multiorgan failure. Other forms
of meningococcal disease such as pneumonia, purulent arthritis, and
pericarditis are less common.
The gold standard for diagnosis is recovery of meningococci from a
sterile site, primarily cerebrospinal fluid (CSF) or blood; however, the
sensitivity of culture, especially in patients who have received antibiotics,
392 / MENINGITIS
9. Methods of control
A. Preventive measures:
1) Educate the public on the need to reduce direct contact and
exposure to droplet infection.
2) Reduce overcrowding in living quarters and workplaces,
such as barracks, schools, camps and ships.
3) Vaccines containing groups A, C, Y and W-135 meningococ-
cal polysaccharides are been available; two polysaccharide
vaccines are currently available on the market although in
most countries only one is available (quadrivalent ACYW-135
vaccine, and bivalent AC). Polysaccharide meningococcal
vaccines against serogroups A and C are safe and effective in
adults and children over 2, but do not elicit long-term
protection, particularly in children under 5. The serogroup A
polysaccharide can induce antibodies in children as young as
3 months, but the C polysaccharide is poorly immunogenic
and ineffective in children under 2. Serogroup Y and W135
polysaccharides are also immunogenic in adults and children
over 2 but immunogenicity and clinical protection have not
been fully documented yet. Meningococcal polysaccharide
vaccines are effective for outbreak control and for preven-
tion among high-risk groups, such as travellers to countries
where disease is epidemic, Hajj pilgrims, military groups, and
individuals with underlying immune dysfunctions. Because
these vaccines are often poorly immunogenic in young
children and have limited duration of efficacy, they are not
generally used in routine childhood immunization programs.
Reimmunization may be considered within 35 years if
indications still exist. No vaccine effective against group B
meningococci is currently licensed, although several have
been developed and show some efficacy in older children
and adults.
Meningococcal serogroup C vaccines were first introduced
in 1999 in the United Kingdom (mass vaccination for ages 2
months to 18 years). Early data suggest that these vaccines
have high efficacy (90%) in infants, children and teenagers,
decrease nasopharyngeal carriage of the bacteria and induce
herd immunity.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Obligatory case report in
most countries, Class 2 (see Reporting).
2) Isolation: Respiratory isolation for 24 hours after start of
chemotreatment.
MENINGITIS / 395
3) Concurrent disinfection: Of discharges from the nose and
throat and articles soiled therewith. Terminal cleaning.
4) Quarantine: Not applicable.
5) Protection of contacts: Close surveillance of household, day
care, and other intimate contacts for early signs of illness,
especially fever, to initiate appropriate therapy without
delay; prophylactic administration of an effective chemother-
apeutic agent to intimate contacts (household contacts,
military personnel sharing the same sleeping space and
people socially close enough to have shared eating utensils,
e.g. close friends at school but not the whole class). Younger
children in day care centers, even if not close friends, should
all be given prophylaxis after an index case is identified.
Rifampicin, ceftriaxone and ciprofloxacin are equally effec-
tive prophylactic agents. Rifampicin is administered twice
daily for 2 days: adults 600 mg per dose; children over 1
month old, 10 mg/kg; under 1 month, 5 mg/kg. Rifampicin
should not be given to pregnant women and may reduce the
effectiveness of oral contraceptives.
For adults, ceftriaxone, 250 mg IM, given in a single dose,
is effective; 125 mg IM for children under 15. Ciprofloxacin,
500 mg PO, may be given as a single dose to adults. Because
in most countries 50% of N. meningitidis isolates are
resistant to sulfadiazine (no longer manufactured in the USA),
the latter is rarely used for prophylaxis. If the organisms have
been shown to be sensitive to sulfadiazine, it may be given to
adults and older children at a dosage of 1 gram every 12
hours for 4 doses; for infants and children, the dosage is
125150 mg/kg/day divided into 4 equal doses, on each of 2
consecutive days. Health care personnel are rarely at risk
even when caring for infected patients; only intimate expo-
sure to nasopharyngeal secretions (e.g. as in mouth-to-mouth
resuscitation) warrants prophylaxis. Because of the efficacy
of prophylaxis, immunization is generally not recommended.
6) Investigation of contacts and source of infection: Throat or
nasopharyngeal cultures are of no value in deciding who
should receive prophylaxis since carriage is variable and
there is no consistent relationship between that found in the
normal population and in an epidemic.
7) Specific treatment: Penicillin given parenterally in adequate
doses is the drug of choice for proven meningococcal
disease; ampicillin and chloramphenicol are also effective.
Penicillin-resistant strains have been reported in many coun-
tries, including Spain, the United Kingdom and the USA;
strains resistant to chloramphenicol have been reported in
France and in Viet Nam. Treatment should start as soon as the
presumptive clinical diagnosis is made, even before menin-
396 / MENINGITIS
Mass vaccination, provide drugs to health units, treat cases according to protocol,
public education.
A. Preventive measures:
II. C. PNEUMOCOCCAL
MENINGITIS ICD-9 320.1; ICD-10 G00.1
1. IdentificationPneumococcal meningitis has a high case-fatality
rate. It can be fulminant and occurs with bacteraemia but not necessarily
with any other focus, although there may be otitis media or mastoiditis.
Onset is usually sudden with high fever, lethargy or coma and signs of
meningeal irritation. It is a sporadic disease in young infants, the elderly
and other high-risk groups, including asplenic and hypogammaglobulinae-
mic patients. Receipt of a cochlear implant and basilar fracture causing
persistent communication with the nasopharynx are predisposing factors
(See Pneumonia, pneumococcal.) Diagnosis may be made by isolation of
MENINGITIS / 401
organisms from blood or CSF. Pneumococcal capsular polysaccharide may
be identified by CIE or LA techniques.
2. Infectious agentStreptococcus pneumoniae is a Gram-positive
diplococcus. Nearly all strains causing meningitis and other severe forms
of pneumococcal disease are encapsulated; there are 90 known capsular
serotypes. The distribution of serotypes varies regionally and with age. In
the USA the 7 serotypes in pneumococcal conjugate vaccine are those that
cause 80% of pneumococcal meningitis in children and the majority of
pneumococcal meningitis in adults.
3. OccurrenceWorldwide; most prevalent among children 2
months to 3 years; in developing countries infants are at highest risk; in the
USA peaks at 6 18 months. The elderly, and adults who are immunocom-
promised or have certain chronic illness, are also at higher risk.
4. ReservoirHumans. Pneumococci are often found in the upper
respiratory tract of healthy persons. Carriage is more common in children
than in adults.
5. Mode of transmissionDroplet spread and contact with respira-
tory secretions; direct contract with a person with pneumococcal disease
generally results in nasopharyngeal carriage of the organism rather than in
disease.
6. Incubation periodUnknown; probably short, 1 4 days.
7. Period of communicabilityAs long as organisms are present,
which may be for a prolonged period especially in immunocompromised
hosts.
8. SusceptibilityAssumed to be universal. Immunity is associated
with the presence of circulating bactericidal and/or anticapsular antibody,
acquired transplacentally, from prior infection or from immunization.
9. Methods of control
404 / MOLLUSCUM CONTAGIOSUM
406 / MONONUCLEOSIS, INFECTIOUS
MONONUCLEOSIS,
INFECTIOUS ICD-9 075; ICD-10 B27
(Gammaherpesviral mononucleosis, Mononucleosis due to
Epstein-Barr virus, Glandular fever, Monocytic angina)
1. IdentificationAn acute viral syndrome characterized clinically by
fever, sore throat (often with exudative pharyngotonsillitis), lymphade-
nopathy (especially posterior cervical) and splenomegaly; characterized
hematologically by mononucleosis and lymphocytosis of 50% or greater,
including 10% or more atypical cells; and characterized serologically by
the presence of heterophile and Epstein-Barr virus (EBV) antibodies.
Recovery usually occurs in a few weeks, but a very small proportion of
individuals can take months to regain their former level of energy. There
is no evidence that this is due to abnormal persistence of the infection in
a chronic form.
In young children the disease is generally mild and more difficult to
recognize. Jaundice occurs in about 4% of infected young adults, although
95% will have abnormal liver function tests; splenomegaly occurs in 50%.
Duration is from 1 to several weeks; the disease is rarely fatal. The disease
is more severe in older adults.
The causal agent, EBV, is also closely associated with the pathogenesis
of several lymphomas and nasopharyngeal cancer (see Malignant neo-
plasms associated with infectious agents). Fatal immunoproliferative dis-
orders involving a polyclonal expansion of EBV infected B-lymphocytes
may occur in persons with an X-linked recessive immunoproliferative
disorder; they can also occur in persons with acquired immune defects,
including patients infected with HIV, transplant recipients and persons
with other conditions requiring long-term immunosuppressive therapy.
About 10%15% of infectious mononucleosis cases are heterophile-
negative. A heterophile-negative form of a syndrome resembling infectious
mononucleosis is due to cytomegalovirus and accounts for 5% to 7% of the
mono syndrome (see Cytomegalovirus infections); other rare causes are
toxoplasmosis and herpesvirus type 6 (see Exanthema subitum following
rubella). A mononucleosis-like illness may occur early in HIV-infected
patients. Differentiation depends on laboratory results that include the
EBV IgM test; only EBV elicits the true heterophile antibody. EBV
accounts for over 80% of both heterophile positive and heterophile
negative cases of the mononucleosis syndrome.
Laboratory diagnosis is based on the finding of a lymphocytosis exceed-
ing 50% (including 10% or more abnormal forms), abnormalities in liver
function tests (AST) or an elevated heterophile antibody titre after
adsorption of the serum on guinea pig kidney. The most sensitive and
commercially available test is the absorbed horse-RBC test; the most
specific of the common tests the beef-cell hemolysin test; and the most
frequently used procedure a commercial, qualitative slide agglutination
assay. Very young children may not show an elevation of the heterophile
MONONUCLEOSIS, INFECTIOUS / 407
titre, and heterophile-negative and clinically atypical forms rarely occur in
the elderly. If available, the IFA test for IgM and IgA antibody specific for
viral capsid antigen (VCA) or antibody against early antigen of the causal
virus is helpful in diagnosis of heterophile-negative cases; antibody specific
for the EBV nuclear antigen (EBNA) is usually absent during the acute
phase of illness. Therefore, a positive anti-VCA titre and a negative
anti-EBNA titre are diagnostic responses of an early primary EBV infection.
4. ReservoirHumans.
9. Methods of control
408 / MONONUCLEOSIS, INFECTIOUS
MUMPS / 409
MUMPS ICD-9 072; ICD-10 B26
(Infectious parotitis)
1. IdentificationAn acute viral disease characterized by fever, swell-
ing and tenderness of one or more salivary glands, usually the parotid and
sometimes the sublingual or submaxillary glands. Not all cases of parotitis
are caused by mumps infection, but other parotitis-causing agents do not
produce parotitis on an epidemic scale. Orchitis, most commonly unilat-
eral, occurs in 20%30% of affected postpubertal males. Testicular atrophy
occurs in about one-third of patients, but sterility is extremely rare. Mumps
orchitis has been reported to be a risk factor for testicular cancer. As many
as 40%50% of mumps infections have been associated with respiratory
symptoms, particularly in children under 5. Mumps can cause sensorineu-
ral hearing loss in both children and adults. Pancreatitis, usually mild,
occurs in 4% of cases; a suggested association with diabetes remains
unproven.
Symptomatic aseptic meningitis occurs in up to 10% of mumps cases;
patients usually recover without complications, though many require
hospitalization. Mumps encephalitis is rare (12/10 000 cases), but can
result in permanent sequelae, such as paralysis, seizures and hydroceph-
alus; the case-fatality rate for mumps encephalitis is about 1%. Mumps
infection during the first trimester of pregnancy is associated with a high
(25%) incidence of spontaneous abortion, but there is no firm evidence
that mumps during pregnancy causes congenital malformations.
Acute mumps infection can be confirmed through: a positive serological
test for mumps-specific IgM antibodies, by seroconversion or by a
significant (at least 4-fold) rise in serum mumps IgG titre as determined by
standard serological assay; or through isolation of mumps virus from an
appropriate clinical specimen (throat swab, urine, CSF). In research
settings, typing methods can distinguish wild-type mumps virus from
vaccine virus.
2. Infectious agentMumps virus, a member of the family Paramyxo-
viridae, genus Rubulavirus.
3. OccurrenceAbout one-third of exposed susceptible people have
inapparent infections; most infections in children under 2 are subclinical.
In temperate climates, winter and spring are peak seasons. In the absence
of immunization mumps is endemic, with an annual incidence usually
greater than 100 per 100 000 population and epidemic peaks every 25
years. In many countries, mumps was a major cause of viral encephalitis.
Serosurveys conducted prior to mumps vaccine introduction found that in
some countries 90% of persons were immune by age 15 years, while in
other countries a large proportion of the adult population remained
susceptible. In countries were mumps vaccine has not been introduced,
the incidence of mumps remains high, mostly affecting children 59.
By the end of 2002, 121 countries/territories included mumps vaccine
410 / MUMPS
A. Preventive measures:
Public education should encourage mumps immunization for
susceptible individuals. Routine mumps vaccination is recom-
mended in countries with an efficient childhood vaccination
program and sufficient resources to maintain high levels of
vaccine coverage. Mumps vaccination is recommended at age
1218 months, as part of MMR. More than 90% of recipients
develop immunity that is long-lasting and may be lifelong.
Live attenuated mumps virus vaccines are available as mono-
valent vaccines or trivalent measles-mumps-rubella (MMR) vac-
cines. Hydrolysed gelatin and/or sorbitol are used as stabilisers in
mumps vaccine, and neomycin as a preservative. Mumps vac-
cines are cold-chain dependent and should be protected from
light.
Different strains of live attenuated mumps vaccine have been
developed in Japan, the Russian Federation, Switzerland and the
USA. All licensed strains are judged acceptable by WHO for
public health programs, except the Rubini strain, which is not
recommended because of demonstrated low efficacy; persons
who received this strain should be revaccinated with another
strain.
In the USA and other industrialized countries only the Jeryl
Lynn strain or strains derived from it are accepted, because they
show no confirmed association with aseptic meningitis. Those
countries recommend 2 doses of MMR at the ages recommended
for measles vaccination.
The reported incidence of adverse events depends on the
strain of mumps vaccine. The most common adverse reactions
MUMPS / 411
are fever and parotitis. Rare adverse reactions include orchitis,
sensorineural deafness, and thrombocytopenia. Aseptic menin-
gitis, resolving spontaneously in less than one week without
sequelae, has been reported at frequencies ranging from 0.1 to
100 cases per 100 000 vaccine doses. This reflects differences in
vaccine strains and their preparation, as well as variations in
study design and case ascertainment. Better data are needed to
establish more precise estimates of aseptic meningitis incidence
in recipients of different strains of mumps vaccine. The rates of
aseptic meningitis due to mumps vaccine are at least 100-fold
lower than rates of aseptic meningitis due to infection with wild
mumps virus.
In addition to routine vaccination with a single dose of
mumps vaccine at 1218 months, some countries schedule
another dose of mumps vaccine and some countries have
conducted mass campaigns to reach broader target groups.
Countries intending to use mumps or MMR vaccine during
mass campaigns should give special attention to planning.
The mumps vaccine strain should be carefully selected, health
workers should receive training on expected rates of adverse
events following immunization, and on community advocacy and
health education activities.
Vaccine is contraindicated in the immunosuppressed; how-
ever, treatment with a low dose of steroids (less than 2 mg/kg/
day) on alternate days, topical steroid use or aerosolized steroid
preparations are no contraindication to administration of mumps
vaccine. For theoretical reasons pregnant women or women
planning a pregnancy in the next month (28 days in the USA)
should not receive mumps vaccine, although no evidence exists
that mumps vaccine causes fetal damage.
MYALGIA, EPIDEMIC / 413
MYALGIA, EPIDEMIC ICD-9 074.1; ICD-10 B33.0
(Epidemic pleurodynia, Bornholm disease, Devils grippe)
1. IdentificationAn acute viral disease characterized by paroxysmal
spasmodic pain in the chest or abdomen, which may be intensified by
movement, usually accompanied by fever and headache. The pain tends to
be more abdominal than thoracic in infants and young children, while the
reverse applies to older children and adults. Most patients recover within
1 week of onset, but relapses occur; no fatalities have been reported.
Localized epidemics are characteristic. It is important to differentiate from
more serious medical or surgical conditions.
Complications occur infrequently and include orchitis, pericarditis,
pneumonia and aseptic meningitis. During outbreaks of epidemic myalgia,
cases of group B coxsackievirus myocarditis of the newborn have been
reported; while myocarditis in adults is a rare complication, the possibility
should always be considered.
Diagnosis is suggested by the appearance of similar symptoms among
multiple family members; it is confirmed by a significant rise in antibody
titre against specific etiologic agents in acute and convalescent sera, or
isolation of the virus in cell culture or neonatal mice from throat secretions
or patient feces.
2. Infectious agentsGroup B coxsackievirus types 13, 5 and 6, and
echoviruses 1 and 6 are associated with the illness. Many group A and B
coxsackieviruses and echoviruses have been reported in sporadic cases.
3. OccurrenceAn uncommon disease, occurring in summer and
early autumn; usually in children and young adults aged 515, but all ages
may be affected. Multiple cases in a household can occur frequently.
Outbreaks have been reported in Europe, Australia, New Zealand and
North America.
4. ReservoirHumans.
5. Mode of transmissionDirectly by fecal-oral or respiratory drop-
let contact with an infected person, or indirectly by contact with articles
freshly soiled with feces or throat discharges of an infected person who
may or may not have symptoms. Group B coxsackieviruses have been
found in sewage and flies, though the relationship to transmission of
human infection is not clear.
6. Incubation periodUsually 35 days.
7. Period of communicabilityApparently during the acute stage of
disease; stools may contain virus for several weeks.
8. SusceptibilityProbably general; type-specific immunity presum-
ably results from infection.
414 / MYALGIA, EPIDEMIC
9. Methods of control
A. Preventive measures: None.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Obligatory report of epidem-
ics, Class 4 (see Reporting).
2) Isolation: Ordinarily limited to enteric precautions. Because
of possible serious illness in the newborn, if a patient in a
maternity unit or nursery develops an illness suggestive of
enterovirus infection, precautions should be instituted at
once. Individuals with suspected enterovirus infections (in-
cluding health personnel) should be excluded from visiting
maternity and nursery units and from contact with infants
and women near term.
3) Concurrent disinfection: Prompt and safe disposal of respi-
ratory discharges and feces; wash or dispose of articles soiled
therewith. Careful attention must be given to prompt, thor-
ough handwashing when handling discharges, feces and
articles soiled therewith.
4) Quarantine: Not applicable.
5) Immmunization of contacts: Not applicable.
6) Investigation of contacts and source of infection: Of no
practical value.
7) Specific treatment: None.
C. Epidemic measures: General notice to physicians of the
presence of an epidemic and the necessity for differentiation of
cases from more serious medical or surgical emergencies.
D. Disaster implications: None.
E. International measures: None.
[D. Lavanchy]
MYCETOMA / 415
MYCETOMA ICD-9 039; ICD-10 B47
NAEGLERIASIS AND ACANTHAMOEBIASIS / 417
NAEGLERIASIS AND
ACANTHAMOEBIASIS ICD-9 136.2; ICD-10 B60.2,
B60.1
(Primary amoebic meningoencephalitis)
1. IdentificationIn naegleriasis, a free-living amoeboflagellate in-
vades the brain and meninges via the nasal mucosa and olfactory nerve; it
causes a typical syndrome of fulminating pyogenic meningoencephalitis
(primary amoebic meningoencephalitis [PAM]) with sore throat, severe
frontal headache, occasional olfactory hallucinations, nausea, vomiting,
high fever, nuchal rigidity and somnolence, and death within 10 days,
usually on the fifth or sixth day. The disease occurs mainly in active
immunocompetent young men and women.
Several species of Acanthamoeba and Balamuthia mandrillaris (lep-
tomyxid amoebae) can invade the brain and meninges of immunocompro-
mised individuals, probably after entry through a skin lesion and without
involvement of the nasal and olfactory tissues; this causes a granulomatous
disease (granulomatous amoebic encephalitis) of insidious onset and
lasting from 8 days to several months; CFR may be high Acanthamoeba.
In addition to causing granulomatous amoebic encephalitis, species of
(A. polyphaga, A. castellanii) have been associated with chronic granu-
lomatous lesions of the skin, with or without secondary invasion of the
CNS. Infections of the eye (Conjunctivitis due to Acanthamoeba, ICD-10
H13.1) and of the cornea (Keratoconjunctivitis due to Acanthamoeba,
ICD-10 H19.2) have resulted in blindness.
Diagnosis of suspected primary or granulomatous amoebic encephalitis
is made through microscopic examination of wet mount preparations of
fresh CSF showing motile amoebae and of stained smears. In suspected
Acanthamoeba infections, diagnosis is made by microscopic examination
of scrapings, swabs or aspirates of the eye and skin lesions; or by culture
on nonnutrient agar seeded with Escherichia coli, Klebsiella aerogenes or
other suitable Enterobacter species. Balamuthia require mammalian cell
cultures for isolation. The trophozoites of Naegleria may become flagel-
lated after a few hours in water. Pathogenic N. fowleri, Acanthamoeba
species and Balamuthia can be differentiated morphologically and
through immunological testing. Amoebae have been misidentified as
macrophages and have been mistaken for Entamoeba histolytica when
microscopic diagnoses are made under low magnification.
2. Infectious agentsNaegleria fowleri, several species of Acan-
thamoeba (A. culbertsoni, A. polyphaga, A. castellanii, A. astronyxis,
A. hatchetti, A. rhysodes) and Balamuthia mandrillaris.
3. OccurrenceThe organisms are distributed globally in the environ-
ment. More than 160 cases of primary amoebic encephalitis in healthy
people, over 100 cases of granulomatous in immunodeficient patients
(including several with AIDS) and over 1000 cases of keratitis, primarily in
418 / NAEGLERIASIS AND ACANTHAMOEBIASIS
A. Preventive measures:
420 / NOCARDIOSIS
[J. Iredell]
422 / ONCHOCERCIASIS
A. Preventive measures:
426 / ORF VIRUS DISEASE
428 / PARACOCCIDIOIDOMYCOSIS
430 / PARAGONIMIASIS
8. SusceptibilitySusceptibility is general.
9. Methods of control
A. Preventive measures:
PEDICULOSIS AND PHTHIRIASIS / 433
PEDICULOSIS AND
PHTHIRIASIS ICD-9 132; ICD-10 B85
1. IdentificationInfestation by head lice (Pediculus capitis) occurs
on hair, eyebrows and eyelashes; infestation by body lice (P. corporis) is
of the clothing, especially along the seams of inner surfaces. Crab lice
(Phthirus pubis) usually infest the pubic area; more rarely facial hair
(including eyelashes in heavy infestations), axillae and body surfaces.
Infestation may result in severe itching and excoriation of the scalp or
body. Secondary infection may lead to regional lymphadenitis (especially
cervical).
2. Infesting agentsThe ectoparaistes Pediculus capitis (head
louse), P. corporis (body louse), Phthirus pubis (crab louse); adult lice,
nymphs and nits (egg cases) infest people. Lice are host-specific and those
of lower animals do not infest humans, although they may be present
transiently. Both sexes feed on blood.
The body louse is the species involved in outbreaks of epidemic typhus
caused by Rickettsia prowazeki, trench fever caused by R. quintana and
epidemic relapsing fever caused by Borrelia recurrentis.
3. OccurrenceWorldwide. Outbreaks of head lice are common
among children in schools and institutions everywhere. Body lice are
prevalent among populations with poor personal hygiene, especially in
cold climates where heavy clothing is worn and bathing is infrequent or
when people cannot change clothes (e.g. in the case of refugees).
4. ReservoirHumans.
5. Mode of transmissionFor head and body lice, direct contact
with an infested person and objects used by them; for body lice, indirect
contact with the personal belongings of infested persons, especially
shared clothing and headgear. Head and body lice can survive for only a
week without a food source. Crab lice are most frequently transmitted
through sexual contact. Lice leave a febrile host; fever and overcrowding
increase transfer from person to person.
6. Incubation periodLife cycle of 3 stages: eggs, nymphs and
adults. The most suitable temperature for the life cycle is 32C (89.6F).
Eggs of head lice do not hatch at temperatures under 22C (71.6F). Under
optimal conditions, lice eggs hatch in 710 days. The nymphal stages last
about 713 days depending on temperatures. The egg-to-egg cycle aver-
ages about 3 weeks. The average life cycle of the body or head louse
extends over a period of 18 days; that of the crab louse, 15 days.
7. Period of communicabilityAs long as lice or eggs remain alive
on the infested person or on fomites. The adults life span is approximately
1 month. Nits remain viable on clothing for 1 month. Body and head lice
434 / PEDICULOSIS AND PHTHIRIASIS
survive for a week without feeding off the host, crab lice only 2 days.
Nymphs survive 24 hours without food.
8. SusceptibilityAny person may become infested under suitable
conditions of exposure. Repeated infestations may result in dermal
hypersensitivity.
9. Methods of control
A. Preventive measures:
1) Educate the public on the value of destroying eggs and lice
through early detection, safe and thorough treatment of the
hair, laundering clothing and bedding in hot water (55C or
131F for 20 min), dry cleaning or dryers set at hot cycle.
2) Avoid physical contact with infested individuals and their
belongings, especially clothing and bedding.
3) Perform regular, direct inspection of children in a group
setting for nits and head lice and, when indicated, of body
and clothing for body lice.
4) In high-risk situations, use appropriate repellents on hair,
skin and clothing.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: Official report not ordi-
narily justifiable; school authorities should be informed,
Class 5 (see Reporting).
2) Isolation: For body lice, contact isolation if possible until 24
hours after application of an effective insecticide.
3) Concurrent disinfection: Clothing, bedding and fomites
should be treated by laundering in hot water, dry cleaning
or applying an effective chemical insecticide (see 9B7).
4) Quarantine: Not applicable.
5) Immunization of contacts: Not applicable.
6) Investigation of contacts and source of infestation: Examine
household and close personal contacts; treat those infested.
7) Specific treatment: For head and pubic lice: 1% permethrin
(a synthetic pyrethroid) cream rinse with 10 minutes
exposure; pyrethrins synergized with piperonyl butoxide
(10 minutes); and malathion 1% and 5 %, an organophos-
phate (7 8 hours). None of these is 100 % effective;
retreatment may be necessary after an interval of 710 days.
Carbaryl 0.5 % and 1 % can also be used but is more toxic
than above-mentioned products. Lindane and benzyl benzo-
ate are no longer recommended or registered because of
toxicity, side-effects and low efficacy.
Resistance to permethrin and pyrethrins is widespread.
Malathion resistance has been detected so far in France and
PEDICULOSIS AND PHTHIRIASIS / 435
the United Kingdom. Carbaryl resistance is emerging in the
United Kingdom.
For body lice: Clothing and bedding should be washed
using the hot water cycle of an automatic washing machine
or dusted with pediculicides using power dusters, hand
dusters or 2-ounce sifter cans. Dusts recommended by
WHO include 1% malathion and 0.5% permethrin.
C. Epidemic measures: Mass treatment as recommended in 9B7
above, using insecticides clearly known to be effective against
prevalent strains of lice. In typhus epidemics, individuals may
protect themselves by wearing silk or plastic clothing tightly
fastened around wrists, ankles and neck, and by impregnating
their clothes with repellents or permethrin.
D. Disaster implications: Diseases for which body and head lice
are vectors are particularly prone to occur at times of social
upheaval (see Typhus fever, section I, Epidemic louse-borne).
E. International measures: None.
[P. Guillet]
436 / PERTUSSIS
442 / PINTA
444 / PLAGUE
C. Epidemic measures:
PLAGUE / 449
1) Investigate all suspected plague deaths with autopsy and
laboratory examinations when indicated. Develop and carry
out case-finding. Establish the best possible facilities for
diagnosis and treatment. Alert existing medical facilities to
report cases immediately and to use full diagnostic and
therapeutic services.
2) Attempt to prevent or mitigate public hysteria by appropriate
informational and educational releases through the press and
news media.
3) Institute intensive flea control in expanding circles from
known foci.
4) Implement rodent destruction within affected areas only
after satisfactory flea control has been accomplished.
5) Protect all contacts as noted in 9B5.
6) Protect fieldworkers against fleas; dust clothing with insecti-
cide powder and use insect repellents daily. Antibiotic pro-
phylaxis should be undertaken for those with close docu-
mented exposure (see 9B5).
E. International measures:
PNEUMONIA / 451
PNEUMONIA
I. PNEUMOCOCCAL
PNEUMONIA ICD-9 481; ICD-10 J13
1. IdentificationAn acute lower respiratory tract bacterial infec-
tion, this is the most common community-acquired pneumonia at all ages.
In Europe and North America, pneumococcal pneumonia is estimated to
affect approximately 100 per 100 000 adults each year. Clinical manifes-
tations typically include sudden onset, high fever (with shaking chill or
rigor and/or other systemic symptoms like myalgia, arthralgia, headache,
malaise), pleural pain, dyspnoea, tachypnoea and cough productive of
rusty sputum. Laboratory findings include leukocytosis (neutrophilia),
elevated C-reactive protein and accelerated ESR. The onset may be less
abrupt, especially in the elderly, and fever, shortness of breath or altered
mental status may provide first evidence of pneumonia. In infants and
young children, fever, vomiting and convulsions may be the initial
manifestations. Typical chest X-ray shows lobar or segmental consolida-
tion; consolidation may be bronchopneumonic, especially in children and
the aged. Pneumococcal pneumonia is an important cause of death in
infants and the aged. Persons suffering from chronic conditions and
immune deficiencies are at increased risk. The case-fatality rate, formerly
20% 40% among hospitalized patients, has fallen to 5%10% with antimi-
crobial therapy, but remains 20% 40% among patients with substantial
underlying disease or alcoholism (it may exceed 50% in the high-risk
groups). In developing countries the case-fatality rates in children are
often over 10% and as high as 60% in infants under 6 months. Secondary
pneumococcal pneumonia is often observed in the vulnerable population
and among previously healthy individuals, following other respiratory
infections (e.g. influenza, RSV), with severe outcomes.
Early causal diagnosis is important for guiding specific treatment. The
presence in sputum of many Gram-positive diplococci together with
polymorphonuclear leukocytes suggests the diagnosis, which can be
confirmed through isolation of pneumococci from blood or, exception-
ally, from lower respiratory tract secretions obtained in adults by percu-
taneous transtracheal aspiration. For severe cases suspected to have
bacterial pneumonia, treatment should not be delayed and empiricial
antimicrobial therapy should start before microbiological confirmation. It
is important to identify the etiological agent together with its antimicrobial
susceptibility.
2. Infectious agentStreptococcus pneumoniae (pneumococcus), a
Gram-positive encapsulated coccus often colonizing the human nasophar-
ynx, where it can be carried asymptomatically. Children carry S. pneu-
moniae more often than adults do. Current data suggest that the 11 most
common serotypes cause at least 75% of invasive disease in all regions.
452 / PNEUMONIA
A. Preventive measures:
PNEUMONIA / 453
1) Avoid crowding in living quarters whenever practical, par-
ticularly in institutions, barracks and ships. Avoid malnutri-
tion and encourage physical activity. Bedridden patients
should be fed or lie in upright position.
2) Because risk of infection and case-fatality rates increase with
age, the benefits of immunization also increase. Administer
to high risk persons (individuals 65 and older and those
with anatomic or functional asplenia, sickle cell disease,
HIV infection and a variety of chronic systemic illnesses,
including heart and lung disease, cirrhosis of the liver, renal
insufficiency and diabetes mellitus) a polyvalent vaccine
containing the capsular polysaccharides of the 11 most
common serotypes that cause 75% of invasive disease in all
regions; this vaccine is not effective in children under 2 and
has no impact on pneumococcal carriage. In February
2000 a new 7-valent conjugate vaccine, which apparently
reduces invasive disease by about 70%, was approved for
use in children even under 2.
For most eligible patients, vaccine need be given only
once; however, reimmunization is generally safe, and vac-
cine should be offered to eligible patients whose immuni-
zation status cannot be determined. Reimmunization is
recommended once for persons over 2 who are at highest
risk for serious pneumococcal infection (e.g. asplenic pa-
tients) and those likely to have a rapid decline in pneumo-
coccal antibody levels, provided that 5 years or more have
elapsed since receipt of the 1st dose of vaccine. Reimmuni-
zation after 3 years should also be considered for children
with functional or anatomic asplenia and those who present
conditions associated with rapid antibody decline after
initial immunization (e.g. nephrotic syndrome, renal failure,
renal transplantation) who would be 10 or older at reimmu-
nization. In addition, persons 65 and older should be given
another dose of vaccine if they received the vaccine more
than 5 years previously and were under 65 at the time of
primary immunization. Most of the pneumococcal antigen
types in the vaccine are poor immunogens in children
under 2. Because of differences in serotype prevalence, the
vaccine may have lower efficacy in developing countries. A
7-valent glycoprotein conjugate vaccine has been approved
for routine infant use in the USA. This has been effective in
preventing pneumococcal pneumonia and meningitis in
young children and infants. The vaccine has some efficacy
against otitis media and against carriage of vaccine-included
pneumococcal serotypes.
Prophylactic use of xylitol, a sugar that inhibits pneumo-
coccal growth, may also represent a feasible intervention
454 / PNEUMONIA
II. MYCOPLASMAL
PNEUMONIA ICD-9 483; ICD-10 J15.7
(Primary atypical pneumonia)
1. IdentificationPredominantly a febrile lower respiratory infection
causing about 20% of pneumonias; less often, a pharyngitis that sometimes
progresses to bronchitis or pneumonia. Onset is gradual with headache,
malaise, cough (often paroxysmal), sore throat and sometimes chest
discomfort that may be pleuritic. Sputum, scant at first, may increase later.
Early patchy infiltration of the lungs is often more extensive on X-rays than
clinical findings suggest. In severe cases, the pneumonia may progress
from one lobe to another and become bilateral. Leukocytosis occurs after
the first week in approximately one-third of cases. Duration varies from a
few days to a month or more. Secondary bacterial infection and other
complications such as CNS involvement and Stevens-Johnson syndrome
are infrequent; fatalities are rare.
Differentiation is required from atypical pneumonitis due to many other
agents: bacteria, adenoviruses, influenza, respiratory syncytial virus, para-
influenza, measles, Q fever, psittacosis, certain mycoses, severe acute
respiratory syndrome (SARS) and tuberculosis.
Diagnosis is based on a rise in antibody titres between acute and
convalescent sera; titres rise after several weeks. The ESR is almost always
high. Nonspecific development of cold hemagglutinins may occur in up to
two-thirds of hospitalized cases; the level of titre increase may reflect the
severity of disease. Rapid diagnosis through PCR and direct immunofluo-
rescence assay (IFA) using throat swabs/sputum is possible in some
countries. The infectious agent may be cultured on special media.
2. Infectious agentMycoplasma pneumoniae belongs to the
Mycoplasmas (Molicutes), placed between bacteria and viruses. Mycoplas-
mas lack cell walls, cell wall synthesis inhibitors such as the penicillins and
cephalosporines are therefore not effective in treatment. With Streptococ-
cus pneumoniae and Haemophilus influenzae, Mycoplasma pneu-
moniae is one of the most common agents of community-acquired
pneumonia.
3. OccurrenceWorldwide; sporadic, endemic and occasionally epi-
456 / PNEUMONIA
III. PNEUMOCYSTIS
PNEUMONIA ICD-9 136.3; ICD-10 B59
(Interstitial plasma-cell pneumonia, PCP)
1. IdentificationAn acute to subacute, often fatal, pulmonary dis-
ease, especially in malnourished, chronically ill and premature infants. In
older children and adults, opportunistic illness associated with diseases of
the immune system and the use of immunosuppressants. It can be a major
problem for people with HIV infection, although incidence has fallen with
the use of highly active antiretroviral therapy (HAART). Clinically, there is
progressive dyspnoea, tachypnoea and cyanosis; sometimes without fever.
About 60% of patients have non-productive cough; productive cough is
less common. Auscultatory signs, other than rales, are usually minimal or
absent. Chest X-ray images typically show bilateral hilar-dominant diffuse
interstitial infiltrates.
Demonstration of the causative agent in material from bronchial brush-
ings, open lung biopsy and lung aspirates or in smears of tracheobronchial
mucus establishes the diagnosis. IFA, or staining with methenamine silver,
toluidine blue O, Giemsa, Gram-Weigert, cresyl-echt-violet identify the
organisms. There is no satisfactory routine culture method or serological
test at present.
2. Infectious agentPneumocystis carinii. Generally considered a
protozoan parasite; recent studies have shown that its DNA sequence
closely resembles that of a fungus.
3. OccurrenceWorldwide; may be endemic and epidemic in debil-
itated, malnourished or immunosuppressed infants. It affected approxi-
mately 60% of patients with HIV infection in the USA, Europe and Australia
before the routine use of prophylactic medication and HAART.
4. ReservoirHumans. Organisms have been demonstrated in ro-
dents, cattle, dogs and other animals, but the ubiquitous presence of the
458 / PNEUMONIA
POLIOMYELITIS, ACUTE / 463
POLIOMYELITIS, ACUTE ICD-9 045; ICD-10 A80
(Polioviral fever, Infantile paralysis)
1. IdentificationA viral infection most often recognized by the
acute onset of flaccid paralysis. Poliovirus infection occurs in the GI tract
with spread to the regional lymph nodes and, in a minority of cases, to the
central nervous system. Flaccid paralysis occurs in less than 1% of
poliovirus infections; over 90% of infections are either inapparent or result
in a nonspecific fever. Aseptic meningitis occurs in about 1% of infections.
A minor illness is recognized in 10% of infections with symptoms including
fever, malaise, headache, nausea and vomiting. If the disease progresses to
major illness, severe muscle pain and stiffness of the neck and back with
flaccid paralysis may occur. The paralysis of poliomyelitis is usually
asymmetric, with fever present at the onset. The maximum extent of
paralysis is reached in a short period, usually within 3 4 days. The site of
paralysis depends on the location of nerve cell destruction in the spinal
cord or brain stem. The legs are affected more often than the arms.
Paralysis of the respiration and/or swallowing muscles can be life-
threatening. Some improvement in paralysis may occur during convales-
cence, but paralysis still present after 60 days is likely to be permanent.
Infrequently, recurrence of muscle weakness following recovery may
occur many years after the original infection has resolved (postpolio
syndrome); this is not believed to be related to persistence of the virus
itself. Given the progress made towards global eradication, poliomyelitis
must now be distinguished from other paralytic conditions by isolation of
virus from stool. Other enteroviruses (notably types 70 and 71), echovi-
ruses and coxsackieviruses can cause an illness simulating paralytic
poliomyelitis.
The most frequent cause of acute flaccid paralysis (AFP) that must be
distinguished from poliomyelitis is Guillain-Barre syndrome (GBS). Paraly-
sis in GBS is typically symmetrical and may progress for periods as long as
10 days. The fever, headache, nausea, vomiting and pleocytosis character-
istic of poliomyelitis are usually absent in GBS; high protein and low cell
counts in the CSF and sensory changes are seen in the majority of GBS
cases. Acute motor axonal neuropathy (China paralytic syndrome) is an
important cause of AFP in northern China and is probably present
elsewhere; it is seasonally epidemic and closely resembles poliomyelitis.
Fever and CSF pleocytosis are usually absent, but paralysis may persist for
several months. Other causes of AFP include transverse myelitis, traumatic
neuritis, infectious and toxic neuropathies, tick paralysis, myasthenia
gravis, porphyria, botulism, insecticide poisoning, polymyositis, trichino-
sis and periodic paralysis.
Differential diagnosis of acute nonparalytic poliomyelitis includes other
forms of acute nonbacterial meningitis, purulent meningitis, brain abscess,
tuberculous meningitis, leptospirosis, lymphocytic choriomeningitis, in-
fectious mononucleosis, the encephalitides, neurosyphilis and toxic en-
cephalopathies.
464 / POLIOMYELITIS, ACUTE
A. Preventive measures:
466 / POLIOMYELITIS, ACUTE
470 / PSITTACOSIS
Q FEVER / 473
Q FEVER ICD-9 083.0; ICD-10 A78
(Query fever)
A. Preventive measures:
RABIES / 477
RABIES ICD-9 071; ICD-10 A82
(Hydrophobia, Lyssa)
1. IdentificationAn almost invariably fatal acute viral encephalomy-
elitis; onset generally heralded by a sense of apprehension, headache,
fever, malaise and indefinite sensory changes often referred to the site of
a preceding animal bite. Excitability and aerophobia are frequent symp-
toms. The disease progresses to paresis or paralysis; spasms of swallowing
muscles leads to fear of water (hydrophobia); delirium and convulsions
follow. Without medical intervention, the usual duration is 2 6 days,
sometimes longer; death is often due to respiratory paralysis.
Diagnosis is made through specific FA staining of brain tissue or virus
isolation in mouse or cell cultures. Presumptive diagnosis by specific FA
staining of frozen skin sections taken from the back of the neck at the
hairline. Serological diagnosis based on neutralization tests in mice or cell
culture.
2. Infectious agentRabies virus, a rhabdovirus of the genus Lyssa-
virus. All members of the genus are antigenically related, but use of
monoclonal antibodies and nucleotide sequencing shows differences
according to animal species or geographical location of origin. Rabies-
related viruses in Africa (Mokola and Duvenhage) have been associated,
rarely, with fatal rabies-like human illness. A new lyssavirus, first identified
in 1996 in several species of flying foxes and bats in Australia, has been
associated with 2 human deaths from rabies-like illnesses. This virus,
provisionally named Australian bat lyssavirus, is closely related to, but not
identical to classical rabies virus. Some of the illnesses due to rabies related
viruses may be diagnosed as rabies by the standard FA test.
3. OccurrenceWorldwide, with an estimated 65 000 87 000 deaths
a year, almost all in developing countries, particularly Asia (an estimated
38 000 to 60 000 deaths) and Africa (estimated 27 000 deaths). Most
human deaths follow dog bites for which adequate post-exposure prophy-
laxis was not or could not be provided. In Latin America a regional dog
rabies control program coordinated by PAHO since 1981 has led to a
reduction by 84% in the number of human deaths with only 56 cases
reported in 2001. During the past 10 years drastic decrease of the numbers
of human deaths have also been reported by several Asian countries
particularly China, Thailand and Viet Nam. Western, central and eastern
Europe including the Russian Federation report less than 50 rabies deaths
annually. From 1958 through 2000, in the USA, 35 of 57 human deaths
from rabies were acquired domestically. Of those infected within the USA,
almost all were bat-associated rabies (strain analysis).
Rabies is a disease primarily of animals. The areas currently free of
autochthonous rabies in the animal population (excluding bats) include
most of Australasia and western Pacific, many countries in Western Europe
(insular and continental), part of Latin America including the Caribbean.
478 / RABIES
Dogs transmit urban (or canine) rabies, whereas sylvatic rabies is a disease
of wild carnivores and bats, with sporadic spillover to dogs, cats and
livestock. In western Europe, fox rabies, once widespread, has decreased
considerably since oral rabies immunization of foxes began in the early
1990s. Since 1985 bat rabies cases have been reported in Denmark,
Finland, France, Germany, Luxembourg, the Netherlands, Spain, Switzer-
land and the United Kingdom. In the USA and Canada, wildlife rabies most
commonly involves racoons, skunks, foxes, coyotes and bats. There has
been a progressive epizootic among racoons in the eastern USA and among
coyotes and dogs in south Texas.
4. ReservoirWild and domestic Canidae, including dogs, foxes,
coyotes, wolves and jackals; also skunks, racoons, mongooses and other
biting mammals. In developing countries, dogs remain the principal
reservoir. Infected populations of vampire, frugivorous and insectivorous
bats occur in Mexico, Central and South America; infected insectivorous
bats in Canada, the USA and Europe. Rabbits, opossums, squirrels,
chipmunks, rats and mice are rarely infected: their bites rarely call for
rabies prophylaxis.
5. Mode of transmissionVirus-laden saliva of rabid animal intro-
duced though a bite or scratch (very rarely into a fresh break in the skin
or through intact mucous membranes). Person-to-person transmission is
theoretically possible, but rare and not well documented. Organ (corneal)
transplants from persons dying of undiagnosed CNS disease have resulted
in rabies in the recipients. Airborne spread has been demonstrated in a
cave where bats were roosting and in laboratory settings, but this occurs
very rarely. Transmission from infected vampire bats to domestic animals
is common in Latin America. In the USA, rabid insectivorous bats rarely
transmit rabies to terrestrial animals, wild or domestic.
6. Incubation periodUsually 3 8 weeks, rarely as short as 9 days or
as long as 7 years; depends on wound severity, wound site in relation to
nerve supply and distance from the brain, amount and strain of virus,
protection provided by clothing and other factors.
7. Period of communicabilityIn dogs and cats, usually for 37 days
before onset of clinical signs (rarely over 4 days) and throughout the
course of the disease. Longer periods of excretion before onset of clinical
signs (14 days) have been observed with Ethiopian dog rabies strains. In
one study, bats shed virus for 12 days before evidence of illness; in
another, skunks shed virus for at least 8 days before onset of clinical signs.
Skunks may shed virus for up to 18 days before death.
8. SusceptibilityAll mammals are susceptible to varying degrees,
which may be influenced by the virus strain. Humans are more resistant to
infection than several animal species; a study in the Islamic Republic of
Iran showed that, of those bitten by proven rabid animals and not treated,
about 40% developed the disease.
RABIES / 479
9. Methods of control
Vaccination
Status Treatment Regimen*
Not previously Wound All postexposure treatment to begin with immediate
vaccinated cleansing thorough cleansing of all wounds with soap and
water. If available, a virucidal agent such as a povi-
done-iodine solution should be used to irrigate the
wounds.
HRIG Administer 20 IU/kg body weight. If anatomically
feasible, the full dose should be infiltrated around
the wound(s); any remaining volume should be ad-
ministered intramuscularly (IM) at an anatomic site
distant from that of vaccine administration. RIG
should not be administered in the same syringe as
the vaccine. Because HRIG may partially suppress
active production of antibody, no more than the
recommended dose should be given.
Vaccine HDCV, RVA, or PCECV, 1.0 ml, IM (deltoid area),
one each on days 0**, 3, 7, 14, and 28.
Previously Wound All postexposure treatment to begin with immediate
vaccinated cleansing thorough cleansing of all wounds with soap and
water. If available, a virucidal agent such as a povi-
done-iodine solution should be used to irrigate
wounds.
RIG RIG should not be administered.
Vaccine HDCV, RVA (rabies vaccine, adsorbed), or PCEV, 1.0
mL, IM (deltoid area), one each on days 0** and 3.
The deltoid area is the only acceptable site of vaccination for adults and older
children. For younger children, the outer aspect of the thigh may be used. Never
administer vaccine in the gluteal area.
**Day 0 is the day the 1st dose of vaccine is administered.
486 / RAT-BITE FEVER
488 / RELAPSING FEVER
A. Preventive measures:
492 / RESPIRATORY DISEASE, ACUTE VIRAL
infections may disable more than half a closed community within a few
weeks (e.g. outbreaks of adenovirus type 4 or 7 in military recruits).
4. ReservoirHumans. Many known viruses produce inapparent
infections; adenoviruses may remain latent in tonsils and adenoids. Viruses
of the same group cause similar infections in many animal species but are
of minor importance as sources of human infections.
5. Mode of transmissionDirectly by oral contact or droplet spread;
indirectly by hands, handkerchiefs, eating utensils or other articles freshly
soiled by respiratory discharges of an infected person. Viruses discharged
in the feces, including enteroviruses and adenoviruses, may be transmitted
by the fecal-oral route. Outbreaks of illness due to adenovirus types 3, 4
and 7 have been related to swimming pools.
6. Incubation periodFrom 1 to 10 days.
7. Period of communicabilityShortly prior to and for the duration
of active disease; little is known about subclinical or latent infections.
Especially in infants, RSV shedding may very rarely persist several weeks
after clinical symptoms subside.
8. SusceptibilitySusceptibility is universal. Illness is more frequent
and more severe in infants, children and the elderly. Infection induces
specific antibodies that are usually short lived. Reinfection with RSV and
parainfluenza viruses is common, but illness is generally milder. Individu-
als with compromised cardiac, pulmonary or immune systems are at
increased risk of severe illness.
9. Methods of control
498 / RICKETTSIOSES, TICK-BORNE
A. Preventive measures:
RUBELLA / 503
RUBELLA ICD-9 056; ICD-10 B06
(German measles)
508 / SALMONELLOSIS
A. Preventive measures:
SCABIES / 513
SCABIES ICD-9 33.0; ICD-10 B86
(Sarcoptic itch, Acariasis)
1. IdentificationA parasitic infestation of the skin caused by a mite
whose penetration is visible as papules, vesicles or tiny linear burrows
containing the mites and their eggs. Lesions are prominent around finger
webs, anterior surfaces of wrists and elbows, anterior axillary folds, belt
line, thighs and external genitalia in men; nipples, abdomen and the lower
portion of the buttocks are frequently affected in women. In infants, the
head, neck, palms and soles may be involved; these areas are usually
spared in older individuals. Itching is intense, especially at night, but
complications are limited to lesions secondarily infected by scratching. In
immunodeficient individuals and in senile patients, infestation often
appears as a generalized dermatitis more widely distributed than the
burrows, with extensive scaling and sometimes vesiculation and crusting
(Norwegian scabies); the usual severe itching may be reduced or absent.
When scabies is complicated by beta-hemolytic streptococcal infection,
there is a risk of acute glomerulonephritis.
Diagnosis may be established by recovering the mite from its burrow
and identifying it microscopically. Care should be taken to choose lesions
for scraping or biopsy that have not been excoriated by repeated
scratching. Prior application of mineral oil facilitates collecting the
scrapings and examining them under a cover slip. Applying ink to the skin
and then washing it off will disclose the burrows.
2. Etiologic agentSarcoptes scabiei, a mite.
3. OccurrenceWidespread. Past epidemics were attributed to pov-
erty, poor sanitation and crowding due to war, movement of refugees and
economic crises. The recent wave of infestation in the USA and Europe has
evolved in the absence of major social disturbances and has affected
people of all socioeconomic levels, groups and standards of personal
hygiene. Endemic in many developing countries.
4. ReservoirHumans; Sarcoptes species and other animal mites can
live on humans but do not reproduce on them.
5. Mode of transmissionTransfer of parasites commonly occurs
through prolonged direct contact with infested skin and also during sexual
contact. Transfer from undergarments and bedclothes occurs only if these
have been contaminated by infested people immediately beforehand.
Mites can burrow beneath the skin surface in 2.5 minutes. Persons with
the Norwegian scabies syndrome are highly contagious because of the
large number of mites present in the exfoliating scales.
6. Incubation periodIn people without previous exposure, 2 6
weeks before onset of itching. People who have been previously infested
develop symptoms 1 4 days after reexposure.
514 / SCABIES
516 / SCHISTOSOMIASIS
ately preceding and during initial egg deposition. Acute systemic manifes-
tations are uncommon but can occur with S. haematobium infections.
7. Period of communicabilityNot communicable from person to
person; people with schistosomiasis may spread the infection by discharg-
ing eggs in urine and/or feces into bodies of water for as long as they
excrete eggs; it is common for human infections with S. mansoni and
S. haematobium to last in excess of 10 years. Infected snails will release
cercariae for as long as they live, a period that may last from several weeks
to about 3 months.
8. SusceptibilitySusceptibility is universal; any immunity develop-
ing as a result of infection is variable and not yet fully investigated.
9. Methods of control
A. Preventive measures:
520 / SEVERE ACUTE RESPIRATORY SYNDROME
The clinical spectrum and course of SARS vary and appear to depend on
immunological factors as yet not fully understood. From a review of
probable cases, dyspnoea sometimes rapidly progresses to respiratory
failure requiring ventilation; about 89% of cases recover and the case
fatality rate is about 11%. From data collected during outbreaks, the
likelihood of death from SARS appears to depend on characteristics of
those infected, including age and presence of underlying disease. Current
understanding, based on limited numbers of patients, suggests that the
case fatality is less than 1% in persons aged 24 years or younger, 6% in
persons aged 25 to 44 years, 15% in persons aged 45 to 64 years, and above
50% in persons aged 65 years or more.
2. Infectious agentSARS is caused by a coronavirus similar, on
electron microscopy, to animal coronaviruses. It is stable in feces and
urine at room temperature for at least 12 days, and for up to 4 days in
stools from patients who manifest diarrhea. The SARS virus loses infectiv-
ity after exposure to different commonly used disinfectants and fixatives.
Heat at 56C (132.8F) kills the SARS coronavirus at approximately 10 000
units per 15 minutes.
3. OccurrenceMajor outbreaks of SARS occurred during the period
November 2002 to July 2003 in Canada, China (including Hong Kong
Special Administrative Region and Taiwan), Singapore and Viet Nam. The
virus is known to have been transported by infected humans to over 20
additional sites in Africa, the Americas, Asia, Australia, Europe, the Middle
East and the Pacific. On July 5, 2003 WHO reported that person-to-person
transmission of the SARS virus had been interrupted at all outbreak sites
and recommended that intensified surveillance be continued to determine
whether or not the disease had become endemic and would reappear, and
so that in the case of re-emergence into human populations it would be
detected. An isolated event in which a laboratory worker became PCR
positive for the SARS virus occurred in Singapore in early September 2003.
A similar isolated laboratory worker infection occurred 3 months later in
Taipei (Taiwan, China), without secondary transmission. A third labora-
tory infection involving 2 workers occurred in Beijing in April 2004. One
of the cases transmitted the infection to a family member and a health
worker, which resulted in a small third generation outbreak and full
containment activities by the Chinese health authorities.
4. ReservoirUnknown. Initial studies in Guandong Province, China,
showed similar coronaviruses in some animal species sold in markets and
further study continues.
5. Mode of transmissionSARS is transmitted from person to person
by close contact: caring for, living with, or direct contact with respiratory
secretions or body fluids of a suspect or probable case of SARS. This is
thought to be primarily spread via droplets and possibly fomites. In one
instance, the virus is thought to have been transmitted from person to
SEVERE ACUTE RESPIRATORY SYNDROME / 523
person through some environmental vehicle, possibly aerosolised sewer-
age or transport of sewerage by mechanical vectors. Retrospective studies
of this particular mode of transmission continue.
6. Incubation periodFrom 3 to 10 days.
7. Period of communicabilityNot yet completely understood.
Initial studies suggest that transmission does not occur before onset of
clinical signs and symptoms, and that maximum period of communicabil-
ity is less than 21 days. Health workers are at great risk, especially if
involved in pulmonary procedures such as intubation or nebulization, and
serve as a major entry point of the disease into the community.
8. SusceptibilityUnknown but assumed to be universal. At present
race and gender appear not to alter susceptibility. Because of the small
numbers of cases reported among children, it has not been possible to
assess the influence of age.
9. Methods of control
A. Preventive measures:
1) Identify all suspect and probable cases using the WHO case
definitions:
Persons who arrive at health care facilities and require
SARS assessment must be rapidly diverted by triage nurses to
a separate area to minimize transmission to other patients
and from probable SARS patients, and be given a face mask,
preferably one that provides filtration of expired air.
Health workers involved in the triage process should wear
a face mask (N/R/P 95/99/100 or FFP 2/3 or equivalent
national manufacturing standard) with eye protection, and
wash hands before and after contact with any patient, after
activities likely to cause contamination and after removing
gloves.
Soiled gloves, stethoscopes and other equipment must be
treated with care as they have potential to spread infection.
Disinfectants such as fresh bleach solutions must be widely
available at appropriate concentrations.
2) Isolation of probable cases:
Probable SARS cases should be isolated and accommo-
dated as follows in descending order of preference: negative
pressure rooms with door closed, single room with own
bathroom facilities, cohort placement in an area with an
independent air supply, exhaust system and bathroom facil-
ities. If an independent air supply is not feasible, air condi-
tioning should be turned off and windows opened (if away
from public places) for good ventilation.
Strict universal precautions for infection control must be
524 / SEVERE ACUTE RESPIRATORY SYNDROME
C. Epidemic Measures:
During the SARS outbreaks of 2003 the perception of risk of
infection by the general population was far greater than the
actual risk of infection. Epidemic measures therefore should
clearly inform the general public.
Establish a national SARS advisory group, including all govern-
mental sectors concerned, to oversee epidemic measures, in-
cluding epidemiological, clinical and other investigations that
are conducted in the quest for more information.
Educate the population about the risk of infection, defining
close contact with a SARS case and the signs and symptoms of
SARS, and providing clear guidance as to how to avoid contact
with SARS cases through mass media and/or other means.
Establish telephone hot line or other means of dealing with
requests from the general public, and ensure that the means of
contacting this resource are clearly provided to the general public.
Ensure adequate triage facilities and clearly indicate to the
general public where they are located and how they can be
accessed.
D. Disaster Implications:
As with other emerging infections, severe adverse economic
impact and socio-economic consequences have been shown to
occur.
E. International Measures:
WHO maintains global surveillance for clinically apparent cases
of SARS (probable and suspect cases). Testing of clinically well
contacts of probable or suspect SARS cases and community-based
serological surveys are being conducted as part of epidemiological
studiesthis may ultimately change our understanding of SARS
transmission (persons who test as SARS CoV positive in these
studies should not be notified as SARS cases to WHO at this time).
WHO provides regular information updates and evidence-based
travel recommendations, effective in limiting the international
spread of infection, through the revision process of the Interna-
tional Health Regulations. A global response facilitating the work
and exchange of information among scientists, clinicians and public
health experts has been shown to be effective in providing
information and effective evidence-based policies and strategies.
[D. Heymann]
SHIGELLOSIS / 527
SHIGELLOSIS ICD-9 004; ICD-10 A03
(Bacillary dysentery)
1. IdentificationAn acute bacterial disease involving the distal small
intestine and colon, characterized by loose stools of small volume accom-
panied by fever, nausea and sometimes toxaemia, vomiting, cramps and
tenesmus. In typical cases, the stools contain blood and mucus (dysentery)
resulting from mucosal ulcerations and confluent colonic crypt microab-
scesses caused by the invasive organisms; many cases present with a
watery diarrhea. Convulsions may be an important complication in young
children. Bacteraemia is uncommon. Mild and asymptomatic infections
occur; illness is usually self-limited, lasting on average 4 7 days. Severity
and case-fatality rate vary with the host (age and pre-existing nutritional
state) and the serotype. Shigella dysenteriae 1 (Shiga bacillus) spreads in
epidemics and is often associated with serious disease and complications
including toxic megacolon, intestinal perforation and the hemolytic-
uraemic syndrome; case-fatality rates have been as high as 20% among
hospitalized cases even in recent years. In contrast, many infections with
S. sonnei result in a short clinical course and an almost negligible
case-fatality rate except in immunocompromised hosts. Certain strains of
S. flexneri can cause a reactive arthropathy (Reiter syndrome), especially
in persons who are genetically predisposed by having HLA-B27 antigen.
Isolation of Shigella from feces or rectal swabs provides the bacterio-
logical diagnosis. Prompt laboratory processing of specimens and use of
appropriate media (differential, low selectivityMacConkey agarto-
gether with high selectivity XLD or S/S agar) increase the likelihood of
Shigella isolation. Isolation of S. dysenteriae type 1 requires special
efforts, since this organism is inhibited by some selective media, including
S/S agar. Outside the human body Shigella remains viable only for a short
period, which is why stool specimens must be processed rapidly after
collection. Infection is usually associated with large numbers of fecal
leukocytes detected through microscopical examination of stool mucus
stained with methylene blue or Gram.
2. Infectious agentsThe genus Shigella comprises 4 species or
serogroups: A, S. dysenteriae; B, S. flexneri; C, S. boydii; D, S. sonnei.
Groups A, B and C are further divided into 12, 14, and 18 serotypes and
subtypes, respectively, designated by arabic numbers and lower case
letters (e.g. S. flexneri 2a). S. sonnei (Group D) consists of a single
serotype. A specific virulence plasmid is necessary for the epithelial cell
invasiveness manifested by Shigellae. The infectious dose for humans is
low (10 100 bacteria have caused disease in volunteers).
3. OccurrenceWorldwide; shigellosis causes an estimated 600 000
deaths per year. Two-thirds of the cases, and most of the deaths, are in
children under 10. Illness in infants under 6 months is unusual. Secondary
attack rates in households can be as high as 40%. Outbreaks occur under
528 / SHIGELLOSIS
C. Epidemic measures:
SHIGELLOSIS / 531
1) Report at once to the local health authority any group of
cases of acute diarrheal disorder, even in the absence of
specific identification of the causal agent.
2) Investigate water, food, and milk supplies, and use general
sanitation measures.
3) Prophylactic administration of antibiotics is not recom-
mended.
4) Publicize the importance of handwashing after defecation;
provide soap and individual paper towels if otherwise not
available.
D. Disaster implications: A potential problem where personal
hygiene and environmental sanitation are deficient (see Typhoid
fever).
E. International measures: WHO Collaborating Centres.
[C. Chaignat]
532 / SMALLPOX
SPOROTRICHOSIS / 537
SPOROTRICHOSIS ICD-9 117.1; ICD-10 B42
1. IdentificationA fungal disease, usually of the skin, often of an
extremity, which begins as a nodule. As the nodule grows, lymphatics
draining the area become firm and cord-like and form a series of nodules,
which in turn may soften and ulcerate. Osteoarticular, pulmonary and
multifocal infections are rare except as regards multifocal infections for
patients with HIV infection. Fatalities are uncommon.
Culture of a biopsy, pus or exudate confirms the diagnosis. Organisms
are rarely visualized by direct smear. Biopsied tissue should be examined
with fungal stains.
2. Infectious agentSporothrix schenckii, a dimorphic fungus.
3. OccurrenceReported worldwide, an occupational disease of
farmers, gardeners and horticulturists. The disease is characteristically
sporadic and relatively uncommon. An epidemic among gold miners in
South Africa involved some 3000 people; fungus was growing on mine
timbers. Contact with infected cats was an exposure risk in a Brazilian
outbreak in 2003.
4. ReservoirSoil, decaying vegetation, wood, moss and hay.
5. Mode of transmissionIntroduction of fungus through the skin
pricks from thorns or barbs, handling of sphagnum moss or slivers from
wood or lumber. Outbreaks have occurred among children playing in and
adults working with baled hay. Pulmonary sporotrichosis presumably
arises through inhalation of conidia. Persons handling sick cats are an
occupational risk group.
6. Incubation periodThe lymphatic form may develop 1 week to 3
months after injury.
7. Period of communicabilityPerson-to-person transmission has
only rarely been documented.
8. SusceptibilityUnknown.
9. Methods of control
STAPHYLOCOCCAL DISEASES / 539
STAPHYLOCOCCAL DISEASES
I. STAPHYLOCOCCAL DISEASE
IN THE COMMUNITY
BOILS, CARBUNCLES,
FURUNCLES,
ABSCESSES ICD-9 680, 041.1; ICD-10 L02;
B95.6-B95.8
IMPETIGO ICD-9 684, 041.1; ICD-10 L01
CELLULITIS ICD-9 682.9; ICD-10 L03
STAPHYLOCOCCAL SEPSIS ICD-9 038.1; ICD-10
A41.0-A41.2
STAPHYLOCOCCAL
PNEUMONIA ICD-9 482.4; ICD-10 J15.2
ARTHRITIS ICD-9 711.0, 041.1; ICD-10 M00.0
OSTEOMYELITIS ICD-9 730, 041.1; ICD-10 M86
ENDOCARDITIS ICD-9 421.0, 041.1; ICD-10 133.0
1. IdentificationThe common bacterial skin lesions are impetigo,
folliculitis, furuncles, carbuncles, abscesses and infected lacerations. The
basic lesion of impetigo is described in section II, 1; a distinctive scalded
skin syndrome is associated with certain strains of Staphylococcus
aureus, which elaborate an epidermolytic toxin. Other skin lesions are
localized and discrete. Constitutional symptoms are unusual; if lesions
extend or are widespread, fever, malaise, headache and anorexia may
540 / STAPHYLOCOCCAL DISEASES
A. Preventive measures:
C. Epidemic measures:
1) The occurrence of 2 or more concurrent cases of staphylo-
coccal disease related to a nursery or a maternity ward is
presumptive evidence of an outbreak and warrants investi-
gation. Culture all lesions to determine antibiotic resistance
pattern and type of epidemic strain. The laboratory should
keep clinically important isolates for 6 months before
discarding them, so as to support possible epidemiological
investigation using antibiotic sensitivity patterns or pulsed-
field gel electrophoresis.
2) In nursery outbreaks, institute isolation precautions for
cases and contacts until all have been discharged. Use a
rotational system (cohorting) where one unit (A) is filled
and subsequent babies are admitted to another nursery (B)
while the initial unit (A) discharges infants and is cleaned
before new admissions. If facilities are present for baby
in-rooming, this may reduce risk. Colonized or infected
infants should be grouped in another cohort. Assignments
STAPHYLOCOCCAL DISEASES / 545
of nursing and other ward personnel should be restricted to
specific cohorts.
Before admitting new patients, wash cribs, beds and
other furniture with an approved disinfectant. Autoclave
instruments that enter sterile body sites, wipe mattresses
and thoroughly launder bedding and diapers (or use dispos-
able diapers).
3) Examine all patient care personnel for draining lesions
anywhere on the body. Perform an epidemiological inves-
tigation, and if one or more personnel are associated with
the disease, culture nasal specimens from them and all
others in contact with infants. It may become necessary to
exclude and treat all carriers of the epidemic strain until
cultures are negative. Treatment of asymptomatic carriers is
directed at suppressing the nasal carrier state, usually
through local application of appropriate antibiotic oint-
ments to the nasal vestibule, sometimes with concurrent
systemic rifampicin for 39 days.
4) Investigate adequacy of nursing procedures, especially avail-
ability of handwashing facilities. Emphasize strict hand-
washing; if facilities are inaccessible or inadequate, consider
use of a hand antiseptic agent (e.g. alcohol) at the bedside.
Personnel assigned to infected or colonized infants should
not work with noncolonized newborns.
5) Although prohibited for routine use in the USA, prepara-
tions containing 3% hexachlorophene may be used during
an outbreak. Full-term infants may be bathed (diaper area
only) as soon after birth as possible and daily until they are
discharged. After bathing is completed, wash hexachloro-
phene off thoroughly because systemic absorption may
result in CNS damage.
D. Disaster implications: None.
E. International measures: WHO Collaborating Centres.
STREPTOCOCCAL DISEASES / 549
STREPTOCOCCAL DISEASES
CAUSED BY GROUP A (BETA
HEMOLYTIC) STREPTOCOCCI
ICD-9 034, 035, 670; ICD-10 A49.1, J02.0, A38, L01.0, A46, 085
(Streptococcal sore throat, Streptococcal infection, Scarlet fever,
Impetigo, Erysipelas, Puerperal fever, Rheumatic fever)
1. IdentificationGroup A streptococci cause a variety of diseases.
The most frequently encountered conditions are streptococcal pharyngi-
tis/tonsillitis (sore throat) (ICD-10 J02.0) and streptococcal skin infections
(impetigo or pyoderma). Other diseases and infections include scarlet
fever (ICD-9 034.1/ICD-10 A38), puerperal fever (ICD-9 670/ICD-10 O85),
septicemia, erysipelas, cellulitis, mastoiditis, otitis media, pneumonia,
peritonsillitis, wound infections and rarely, necrotizing fasciitis, rheumatic
fever and a toxic shock-like syndrome. One or other form of clinical
disease often predominates during outbreaks.
Symptoms may be minimal or absent; patients with streptococcal sore
throat typically exhibit sudden onset of fever, exudative tonsillitis or
pharyngitis (sore throat), with tender, enlarged anterior cervical lymph
nodes. The pharynx, the tonsillar pillars and soft palate may be injected
and oedematous; petechiae may be present against a background of diffuse
redness. Coincident or subsequent otitis media or peritonsillar abscess
may occur; as may acute glomerulonephritis (15 weeks, mean 10 days) or
acute rheumatic fever (mean 19 days). Rheumatic heart (valvular) disease
occurs days to weeks after acute streptococcal infection, Sydenham
chorea several months following infection.
Streptococcal skin infection (pyoderma, impetigo) is usually superficial
and may proceed through vesicular, pustular and encrusted stages.
Scarlatiniform rash is unusual and rheumatic fever is not a sequel;
however, glomerulonephritis may occur later, usually 3 weeks after the
skin infection.
Scarlet fever is a form of streptococcal disease characterized by a skin
rash, occurring when the infecting strain produces a pyrogenic exotoxin
(erythrogenic toxin) and the patient is sensitized but not immune to the
toxin. Clinical characteristics may include all symptoms associated with a
streptococcal sore throat (or with a streptococcal wound, skin or puer-
peral infection) as well as enanthem, strawberry tongue and exanthem.
The rash is usually a fine erythema, commonly punctate, blanching on
pressure, often felt (like sandpaper) better than seen and appearing most
often on the neck, chest, folds of the axilla, elbow, groin and inner
surfaces of the thighs.
Typically, the scarlet fever rash does not involve the face, but there is
flushing of the cheeks and circumoral pallor. High fever, nausea and
vomiting often accompany severe infections. During convalescence, des-
quamation of the skin occurs at the tips of fingers and toes, less often over
wide areas of trunk and limbs, including palms and soles; it is more
550 / STREPTOCOCCAL DISEASES
558 / STRONGYLOIDIASIS
A. Preventive measures:
[L. Savioli]
SYPHILIS / 561
SYPHILIS
I. VENEREAL SYPHILIS ICD-9 090-096; ICD-10 A50-A52
(Lues)
1. IdentificationAn acute and chronic treponemal disease charac-
terized clinically by a primary lesion, a secondary eruption involving skin
and mucous membranes, long periods of latency, and late lesions of skin,
bone, viscera, the CNS and cardiovascular system. The primary lesion
(chancre) usually appears about 3 weeks after exposure as an indurated,
painless ulcer with a serous exudate at the site of initial invasion. Invasion
of the bloodstream precedes the initial lesion; a firm, nonfluctuant,
painless satellite lymph node (bubo) commonly follows.
Infection may occur without a clinically evident external chancre; e.g.
in the rectum or on the cervix. After 4 6 weeks, even without specific
treatment, the chancre begins to involute and, in most cases, a generalized
secondary eruption appears, often accompanied by mild constitutional
symptoms. A symmetrical maculopapular rash involving the palms and
soles, with associated lymphadenopathy, is classic. There is some evidence
that HIV immunosupressed patients may have less defence against CNS
infection. Secondary manifestations resolve spontaneously within weeks
to 12 months; all untreated cases will go on to latent infection for weeks
to years, and one-third will exhibit tertiary syphilis signs and symptoms. In
the early years of latency, there may be recurrence of infectious lesions of
the skin and mucous membranes.
CNS disease, manifested as acute syphilitic meningitis, may occur at any
time in secondary or early latent syphilis, later as meningovascular syphilis,
and finally as paresis or tabes dorsalis. Latency sometimes continues
through life. In other instances, and unpredictably, 520 years after initial
infection, disabling lesions occur in the aorta (cardiovascular syphilis) or
gummas may occur in the skin, viscera, bone and/or mucosal surfaces.
Death or serious disability rarely occurs during early stages; late manifes-
tations shorten life, impair health and limit occupational efficiency. The
widespread use of antimicrobials has decreased the frequency of late
manifestations. Concurrent HIV infection may increase the risk of CNS
syphilis; neurosyphilis must be considered in the differential diagnosis of
HIV-infected individuals with CNS symptoms.
Fetal infection results in congenital syphilis and occurs with high
frequency in untreated early infections of pregnant women. It frequently
causes abortion or stillbirth and may cause infant death through preterm
delivery of low birthweight infants or from generalized systemic disease.
Congenital infection may result in late manifestations that include involve-
ment of the CNS with occasional stigmata such as Hutchinson teeth (small,
wide-spaced, greyish incisors), saddlenose, sabre shins (periostitis), inter-
stitial keratitis and deafness. Congenital syphilis can be asymptomatic,
especially in the first weeks of life.
The laboratory diagnosis of syphilis is usually made through serological
testing of blood (and CSF when indicated). Reactive tests with nontrepo-
562 / SYPHILIS
nemal antigens (e.g. RPR [rapid plasma reagin] or VDRL [Venereal Disease
Research Laboratory]) must be confirmed by tests using treponemal
antigens (i.a., FTA-Abs [fluorescent treponemal antibody absorbed] or
TPHA [T. pallidum hemagglutinating antibody]), when available, to aid in
excluding biological false-positive reactions. For screening newborns,
serum is preferred over cord blood, which produces more false-positive
reactions. Primary and secondary syphilis can be confirmed through
darkfield or phase-contrast examination or FA antibody staining of exu-
dates from lesions or aspirates from lymph nodes if no antibiotic has been
administered. Serological tests are usually nonreactive during the early
primary stage while the chancre is still present; a darkfield examination of
all genital ulcerative lesions can be useful, particularly in suspected early
seronegative primary syphilis.
2. Infectious agentTreponema pallidum, subsp. pallidum, a spi-
rochaete.
3. OccurrenceWidespread; in industrialized countries sexually ac-
tive young people between 20 and 29 are primarily involved. Racial
differences in incidence reflect social rather than biological factors.
Syphilis is usually more prevalent in urban than rural areas, and in some
cultures, in males more than in females. After some decline in the late
1970s and early 1980s, incidence has increased again in recent years,
notably in western Europe and the USA; in Eastern Europe, contributing
factors include a decline in the economy, a breakdown of health systems
and an increase in main city sex trade.
4. ReservoirHumans.
5. Mode of transmissionDirect contact with infectious exudates
from obvious or concealed, moist, early lesions of skin and mucous
membranes of infected people during sexual contact; exposure nearly
always occurs during oral, anal or vaginal intercourse. Transmission by
kissing or fondling children with early congenital disease occurs rarely.
Transplacental infection of the fetus occurs during the pregnancy of an
infected woman.
Transmission can occur through blood transfusion if the donor is in the
early stages of disease. Infection through contact with contaminated
articles may be theoretically possible but is extraordinarily rare. Health
professionals have developed primary lesions on the hands following
unprotected clinical examination of infectious lesions.
6. Incubation period10 days to 3 months, usually 3 weeks.
7. Period of communicabilityCommunicability exists when moist
mucocutaneous lesions of primary and secondary syphilis are present. The
distinction between the infectious primary and secondary stages and the
noninfectious early latent stage of syphilis is somewhat arbitrary with
regard to communicability, since primary and secondary stage lesions may
SYPHILIS / 563
not be apparent to the infected individual. Lesions of secondary syphilis
may recur with decreasing frequency up to 4 years after infection, but
transmission of infection is rare after the first year. In the USA infectious
early syphilis is usually defined as ending after the first year of infection.
Transmission of syphilis from mother to fetus is most probable during
early maternal syphilis but can occur throughout the latent period.
Infected infants may have moist mucocutaneous lesions that are more
widespread than in adult syphilis and are a potential source of infection.
8. SusceptibilitySusceptibility is universal, though only approxi-
mately 30% of exposures result in infection. Infection leads to gradual
development of immunity against T. pallidum and, to some extent, against
heterologous treponemes; immunity often fails to develop because of early
treatment in the primary and secondary stages. Concurrent HIV infection
may reduce the normal host response to T. pallidum.
9. Methods of control
E. International measures:
1) Examine groups of adolescents and young adults who move
from areas of high prevalence for treponemal infections.
2) Adhere to agreements among nations as to records, provision
of diagnostic and treatment facilities and contact interviews
at seaports for foreign merchant seamen (e.g. Brussels Agree-
ment).
3) Provide for rapid international exchange of information on
contacts.
4) WHO Collaborating Centres.
[F. Ndowa]
SYPHILIS
II. NONVENEREAL ENDEMIC
SYPHILIS ICD-9 104.0; ICD-10 A65
(Bejel, Njovera)
1. IdentificationAn acute disease of limited geographic distribu-
tion, characterized clinically by an eruption of skin and mucous mem-
branes, usually without an evident primary sore. Mucous patches of the
mouth are often the first lesions, soon followed by moist papules in
skinfolds and by drier lesions of the trunk and extremities. Other early skin
lesions are macular or papular, often hypertrophic, and frequently circi-
nate; lesions resemble those of venereal syphilis. Plantar and palmar
hyperkeratoses occur frequently, often with painful fissuring; patchy
depigmentation/hyperpigmentation of the skin and alopecia are common.
Inflammatory or destructive lesions of skin, long bones and nasopharynx
are late manifestations. Unlike venereal syphilis, bejel now rarely shows
neurological or cardiovascular involvement. The case-fatality rate is low.
Darkfield examination can demonstrate organisms in lesions during
early disease. Serological tests for syphilis are reactive in the early stages
and remain so for many years then gradually tend toward reversal;
response to treatment as in venereal syphilis.
2. Infectious agentTreponema pallidum, subsp. endemicum, a
spirochete indistinguishable from that of syphilis except through molec-
ular testing.
3. OccurrenceA common disease of childhood in localized areas
with poor socioeconomic conditions and primitive sanitary and dwelling
arrangements. Low level transmission in a few foci in the eastern
Mediterranean including the Middle East; major foci exist in the Sahel
region of Africa.
SYPHILIS / 567
4. ReservoirHumans.
5. Mode of transmissionDirect or indirect contact with infectious
early lesions of skin and mucous membranes; the shared use of eating and
drinking utensils and generally unsatisfactory hygienic conditions favor
the latter. Congenital transmission does not occur.
6. Incubation periodFrom 2 weeks to 3 months.
7. Period of communicabilityUntil moist eruptions of skin and
mucous patches disappear; sometimes several weeks or months.
8. SusceptibilitySimilar to that for venereal syphilis.
9. Methods of control
A. Preventive measures: See Yaws, 9A.
B. Control of patient, contacts and the immediate environment:
1) Report to local health authority: In selected endemic areas; in
most countries not a reportable disease, Class 3 (see Report-
ing).
2), 3), 4), 5), 6) and 7) Isolation, Concurrent disinfection,
Quarantine, Immunization of contacts, Investigation of con-
tacts and source of infection, and Specific treatment: See
Yaws, 9B, applicable to all nonvenereal treponematoses.
C. Epidemic measures: Intensification of preventive and control
activities.
D. Disaster implications: None.
E. International measures: See Yaws, 9E. WHO Collaborating
Centres.
[G.M. Antal]
568 / TAENIASIS
A. Preventive measures:
570 / TAENIASIS
572 / TETANUS
A. Preventive measures:
Clean,
minor
wounds All other wounds
History of tetanus
immunization (doses) Td2 TIG Td2 TIG
Uncertain or 3 Yes No Yes Yes
3 or more No3 No No4 No
1
Important details in the text.
2
For children under 7, DTaP or DTP (DT, if pertussis vaccine contraindicated) preferred
to tetanus toxoid alone. For persons 7 or older, Td preferred to tetanus toxoid alone.
3
Yes, if more than 10 years since last dose.
4
Yes, if more than 5 years since last dose. More frequent boosters are not needed and
can accentuate side-effects.
TETANUS / 577
TETANUS NEONATORUM ICD-9 771.3; ICD-10 A33
Tetanus neonatorum is a serious health problem in many developing
countries where maternity care services are limited and immunization
against tetanus is inadequate. In the past 10 years the incidence of tetanus
neonatorum has declined considerably in many developing countries
thanks to improved training of birth attendants and to immunization with
tetanus toxoid for women of childbearing age. Despite this decline, WHO
estimates that tetanus neonatorum still causes about 200 000 deaths each
year, mainly in the developing world. Most newborn infants with tetanus
have been born to nonimmunized mothers delivered by an untrained birth
attendant outside a hospital.
The disease usually occurs through introduction via the umbilical cord
of tetanus spores during delivery through the use of an unclean instrument
to cut the cord, or after delivery by dressing the umbilical stump with
substances heavily contaminated with tetanus spores, frequently as part of
natal rituals.
In neonates, inability to nurse is the most common presenting sign.
Tetanus neonatorum is typified by a newborn infant who sucks and cries
well for the first few days after birth but subsequently develops progres-
sive difficulty and then inability to feed because of trismus, generalized
stiffness with spasms or convulsions and opisthotonos. The average
incubation period is about 6 days, with a range from 3 to 28 days. Overall,
case-fatality rates for neonatal tetanus are very high, exceeding 80% among
cases with short incubation periods. Neurological sequelae including mild
retardation occur in 5% to over 20% of those children who survive.
Prevention of tetanus neonatorum can be achieved through a combina-
tion of 2 approaches: a) improving maternity care with emphasis on
increasing the tetanus toxoid immunization coverage of women of child-
bearing age (especially pregnant women), and b) increasing the propor-
tion of deliveries attended by trained attendants.
Important control measures include licensing of midwives; providing
professional supervision and education as to methods, equipment and
techniques of asepsis in childbirth; and educating mothers, relatives and
attendants in the practice of strict asepsis of the umbilical stump of
newborn infants. The latter is especially important in many areas where
strips of bamboo are used to sever the umbilical cord or where ashes, cow
dung poultices or other contaminated substances are traditionally applied
to the umbilicus. In those areas, any woman of childbearing age visiting a
health facility should be screened and offered immunization, no matter
what the reason for the visit.
Nonimmunized women should receive at least 2 doses of tetanus toxoid
according to the following schedule: the first dose at initial contact or as
early as possible during pregnancy, the second dose 4 weeks after the first
and preferably at least 2 weeks before delivery. A third dose could be given
6 12 months after the second, or during the next pregnancy. An
additional 2 doses should be given at annual intervals when the mother is
578 / TETANUS
TOXOCARIASIS / 579
TOXOCARIASIS ICD-9 128.0; ICD-10 B83.0
(Visceral larva migrans, Larva migrans visceralis, Ocular larva
migrans, Toxocara [canis] [cati] infection)
1. IdentificationA chronic infection and usually mild disease, pre-
dominantly of young children but increasingly recognized in adults,
caused by migration of larval forms of toxocara species in the organs and
tissues. It is characterized by eosinophilia of variable duration, hepatomeg-
aly, hyperglobulinaemia, pulmonary symptoms and fever. With an acute
and heavy infection, the WBC count may reach 100 000/mm3 or more (SI
units more than 100 109/L), with 50%90% eosinophils. Symptoms may
persist for a year or longer; symptomatology is related to total parasite
load. Pneumonitis, chronic abdominal pain, a generalized rash and focal
neurological disturbances may occur, as may endophthalmitis (caused by
larvae entering the eye), usually in older children; this can result in loss of
vision in the affected eye (ocular larva migrans). Retinal lesions must be
differentiated from retinoblastoma and other retinal masses. The disease is
rarely fatal.
ELISA testing with larval-stage antigens is 75%90% sensitive in visceral
larva migrans and in ocular infections. Western blotting procedures can be
used to increase specificity of the ELISA screening test.
2. Infectious agentsToxocara canis and T. cati, predominantly the
former.
3. OccurrenceWorldwide. Severe disease occurs sporadically and
affects mainly children aged 14 40 months, but also in older age groups.
Siblings often have eosinophilia or other evidence of light or residual
infection. Serological studies in asymptomatic children have shown a
wide range in different populations. Internationally, seroprevalence
ranges from lows of 0% 4% in Germany and urban Spain (Madrid) to
83% in some Caribbean subpopulations. Adults are less often acutely
infected.
4. ReservoirFor dogs and cats, T. canis and T. cati, respectively.
Puppies are infected by transplacental and transmammary migration of
larvae and pass eggs in their stools by the time they are 3 weeks old.
Infection among bitches may end or become dormant with sexual
maturity; with pregnancy, however, T. canis larvae become active and
infect the fetuses, and also newborn pups through milk. Similar though
less marked differences apply for cats; older animals are less susceptible
than young.
5. Mode of transmissionFor most infections in children, by direct
or indirect transmission of infective toxocara eggs from contaminated soil
to the mouth, directly by contact with infected soil or indirectly by eating
unwashed raw vegetables. Some infections may occur through ingestion
of larvae in raw liver from infected chickens, cattle and sheep.
580 / TOXOCARIASIS
Eggs are shed in feces of infected dogs and cats; up to 30% of soil
samples from certain parks in the United Kingdom and the USA contained
eggs; in certain parks in Japan, up to 75% of sandboxes contained eggs.
Eggs require 13 weeks incubation to become infective, but remain viable
and infective in soil for many months; they are adversely affected by
desiccation.
After ingestion, embryonated eggs hatch in the intestine; larvae pene-
trate the wall and migrate to the liver and other tissues via the lymphatic
and circulatory systems. From the liver, larvae spread to other tissues,
particularly the lungs and abdominal organs (visceral larva migrans) or the
eyes (ocular larva migrans), and induce granulomatous lesions. The
parasites cannot replicate in the human or other end-stage hosts; viable
larvae may remain in tissues for years, usually in the absence of symptom-
atic disease. When the tissues of end-stage hosts are eaten, the larvae may
be infective for the new host.
6. Incubation periodIn children, weeks or months, depending on
intensity of infection, reinfection and sensitivity of the patient. Ocular
manifestations may occur as late as 4 10 years after initial infection. In
infections through ingestion of raw liver, very short incubation periods
(hours or days) have been reported.
7. Period of communicabilityNo direct person-to-person transmi-
sion.
8. SusceptibilityLower incidence in older children and adults relat-
ing mainly to lesser exposure. Reinfection can occur.
9. Methods of control
A. Preventive measures:
1) Educate the public, especially pet owners, concerning
sources and origin of the infection, particularly the danger of
pica, of exposure to areas contaminated with feces of
untreated puppies and of ingestion of raw or undercooked
liver of animals exposed to dogs or cats. Parents of toddlers
should be made aware of the risk associated with pets in the
household and how to minimize them.
2) Prevent contamination of soil by dog and cat feces in areas
immediately adjacent to houses and childrens play areas,
especially in urban areas and multiple housing projects.
Encourage cat and dog owners to practice responsible pet
ownership, including prompt removal of pets feces from
areas of public access. Control stray dogs and cats.
3) Require removal of canine and feline feces passed in play
areas. Childrens sandboxes offer an attractive site for defe-
cating cats; cover when not in use.
4) Deworm dogs and cats beginning at 3 weeks of age, repeated
3 times at 2-week intervals, and every 6 months thereafter.
GNATHOSTOMIASIS / 581
Also treat lactating bitches. Dispose of feces passed as a result
of treatment, as well as other stools, in a sanitary manner.
5) Always wash hands after handling soil and before eating.
6) Teach children not to put dirty objects into their mouths.
CUTANEOUS LARVA
MIGRANS ICD-9 126; ICD-10 B76.9
DUE TO ANCYLOSTOMA
BRAZILIENSE ICD-9 126.2; ICD-10 B76.0
DUE TO ANCYLOSTOMA
CANINUM ICD-9 126.8; ICD-10 B76.0
(Creeping eruption)
Infective larvae of dog and cat hookworms, Ancylostoma braziliense
and A. caninum, cause a dermatitis called creeping eruption, that affects
utility workers, gardeners, children, seabathers and others who come in
contact with damp sandy soil contaminated with dog and cat feces; in the
USA, most prevalent in the southeastern areas. The larvae enter the skin and
migrate intracutaneously for long periods; eventually they may penetrate to
deeper tissues. Each larva causes a serpiginous track, advancing several
millimeters to a few centimeters a day, with intense itching especially at night.
The cutaneous disease is self-limited, with spontaneous cure after weeks or
months. Freezing the area with ethyl chloride spray can kill individual larvae.
Thiabendazole is effective as a topical ointment; albendazole or ivermectin is
effective systemically. A. caninum larvae may migrate to the small intestine
where they cause eosinophilic enteritis; these zoonotic infections respond to
treatment with pyrantel pamoate, mebendazole or albendazole.
[A. Montresor]
TOXOPLASMOSIS / 583
TOXOPLASMOSIS ICD-9 130; ICD-10 B58
CONGENITAL
TOXOPLASMOSIS ICD-9 771.2; ICD-10 P37.1
1. IdentificationA systemic coccidian protozoan disease; infections
are frequently asymptomatic, or present as acute disease with lymphade-
nopathy only, or resemble infectious mononucleosis, with fever, lymph-
adenopathy and lymphocytosis persisting for days or weeks. Development
of an immune response decreases parasitaemia, but Toxoplasma cysts
remaining in the tissues contain viable organisms. These cysts may
reactivate if the immune system becomes compromised. Among immuno-
deficient individuals, including HIV-infected patients, primary or reacti-
vated infection may cause a maculopapular rash, generalized skeletal
muscle involvement, cerebritis, chorioretinitis, pneumonia, myocarditis
and/or death. Cerebral toxoplasmosis is a frequent component of AIDS.
A primary infection during early pregnancy may lead to fetal infection
with death of the fetus or manifestations such as chorioretinitis, brain
damage with intracerebral calcification, hydrocephaly, microcephaly, fe-
ver, jaundice, rash, hepatosplenomegaly, xanthochromic CSF and convul-
sions evident at birth or shortly thereafter. Later in pregnancy, maternal
infection results in mild or subclinical fetal disease with delayed manifes-
tations such as recurrent or chronic chorioretinitis. In immunosuppressed
pregnant women who are Toxoplasma-seropositive, a reactivation of
latent infection may rarely result in congenital toxoplasmosis.
Diagnosis is based on clinical signs and supportive serological results,
demonstration of the agent in body tissues or fluids by biopsy or necropsy,
or isolation in animals or cell culture. Rising antibody titres are corrobora-
tive of active infection; the presence of specific IgM and/or rising IgG titres
in sequential sera of newborns is conclusive evidence of congenital
infection. High IgG antibody levels may persist for years with no relation
to active disease.
2. Infectious agentToxoplasma gondii, an intracellular coccidian
protozoan of cats, belonging to the family Sarcocystidae, in the class
Sporozoa.
3. OccurrenceWorldwide in mammals and birds. Infection in hu-
mans is common.
4. ReservoirThe definitive hosts of T. gondii are cats and other
felines, which acquire infection mainly from eating infected mammals
(especially rodents) or birds, probably also from oocysts acquired during
natural licking/grooming. Felines alone harbour parasites in the intestinal
tract, where the sexual stage of life cycle occurs, resulting in excretion of
oocysts in feces for 10 20 days, rarely longer.
The intermediate hosts of T. gondii include sheep, goats, rodents,
swine, cattle, chickens and birds; all may carry an infective stage of
584 / TOXOPLASMOSIS
TRACHOMA / 587
TRACHOMA ICD-9 076; ICD-10 A71
1. IdentificationA chlamydial conjunctivitis of insidious or abrupt
onset; the infection may persist for a few years if untreated, but the
characteristic lifetime duration of active disease in hyperendemic areas is
the result of frequent reinfection. The disease is characterized by the
presence of lymphoid follicles and diffuse conjunctival inflammation
(papillary hypertrophy), particularly on the tarsal conjunctiva lining the
upper eyelid. The inflammation produces superficial vascularization of the
cornea (pannus) and scarring of the conjunctiva, which increases with the
severity and duration of inflammatory disease.
The marked conjunctival scarring causes in-turning of eyelashes and lid
deformities (trichiasis and entropion) that in turn cause chronic abrasion
of the cornea and scarring with visual impairment and blindness later in
adult life. Secondary bacterial infections frequently occur in populations
with endemic trachoma and contribute to the communicability and
severity of the disease.
Early trachoma in some developing countries is an endemic childhood
disease. Early stages of trachoma may be indistinguishable from conjunc-
tivitis caused by other bacteria (including genital strains of Chlamydia
trachomatis). Differential diagnosis includes molluscum contagiosum
nodules of the eyelids, toxic reactions to chronically administered eye
drops and chronic staphylococcal lid-margin infection. An allergic reaction
to contact lenses (giant papillary conjunctivitis) may produce a trachoma-
like syndrome with tarsal nodules (giant papillae), conjunctival scarring
and corneal pannus.
Laboratory diagnosis is made through Giemsa-stained smears for the
detection of intracellular chlamydial elementary bodies in epithelial cells
of conjunctival scrapings; IF after methanol fixation of the smear; detec-
tion of chlamydial antigen by EIA or DNA by probe; or isolation of the
agent in special cell culture.
2. Infectious agentChlamydia trachomatis serovars A, B, Ba and
C. Some strains are indistinguishable from those of chlamydial conjuncti-
vitis; serovars B, Ba and C have been isolated from genital chlamydial
infections.
3. OccurrenceWorldwide, as an endemic disease most often of
poor rural communities in developing countries. In endemic areas,
trachoma presents in childhood, then subsides in adolescence, leaving
varying degrees of potentially disabling scarring. Blinding trachoma is still
widespread in the Middle East, northern and sub-Saharan Africa, parts of
the Indian subcontinent, southeastern Asia and China. Pockets of blinding
trachoma also occur in Latin America, Australia (among Aboriginals) and
the Pacific islands.
The disease occurs among population groups with poor hygiene,
poverty and crowded living conditions, particularly in dry dusty regions.
588 / TRACHOMA
4. ReservoirHumans.
9. Methods of control
A. Preventive measures:
590 / TRENCH FEVER
592 / TRICHINELLOSIS
TRICHOMONIASIS / 595
TRICHOMONIASIS ICD-9 131; ICD-10 A59
1. IdentificationA common and persistent protozoan disease of the
genitourinary tract, characterized in women by vaginitis, with small
petechial or sometimes punctate red strawberry spots and a profuse,
thin, foamy, greenish-yellow discharge with foul odor. The disease may
cause urethritis or cystitis but is frequently asymptomatic; it may also
cause obstetric complications and may facilitate HIV infection. In men, the
infectious agent invades the prostate, urethra or seminal vesicles; it often
causes only mild symptoms but may cause as much as 5%10% of
nongonococcal urethritis in some areas.
Trichomoniasis often coexists with gonorrhoea, in some studies up to
40% of persons with gonorrhoea have concurrent trichomoniasis, and the
majority of women with trichomoniasis also have bacterial vaginosis; a full
assessment for STI pathogens (STI check) must be carried out when
trichomoniasis is diagnosed.
Diagnosis is through identification of the motile parasite, either by
microscopic examination of discharges or by culture, which is more
sensitive. The organisms can be seen on a Papanicolaou smear. PCR testing
is available but is insufficiently reliable for routine use.
2. Infectious agentTrichomonas vaginalis, a flagellate protozoan.
3. OccurrenceWidespread; a frequent disease, primarily of adults,
with the highest incidence among females 16 35 years. Overall, about
20% of females may become infected during their reproductive years.
4. ReservoirHumans.
5. Mode of transmissionThrough contact with vaginal and ure-
thral discharges of infected people during sexual intercourse.
6. Incubation period 4 20 days, average 7 days; many are symp-
tom-free carriers for years.
7. Period of communicabilityFor the duration of the persistent
infection, which may last years.
8. SusceptibilitySusceptibility to infection is general, but clinical
disease is seen mainly in females.
9. Methods of control
TRICHURIASIS / 597
TRICHURIASIS ICD-9 127.3; ICD-10 B79
(Trichocephaliasis, Whipworm disease)
1. IdentificationA nematode infection of the large intestine, usually
asymptomatic. Heavy infections may cause bloody, mucoid stools and
diarrhea. Rectal prolapse, clubbing of fingers, hypoproteinemia, anemia
and growth retardation may occur in heavily infected children.
Diagnosis is made through demonstration of eggs in feces or sigmoido-
scopic observation of worms attached to the wall of the lower colon in
heavy infections. Eggs must be differentiated from those of Capillaria
species.
2. Infectious agentTrichuris trichiura (Trichocephalus trichiurus)
or human whipworm, a nematode.
3. OccurrenceWorldwide, especially in warm, moist regions.
4. ReservoirHumans. Animal whipworms do not infect humans.
5. Mode of transmissionIndirect, particularly through pica or
ingestion of contaminated vegetables; no immediate person-to-person
transmission. Eggs passed in feces require a minimum of 10 14 days in
warm moist soil to become infective. Hatching of larvae follows ingestion
of infective eggs from contaminated soil, attachment to the mucosa of the
caecum and proximal colon, and development into mature worms. Eggs
appear in the feces 70 90 days after ingestion of embryonated eggs;
symptoms may appear much earlier.
6. Incubation periodIndefinite.
7. Period of communicabilitySeveral years in untreated carriers.
8. SusceptibilitySusceptibility is universal.
9. Methods of control
A. Preventive measures:
TRYPANOSOMIASIS / 599
TRYPANOSOMIASIS ICD-9 086; ICD-10 B56-B57
I. AFRICAN
TRYPANOSOMIASIS ICD-9 086.3-086.5; ICD-10 B56
(Sleeping sickness)
1. IdentificationA systemic protozoal disease. In the early stage, a
painful chancre, originating as a papule and evolving into a nodule, may be
found at the primary tsetse fly bite site; there may also be fever, intense
headache, insomnia, painless enlarged lymph nodes, local oedema and
rash. In the late stage, after the parasite crosses the blood-brain barrier,
neurological signs such as disturbances of circadian rhythm, sensory
disturbances, endocrine dysfunction, disorders of tonus and mobility,
abnormal movements, mental changes or psychiatric disorders are corre-
lated to the localisation of trypanosomes in the CNS; cardiac symptoms
may occur in both gambiense and rhodesiense forms.
Disease due to Trypanosoma brucei gambiense (ICD-9 086.3; ICD-10
B56.0) may run a course of several years; the T. b. rhodesiense disease
(ICD-9 086.4; ICD-10 B56.1) is lethal within weeks or months without
treatment. Both are always fatal without treatment.
Diagnosis, which cannot be based on clinical symptoms only, depends
on finding trypanosomes in blood, lymph or eventually CSF; so does
staging of the disease. Parasite-concentration techniques (capillary tube
centrifugation, or minianion exchange centrifugation) are almost always
required in gambiense and less often in rhodesiense disease. Inoculation
on laboratory rats or mice is sometimes useful in rhodesiense disease.
Standard bioclinical parameters such as anemia and thrombocytopenia
may provide indirect diagnostic evidence for trypanosomiasis. High IgM in
blood point to the need for specific examinations. IgM concentrations in
T. b. gambiense patients can be increased up to 16 times as a result of
polyclonal, non-specific B-cell activation. The accompanying poly-specific
immune response leads to production of non-trypanosome specific anti-
bodies and auto-antibodies e.g. against fibrin, fibrinogen, DNA, red blood
cells, thymocyte antigens and CNS components such as myelin, galacto-
cerebrosides and neurofilament. T. b. gambiense-specific IgG and IgM
antibodies are present in high concentrations and are mainly directed
against the immunodominant surface glycoprotein antigens of the para-
site. They are detectable by ELISA or immunofluorescence, using purified
trypanosomal glycoproteins or whole trypanosomes of selected antigen
types. The screening test of choice for T. b. gambiense is the card
agglutination test for trypanosomiasis (CATT), a simple 5-minute test based
on the agglutination of whole, fixed and stained trypanosomes in the
presence of specific antibodies. Almost every control program in
T. b. gambiense endemic areas uses it for seroscreening of at-risk
populations.
2. Infectious agentsTrypanosoma brucei gambiense and
T. b. rhodesiense, hemoflagellates. Criteria for species differentiation are
600 / TRYPANOSOMIASIS
not absolute; isolates from cases of virulent, rapidly progressive disease are
considered to be T. b. rhodesiense, especially if contracted in eastern
Africa; western and central African cases are usually more chronic and
considered to be due to T. b. gambiense.
3. OccurrenceThe disease is confined to tropical Africa between
15N and 20S latitude, corresponding to the distribution of the tsetse fly.
WHO estimates some 300 000 to 500 000 people are currently infected,
with up to 60 million people in 36 countries at risk of contracting the
disease. Sleeping sickness, which occurs at over 250 foci in the poorest
areas of some of the least industrialized countries, ranks high in terms of
disability-adjusted life years (DALY).
Outbreaks can occur when human-fly contact is intensified, or when
movement of infected flies or reservoir hosts introduces virulent trypano-
some strains into a tsetse-infested area or populations are displaced into
endemic areas.
4. ReservoirIn T. b. gambiense infection, humans are the major
reservoir; however, the role of domestic and wild animals is not clear. Wild
animals, especially bushbucks and antelopes, and domestic cattle are the
chief animal reservoirs for T. b. rhodesiense.
5. Mode of transmissionThrough the bite of infective Glossina,
the tsetse fly. Six species are the main vectors in nature: G. palpalis,
G. tachinoides, G. morsitans, G. pallidipes, G. swynnertoni and
G. fuscipes. The fly is infected by ingesting blood of a human or animal that
carries trypanosomes. The parasite multiplies in the fly for 1230 days,
depending on temperature and other factors, until infective forms develop
in the salivary glands. Once infected, a tsetse fly remains infective for life
(average 3 months but as long as 10 months); infection is not passed from
generation to generation in flies. Congenital transmission can occur in
humans. Direct mechanical transmission by blood on the proboscis of
Glossina and other biting insects, such as horseflies, or in laboratory
accidents, is possible.
6. Incubation periodIn T. b. rhodesiense infections, usually 3 days
to a few weeks; T. b. gambiense infection has a longer incubation period
of up to several months or even years.
7. Period of communicabilityCommunicable to the tsetse fly as
long as the parasite is present in the blood of the infected person or
animal. Parasitemia in humans occurs in waves of varying intensity in
untreated cases and occurs at all stages of the disease.
8. SusceptibilitySusceptibility is general. Occasional inapparent or
asymptomatic infections have been documented with both T. b. gambi-
ense and T. b. rhodesiense. Spontaneous recovery in cases with the
gambiense form without CNS involvement has been claimed, but has not
been confirmed.
TRYPANOSOMIASIS / 601
9. Methods of control
II. AMERICAN
TRYPANOSOMIASIS ICD-9 086.2; ICD-10 B57
(Chagas disease)
1. IdentificationThe acute disease, with variable fever, lymphade-
nopathy, malaise, and hepatosplenomegaly generally occurs in children;
although the majority of infections are asymptomatic or paucisymptom-
atic. In 20%30% of infections, irreversible chronic manifestations gener-
ally appear later in life. An inflammatory response at the site of infection
(chagoma) may last up to 8 weeks. Unilateral bipalpebral-oedema (Romana
sign) occurs in a small percentage of acute cases. Life-threatening or fatal
manifestations include myocarditis and meningoencephalitis.
Chronic irreversible sequelae include myocardial damage with cardiac
dilatation, arrhythmias and major conduction abnormalities, and intestinal
tract involvement with megaoesophagus and megacolon. Megavisceral
manifestations occur mainly in central Brazil. The prevalence of megavis-
cera and cardiac involvement varies according to regions; the latter is not
as common north of Ecuador as in southern areas. In AIDS patients, acute
myocarditis and severe multifocal or diffuse meningoencephalitis with
necrosis and hemorrhage occur as relapses of chronic infection. This has
also been reported in cases of chronic Chagas disease with non-AIDS
immunosuppression.
Infection with Trypanosoma rangeli occurs in foci of endemic Chagas
disease extending from Central America to Colombia and Venezuela;
prolonged parasitaemia occurs, sometimes coexisting with T. cruzi flagel-
lates (with which T. rangeli shares reservoir hosts)no clinical manifes-
tations attributable to T. rangeli have been noted.
Diagnosis of Chagas disease in the acute phase is established through
demonstration of the organism in blood (rarely, in a lymph node or skeletal
muscle) by direct examination or after hemoconcentration, culture or
xenodiagnosis (feeding noninfected triatomid bugs on the patient and
finding the parasite in the bugs feces several weeks later).
Parasitemia is most intense during febrile episodes early in the course of
infection. In the chronic phase, xenodiagnosis and blood culture on
diphasic media may be positive, but other methods rarely reveal parasites.
Parasites are differentiated from those of T. rangeli by their shorter length
(20 micrometers vs 36 micrometers) and larger kinetoplast. Serologic tests
are valuable for individual diagnosis as well as for screening purposes.
2. Infectious agentTrypanosoma cruzi (Schizotrypanum cruzi), a
604 / TRYPANOSOMIASIS
TUBERCULOSIS / 607
TUBERCULOSIS ICD-9 010-018; ICD-10 A15-A19
(TB, TB disease)
1. IdentificationA mycobacterial disease that is a major cause of
disability and death in most of the world, especially developing countries.
The initial infection usually goes unnoticed; tuberculin skin test sensitivity
appears within 210 weeks. Early lung lesions commonly heal, leaving no
residual changes except occasional pulmonary or tracheobronchial lymph
node calcifications. About 10% of those initially infected will eventually
develop active disease, half of them during the first 2 years following
infection; 90% of untreated infected individuals will never develop active
TB. Appropriate completion of treatment for latent TB infection (LTBI) can
considerably reduce the lifetime risk of clinical tuberculosis (TB disease)
and is effective in persons with HIV infection.
In some individuals, initial infection may progress rapidly to active
tuberculosis. This is more common among infants, where the disease is
often disseminated (e.g. miliary) or meningeal, and in the immunosup-
pressed, such as HIV-positive individuals.
Extrapulmonary TB occurs less commonly (30%) than pulmonary TB
(70%). Children and persons with immunodeficiencies, such as HIV
infection, have a higher risk of extrapulmonary TB, but pulmonary disease
remains the most common type worldwide, even in these more suscepti-
ble groups. TB disease may affect any organ or tissue; in order of
frequency: lymph nodes, pleura, pericardium, kidneys, bones and joints,
larynx, middle ear, skin, intestines, peritoneum, eyes.
Pulmonary TB may arise from exogenous reinfection or endogenous
reactivation of a latent focus originating from the initial sub-clinical
infection. If untreated, about 65% of patients with sputum smear-positive
pulmonary tuberculosis die within 5 years, most of these within 2 years.
The classification of TB for treatment purposes is based mainly on the
presence or absence of tubercle bacilli in the sputum. A smear positive for
acid-fast bacilli (AFB) is indicative of high infectiousness. Fatigue, fever,
night sweats and weight loss may occur early or late; localizing symptoms
of cough, chest pain, hemoptysis and hoarseness become prominent in
advanced stages. Radiography of the chest reveals pulmonary infiltrates,
cavitations and, later, fibrotic changes with volume loss, all most com-
monly in the upper segments of the lobes.
Immunocompetent people who are or have been infected with Myco-
bacterium tuberculosis, M. africanum or M. bovis usually react to an
intermediate strength tuberculin skin test equivalent to 5 IUs of the
International Standard of Purified Protein Derivative-Standard (PPD-S). A
positive reaction is defined as a 5, 10, or 15 mm induration according to
the risk of exposure or disease. Among persons with active TB disease
10%20% may have no reaction to PPDa negative skin test does not
therefore rule out active TB disease. Interpreting the PPD skin test
induration size is important to define positivity and the need to start
treatment of latent TB infection (previously termed chemoprophylaxis or
608 / TUBERCULOSIS
620 / TULAREMIA
follows recovery; reinfection is extremely rare and has been reported only
in laboratory staff.
9. Methods of control
A. Preventive measures:
624 / TYPHOID FEVER
630 / TYPHUS FEVER
A. Preventive measures:
E. International measures:
A. Preventive measures:
WARTS, VIRAL / 637
WARTS, VIRAL ICD-9 078.1; ICD-10 B07
(Verruca vulgaris, Common wart, Condyloma acuminatum,
Papilloma venereum)
1. IdentificationA viral disease manifested by diverse skin and
mucous membrane lesions. These include: the common wart, a circum-
scribed, hyperkeratotic, rough-textured, painless papule, varying in size
from a pinhead to large masses; filiform warts, elongated, pointed, delicate
lesions that may reach 1 cm in length; laryngeal papillomas on vocal cords
and the epiglottis in children and adults; flat warts, smooth, slightly
elevated, usually multiple lesions varying in size from 1 mm to 1 cm;
venereal warts (condyloma acuminatum), cauliflower like fleshy growths,
most often seen in moist areas in and around the genitalia, around the anus
and within the anal canal, which must be differentiated from condyloma
lata of secondary syphilis; flat papillomas of the cervix; and plantar warts,
flat, hyperkeratotic and often painful lenous of lesions of the plantar
surface of the feet.
Both laryngeal papillomas and genital warts have occasionally become
malignant. The warts in epidermodysplasia verruciformis occur usually on
the torso and upper extremities, usually appearing in the first decade of
life; they often undergo malignant transformation to squamous cell
carcinomas in young adulthood.
The diagnosis is usually based on the typical lesion. If there is doubt, the
lesion should be excised and examined histologically.
2. Infectious agentHuman papillomavirus (HPV) of the papovavirus
group of DNA viruses (the human wart viruses). At least 70 HPV types have
been associated with specific manifestations and more than 20 types of
HPV can infect the genital tract. Most genital HPV infections are asymp-
tomatic, subclinical, or unrecognized. Visible genital warts are usually
caused by HPV types 6 or 11: they can also cause warts on the uterine
cervix and in the vagina, urethra, and anus, and are sometimes symptom-
atic. Other HPV types in the anogenital region, types 16, 18, 31, 33, and
35, have been strongly associated with cervical dysplasia; they have been
associated also with vulvar, penile, and anal squamous intraepithelial
neoplasia (i.e. squamous cell carcinoma in situ, bowenoid papulosis,
erythroplasia of Queyrat, or Bowen disease of the genitalia). Type 7 is
associated with warts in meat handlers and veterinarians. Types 5 and 8
are associated with epidermodysplasia verruciformis.
3. OccurrenceWorldwide.
4. ReservoirHumans.
5. Mode of transmissionUsually through direct contact. Warts may
be autoinoculated, such as by razors in shaving; contaminated floors are
frequently incriminated as the source of infection. Condyloma acumina-
tum is usually sexually transmitted; laryngeal papillomata in children are
638 / WARTS, VIRAL
probably transmitted during passage of the infant through the birth canal.
The viral types in the genital and respiratory tracts are the same.
6. Incubation periodAbout 23 months; range is 120 months.
7. Period of communicabilityUnknown, probably at least as long
as visible lesions persist.
8. SusceptibilityCommon and flat warts are most frequently seen in
young children, genital warts in sexually active young adults, and plantar
warts in school-age children and teenagers. The incidence of warts is
increased in immunosuppressed patients.
9. Methods of control
640 / YAWS
YELLOW FEVER / 643
YELLOW FEVER ICD-9 060; ICD-10 A95
1. IdentificationAcute infectious viral disease of short duration and
varying severity. The mildest cases may be clinically indeterminate; typical
attacks are characterized by sudden onset, fever, chills, headache, back-
ache, generalized muscle pain, prostration, nausea and vomiting. The
pulse may be slow and weak out of proportion to the elevated tempera-
ture (Faget sign). Jaundice is moderate early in the disease and intensifies
later. Albuminuria, sometimes pronounced, and anuria may occur. Leuko-
penia appears early and is most pronounced about the fifth day. Most
infections resolve at this stage. Some cases progress after a brief remission
of hours to a day into the ominous stage of intoxication manifested by
hemorrhagic symptoms including epistaxis, gingival bleeding, hemateme-
sis (coffee-ground or black), melaena, and liver and renal failure; 20%50%
of jaundiced cases are fatal. The overall case-fatality rate among indigenous
populations in endemic regions is 5% but may reach 20% 40% in
individual outbreaks.
Laboratory diagnosis is through isolation of virus from blood by
inoculation (suckling mice, mosquitoes or cell cultures, especially mos-
quito cells); through demonstration of viral antigen in the blood by ELISA
or liver tissue by use of labelled specific antibodies; and through demon-
stration of viral genome in blood and liver tissue by PCR or hybridization
probes. Serological diagnosis includes demonstrating specific IgM in early
sera or a rise in titre of specific antibodies in paired acute and convalescent
sera. Serological cross-reactions occur with other flaviviruses. Recent
infections can often be distinguished from vaccine immunity by comple-
ment fixation testing. The demonstration of typical lesions in the liver
confirms the diagnosis.
Tanzania. There is no evidence that yellow fever has ever been present in
Asia; in western Kenya, sylvatic yellow fever was reported in 19921993.
4. ReservoirIn urban areas, humans and Aedes mosquitoes; in forest
areas, vertebrates other than humans, mainly monkeys and possibly
marsupials, and forest mosquitoes. Transovarian transmission in mosqui-
toes may contribute to maintenance of infection. Humans have no
essential role in transmission of jungle yellow fever, but are the primary
amplifying host in the urban cycle.
5. Mode of transmissionIn urban and certain rural areas, the bite
of infective Aedes mosquitoes. In South American forests, the bite of
several species of forest mosquitoes of the genus Haemagogus. In eastern
Africa, Ae. africanus is the vector in the monkey population, while
semidomestic Ae. bromeliae and Ae. simpsoni, and probably other Aedes
species, transmit the virus from monkeys to humans. In large epidemics in
Ethiopia, epidemiological evidence incriminated Ae. simpsoni as a person-
to-person vector. In western Africa, Ae. furcifer-taylori, Ae. luteocephalus
and other species are responsible for spread between monkeys and
humans. Ae. albopictus has been introduced into Brazil and the USA and
has the potential for bridging the sylvatic and urban cycles of yellow fever
in the Western Hemisphere, even though no involvement of this species
in yellow fever transmission has been documented.
6. Incubation periodFrom 3 to 6 days.
7. Period of communicabilityBlood of patients is infective for
mosquitoes shortly before onset of fever and for the first 35 days of
illness. The disease is highly communicable where many susceptible
people and abundant vector mosquitoes coexist; it is not communicable
through contact or common vehicles. The extrinsic incubation period in
Ae. aegypti is commonly 9 12 days at the usual tropical temperatures.
Once infected, mosquitoes remain so for life.
8. SusceptibilityRecovery from yellow fever is followed by lasting
immunity; second attacks are unknown. Mild inapparent infections are
common in endemic areas. Transient passive immunity in infants born to
immune mothers may persist for up to 6 months. In natural infections,
antibodies appear in the blood within the first week.
9. Methods of control
A. Preventive measures:
C. Epidemic measures:
648 / YERSINIOSIS
A. Preventive measures:
1) Prepare meat and other foods in a sanitary manner, avoid
eating raw pork and pasteurize milk; irradiation of meat is
effective.
2) Wash hands prior to food handling and eating, after han-
dling raw pork and after animal contact.
3) Protect water supplies from animal and human feces; purify
appropriately.
4) Control rodents and birds (for Y. pseudotuberculosis).
5) Dispose of human, dog and cat feces in a sanitary manner.
6) During the slaughtering of pigs, head and neck should be
removed from the body to avoid contaminating meat from
the heavily colonized pharynx.
C. Epidemic measures:
[E. Carniel]
652 / ZYGOMYCOSIS
ZYGOMYCOSIS
(Phycomycosis)
Zygomycosis is the term encompassing a polymorphic disease of
multiple etiology caused by rapidly growing moulds of the class Zygomy-
cetes. Infections due to Mucorales or to Entomophthorales present distinct
epidemiological, clinical and pathological forms. The mainly histopatho-
logical differences between them are the eosinophilic perihyphal material
or Spendore-Hoeppli reaction seen in entomophthoromycosis.
INFECTIONS DUE TO
MUCORALES ICD-9 117.7; ICD-10 B46.0-B46.5
1. IdentificationInfections caused by fungi of the order Mucorales
leading to opportunistic disease. These fungi have an affinity for blood
vessels, and cause thrombosis, infarction and tissue necrosis. The mycosis
has an acute or subacute course. In debilitated persons it is the most
fulminant fungal infection known. The 4 main systemic forms of the
disease are the rhinocerebral, pulmonary, gastrointestinal and dissemi-
nated types. The underlying disease influences the portal of entry of the
fungus. Rhinocerebral disease represents one-third to one-half of all cases
and usually presents as nasal or paranasal sinus infection, most often
during episodes of poorly controlled diabetes mellitus. Necrosis of the
turbinates, perforation of the hard palate, necrosis of the cheek or orbital
cellulitis, proptosis and ophthalmoplegia may occur. Infection may pene-
trate to the internal carotid artery or extend directly to the brain and cause
infarction. Patients receiving immunosuppressive agents or deferoxamine
are susceptible to either rhinocerebral or pulmonary zygomycosis. In the
pulmonary form of disease, the fungus causes thrombosis of pulmonary
blood vessels and infarcts of the lung. In the gastrointestinal form, mucosal
ulcers or thrombosis and gangrene of stomach or bowel wall may occur.
Disseminated type usually occurs in patients with hematological malig-
nancy. Nosocomial cases have been reported.
Diagnosis is through microscopic demonstration of distinctive broad
nonseptate hyphae on tissue section and through culture of biopsy tissue.
Wet preparations and smears may be examined. Cultures alone are not
diagnostic because fungi of the order Mucorales are frequently found in
the environment. To be considered as an agent of the mycosis the fungus
must survive and multiply at a temperature of 37C (98.6F).
2. Infectious agentsSome species of Rhizopus, especially
R. arrhizus, have caused most of the culture-positive cases of zygomyco-
sis. In addition to Rhizopus, Mucor and Absidia, human diseases due to
Rhizomucor, Apophysomyces, Cunninghamella, Saksenaea and Syn-
cephalastrum spp. have all been identified.
3. OccurrenceWorldwide. Incidence may be increasing because of
longer survival of patients with immunosuppression due to disease or
ZYGOMYCOSIS / 653
medication, with diabetes mellitus and certain blood dyscrasias, especially
acute leukaemia and aplastic anemia, as well as the use of deferoxamine
for aluminium or iron overload in patients receiving chronic hemodialysis
for renal failure.
4. ReservoirMembers of the order Mucorales are common sapro-
phytes in the environment.
5. Mode of transmissionInhalation or ingestion of fungal spores by
susceptible individuals. Direct inoculation in IV drug users and at sites of
IV catheters and cutaneous burns may occur.
6. Incubation periodUnknown. Fungus spreads rapidly in suscep-
tible tissues.
7. Period of communicabilityNo direct person-to-person or ani-
mal-to-person transmission.
8. SusceptibilityThe rarity of infection in healthy individuals de-
spite the abundance of Mucorales in the environment indicates natural
resistance. Corticosteroid use, metabolic acidosis, deferoxamine and im-
munosuppressive treatment predispose to infection. Malnutrition predis-
poses to the gastrointestinal form.
9. Methods of control
BASIDIOBOLOMYCOSIS
Basidiobolus ranarum causes the subcutaneous form of entomophtho-
ramycosis presenting as a granulomatous inflammation. The fungus is
ubiquitous, occurring in decaying vegetation, soil and the gastrointestinal
tract of amphibians and reptiles. The disease presents as a firm painless
and sharply circumscribed subcutaneous mass, fixed to the skin, mainly in
children and adolescents, more commonly in males. Common sites of
infection are the buttocks, thighs and chest. The infection may heal
spontaneously. Recommended treatment is oral potassium iodide.
CONIDIOBOLOMYCOSIS
Conidiobolus coronatus, occurring in soil and decaying vegetation,
causes the mucocutaneous form of entomophthoramycosis. This usually
originates in the paranasal skin or nasal mucosa and presents as nasal
obstruction or swelling of the nose or adjacent structures. The lesion may
spread to involve contiguous areas, such as lip, cheek, palate or pharynx.
The disease is uncommon and occurs principally in adult males. Recom-
mended treatment is oral potassium iodide or IV amphotericin B.
For both forms of entomophthoramycosis, incubation periods and
modes of transmission are unknown. Person-to-person transmission does
not occur.
A few cases of a rare primary visceral form of conidiobolomycosis due
to C. incongruus have been reported in patients (immunocompromised or
not) as lung infections spreading to contiguous organs.
[L.C. Severo]
Abbreviations and acronyms used in
Control of Communicable Diseases Manual
AAP American Academy of Pediatrics
ACIP Advisory Committee on Immunization Practices (CDC)
AFB acid-fast bacilli
AFP acute flaccid paralysis
AHC acute hemorrhagic conjunctivitis
AIDS acquired immunodeficiency syndrome
ALT alanine aminotransferase (was SGPT)
aP acellular Pertussis [vaccine]
AST aspartate aminotransferase (was SGOT)
AZT azidothymidine
BCG bacille Calmette-Guerin
BPF Brazilian purpuric fever
BSE bovine spongiform encephalitis
BSL biosafety level (i.e. BSL-1, -2, -3, -4)
ca circa
CAT computerized axial tomography
CD4 antigen of T-helper lymphocytes
CDC Centers for Disease Control and Prevention
CF complement fixation
CIE counterimmunoelectrophoresis
CJD Creutzfeldt-Jakob disease
cm centimeter
CMV cytomegalovirus
CNS central nervous system
CRS congenital rubella syndrome
CSF cerebrospinal fluid
CTF Colorado tick fever
DAEC diffuse-adherence Entamoeba coli
DAT dried antigen test
DEC diethylcarbamazine citrate
DFA direct fluorescent antibody
DHF/DSS dengue hemorrhagic fever/dengue shock syndrome
DIC disseminated intravascular coagulation
DNA desoxyribonucleic acid
DT diphtheria/tetanus vaccine
DTaP diphtheria/tetanus toxoids and acellular Pertussis vaccine
DTP diphtheria/tetanus toxoids and whole cell Pertussis vaccine
EAggEC enteroaggregative Entamoeba coli
EBV Epstein-Barr virus
EEE Eastern equine encephalitis
EEG electroencephalogram
e.g. for instance
EHEC enterohemorrhagic Entamoeba coli
EIA enzyme immunoassay
EIEC enteroinvasive Entamoeba coli
EKC epidemic keratoconjunctivitis
ELISA enzyme-linked immunosorbent assay
EM electron microscopyalso erythema migrans
EMB ethambutol
ENL erythema nodosum leprosum
EPEC enteropathogenic Entamoeba coli
EPI Expanded Programme on Immunization, WHO
ERIG equine rabies immune globulin
ESR erythrocyte sedimentation rate
ETEC enterotoxic Entamoeba coli
FA direct fluorescent or immunofluorescent antibody test
FAO Food and Agriculture Organization of the United Nations
FEE Far eastern equine encephalitis
G6PD glucose-6-phosphate dehydrogenase
GBS Guillain-Barre syndrome
GI gastrointestinal
GSS Gertsmann-Staussler-Scheinker syndrome
HA hemagglutination
HAART highly active antiretroviral therapy
HAI/HI hemagglutination inhibition
HAV hepatitis A virus
HBV hepatitis B virus
HBcAg hepatitis B core antigen
HBIG hepatitis B immunoglobulin
HBsAg hepatitis B surface antigen
HCC hepatocellular carcinoma
HCV hepatitis C virus
HDCV human diploid cell rabies vaccine
HDV hepatitis D virus
HEPA high efficiency particulate air [filters]
HEV hepatitis E virus
HHV human herpesvirus
HIb Haemohilus influenzae type b
HIV human immunodeficiency virus
HPV human papillomavirus
HRIG human rabies immune globulin
HSV herpes simplex virus
HTLV human T-cell lymphotropic virus
HUS hemolytic uremic syndrome
ICD International Classification of Diseases
ID intradermal
IEM immune electron microscopy
IF immunofluorescent testing
IFA/IFAT indirect immunofluorescent antibody/assay
IG immune globulin (serum)
IgA immunoglobulin class A
612
EXPLANATION OF TERMS / 613
source to a susceptible host; either directly or indirectly through an
intermediate plant or animal host, vector or the inanimate environ-
ment. (Synonym: infectious disease)
16. HostA person or other living animal, including birds and arthro-
pods, that affords subsistence or lodgement to an infectious agent
under natural (as opposed to experimental) conditions. Some
protozoa and helminths pass successive stages in alternate hosts of
different species. Hosts in which a parasite attains maturity or
passes its sexual stage are primary or definitive hosts; those in
which a parasite is in a larval or asexual state are secondary or
intermediate hosts. A transport host is a carrier in which the
organism remains alive but does not undergo development.
Age
The schedule proposed by the USA and applicable to most other industrialized
countries is as follows:
700
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All images courtesy of the CDC Public Health Image Library (unless otherwise indicated).
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This micrograph of brain tissue reveals the Cattle such as the one pictured here, which
cytoarchitectural histopathologic changes are affected by BSE experience progressive
found in bovine spongiform encephalopa- degeneration of the nervous system.
thy. The presence of vacuoles, i.e. micro- Behavioral changes in temperament (e.g.,
scopic holes in the gray matter, gives the nervousness or aggression), abnormal pos-
brain of BSE-affected cows a sponge-like ture, incoordination and difficulty in ris-
appearance when tissue sections are exam- ing, decreased milk production, and/or
ined in the lab. (BSE) loss of weight despite continued appetite
are followed by death in cattle affected by
BSE. (BSE)