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COMBATING THE RE-EMERGENCE OF

MONKEYPOX IN NIGERIA

BY:

DIJI-GESKE RUTH

MATRIC NO: 16PCQ01448

A SEMINAR REPORT SUBMITTED TO THE DEPARTMENT OF BIOLOGICAL


SCIENCES (MICROBIOLOGY UNIT), COLLEGE OF SCIENCE AND
TECHNOLOGY, COVENANT UNIVERSITY, OTA NIGERIA

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DEDICATION

This review is first dedicated to God, the source of all wisdom. And then to all who have
borne the brunt of monkeypox infection.

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CERTIFICATION

This is to certify that this review titled COMBATING THE RE-EMERGENCE OF


MONKEYPOX IN NIGERIA, is a record of a seminar work carried out in the Department
of Biological Sciences, College of Science and Technology, Covenant University by DIJI-
GESKE RUTH under the supervision of Dr. G.I Olasehinde.

…………………… ………………………

Dr. Olasehinde G.I Dr. Conrad O.

Supervisor (PG Coordinator, Microbiology Unit)

Dr. Olasehinde G. I.

(HOD Biological Sciences)

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TABLE OF CONTENT

Dedication 2

Certification 3

Table of content 4

Summary 6

CHAPTER ONE

Introduction 7

CHAPTER TWO

2.1 Monkeypox 8

2.2 History, outbreaks and epidemiology 8

2.3 Transmission cycle 12

2.4 Disease pathogenegis 13

2.5 Diagnosis and Differential diagnosis 18

2.6 Treatment and vaccine intervention 20

2.7 Transmission control initiative 21

CHAPTER THREE

3.1 Monkeypox in Nigeria 25

3.2 Measures for eradication of monkeypox 26

3.3 Challenges surrounding monkeypox in context 27

3.3.1 Co-infection 29

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CHAPTER FOUR

4.1 Factors influencing disease emergence and re-emergence 30

4.2 Preventing emergence and re-emergence 31

4.3 The possibility of resistance 33

4.4 Socio-economic impact of re-emerging diseases 33

4.5 Health and psychological impact 34

4.6 Ecological consequences 35

CHAPTER FIVE

Conclusion 36

References 37

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SUMMARY

The re-emergence of Monkeypox infection in Nigeria after a thirty nine year hiatus, having
occurred in the 1970’s, is a major threat to public health. In recent times, there have been one
hundred and sixteen suspected cases and thirty eight confirmed cases in Nigeria. Thus
signalling a distress call for continued and increased public health measures such as
monitoring and surveillance (Breman, 2002), government commitment, the synergy of public
and private health sectors as well as inter and intra-professional bodies. Human monkeypox
is a rare zoonotic viral disease characterized by exanthemata and lymphadenopathy amongst
other viral clinical manifestations (CDC, 2015). It is found in the remote areas of Western and
central sub-Saharan Africa and is an important public health issue in these areas (Rimoin et
al., 2005). It belongs to the same family (Orthopoxvirus) as the eradicated smallpox virus and
other pox viruses and presents similar but less virulent clinical features than smallpox
(Gilbourne, 2014). However it has become the most important Orthopoxvirus since the
eradication of smallpox and takes the lead from where smallpox stopped (Giulio and
Eckburg, 2004). Its host reservoirs are animals and humans, with primary infection occurring
between animals and secondary infection occurring from animals-humans or human–human
(CDC, 2015). Though it was first discovered in laboratory Macaque monkeys, its primary
host reservoir remains speculative (Tanya et al., 2006). There are no proven treatments for
the disease, however a beacon of hope hails from the smallpox vaccinia vaccine which has
demonstrated effectiveness in preventing being infected with the virus but with the
eradication of smallpox, the production of the vaccine was brought to a halt (WHO, 2016).
Faced with the possibility of monkeypox being a potential agent of bioterrorism and fearing
the development and spread of more virulent strains (Dana and Frank, 2003), it becomes
expedient to research and develop new therapeutic agents. It is also important to create a
stockpile of new vaccines against unpleasant future occurrences while also effectively dealing
with the underlying factors that influence the emergence and re-emergence of these diseases.

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CHAPTER ONE

1.1 INTRODUCTION

Globally, there have only been few recorded successes as regards eradication of infectious
diseases. One of the greatest breakthroughs in the field of science and public health came
with the production of vaccines and the completely eradication of small pox globally in 1979.
Unfortunately, this feat was only followed by the eradication of rinderpest disease in the year
2011, making them the only infectious diseases to be eradicated globally till date – of which
both are viral in nature (Clark, 2011). However, this is only a measure of the multitude of
infectious diseases ravaging various regions of the earth, and it is expedient that measures
continue to be put in place to contain them in order to prevent their spread and preserve the
human race.

According to Dr. Anne Rimoin from the University Of California Los Angeles School Of
Public health, Monkeypox which is a rare viral and highly infectious disease emerged under
the radar after the eradication of small pox due to the lack of surveillance. From her survey,
the incidence of cases of disease arising from monkey pox infection in the Democratic
Republic of Congo between the year 2005 and 2007 where this disease has been prevalent
was 20 times higher than that obtained by the WHO in 1987.

The first manifestation of monkey pox disease was seen in 1970 in the DRC, even though the
virus responsible for the disease was originally discovered when a pox-like disease among
monkeys was being investigated in the year 1958 in the State Serum Institute of Copenhagen,
Denmark.

The disease which had retained a limited region of prevalence since its discovery have now
began to spread its tentacles, and at the time of this write up just arrived the shores of Nigeria
sending shockwaves through the masses as they were faced with the reality of combating or
allowing the disease.

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CHAPTER 2

2.1 MONKEY POX

Monkeypox is a distinctively rare disease, first to be detected in African monkeys in the year


1958. It is of viral origin and belongs to the same family virus – Poxviridae that cause
diseases such as Smallpox and Cowpox, and bears an identical genus – Orthopoxvirus, with
Smallpox (Gilbourne, 2014). However, it is different from Smallpox and has a far less
mortality rate than that recorded in the era smallpox. Monkeypox is apparently the most
virulent and significant Orthopoxvirus infection in human beings following the eradication of
smallpox in 1970 and at present it still lacks proven treatment (Giulio and Eckburg, 2004).

Monkeypox is conveyed primarily from animal to animal and secondarily from animal to
human/ human to human and can cause diseases in both. It is clinically important because its
clinical manifestations are similar to other pox related viral illnesses, thus making it often
times clinically indistinguishable.

2.2 HISTORY, OUTBREAKS AND EPIDEMIOLOGY

The monkeypox virus was first recovered from captured monkeys originating from Asian
regions of Malaysia, India, and the Philippines (Tanya et al, 2006), and was first identified in
1958 by Preben von Magnus in a laboratory in Copenhagen, Denmark in crab-eating
macaque monkeys (Macaca fascicularis). The first incident of monkeypox infection in
humans occurred in a 9 months old infant in the Democratic Republic of Congo in the year
1970 where it eventually became endemic following major outbreaks between 1970 and 1986
in which over 400 cases were recorded(Meyer et al, 2001). Another major outbreak occurred
between 1996 and 1997(Tanya et al, 2006). Afterwards, several other cases in the DRC and
some parts of West Africa have been reported, with most of them occurring in rural and
rainforest areas. There are basically two strains of monkeypox in existence – the less
pathogenic West African strain and the more pathogenic Central African strain. Severity of
the disease in human is dependent on the strain responsible for the infection.

Nigeria had its first record of monkeypox in 1971 with 2 cases reported, and one case
following in 1978. There had not been further cases until most recently in 2017 where

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outbreaks were speculated to cut across twenty one States which include Bayelsa, Cross
Rivers, Lagos, Nassarawa, Ekiti, Enugu, Rivers, Akwa Ibom, Delta, Imo, Kastina, Kwara,
Benue, Ondo, Edo, Kogi, Kano, Niger, Oyo, Abia and FCT, with the highest suspected and
confirmed cases occuuring in Bayelsa State. A total of one hundred and sixteen suspected
cases and thirty eight confirmed cases were reported.

In the year 2003 in the USA, beginning with the manifestation of symptoms in a 3 year old
girl who had been bitten by a prairie dog, some other persons who had prior contact with pet
praire dogs were diagnosed as having been infected with the disease, thus making this the
first case to be reported outside the continent of Africa (WHO, 2016). A total of 81 cases
were reported (Daniel, 2004). Following this, there have been eight more outbreaks in the
USA and Netherland in ten years. Subsequent in 2005 and 2009, there were outbreaks in
Sudan and DRC respectively. According to the WHO, 2 deaths resulting from 26 cases were
reported in the year 2016.

Investigations tracking the occurrence of the disease in the United States imply that the virus
probably got into the USA via a consignment containing about 800 little animals from Ghana
to Texas. It is assumed that Prairie dogs became infected due to close proximity with a
diseased Gambian giant-pouched rat (Cricetomys gambianus) brought into the USA via
cargo. The animal were sold an animal vendor along with other animals on board the freight.
All the animals which include dormice and rope squirrels confirmed positive for monkeypox
virus. As of July 2003, 72 cases of human monkeypox were under investigation in Illinois,
Indiana, Kansas, Missouri, Ohio, and Wisconsin with 37 cases confirmed through laboratory
analysis. The ratio in reported case fatality is 1:10 as monkeypox has been reported to cause
death in as many as 1 in 10 persons who contract the disease in Africa (WHO, 2016).

From surveys conducted by investigators supported the National institute of child health and
human development, it was reported that The incidence of monkeypox cases between 2005
and 2007 was 20 times higher than the incidence found by WHO surveys in the 1980s. The
current survey also showed that those most likely to be infected were children younger than
age 15 years, gender irrespective. Average incidence rates across the surveyed regions were
highest in forested areas and lowest in savannah or grassland areas.

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Fig 1: MONKEYPOX DISTRIBUTION MAP IN AFRICA (Levine, 2007)

In Africa, though the over-all case fatality is 1% - 10%, it is as high as 17% in the DRC.
Children below the age of 15 are mostly infected with higher mortality rate. In 2005, South
Sudan was reported to have its first outbreak of human monkeypox virus infection spread by
transfer from animal reservoirs (Damon et al, 2006).

Animals serve as reservoirs for this infection and some such as other primates, rodents and
rabbits have been implicated as being vulnerable to the monkeypox infection. Although the
definitive natural reservoir is still unknown, studies point to rope squirrels of the African
genus, Funisciurus(Tanya et al,2006). Epidemiological study reveal endemicity of
monkeypox in the African rope Squirrels.

According to the centre for disease prevention and control, the virus responsible for
monkeypox has only been isolated twice from an animal. In the first instance (1985), the

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virus was recovered from an apparently ill African rodent (rope squirrel) in the Equateur
Region of the Democratic Republic of Congo. In the second (2012), the virus was recovered
from a dead infant mangabey found in the Tai National Park, Cote d’Ivoire.

Epidemiologic studies of monkeypox infections in humans show that people not vaccinated
against smallpox and younger children can have severe disease and complications, which
supports the significance of host susceptibility and previous immunity (Breman, 2000).

Monkeypox accounts for the less severe rate of secondary attack (3%) and mortality due to
immunization with smallpox vaccines which also reported efficient in handling the
monkeypox infection (Rimoin et al, 2007) due to the fact that it was discovered in the ‘70s
after the complete eradication of smallpox globally. However, between the ‘90s and the new
millennium, the secondary attack rate has spike up to as high as 78%, perharps owing to the
halt of vaccination with the smallpox vaccine following the eradication of smallpox, which
made people born after the ‘70s miss the shot thus reducing their immunity.

Fig 2: Monkeypox strain distribution map in Africa (Levine et al, 2007)

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One study reported that even though previous publications have showed attack rates of 3%–
11%, a median attack rate of 50%, and 1 family had 100% of persons affected. The
previously published attack rates are considerably lower than those for other viruses with
similar routes of transmission; for example, smallpox has attack rates of 35%–88%, and
variola virus had an attack rate of 90% (Leisha et al, 2016). The difference between the
findings from recent and previous reports may result from several different causes. First, the
high attack rate reported possibly results from changing individual- and population-level
immunity caused by elimination of routine childhood smallpox vaccination. Earlier
investigations may have found lower attack rates because more persons had vaccine-derived
immunity; however, some persons in the outbreak that was investigated in this study had
MPXV infection and prior smallpox vaccination, which suggest possible waning immunity
over time, a factor that should be considered in future investigations. Secondly, a viral strain
different from that found in previous investigations could have circulated in this outbreak and
resulted in the high attack rate. Thirdly, the high attack rate possibly reflects a high rate of
case-patient identification in the investigation. It was observed that though many persons are
often affected in a household but only 1 household member usually seeks medical attention,
causing only 1 case to be recorded or investigated for surveillance. Case reporting on the
basis of persons seeking healthcare may have caused the surveillance system to underestimate
of the number of human monkeypox cases. Using in-home interviews, many previously
unidentified cases were uncovered, enabling the calculation of a more accurate attack rate
(Leisha et al, 2016).

2.3 TRANSMISSION CYCLE

Transmission could occur from direct contact with the virus from the body fluid of the animal
or through bites of infected animals. It could also be from human to human through
respiration of droplets from infected humans and contact with formites from the body fluids
of infected persons, or from viral contaminated materials. Entry points in humans are broken
skin, respiratory tract and membrane mucosa of eyes, ears and mouth.

Transmission from animal-to-human may occur through bites or scratches, eating improperly
cooked infected bush meat, direct contact with body fluids or lesion material, or indirect
contact with lesion material, such as through contaminated bedding.

Human-to-human transmission is assumed to occur predominantly through large respiratory


droplets, direct and indirect body fluids or lesion materials, such as through contaminated

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clothing. Respiratory droplets usually cannot travel more than a few feet; therefore sustained
face-to-face contact is required (CDC, 2016). Though monkeypox is highly pathogenic to
humans, transmission between humans is relatively poor.

Fig 3: Monkeypox versus smallpox pathway (Jehu, 2017)

2.4 DISEASE PATHOGENESIS

Signs of Monkeypox infection in humans begins typically with the onset of fever, muscle
aches (myalgia), headaches, backaches and extensive weakness(asthenia), presenting
symptoms that are identical with smallpox with the exception of the development of swollen
lymph nodes (lymphadenopathy) which is usually absent in cases of smallpox. This is called
the invasion period and it often lasts between 0 – 5 days. The incubation period for
monkeypox is usually 7−14 days but can range from 5−21 days.

TABLE 1: MONKEYPOX VS SMALLPOX

MONKEYPOX SMALLPOX
Affect humans and animal Affects only humans
Mortality rate of 1:10 Extremely high mortality rate

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Lymphadenopathy Absence of swollen lymph nodes
Self-limiting None self-limiting
Large lesions Smaller lesions
Scabs fall off. No disfiguration Causes disfiguration

Fig 4: African child showing lesions on face and palms (Nigerian Tribune, 2017)

Progression of lesions occurs through the following stages before falling off: Macules,
papules, vesicles, pustules and scabs. This state of the infection is known as the skin eruption
period and it occurs within 10 days. Development of rash may appear within 1 to 3 days
(sometimes longer) following the appearance of fever, frequently commencing on the face
and then spreading to other parts of the body. The face, palms and feet are mostly affected. It
may take up to 3 weeks for scabs to disappear.

The lesions affect the mucous membrane of the mouth in about 70% of cases, genitalia in
30%, conjunctivae and cornea in 20%. Lesions mays be as much as a thousand covering all
these areas. The entire duration of the illness is about 2−4 weeks.

From studies, it has been observed that both clinically and epidemiologically important
differences exist between human monkeypox in the United States and in Africa. And this

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may be attributed to factors that include mode of transmission (skin inoculation versus
ingestion), the training backgrounds of those who saw and documented disease outbreaks, the
skin colour of affected patients and the virulence of monkeypox virus strains (Tanya et al,
2006).

TABLE 2: CDC EXPLOSION PERIOD TABLE (CDC, 2014)

Stage
Stage Duration Characteristics

Enanthem  The first lesions to develop are on the tongue and in the mouth.

Macules 1−2 days  Following the enanthem, a macular rash appears on the skin, starting

on the face and spreading to the arms and legs and then to the hands and feet,

including the palms and soles.

 The rash typically spreads to all parts of the body within 24 hours becoming most

Concentrated on the face, arms, and legs (centrifugal distribution).

Papules 1−2 days  By the third day of rash, lesions have progressed from macular (flat) to papular

(raised).

Vesicles 1−2 days  By the fourth to fifth day, lesions have become vesicular (raised and filled with

clear fluid).

Pustules 5−7 days  By the sixth to seventh day, lesions have become pustular (filled with opaque

fluid) – sharply raised, usually round, and firm to the touch (deep seated).

 Lesions will develop a depression in the center (umbilication).


 The pustules will remain for approximately 5 to 7 days before beginning to crust.

Scabs 7−14 days  By the end of the second week, pustules have crusted and scabbed over.

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Stage
Stage Duration Characteristics

 Scabs will remain for about a week before beginning to fall off

TABLE 3:  Comparison of clinical features between human monkeypox, smallpox,


and chickenpox*(CDC, 2014 - modified from Breman and Henderson, 2002)

Disease characteristics Monkeypox Smallpox† Chickenpox

History

Recent contact with exotic Yes No No


animal

Recent exposure to patient


with vesicular rash Possible‡ Yes Yes

Previous vaccination 10–15% Rare Yes


against smallpox

Incubation period (days) 10–14 10–14 14–16

Prodromal phase (days) 1–3 2–4 0–2

Physical examination

Prodromal fever and Yes Yes Yes (mild)


malaise

Lymphadenopathy Yes No No

Distribution of skin lesions Centrifugal (80%) or Centrifugal Centripetal


centripetal (5%)

Depth of skin lesions Superficial Deep Superficial

Evolution of skin lesions Monomorphic (80%) or Monomorphic Plemorphic

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Disease characteristics Monkeypox Smallpox† Chickenpox

pleiomorphic (20%)

Desquamation (days after 22–24 14–21 6–14


onset)

Lesions on palms and Common Common Rare


soles

Extracutaneous manifestations

Secondary skin/soft-tissue 19% Possible Possible


infection

Pneumonitis 12% Possible 3–16%

Ocular complications 4–5% 5–9% No

Encephalitis <1% <1% <1%

Laboratory diagnosis

DNA detection (eg, PCR) MPV Variola virus VZV

Electron microscopy Poxvirus particles Poxvirus particles Herpesvirus

Culture on chick Characteristic pocks Characteristic pocks No growth


chorioallantois

Serology Orthopoxvirus and Orthopoxvirus and Varicella


MPV antibodies variola virus antibodies
antibodies

Monkeypox virus complications include encephalitis, severe dehydration caused by vomiting


and diarrhoea (or difficulty in drinking due to mouth lesions), tonsillitis, pharyngitis, oedema
of the eyelids, respiratory symptoms such as bronchopneumonia corneal scarring which
causes extensive and permanent damage to the eyes and the lasting effect of monkeypox
pitted scars on skin of survivors. Moreover, corneal scarring can cause extensive and
permanent damage to the eyes. Biochemistry indicates leucocytosis, elevated transaminase
levels, reduced blood urea nitrogen level and hypoalbuminemia (Katy and Peter, 2016). The

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route of MPXV infection (through bites or mucocutaneous) influences the time course and
manifestations of illnesses.

2.5 DIAGNOSING MONKEYPOX

There are various differential diagnoses which must be considered when taking the
diagnosis of monkeypox and the include other illnesses accompanied by rash, such as,
smallpox, chickenpox, syphilis, measles, scabies, some bacterial skin infections, and
allergies resulting from medications. The main distinguishing clinical feature of
monkeypox from smallpox remains the presence or development of enlarged lymph
nodes(lymphadenopathy).

Monkeypox can be diagnosed in laboratories using test methods that can identify virus
such as:

 Quantitative polymerase chain reaction (PCR) assay


 enzyme-linked immunosorbent assay (ELISA)
 antigen detection tests
 virus isolation by cell culture

Other technical methods include

 Immunohistochemistry
 Electron microscopy

Western blot analysis for specific IgG antibody may be used in determining the virus.
Other tools that may be used include assays for plague reduction neutralization and
haemagglutination inhibition, but due to antigenic and serological cross-reactivity
displayed by monkeypox virus with other othopoxviruses, complications arise in the use
of antibody-based tests in specific diagnosis.

Consequentially, a recent improved diagnostic tool has conquered this challenge by


preadsorbing samples with vaccinia antigens prior to ELISA. Effective communication and
precautionary measures between specimen collection teams and laboratory staff is essential to
maximizing safety in the manipulation of monkeypox specimens. This is especially relevant
in hospital settings, where laboratories routinely process specimens from patients with a
variety of infectious and/or non-infectious conditions. A labelling system should clearly

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distinguish all specimens, including those from monkeypox patients which require special
handling.

Laboratory exposures to poxviruses occur primarily through needle-stick injuries, direct


contact with the specimen or aerosols that may be generated by laboratory procedures. Sharps
should not be included with any specimens, and should be disposed of in appropriate
puncture-resistant containers for autoclave of infectious waste.

Collection of specimen can begin after appropriate consultations have been made. Procedures
and materials used will vary depending on the phase of the rash.

However, these techniques are unavailable and inaccessible in African rural areas, where
the disease is prevalent, and thus are not important for its diagnoses there.

TABLE 4: SPECIMEN COLLECTION FOR MONKEYPOX DIAGNOSIS (CDC, 2014).

Disease Phase Specimens to Collect

Prodrome Tonsillar tissue swab

Nasopharyngeal swab

Acute serum and whole blood

Rash*

Macules or Papules Tonsillar tissue swab

Lesion biopsy

Acute serum and whole blood

Vesicles or Pustules Lesion fluid, roof, or biopsy

Electron microscopy grid (if Supplies

are available). Acute serum and whole blood.

Scabs or Crusts Lesion scab or crust

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Disease Phase Specimens to Collect

Acute serum and whole blood

Post-Rash Convalescent serum

There are few scientific studies pertaining to the transmission of monkeypox virus and most
were conducted in Africa. Person-to-person transmission of monkeypox virus is believed to
occur by the same mechanisms exploited by variola virus during the smallpox era, namely via
respiratory droplets or by direct contact with lesion material.

2.6 TREATMENT OF MONKEYPOX AND VACCINE INTERVENTION

There are no existing specific treatments or vaccinations accessible for this disease. However,
outbreaks can be controlled and broad spectrum antiviral agents can be used in very severe
cases though their efficacy remains unknown. Three antiviral agents are currently being
assessed, they include (Simi, 2015);

 ST-246 which prevents the release of the virus from the cell. It has been reported to
be effective in controlling the infection of various Orthopox viruses and is partially
being used as a treatment agent for Orthopox virus infection. However, it has not been
licensed to treat monkeypox infections.
 Cidofovir: This inhibits the enzyme responsible for viral multiplication. Adverse
effect manifests as renal toxicity. It is temporarily allowed for the treatment of
other Orthopoxvirus infections.
 CMX-001: This is a modified version of cidofovir compound. It does not cause renal
toxicity and has been reported effective in controlling the replication phase of
various Orthopox viruses. It is a work in progress.

Vaccines used against smallpox in the past yielded 85% efficiency in preventing monkeypox
infection. But due to the global eradication of smallpox, production of the vaccine has long
been discontinued. It was however reported that those who contracted monkeypox infection
after receiving vaccines against smallpox were insignificantly affected by the disease.

Eligibility for smallpox vaccine

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 Public-health and animal control workers who are inversting human/ animal
monkeypox cases.
 Health-care workers and people in close proximity with monkeypox patients in the
past four days (vaccination should be considered up to 14 post exposure).
 Laboratory workers who work with specimens that may contain monkeypox virus.

Ineligibility for smallpox vaccine

 Immunocompetent persons which include infants, HIV patients, cancer patients, those
with life threatening allergies to any of the components of smallpox vaccine
(streptomycin, polymycin B, neomycin, Chlortetracycline).

The CDC recommends vaccinia immune globulin (VIG) to be used as prophylactics in


severely immunodeficient persons exposed to MPXV. Advances in vaccinations and antiviral
treatments since the eradication of smallpox is encouraging.There is however further progress
in the development of third generation modified vaccinia Ankara (MVA) vaccines, which
include ACAM3000 and TBC-MVA[58], and clinical trials are still in progress for antiviral
therapies. In animals, antiviral compounds are more efficient in reducing mortality than the
use of therapeutic smallpox vaccine.

2.7 PREVENTING AND TRANSMISSION CONTROL INITIATIVE

CDC recommends that people scrutinizing monkeypox outbreaks and involved in taking care
of infected people or animals should receive smallpox vaccination in order to protect
themselves against being infected. Also, those who have had close contact with individuals or
animals diagnosed with monkeypox infection should also be vaccinated. These people may
be vaccinated up to 14 days after exposure. CDC does not recommend pre-exposure
vaccination for unexposed veterinarians, veterinary staff, or animal control officers, unless
such people are directly involved in field investigations. Only trained personnel in suitable
laboratories should handle samples taken from suspected persons or animals.

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Restriction and ban on animal trade and importation into countries, regions and states
imitating the joint order issued by CDC and the United States Food and Drugs
Administration in 2003 banning importation of rodents from Africa, may be effective
against the spread of the virus.

WHO recommends that captive animals should not be inoculated against smallpox. But
rather suspected and potentially infected animals should be isolated from other animals
and placed into immediate quarantine. While animals that have been in contact with any
infected animal should be quarantined and observed for 30 days, observing all safety
precautions.

Creating awareness, taking surveillance measures and providing rapid identification of new
cases is vital in preventing outbreaks and managing the virus in the absence of proven
treatment and vaccines. Awareness should be created on the risk of contracting the disease
through improperly cooked meat and via lack of safety precaution during animal handling
and butchering. In the DRC, film-based educational activities have been effective in raising
MPX awareness, but additional health education campaigns focused on the handling of
potential animal reservoirs is needed (Katy & Peter, 2016).

Furthermore, the main reason for hunting monkeys and rodents as meat is due to the poverty
stricken state of many people living in Western and Central regions of Africa, which causes
direct and unhindered contact with the virus-carrying animals. Infection with the virus
especially in immune-compromised individual such as people with HIV/AIDS is further
enhanced by the process of deforestation and Urbanization. With respect to this, enhancing
the standard of living of the people in infection-prone areas such as providing alternative
source of food, job creation, educational campaigns and reducing deforestation activities will
do much in reducing the outbreak of the disease, and improving the general well-being of the
people.

In addition, the World Health Organization’s WaSH initiative which projects the importance
of clean drinking water, good sanitation and hygiene especially after contact with sick people
along with protective clothing for those dealing with infected persons may help in avoiding
the risk of being infected.

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2.7.1 Clinical/home precautions to Prevent Transmission (CDC)

Isolation

Suspected patients should be immediately isolated in a negative air pressure room. In the
absence of a negative air pressure room, a private examination room should be used. In an
instance where both options are not available precautions such as wearing patients surgical
masks and covering patients exposed lesions using sheets or gowns should be taken to curtail
exposure to immediate persons.

Personal Protective Equipment (PPE)

Personal protective equipment should be slipped into before coming in contact with patient
and disposed after use/ upon leaving isolation room.

Optimal personal protective measures include:

 Use of disposable gown and gloves for patient contact.


 Use of filtering disposable respirator that has been fit-tested for the healthcare worker
using it, especially for extended contact in the inpatient setting.
 Use of eye protection (e.g., face shields or goggles), as recommended under standard
precautions, if medical procedures may lead to splashing or spraying of a patient’s body
fluids.

 Proper hand hygiene after all contact with an infected patient and/or their environment
during care.
 Correct containment and disposal of contaminated waste (e.g., dressings) in accordance
with facility-specific guidelines for infectious waste or local regulations pertaining to
household waste.
 Care when handling soiled laundry (e.g., bedding, towels, personal clothing) to avoid
contact with lesion material.
o Soiled laundry should never be shaken or handled in manner that may disperse
infectious particles.
 Care when handling used patient-care equipment in a manner that prevents contamination
of skin and clothing.
o Ensure that used equipment has been cleaned and reprocessed appropriately.

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 Ensure procedures are in place for cleaning and disinfecting environmental surfaces in the
patient care environment.
o Any EPA-registered hospital disinfectant currently used by healthcare facilities for
environmental sanitation may be used.  Follow the manufacturer’s recommendations
for concentration, contact time, and care in handling

CHAPTER THREE

3.1 MONKEYPOX IN NIGERIA

The only incidence of monkeypox in Nigeria occurred in the year 1971 and 1978 respectively
with only three cases reported in both years. However, most recently, suspected outbreaks
have been spreading across the Nation. Affected state include Bayelsa, Imo, Benue, Ondo,
Oyo, Kogi, Kastina, Edo, Niger, Kano, Abia, Akwa Ibom, Cross River, Ekiti, Lagos, Enugu,
Imo, Delta, Nasarawa, Rivers, and FCT, with the most occurence in Bayelsa State. As a measure
to monitor the events of this endemic and control the spread of the virus, a centre was
established by the Nigerian Centre for Disease Control (NCDC) and the epidemiological
team of the state Ministry of Health.

The NCDC assigned a team of eleven people including a medical doctor who were under
surveillance and quarantined in the Niger Delta University Teaching Hospital (NDUTH) to
awaited the delivery of results for samples sent to the WHO and Senegal, while monitoring
those who came in contact with infected persons (Ebitimitula, 2017).

It was confirmed that of the 116 samples sent to Dakar, Senegal for confirmation, a totalof
thirty eight samples turned out positive with the likely source of transmission being zoonotic,
followed by secondary human-to-human transmission (NCDC, 2017). Samples however
could not be tested in Nigeria due to lack of well-equipped and appropriate laboratories.
24
There are basically two clads of monkeypox virus – the West African strain and the Central
African strain. The outbreak in Nigeria was caused by the less virulent and non-deadly West
African strain, which manifests in milder disease symptoms, fewer deaths and limited human-
to-human transmission.

However most of the results gotten reported negative, even though the symptom manifested
are those of monkeypox ( Adewole, 2017), hence making it unknown whether, it is a new
strain or another infection to be worried about.

3.2 MEASURES FOR ERADICATING MONKEYPOX

The outbreak of monkeypox virus in the United States clearly demonstrates the ability of new
diseases to emerge and migrate due to casual movement of species from place to place. There
is a call of urgency for research and development of therapeutic agents and new vaccines for
the treatment and prevention of poxvirus infections.

In 1981, the WHO began supporting several surveys following cases of human monkeypox
infections in Africa; conversely, owing to very few cases reported, the surveys were halted in
1986. However, due to potential bioterrorism attack with smallpox virus in 2002, surveillance
programs were designed to monitor febrile rash illnesses in humans; and these programs may
be instrumental in detecting emerging infections (Breman, 2002). Hence, the outbreak of
monkeypox virus infection should serve as a prompt to monitoring these surveillance
programs.

In 2002, military personnels and health- workers who were potentially at risk of being
infected with orthopox virus were being vaccinated with vaccine strain of Dryvax, following
bioterrorism attack with Variola Virus. Nevertheless, an extreme rate of adverse effect in
association with the smallpox vaccine has been observed, thus preventing other countries
from recommending the smallpox vaccine as a preventive therapy (Qutaishat, 2003).

25
Accordingly, it was concluded in the final reports of the Global Commission for the
Certification of Smallpox Eradication in 1979 that continued smallpox vaccination to prevent
human monkeypox was not justified (Daniel, 2004), but did however suggest that measures
be taken to assess the public-health implication of emerging zoonosis more accurately . In
addition to the recognised adverse effects related with smallpox vaccination in
immunocompetent patients, the emergence of AIDS in the 1980s further intensified concerns
over the use of the vaccine (Heyman, 1998). 

According to (Stittelaar et al, 2007), antiviral therapies are more effective than smallpox
vaccines and should serve as complements because post-exposure vaccination do not
essentially provide protection against lethal infections of OrthopoxVirus (OPV), neither is
there guaranteed protection against infection with OPV during the time-lapse between
vaccination and antibody development protection, and those available such as Cidofovir and
ST-246, have only been successfully used in treating a child with severe eczema vaccinatum
(Vora et al, 2008).

An important criterion for licensing drugs or vaccines in order to prevention or treat human
infectious diseases such as monkeypox, is the ability of these compounds to render adequate
protection in the case of a challenge with the pathogen in one or more animal models. Based
on this legislation, the United States Food and Drug Administration (FDA) recommend the
testing of drugs or vaccines directed against such human diseases in at least two animals, one
of which should be non-rodent specie (ideally nonhuman primate). This is because in vivo
studies of monkeypox virus cannot be done in humans owing to ethical reasons surrounding
the lethal conditions of the test (Marit et al, 2010). Therefore, nonhuman primates due to their
close relatedness to humans are experimentally considered test specie for vaccines and
antiviral compounds.

For eradication to be made possible, it is crucial that rural areas where endemicity of the
disease prevails are provided with easily accessible, low cost and user friendly technologies
to aid in cultivating and identifying the virus in order to implement a treatment plan before
complications arise. Tetracore Orthopox Biothreat Alert is one of such new techniques that
offer this possibility. It does not require a huge expertise and demanding temperature
conditions are not required to perform tests.

Another vital key for zoonotic infections such as monkeypox virus to be eradicated from the
globe, there must be synergy of inter, intra and trans-professional parameters in place i.e.

26
public health and medical specialists alone are not sufficient to dealing with the challenges of
zoonotic viral infections but a clear understanding of parameters such as environmental
science, veterinary, political behaviour, human social science behaviour, evolutionary
changes, may suffice in rendering a more straight forward solution (Cascio, 2010).

Currently, notwithstanding the improvements in laboratory science, methods of tackling


infectious diseases continue to be the same as those nearly a century ago and they include
public health awareness, isolation, sanitation and hygiene, reducing congestion, and
surveillance programs as vital tools. Mitigating the impact of this disease will require the
commitment of government, industry, and public and private partnership on a social, political,
and economic platform (Sharon and Dana, 2014).

3.3 CHALLENGES SURROUNDING MONKEYPOX IN CONTEXT

The smallpox Vaccinia virus vaccine has been used and proven effective in time past against
infectious cases of monkeypox due to the similarities they share phylogenetically. However,
there is a down-toll to this success because the live vaccinia virus in the vaccines could be re-
activated in immunocompromised persons, leading to further complications. Inactivated
vaccinia viruses are also used as vaccines but they are not as effective as the live virus
(Smitha, 2015).

Another challenge facing the monkeypox infection is difficulty in using Serological testing
for MPV antigens due to the closeness in antigenic variations found between the surface
antigens of orthopoxviruses. Though there are several serological methods available, some of
which include virus-neutralising test, haemagglutination-inhibition assay and detection of
specific viral antibodies, serological test are not useful for the diagnosis of acute infections
because of the varying dimension of its sensitivity and thus cannot be used reliably to test any
case of orthopoxvirus (Damon, 2003).

In the area of vaccine production, although safety studies and in vivo efficacy of vaccines
should be carried out on humans, ethically this is impossible due to the lethal consequences
involved in such experiments. Hence vaccines and antiviral compounds are tested only on
non-human primates owing to their close-relatedness to humans. The nonhuman primate
animal model used for monkeypox virus vaccine experiment to successfully induces clinical
disease is the macaque species - cynomolgus (Macaca fascicularis) and rhesus macaques

27
(Macaca mulatta) respectively. However, a major limitation to the use of these animals is the
lethal downside of infection caused by high infectious doses (Jordan, 2006).

However, given the possibility of monkeypox vaccine production or the authorization to


continue with the smallpox vaccinia virus vaccine, a variety of issues may contrive to prevent
the authorized vaccines among the general public from being feasible. Cost being the
principal limitation, alongside vaccine availability, and reactogenicity – as in the case of
smallpox vaccine which contains live virus, produced a large number of contra-indications
such that an estimated 30%–50% of the general public would not be eligible to be given the
vaccine in the case of an exposure or risk to an exposure (Sharon, 2014).

Furthermore, variations in epidemiological studies blur the understanding of the virulence


and transmissibility of monkeypox virus infection in humans. There also is the underlying
concern of unreported cases to healthcare, thereby preventing the surveillance monitoring
system from accurately estimating the number of human monkey cases. Moreover, since
there are no proven treatments for this infection and according to records it remains the most
important infection in the family of orthopoxvirus after the eradication of smallpox,
insecurity lies in its potential as an agent of bioterrorism Monkeypox is the most important
orthopoxvirus infection in human beings since the eradication of smallpox in the 1970s
(giulio and eckburg, 2004).

3.3.1 CO-INFECTION

Monkeypox has been reported to be detected alongside chickenpox and requires adequate
care and sensitivity carrying out test due to similarities in the clinical features of both
diseases. In a co-infection with chickenpox, 75% of the rash is from monkeypox while 15%
results from chickenpox.

28
CHAPTER FOUR

4.1 FACTORS INFLUENCING DISEASE EMERGENCE AND RE-


EMERGENCE

The factors responsible for zoonotic diseases in humans are often dependent on the reforms
of human behaviours, climatic and environmental change, and pathogenically related factors.
The resurgence and epidemiology of zoonoses are complex and dynamic, being influenced by
varying parameters that can roughly be categorized as human-related, pathogen-related, and
climate/environment-related; however, there is significant interplay between these factors
(Cascio et al,2011).

TABLE 5: INFECTION-DEPENDENT FACTORS (Cascio et al, 2011)

HUMAN-RELATED FACTORS CLIMATIC PATHOGEN


FACTORS RELATED
FACTORS
MODERN INDUSTRALIZAT POLITICS SCIENCE
LIFE

29
TRREND ION
Ecotourism Urbanization/ State reforms Novel Global Ecosystem
Megacities diagnostic warming disruption/
s Population
rearrangement
Pet Intensive Conflicts Novel Genomic
ownership husbandry system high risk variability/
population Species
jumping/ Re-
assortment
Culinary Food-chain Loosening Biodiversity
habits e.g industry border influences/
raw meat automation control Biological
comsumptio pollution
n
Global Global trade Free-trade Virulence/
travel interaction economy Resistance
selection
stress
Human intrusion in Surveillance
ecosystem e.g. & public
deforestation health
infrastructure
breakdown
Hierarchy
issues

4.2 PREVENTING RE-EMERGENCE

Cessation of control activities plays a major role in the consequent re-emergence of


indigenous transmission of infectious diseases. However, cited as some of the reasons for
draw back on control activities are decreased funding, apathy, lack of encouragement and

30
awareness, and weakness in surveillance resulting in delayed detection of human infection
(Heymann, WHO).

Re-introduction of infectious diseases in present times occur both locally and across borders
and continents; thus it is expedient that measures continue to be in place to keep infectious
agents in check. For instance, between the year 2003 and 2005, Poliomyelitis in Northern
Nigeria spread and was re-introduced into some other countries in Africa and regions of the
world which include Asia and the Middle East (altogether 18 polio-free zones), where
intervention had been stopped and monitoring, control and surveillance neglected both by
public health professionals and Government bodies (WHO, 2008).

Similarly, after the eradication of smallpox globally, vaccination in all countries of the world
was discontinued notwithstanding the stockpile of smallpox viruses left reserved in two major
laboratories.

Fig 5: factors influencing emergence of infectious diseases (Simmerman, 2017)

According to the WHO, in other to prevent and/or control re-emergence of infectious


diseases, surveillance must be continued, there should be an international stock-pile of
vaccines readily available and control interventions hiked.

31
Fig 6: Map of Emerging and Re-emerging diseases (Boston University, 2016)

4.3 THE POSSSIBILITY OF RESISTANCE

The close similarity in clinical features of monkeypox to smallpox makes it difficult to


clinically distinguish between both infections without the use of specific diagnostic tests. The
smallpox vaccine in the past which proved effective against the infection of monkeypox is
presently not readily available following the eradication of smallpox, thus concerns are rising
that with the limited availability of smallpox vaccines in the current setting, monkeypox
could become a more competent human pathogen, hence leading to resistance to antiviral
drugs which are presently being developed for the treatment of the disease. 

Currently, Cidofovir among other antiviral drugs is the most effective antiorthopoxvirus agent
undergoing pre-clinical study, and is at the verge of being licenced.

From the study of Donald et al, on resistant strains of monkeypox and other orthopox viruses,
cross-resistance was observed toward cyclic HPMPC (a prodrug form of cidofovir) for all the
resistant poxviruses tested. Monkeypox virus was cross resistant to HPMPA. Application of
the data from the study of Donald et al to a possible clinical situation suggests the possibility
that treatment of variola or monkeypox virus infections in humans could lead to the

32
emergence of CDV-R viruses that are cross resistant to other antiviral compounds (Donald, et
al).

Resistance to other microbial infections may also be instigated due to self- prescription and
medication, wrong prescription by unsuspecting / unqualified personnel, the use of drugs
inappropriately in the bid to get rid of the symptoms being experienced as well as taking
antibiotics as prophylaxis against infection, thus further breaking down the immunity of
infected persons and prolonging duration of illness.

4.4 SOCIO-ECONOMIC IMPACT OF RE-EMERGING DISEASES

All through history, human lives have been shaped by emerging infectious diseases have
shaped the course of human history and have caused innumerable death and misery. The
extent of zoonotic disease burden on human health procures an annual death record of
hundreds of thousands and tens of millions of infectious incidences. Advancements in science
and high through-put technologies round the globe notwithstanding, infectious diseases
continue to emerge at an alarmingly rapid pace, with the majority of them activated by wars,
loss of social consistency, natural disasters.

Policy creations and educational awareness against infectious diseases are vital in every
nation because no country is insusceptible to epidemics, which impacts both the economy and
society. The epidemic impact of an infection on a nation is of varying degrees depending on
the length of duration and severity. The emergence of an infectious disease in a nation is a
huge threat and poses a health risks both to human and animal population. EIDs pose a major
risk to the health and welfare of global human and animal populations. Severe disruption of
the national food chain in the case of infections in animals will eventually impact on humans
causing health hazards. Moreover, the amount of man-power and hours of productivity lost
greatly affects the GDP of any economy.

Most recently round the globe; novel infectious agents alongside the re-emergence of
previously epidemic infectious agent have been on the rise. An example is the re-emergence
of Ebola virus which far exceeded the previous records of the disease in West Africa (Sharon
and Dana, 2014). Outbreaks of epidemics pose heavy tolls on humans and society, as several
death occur leaving families helplessly stranded and dependent on the society for help
especially in the case of the loss of a breadwinner. People get displaced from work, cancel
financial project, and pack up personal businesses, schools get shut down and academics

33
delayed, tourism is affected, international trade most likely withdraw as borders become
closed. In essence every aspect of the country’s economy is affected and without timely
interventions may become crippled.

Consequently, owing to the existence of prevalent population susceptibility to these agents,


the survival of nations are placed at risk given the instance a bioterrorism event. Of which
most of the biological weapons in existence today are of zoonotic nature, and consists of high
research cost and a great deal of time required to prepare for possible attacks (Cascio et al,
2011).

4.5 HEALTH AND PSYCHOLOGICAL IMPACT

Monkeypox virus has created disproportionate fear in the hearts invaded communities as is
the case with other viral epidemics, due to the rapid and invisible mode of transmission to
which it owes its high morbidity and mortality. Outbreaks of viral diseases which are
extremely contagious fronts affected persons as victim and equally as vector (Pappas et al,
2009).

Severe and disfiguring infections such as the MPV are characteristically accompanied by
major depressive disorders characterized by depressive episodes and symptoms such as
depressed mood (Coughlin, 2014), inability to concentrate, loss of interest in most daily
activities, significant weight loss or gain, sleeping disturbances, fatigue or loss of energy,
feelings of worthlessness or excessive or inappropriate guilt, suicide attempts or recurrent
thoughts of death or suicide. In Nigeria, one victim from the recent outbreak in Bayelsa State
committed suicide despite nearing recovery (Umeha, 2017).

Infected individuals who are left with pitted scar may carry on with feelings of inferiority and
inadequacies due to their disfiguring looks, hence crippling their minds and becoming
mentally invalid and dependent.

Actions carried out by health operatives and surveillance groups such as isolating infected
individuals and other infringements of rights in the bid to control the spread of the disease
may also inadvertently contribute to health deterioration and diverse psychological disorders.
Effects however of the disease on overall health and psychology vary among individuals.

4.6 ECOLOGICAL CONSEQUENCES

34
The subject of ecological consequences of pathogen-induced changes in hosts is as delicate as
that of dramatic impact of pathogens on their hosts. The effect of pathogens on host
behaviour, reproduction, and mortality largely influences community interactions such as
competition, facilitation, predation, and invasion (Valerie). These pathogen-induced changes
in host individuals and communities can have strong impacts on ecosystem processes (e.g.,
productivity, nutrient cycling) and landscape structure and function (e.g., disturbance
regimes, land use, land-atmosphere interactions).

CHAPTER FIVE

CONCLUSION

In a rapidly changing world that is fast advancing in scientific knowledge and technology,
infectious diseases still thrive and have remained on the rise. The long chain of incessant
outbreaks of human monkeypox in Africa and its spread to regions across the globe where it
was never previously reported indicated the red light. Its re-emergence in countries such as
Nigeria where it had been non-existent for 39 years, calls for a commitment to vigilance,
surveillance, intensity in research and development of antiviral therapies, while not
neglecting the good old sanitation and hygiene self-support therapy

It is highly significant that this orthopoxvirus remains at the vanguard of potential emerging
infectious diseases. Even though smallpox has since been eradicated from the human
population, there exists the potential for monkeypox to carry the flag. The extended person-
to-person chain of monkeypox transmissions in the Republic of Congo (2003) reveals the
potential of further adaptation of the virus to become a more successful human pathogen
(Learned et al, 2005). Moreover, since the human population is continuously changing due to
35
factors such as ecological disturbances and advancement of new infectious diseases such as
HIV, this may provide the platform for a more efficient spread of monkeypox disease.

Faced with the possibility of monkeypox being a potential agent of bioterrorism and fearing
the development and spread of more virulent strains, it becomes expedient for national and
international bodies to synergize and begin to develop and create stockpiles of vaccines and
antivirals against unpleasant future occurrences.

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