"SCRUB TYPHUS"

Dr. Madhusudan Swarnkar

Sr. Professor
Community Medicine, JMC
 “SCRUB TYPHUS”
• Chigger borne typhus, Tsutsugamushi fever, Mite-borne typhus fever,
Tropical typhus, ICD-10 – A75.3.

• It was first observed in Japan (1899) where it was found to be transmitted

by mites. The disease was, therefore, called tsutsugamushi (from tsutsuga
meaning dangerous and mushi meaning insect or mite).

• The mites are often found in tightly circumscribed foci (belts or islands)
in areas of scrub vegetation, hence the name of the disease.

• In Greek, the word typhos means “stupor caused by a fever.”

Historically linked to war and military operation
• Soldiers were exposed to chigger bites in forest areas during the military
operation.
• Thousands of cases in the Far East during the Second World War.
• It is estimated that 36,000 soldiers were either incapacitated or died during
World War II.
• Severe epidemics of the disease occurred among troops in Myanmar (Burma)
and Sri Lanka (Ceylon) during World War II.
• It was suspected to be the leading cause of pyrexia of unknown origin (PUOs)
in forces of the United States (US) of America during the Viet Nam conflict.
GLOBAL SCENARIO- Scrub typhus affected countries
• Scrub typhus is endemic to a part of the world known as the “Tsutsugamushi
Triangle”, which extends from northern Japan and far-eastern Russia in the north, to
northern Australia in the south, and to Pakistan and Afghanistan in the west.
• “Mite island” “Typhus Islands.”
 INDIAN SCENARIO
• Scrub typhus is a reemerging infectious disease in India

• Outbreaks in areas located in the sub-Himalayan belt, from Jammu to

Nagaland.

• Outbreaks of scrub typhus are reported in southern India during the cooler
months of the year.

• In India, scrub typhus has been reported from – Rajasthan, Himachal

Pradesh, Jammu & Kashmir, Vellore, Sikkim, Darjeeling, Nagaland &
Manipur.
 DISEASE TRANSMISSION
• Scrub typhus is transmitted by trombiculid mite Leptotrombidium delicense
• Chigger (larval stage)mites act as the primary reservoirs for O.tsutsugamushi
• The L. deliense group of vector mites are widely distributed all over the
country coexisting primarily with rodents and other small mammals.
• Once they are infected in nature by feeding on the body fluid of small
mammals, they maintain the infection throughout their life stages and pass the
infection to their eggs (transovarial transmission).
• Similarly, the infection passes from the egg to the larva or adult in a process
called transtadial transmission.
• Mites are both the vector and the reservoir.
• Humans are accidental host.
• Incubation Period: 1 – 3 weeks (5 to 20 days with mean 10-12 days)
 Agent : Rickettsial Diseases
• Scrub typhus caused by Orientia tsutsugamushi.
• These organisms are primarily parasites of arthropods such as lice, fleas,
ticks and mites, in which they are found in the alimentary canal.
• Transmitted by arthropod vectors,
• They are small, gram negative bacilli can be seen with Giemsa stain or a
modified version of Gimenez stain.
• Obligate intracellular parasitism,
• No vacuolar membrane.
• It lacks lipopolysaccharide and peptidoglycan and does not have an outer
slime layer.
• In vertebrates, including humans, they infect the vascular endothelium
and reticuloendothelial cells.
• On the body of small mammalian hosts, the
chiggers attach in clusters on the tragus of the ear,
the belly and on the thighs
• Chigger index
• (average number of chiggers infesting a single
host)
• >0.69 (critical value) is an indicator for
implementation of vector control measures.
 CLINICAL PICTURE
• The chigger bite is painless and may become noticed as a transient localized itch.
• A Papule develops at the site of inoculation.
• The papule ulcerates and eventually heals with development of a black eschar.
• General symptoms are sudden fever (>40ºC [104ºF]) with relative bradycardia,
severe headache, conjunctival congestion, apathy, myalgia, generalized ach
coupled with lymphadenopathy, photophobia and a dry cough.
• Approximately one week later, a spotted and then maculopapular rash appears first
on the trunk and then on the extremities and rarely involves the face, palms and
soles.
• Complications are interstitial pneumonia with or without ARDS (30 to 65% of
cases), meningoencephalitis, myocarditis, acute hepatic failure, acute renal failure
& DIC.
• Symptoms generally disappear after two weeks even without treatment.
• In severe cases with pneumonia and myocarditis, the mortality rate may reach 30%.
ESCHAR : A punched out ulcer covered with a blackened scab which indicates the location
of the mite bite.
 DIAGNOSIS
• Blood counts: Normal WBC or Early lymphopenia with late lymphocytosis
&Thrombocytopenia.

• Liver function tests: Elevated transaminases (75– 95% of patients) Hypoalbuminemia

(about 50% of cases),

• Renal function tests: Creatinine may be elevated in severe cases.

• Chest X-ray: It may reveal pneumonitis, pleural effusion or bilateral infiltrates.
• Ultrasound abdomen: It may reveal liver or spleen enlargement

• Scrub typhus may be diagnosed in the laboratory by:

• (i) Isolation of the organism
• (ii) Serology
• (iii) Molecular diagnosis (PCR).
Collection, storage & transportation of specimen
• As rickettsiae are highly infectious and have caused several serious and fatal
infections among laboratory workers, it comes under Risk Group 3
organisms.
• So collection, transportation and storage of specimens are extremely vital
steps in laboratory diagnosis and hence, must be undertaken with utmost
care.
• Specimen
• Serum/Blood collected in tubes containing EDTA or Sodium citrate
(4-5 ml of venous blood)
• Blood clot/Skin or lymph-node biopsy
• Dispatch the specimen immediately to laboratory at 2-8ºC (ice box) as soon
as possible. In case the delay is inevitable, keep the specimen at + 4ºC in a
refrigerator.
 (ii) Serological Diagnosis
• A significant increase in antibodies in the serum of the patient during the course
of infection and convalescence. (An IgM titer >1:32 and/or a four-fold increase
of titers between two sera confirm a recent infection.)
• In cases of infection with O. tsutsugamushi, a significant IgM antibody titer is
observed at the end of the first week, whereas IgG antibodies appear at the end
of the second week
• Several serological tests are currently available for the diagnosis of rickettsial
diseases like
Weil-Felix Test (WFT),
Indirect Immunoflourescence (IIF),
Indirect Immunoperoxidase tests (IIP),
Enzyme linked Immunosorbent assay (ELISA) Most sensitive tests
available
 (iii) Molecular Diagnosis – PCR
• Polymerase chain reaction (PCR) is possible from skin rash biopsies, lymph
node biopsies or EDTA blood.

• Real-time PCR assays are as sensitive as standard PCR but are more rapid
and can give quantitative results.

• Facilities for laboratory diagnosis of Rickettsial diseases are available at

National Centre for Disease Control, Delhi where samples can be sent for
confirmation.
 TREATMENT
• Prompt institution of effective antibiotic therapy against rickettsiae is the single
most effective measure for preventing morbidity and mortality due to rickettsial
diseases.
• Doxycycline, Chloramphenicol, Azithromycin & Tetracyclines remain the
only proven therapy for the rickettsial diseases.
• Doxycycline is the drug of choice, 100 mg twice daily for 7-15 days
• Treatment for less than a week is initially curative but may be followed by
relapse.
• Chloramphenicol - 500 mg four times a day for 7-15 days (for children 150
mg/kg/day for 5 days)
• Azithromycin or chloramphenicol is useful for treating infection in children or
pregnant women.
• These antibiotics are bacteriostatic.
 PREVENTION & CONTROL
• The mite vectors of scrub typhus are especially amenable to control because
they are often found in distinct areas (Typhus Island).

• These foci can be eliminated by treating the ground and vegetation with
residual insecticides, reducing rodent populations and destroying limited
amounts of local vegetation.

• Persons who cannot avoid infested terrain should wear protective clothing,
impregnate their clothing and bedding with a mitecide (e.g. benzyl benzoate)
and apply a mite repellent (diethyltoluamide, dibutyl phthalate) to exposed
skin.

• An effective vaccine for humans has not been developed till now, mainly due
to serotypic heterogeneity of the organism.
Visceral Leishmaniasis (VL)
• Also known as Kala-azar.

• Most severe form of leishmaniasis

• Caused by a protozoan parasite of the Leishmania genus

• transmitted to man by the bite of female phlebotomine sandfly.

• Second largest parasitic killer in the world

• HIV/VL co-infection—an emerging problem

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 Visceral Leishmaniasis
• Leishmaniasis (a group of protozoa) diseases caused by parasites of the genus
Leishmania

• They are responsible for various syndromes in humans - kala-azar or visceral

leishmaniasis (VL), Cutaneous leishmaniasis (CL), Mucocutaneous leishmaniasis
(MCL), anthroponotic cutaneous leishmaniasis (ACL), zoonotic cutaneous
leishmaniasis (ZCL), post- kala-azar dermal leishmaniasis (PKDL), etc .

• The visceral type of disease, kala-azar, is still an important disease in India.

• The majority of the leishmaniasis are zoonoses involving wild or domestic mammals
(rodents, canines).

• Some forms (e.g., Indian kalaazar) are considered to be nonzoonotic infections

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History

• The agent of the disease was first isolated in India by Scottish doctor
William Leishman and Irish physician Charle donovan

• Species was named for both of them-Leishmania donovani

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Problem Statement
• 90% of visceral leishmaniasis reported from 6 countries-India, Bangladesh,
Brazil, Nepal, South Sudan & Sudan.

• Kala-azar situation is worsening due to the occurrence of asymptomatic

cases, post-kala-azar dermal leishmaniasis (PKDL), undernutrition , and
kala-azar/HIV coinfection.

• Kala-azar is endemic in 54 districts in Bihar (33), West Bengal (11) ,

Jharkhand (4) and Uttar Pradesh (6) .

• Kala-azar has been declared as notifiable disease in Bihar and West Bengal.
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 Epidemiological determinants
Agent factors
• Leishmania donovani is the causative agent of kala-azar (VL);
• L. tropica is the causative agent of cutaneous leishmaniasis (oriental sore);
• L. braziliensis is the causative agent of mucocutaneous leishmaniasis.
• Life cycle completed in 2 hosts –a vertebrate and an insect
• Reservoirs of infection: There is a variety of animal reservoirs, e.g. dogs,
jackals, foxes, rodents and other mammals.

• Indian kala-azar is considered to be a non-zoonotic infection with man as

the sole reservoir.
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 Host factors

• Infection can occurs in all age groups and both genders.

• Peak age of kala-azar infection is 5-9 years.

• Males are affected more often than females

• Population(migrants, labourers, tourists) movement spread the infection from

endemic to non-endemic regions

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• The disease usually strikes the poorest of the poor. Poor housing and
domestic sanitary conditions (e.g. lack of waste management, open
sewerage may increase sandfly breeding and resting sites, as well as their
access to humans.
• Crowded housing, sleeping outside or on the ground may increase risk

• MALNUTRITION: Diets lacking protein-energy; iron, vitamin A and zinc

increases the risk that an infection will progress to kalaazar.

• OCCUPATION : The disease strongly associates with occupation. People who

work in various farming practices, forestry, mining and fishing have a great
risk of being bitten by sandflies.

• Recovery from kala-azar gives a lasting immunity

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 Environmental factors

• ALTITUDE : Kala-azar is mostly confined to the plains; it does not occur in

altitudes over 2000 feet (600 metres).

• SEASON : Generally there is high prevalence during and after rains.

• RURAL AREAS : The disease is generally confined to rural areas, where

conditions for the breeding of sandflies readily exist compared to urban
areas.

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 VECTORS :

• In India, P. argentipes (Sandfly) is a proven vector of kala-azar.

• Sandflies breed in cracks and crevices in the soil and buildings, tree holes.
caves etc.

• Overcrowding, ill-ventilation and accumulation of organic matter in the

environment facilitate transmission.
• Their habits are primarily nocturnal.
• Only the females bite.
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 Mode of transmission
• In India, Kala-azar is transmitted from person to person by the bite of the
female phlebotomine sandfly,
• P. argentipes which is a highly anthrophilic species.
• Contamination of bite wound or when insect crushed during feeding
• Transmission of kala-azar has also been recorded by blood transfusion,
and is also possible by contaminated syringes and needles.
• Extrinsic IP is 4 to 25 days, time taken for development of parasite in
insect vector
• The incubation period in man is quite variable, generally 1 to 4 months;
range is 10 days to 2 years.
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 Clinical features- V.leishmaniasis
• The classical features of kala-azar are fever,
splenomegaly and hepatomegaly
accompanied by anaemia and weight-loss.
• A family history of the disease is also
common.
• Darkening of the skin of the face, hands, feet
and abdomen is common in India.(Black
sickness)
• Atypical features of the disease (e.g.
lymphadenopathy) may also occur.
• Kala-azar, if left untreated, has a high
mortality 32
Post Kala-azar Dermal
Leishmaniasis(PKDL)

• Skin lesions following treatment

ranging from hypo pigmented macules
to frank nodules
• Skin lesions appear in India one to
several years after treatment.
• Parasites are numerous in the lesion.

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 Diagnosis: Visceral Leishmaniasis
Rapid diagnostic test:
• The rk39 - rapid diagnostic test : The rapid dipstick test has become the
mainstay in the serological diagnosis of Kala-azar, and is the method of
choice for diagnosis of the disease.
• The rk39 - rapid diagnostic test is based on the recombinant k39 protein.
Parasitological diagnosis:
• The demonstration of the parasite LD bodies in the aspirates of the spleen,
liver, bone marrow, lymph nodes or in the skin (in the case of CL) is the only
way to confirm VL or CL conclusively.
• The parasite must be isolated in culture to confirm the identity of the parasite.

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Aldehyde test of Napier:
• 1 to 2 ml of serum from a case of kala-azar is taken and a drop or two of 40
per cent formalin is added.
• A positive test is indicated by jellification to milk-white opacity like the white
of a hard-boiled egg so that in ordinary light newsprint is invisible through it.
Serological tests:
• Direct Aggutination test (DAT), rk39 dipstick test, ELISA and the indirect
fluorescent antibody test (IFAT) are considered most suitable.

• Being a simple test where blood samples can be collected on a filter paper
strip and examined at leisure in laboratory, the ELISA test has a wide
potential both for diagnosis as well as for epidemiological field surveys.
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CONTROL MEASURES
In the absence of an effective vaccine, the control measures comprise
the following :
• Control of reservoir
• Sandfly control
• Personal prophylaxis

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1. Control of reservoir
• Since man is the only reservoir of kala-azar in India, active and passive
case detection and treatment of those found to be infected (including
PKDL) may be sufficient to abolish the human reservoir and control
the disease.

• House-to-house visits and mass surveys may be undertaken in

endemic areas for early detection of cases.

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Following drugs are used for the treatment of kala-azar in Indian
programme:
• Single dose Liposomal Amphotericin B (LAMB) injection
• Miltefosine capsules
• Amphotericin B deoxycholate injection
• Combination of Paramomycin injection intramuscular & Miltefosine
capsules
• Amphotericin B emulsion

Miltefosine is relatively safe oral drug for the treatment of Kala-azar.

The treatment is provided as Directly Observed Treatment (DOT) with
patient coding system being followed for each patient registered at the
treatment centre. 39
 2. Sandfly control
• The application of residual insecticides has proved effective in the control
of sandflies. DDT is the first choice since the vector of kala-azar, P.
argentipes is susceptible to DDT.

• Insecticide spraying should be undertaken in human dwellings, animal

shelters and all other resting places upto a height of 6 feet (2 metres) from
floor level.

• Spraying should be preceded and followed by an assessment of

susceptibility. Any sign of resistance in vector should lead to an immediate
change in insecticide. BHC should be kept as a second line of defence. 40
• Spraying should be repeated at regular intervals to keep down the
density of sandflies.

• For long-lasting results, insecticidal spraying should be combined

with sanitation measures:
• elimination of breeding places (e.g., cracks in mud or stone walls,
rodent burrows, removal of firewood, bricks or rubbish around
houses),
• location of cattle sheds and poultry at a fair distance from human
dwellings, and
• improvement of housing and general sanitation.

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3. Personal prophylaxis
• The risk of infection can be reduced through health education and by
the use of individual protective measures such as avoiding sleeping on
floor, using fine- mesh nets around the bed.
• Insect repellents (in the form of lotions, creams, or sticks) for
temporary protection and keeping the environment clean.

• There are no drugs for personal prophylaxis.

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 POINTS TO REMEMBER
• Scrub typhus is a re-emerging disease in India.

•It is an important cause of community acquired undifferentiated febrile illness in India.

•It has to be considered in the differential diagnosis of sepsis and multiorgan

dysfunction syndrome.

• Search for an eschar in hidden areas of body.

• Diagnosis is done by IgM scrub typhus ELISA.

• Doxycycline is the drug of choice.

•Thank you

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