3. SCRUBTYPHUS-Introduction
• Also known as -Japaneseriver fever
• known in Japanese folk to be associated with the jungle mite or
chigger, termed ‘tsutsugamushi’ inJapanese.
(tsutsuga =disease,harm, noxious and mushi =bug)
• isa zoonosis,with humansbeing accidental,dead end hosts.
4. Historical Perspective
• Rickettsial infection hasbeen one of the great scourges of mankind,
occurring in devastating epidemics during times of war and famine.
• Hippocrates in 460 bc used the termtyphus,
meaning ‘smoke’, to describe the ‘confused
state of the intellect – atendency to stupor’
associated with highfevers.
5. • Napoleon’s retreat fromMoscow
wasforced by rickettsial disease
breaking out among histroops.
• Lenin is said to have remarked, in
reference to rickettsial disease during
Russianrevolution,“either socialism will
defeat the louse or the louse will defeat
the socialism”
6. • Its impact on immunologically naive Allied
troops between 1942 and 1945 resulted in
18000 cases and 639 deaths (4.0%), as
well as an estimated 20000 cases in
Japanese troops.
• First batch of scrub typhus vaccine
used to inoculate human subjects was
dispatched to India for use by the
Allied Land Forces, South-East Asia
Command, in June 1945.
• Leading cause of pyrexia of unknown
origin (PUOs) in forces of USA during
the Vietnam conflict.
9. Indian Scenario
• In India, the disease had occurred among troops
during the Second World War in Assam and West
Bengal, and in the 1965 Indo-Pak war.
• There was a resurgence of the disease in 1990 in a
unit of an army deployed at the Pakistan border of
India.
• Occurrence reported from several states in India
including Jammu and Kashmir, Himachal
Pradesh, Uttarakhand, Bihar, West Bengal,
Meghalaya, Rajasthan, Maharashtra, Karnataka,
Tamil Nadu and Kerala.
• Scrub typhus accounts for upto 50% of
undifferentiated fever presenting to hospitals
and It remains a major uderdiagnosed
(suspected) cause of undifferentiated fever.
10. Agent of Scrub Typhus
Budding of O. tsutsugamushi on the cellular surface
• Gram-negative, rod-shaped (cocco-bacillus) bacterium
Orientia (Rickettsia) tsutsugamushi.
• wide phenotypic and genotypicdiversity
• reported serotypes are
Karp, Kato, Gilliam, Boryong,Kawazaki
• does not have a vacuolar membrane and
hence it grows freely in the cytoplasm of
infected cells.
• Cell wall lackslipopolysaccharide and
peptidoglycan and doesnot haveanouter
slime layer
11. Vector - PrimaryReservoir
• Transmitted by bite of infected larvae of the trombiculid mite
Leptotrombidium deliense (“chiggers”)
• feeds on lymph and tissue fluid rather than blood.
• bite of the mite leaves a characteristic black eschar
12. Earlier it was thought that
rodents were the natural
reservoir of infection,but it is
now believed that mites are
both the vector and the
reservoir.
Natural Reservoir
13.
14. Grasslands
Areas Around Houses
Rice Fields
The term scrub of
scrub typhus came
from the type of
vegetations (terrain
between woods &
clearings) that harbor
the vectors.
Moist Areas: Swamp & Bog
Chigger’s Habitats
16. ClinicalPresentation– Eschar
…a pathognomonicsign
• Apainless papule occurs at the bite site, later ulcerates, & transforms into
a black crust or ‘eschar’in a variable proportion of patients, the border of
the eschar is surrounded by reddisherythema.
• Difficult tospot in darker individuals; moist intertriginous surfacesmay be
missed if not looked intocarefully
18. Onset:Appears at the end of the 1st week, lasts
3~7days.
Location: Chest, abdomen, whole trunk, or upper
and lower limbs. rarely involves the face, palms
and soles.
Initially rash is in the form of pink, blanching,
discrete maculae which subsequently becomes
maculopapular, petechial or hemorrhagic.
Maculopapular Rash
19. Lymphadenopathy
• Regional lymphadenopathy:
•occurs at the end of the 1st week.
•localize: the draining lymph node around the primary
eschar
•characterized by tenderness and enlargement
• Generalized lymphadenopathy: appears 2-3 days later.
21. ClinicalPresentation- Complications
• More virulent strains of O.tsutsugamushi can cause
Respiratory
• interstitial
pneumonitis
• overwhelming
pneumonia with ARDS
Cardiac
•Toxic myocarditis
Hematological
• Thrombocytopenia
• Pancytopenia
• disseminated
intravascular
coagulation (DIC)
Neuropsychiatric
• Meningitis, Encephalitis
• Cochlear component of 8th nerve
involvement
• Transverse Myelitis
Abdominal
• acute hepatic failure
• acute renal failure
• GI bleeding
• para-aortic, portahepatic and the
splenic hilar lymphadenopathy
22. DDx– “typhus-like illness”
Typhus
(SFG, TG and/or STG)
distinguished only by specific serological tests with
acute and convalescent samples (IFA, IIP, ELISA, RFD) or
PCR assays tests, same treatment for all
Malaria by stained blood films, antigen detection assays
Arbovirus infections
(e.g. dengue, chikungunya)
serological methods (NS1, IgM, IgG assays). Dengue rash
is finer and more erythematous than scrub typhus and
with marked thrombocytopenia
Leptospirosis PCR (full blood) or culture (blood, CSF)
Relapsing fever
(lice or ticks)
demonstration of Borrelia in blood smears, serology or
PCR
Meningococcal disease blood and CSF cultures
Typhoid blood and bone marrow cultures
Viral fevers with macular rash, for example Epstein–Barr virus,
infectious mononucleosis, and primary HIV infection,
distinguished serologically
24. TheProblems faced by us..
• Diagnosis is greatly hampered by the lack of accurate andaccessible
laboratory diagnosis.
• Given the large populations of India and China, the numbers
potentially exposed areenormous.
• With the growth of ecotourism in Asia, more travellers are returning
to non-endemic areas with thisdisease.
25. LABORATORY DIAGNOSIS
Weil-Felix test
ELISA based tests, particularly immunoglobulin M
(IgM) capture assays
Molecular diagnosis byPCR
Indirect ImmunoperoxidaseAssay(IPA)
ImmunofluorescenceAssay(IFA) GOLD STANDARD
26. WEILFELIX TEST
• Sharing of the antigens between rickettsia and proteus is the basis of
this heterophile antibodytest.
• Demonstrates agglutinins to Proteus vulgaris strain OX19,OX2
and Proteus mirabilis OXK..
• Though this test lacks high sensitivity and specificity but still
serves as a useful and inexpensive diagnostic tool for
laboratory diagnosis of rickettsial disease.
• Should be carried out only after 5-7 days of onset of fever.
27. IgM and IgG ELISA
• ELISA techniques, particularly immunoglobulin M (IgM) capture
assays for serum, are probably the most of sensitive tests
available for rickettsial diagnosis.
• In cases of infection with O. tsutsugamushi,
• a significant IgM antibody titre is observed at the end of
1st week,
• IgG antibodies appear at the end of 2nd week.
28. Polymerase ChainReaction (PCR)
• a rapid and specific test for diagnosis, available only at few
centres in India.
• can be used to detect rickettsial DNA in whole blood and
eschar samples.
• P C R is targeted at the gene encoding the major 56 Kda
and/or 47 KdHTRa surface antigen gene.
• The results are best within first week for blood samples
because of presence of rickettsemia in first 7-10 days.
29. Immunufluoroscence Assay(IFA)
• This is a reference serological method for
diagnosis of Rickettsial Diseases
• considered serological ‘gold standard’; however, cost
and requirement of technical expertise limit its wide
use.
• IFA slide presents antigens from only 3 serotypes
namely Karp, Kato and Gilliam
• Therefore, it is recommended only for research
and in areas where sero-prevalence of rickettsial
diseases has been established
30. Immunoperoxidase Assay(IPA)
• is amodification of IFAtechnique that
replaces the fluorochrome with
peroxidase.
• Slide is observed using abright-field
microscope.
• Staining reaction is positive whenO.
tsutsugamushi particles stain light
brown. Control Infected
31. Supportive laboratoryInvestigations
• ChestX-Rayshowing infiltrates, mostly
bilateral
• WBCcount may become elevated tomore
than 11,000 / cu. mm.
• Thrombocytopenia (i.e. <1,00,000/ cu.mm)is
seenin majority ofpatients.
Before admission
• RaisedTransaminaselevels are commonly
observed
After treatment
32. Suspected/Clinical case
• Acute undifferentiated febrile illness of 5 days or more
with or without eschar – suspect Rickettsial infection.
• If eschar is present, fever of less than 5 days duration should
be considered as scrub typhus.
• Other presenting features: headache and rash,
lymphadenopathy, multi-organ involvement like liver, lung and
kidney involvement.
33. Probablecase
Points to consider as positive for typhus and spotted fever
groups of Rickettsiae.
A suspected clinical case
titres of 1:80 or above in OX2, OX19 and OXK
antigens by Weil Felix test
optical density (OD) > 0.5 for IgM by ELISA
34. TREATMENT
• Without waiting for laboratory confirmation of the Rickettsial
infection, antibiotic therapy should be instituted when
rickettsial disease is suspected.
• Preantibiotic era -- Mortality was variable.
• Antibiotic therapy brings about prompt disappearance of the
fever and dramatic clinical improvement.
35. Primary Health CentreLevel
• Lesssevere cases.....
ADULT CHILDREN IN PREGNANCY
Doxycycline 200 mg/day in
two divided doses for 7
days
Or
Azithromycin 500 mg in a
single oral dose for 5
days.
Doxycycline 4.5 mg/kg
body weight/day in two
divided doses for 7 days
Or
Azithromycin 10mg/kg body
weight in a single oral dose
for 5 days.
Azithromycin 500 mg in a
single oral dose for 5
days.
36. Primary Health CentreLevel
If presents with Complications
• Refer to secondary or tertiary centre - ARDS, acute renal
failure, meningo encephalitis, multi-organ dysfunction.
• Doxycycline should be initiated before referring the patient.
• In addition to recommended management of community
acquired pneumonia, Doxycycline is to be initiated
whenscrub typhus is considered likely.
37. Secondary and Tertiary Care
I.V Doxycycline
• (wherever available) 100mg twice daily in 100 ml normal saline to be
administered as infusion over half an hour initially followed by oral
therapy to complete 7-15 days of therapy.
I.V Azithromycin
• in the dose of 500mg IV in 250 ml normal saline over 1 hour once daily
for 1-2 days followed by oral therapy to complete 5 days of therapy.
I.V Chloramphenicol
• 50-100 mg/kg/d 6 hourly doses to be administered as infusion over 1
hour initially followed by oral therapy to complete 7-15 days of
therapy.
38. Prophylaxis
• Recommended under special circumstances where disease is
endemic.
• Oral chloramphenicol or tetracycline given once every 5
days for thirty-five days or weekly doses of doxycycline during
and for 6 weeks after exposure have both been shown to be
effective regimens.
• Resistance to antibiotics has been noted in several areas,
therefore prophylaxis with antibiotics cannot be guaranteed.
39. Vaccine against scrub typhus?
• There is enormous antigenic variation in Orientia
tsutsugamushi strains, and immunity to one strain does
not confer immunity to another…
• A vaccine developed for one locality may not be protective in
another locality, because of antigenic variation.
• This complexity continues to hamper efforts to produce a
viable vaccine against O.tsutsugamushi.
40. PREVENTION
• Protective clothing.
• Insect repellents containing dibutyl phthalate, benzyl
benzoate, diethyl toluamide etc applied to the skin and
clothing to prevent chigger bites.
• Do not sit or lie on bare ground or grass.
• Clearing of vegetation and chemical treatment of the soil may
help to break up the cycle of transmission from chiggers to
humans to other chiggers.
42. Public
Education
Take home message:-
Scrub typhus is a re-emerging disease in India.
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.
Failure of early diagnosis is associated with significant mortality and morbidity and also leads to
expensive PUO workup.
Search for an eschar in hidden areas of body.
Screening by Weil-Felix & Diagnosis is done by IgM scrub typhus ELISA
Drug of choice - - - - Doxycycline.
43. REFERENCES-
Public
Education
•PARK’S TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE
-23RD EDITION
•COMMUNITY MEDICINE WITH RECENT ADVANCES
-BY A.H.SURYAKANTHA ; 4TH EDITION
•HARRISON’S MANNUAL OF INTERNAL MEDICINE -19TH EDITION
•DAVIDSON’S PRINCIPLES AND PRACTICE OF MEDICINE-21ST EDITION
•WIKIPEDIA AND GOOGLE FOR WEB REFERENCES
