The document discusses scrub typhus, a common rickettsial disease seen in India. It is caused by the bacteria Orientia tsutsugamushi and transmitted by the bites of larval trombiculid mites. Symptoms include fever, rash, and often a characteristic eschar at the bite site. Complications can include pneumonia, meningitis, and multi-organ failure. Diagnosis is made through serology, PCR, or culture. Doxycycline is the treatment of choice, with azithromycin as an alternative, especially in pregnant women and children. Managing complications may require intravenous antibiotics in hospital. Scrub typhus has reemerged as an important cause of febrile

1. Presenter : Dr. Dhileeban Maharajan
Moderator : Dr. Salam Ranabir

2.  Most common re-emerging diseases in India
 Documented in India since 1930
 First reported in Assam during second world war
 Scrub is the commonest Rickettsioses
 *50% of undifferentiated fever due to Rickettsioses (*Selected Areas)

3.  Obligate intracellular, gram-negative bacteria
 Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and
Anaplasma
 Divided into typhus group and spotted fever group
 Orientia spp. makes up the scrub typhus group
 Zoonoses where human beings are accidentally involved

5.  Among the major groups of
rickettsioses, commonly reported
diseases in India are
 scrub typhus
 murine flea-borne typhus
 Indian Tick Typhus
 Q fever.

6.  Among Rickettsioses, scrub is the commonest
 Mite borne infectious disease
 Orientia tsutsugamushi
 Transmitted through Larval mites or “chiggers”
 Belonging to family Trombiculidae
 Only larval stages take blood meal

7.  Rodents (wild rats - Rattus) - Natural hosts for scrub typhus
 Field rodent and vector mites act as reservoir
 Between the two the infection perpetuates in nature
 Mite islands
 Chiggers, too small to be seen by the naked eye,
 Feed usually on rodents and accidentally on humans

8.  Transmit infection during the prolonged feeding which can last
1-3 days
 Incidence of scrub typhus is higher among rural population

9.  Obligate intracellular pathogens
 Rod shaped bacterium.
 Can be cultured in cell monolayers.
 Gram Staining - appear as gram negative bacteria.
 Highly virulent - need biosafety level 3 facilities
 Exhibit extensive genomic and antigenic heterogeneity
(Orientia tstsugamushi)

10.  Found throughout the mites body but
greatest number in salivary glands.
 Does not have a vacuolar membrane -
grows freely in the cytoplasm of infected
cells
 Needs to infect eukaryotic cells in order to
multiply
Serotypes
1. Karp
2. Gilliam
3. Kawazaki
4. Boryon
5. Kato

11.  First described in China in 313 AD
 First isolated in Japan in 1930
 Asia Pacific Rim
 2/3 are Farmers
 Highest in 40 to 60 years
 80% during summer and autumn
Tsutsugamushi Triangle
Regions where scrub
typhus is endemic

12.  60 species of mites
 Chigger mites (0.2 to 0.4mm)
 Both Vector and Reservoir
 Transovarial transmission
 Transstadial transmission
(Larval trombiculid mites - Chiggers)

15. Chigger Bite
Bacteria multiply at
Innoculation site
Attach to
Endothelial cells
Stimulate Phagocytosis
Escapes Phagosomes
Replicate in cytoplasm
Disseminate into multiple organs
(Through endothelial cells and macrophages)
Type 1 immune
response
Papule
Ulcer
Necrosis
Eschar
+
Lymphadenopathy
Cytokines

16.  Geographically focal disease
 Mite islands

17.  Incubation period of 6–21 days
 Mild and self-limiting to fatal.
 Scrub typhus lasts for 14 to 21 days without treatment.
 Death may occur end of 2nd week due to complications.

19.  Common symptoms
 Fever (High Grade > 104 F; Median 14.4 days)
 Intense Generalized Headache
 Diffuse myalgias
 Nausea, Vomiting, Diarrhea
 Cough

20.  Maculopapular rash
 Blood-shot eyes
 Papule followed by an eschar at the
site of chigger feeding

21.  50% Develop Rash
 Nonpruritic
 Macular or maculopapular rash
 Face also involved
 Begins in the abdomen and spreads to extremities

22.  Only in 46% (5 to 80%) patients
 1 cm in size
 Painless papule at chigger bite site
 Central necrosis
 Then characteristic black crust
 One or multiple eschars may develop

24.  Relative bradycardia
 Lymphadenopathy - Tender lymph node, usually proximal to
site of mite bite
 • Hepatomegaly and splenomegaly can be observed

25. Respiratory-
 Cough
 Acute Respiratory Distress Syndrome
 Pathogenesis of ARDS in scrub typhus not known, thought to be
immunological response of the lung to the infection without
direct invasion of the organism
 Diffuse alveolar damage without evidence of vasculitis.

26. Neurological
• Involvement of blood vessels in the central nervous
system may produce meningitis
• slight intellectual blunting to coma or delirium
• In severe cases, evolution to a multiple-organ dysfunction
syndrome with hemorrhage can be observed

27.  Overwhelming pneumonia with ARDS–like presentation
 Acute Kidney Injury
 Atypical pneumonia,
 Myocarditis, Congestive heart failure
 Pulmonary edema
 Circulatory collapse
 Disseminated intravascular coagulation (DIC).

28.  Some patient recover spontaneously.
 Case-fatality rate for untreated classic cases is 70%
(the fatality rate ranges from 0 to 30%.)

29.  No laboratory test is reliable in early phase
 Usually recognized with symptoms signs laboratory
features with epidemiological clues

30. 1. Immunofluorescence and immunoperoxydase assays
2. Rapid immunochromatographic Flow Assay (RFA)
3. Dot blot immunoassay
4. The Weil-Felix test
5. Orientia tsutsugamushi can be cultivated on L929 cells.
6. ELISA
7. PCR (Polymerase Chain Reaction)
8. Sequencing of the 56-kDa protein gene

31.  Sharing of antigens between rickettsia and proteus is the basis
 Agglutinins to P.vulgaris strain OX19, OX2 and P.mirabilis OXK.
 Lacks sensitivity
 Serves as a useful and inexpensive diagnostic tool
 Should be carried out only after 5-7 days of onset of fever.
 Titre of 1:80 to be considered possible infection.

32.  Immunoglobulin M (IgM) capture assays for serum, are probably the
most of sensitive tests available for rickettsial diagnosis
 Presence of IgM antibodies, indicate comparatively recent infection
 Significant IgM antibody titre is observed at the end of 1st week
 IgG antibodies appear at the end of 2nd week.
 The cut off value is Optical Density of 0.5.

33.  Rapid and specific test for diagnosis.
 Can be used to detect rickettsial DNA in whole blood and eschar
samples.
 PCR is targeted at the gene encoding the major 56 Kda and/or 47
Kda surface antigen gene.
 The results are best within first week for blood samples because
of presence of rickettsemia in first 7-10 days.

34.  This is a reference serological method and considered
serological ‘gold standard’
 Cost and requirement of expertise limit its wide use.
 Recommended only for research and in areas where sero-
prevalence is high

35.  It gives comparable result as IFA but requires special
instrument and experienced personnel for interpretation of
the test.

36.  Thrombocytopenia in severe illness
 Elevation in hepatic enzymes
 Leukopenia or leukocytosis
 Infiltrates in chest X-ray (Mostly bilateral)

37.  Malaria and dengue
 Leptospirosis
 Other rickettsial diseases
 Typhoid fever
 Anthrax
 Spider bite

38. Definition of Suspected/clinical case:
 Acute undifferentiated febrile illness of 5 days or more with or
without eschar should be suspected as a case of Rickettsial
infection.
 If eschar is present, fever of less than 5 days duration should be
considered as scrub typhus.
 Other presenting features may be headache and rash,
lymphadenopathy, multi-organ involvement like liver, lung and
kidney involvement.
 Dengue, malaria, pneumonia, leptospirosis and typhoid – D/D

39. Definition of Probable case:
 A suspected clinical case showing titres of 1:80 or above in OX2,
OX19 and OXK antigens by Weil Felix test
 An optical density (OD) > 0.5 for IgM by ELISA
 Considered positive for typhus and spotted fever groups of
Rickettsiae.

40. Definition of Confirmed case:
 Rickettsial DNA is detected in eschar samples or whole blood by
PCR
 Rising antibody titers on acute and convalescent sera detected
by Indirect Immune Fluorescence Assay (IFA) or Indirect
Immunoperoxidase Assay (IPA)

41.  Paucity of evidence based on randomized controlled trials for
the management of Scrub typhus
 Without waiting for laboratory confirmation of the Rickettsial
infection, antibiotic therapy should be instituted when rickettsial
disease is suspected

42. At Primary level:
 Recognition of disease severity. Patients comes with
complications, considers it as rickettsial infection, treatment
with doxycycline should be initiated before referring.
 Referral to secondary or tertiary centre in case of complications
like ARDS, acute renal failure, meningo-encephalitis, multi-organ
dysfunction.

43.  Community acquired pneumonia, doxycycline is to be initiated
when scrub typhus is considered likely.
 In fever cases , duration of 5 days or more where malaria, dengue
and typhoid have been ruled out Doxy should be started

44. Adults
 Doxycycline 200 mg/day in two divided doses for individuals
above 45 kg for duration of 7 days.
(Patients should be advised to swallow capsules with
plenty of fluid during meals while sitting or standing)
 Azithromycin 500 mg in a single oral dose for 5 days.

45. Children
 Doxycycline in the dose of 4.5 mg/kg body weight/day in two
divided doses for children below 45 kg
 Azithromycin in the single dose of 10mg/kg body weight for 5
days.

46. Pregnant women
 Azithromycin is the drug of choice in pregnant women, as
doxycycline is contraindicated
 Azithromycin 500 mg in a single dose for 5 days.
During pregnancy, scrub typhus may lead to spontaneous
abortion, stillbirth, preterm delivery and small for gestational
age infants

47. Secondary and Tertiary care:
 The treatment as specified above in uncomplicated cases.
 In complicated cases the following treatment is to be initiated –
 i) Intravenous 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.

48.  Intravenous 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.
 Intravenous 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.

49.  Management of the individual complications should be done as
per the existing practices
 Doxycycline and/or Chloramphenicol resistant strains have
been seen in South-East Asia.
(These strains are sensitive to Azithromycin)

50.  In endemic areas, wear full-length clothing, socks and shoes.
Avoid walking barefoot.
 Apply, as necessary, insect repellents containing dibutyl
phthalate, benzyl benzoate, diethyltoluamide, and other
substances to the skin and clothing to prevent chigger bites.
 Do not sit or lie on bare ground or grass; use a suitable
groundsheet or other ground cover.

51. Community
 Rapid case identification by health-care workers.
 Public education on case recognition and personal protection
 Rodent control and improve living conditions

52.  Recommended for short period, high- risk exposure.
 Weekly doxycycline started before and for 6 weeks after
exposure is recommended.
 No vaccine is available for scrub typhus

53.  Research and development should focus on following issues:
 (i) Vaccines for rickettsial diseases
 (ii) Rapid diagnostic card test combining antigen and antibody
 (iii) Intravenous preparation of doxycycline
 (iv) Robust surveillance and reporting system.

54.  Scrub typhus is a re-emerging disease in India.
 Important cause of community acquired undifferentiated febrile illness
 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.