Scrub typhus explained in an easy to understand manner

1. SCRUB TYPHUS
SPEAKER: SREETAMA CHOWDHURY
CHAIRPERSON: Prof. G.C.DAS

2. GLOBAL BURDEN OF SCRUB TYPHUS :
• First reported from Japan in 1899.
• In 1999 WHO stated that ‘’scrub typhus’’ is probably one of the most under
diagnosed and under reported febrile illness.
• One million case of scrub typhus occur each year with an estimated fatality
of 10%.

3. GEOGRAPHICAL DISTRIBUTION OF SCRUB TYPHUS
• 8 million km sq area
• Extends from Russia
in the north,
Afghanistan in the
west, Japan in the
east, Australia in the
south.

4. SCENARIO OF SCRUB TYPHUS IN INDIA
• First recognised as a typhus like fever
in 1917.
• Predominant amongst the military
personnel of the Assam-Myanmar
border during the World war II and the
1965 Indo-Pak war.
• Peak incidence: August to October
• Vector: Leptotrombidium delicense
• Seroprevalence:31.8 % (Shivalli et al)

5. CLASSIFICATION AND MODE OF TRANSMISSION
• Obligate intracellular bacteria under Alphaproteobacteriae
• Transmitted by vector mites(chiggers) under family Tromboculidae
• Host: wild rats of subgenus Rattus, accidental hosts- humans
• Serotypes : Boryan, Gillian, Karp, Kato, Kawazaki

6. LIFE CYCLE OF A TROMBICULID

7. PATHOPHYSIOLOGY OF SCRUB TYPHUS
• Hallmark : Disseminated vasculitis with perivasculitis
• Involvement of brain and lungs can cause fatal outcome
• O.tsutsugamushi infects endothelial cells of all organs with infected macrophages and
cardiac myocytes
• Type 1 immune response  upregulation of IFN-alpha, IL-15, IL-18.
TNF-alpha, IL- 1b, IL-6 upregulate CAMs on leucocyte and host endothelial cells
 leucocyte transmigration
• Endothelial recruitment of lymphocyte and neutrophil from eschar  Dissemination by
increased vascular permeability / hematogenous spread/ circulation of pre-apoptotic
endothelial cells.
• Increased expression of sL-selectin reflects homing potential of lymphocytes to
peripheral LN.

8. HISTOPATHOLOGICAL PICTURE
HPE of eschar showing vasculitis with perivasculitis and infiltration with inflammatory cells and
macrophages

9. PRESENTING MANIFESTATIONS
• Fever : Abrupt onset, high grade with headache, myalgia and arthralgia
• Maculopapular rash (35-43% cases)
• Eschar: Painless, non-pruritic crusty necrotic lesion, with/without erythematous halo.
Maybe associated with regional lymphadenopathy. (7-97% cases)
• Hepatosplenomegaly and lymphadenopathy
• Periorbital or pedal edema/ Conjunctival hyperaemia

10. SYSTEMIC MANIFESTATIONS AND COMPLICATIONS
• CNS: Aseptic meningitis, Meningoencephalitis (14-83%) , AES
• Gastrointestinal : Vomiting, Nausea, Diarrhoea, Abdominal pain
• Pneumonia and ARDS
• Acute Renal Failure
• Complications: Shock(4-44%),Respiratory distress(36%),DIC, ARDS(12%), HLH,
purpura fulminans, gangrene, myocarditis

11. CASE DEFINITION:
• Suspected case:A patient having compatible clinical scenario, suggestive epidemiological
features and absence of definite alternative.
Compatible scenario:
1. Undifferentiated fever > 5 days
2. Sepsis of unknown etiology
3. Fever with rash
4. Fever with oedema
5. Dengue like disease
6. Fever with headache and myalgia
7. Fever with hepatosplenomegaly and/or lymphadenopathy
8. Aseptic meningitis / Meningoencephalitis/ AES
9. Fever with cough and pulmonary infiltrate or community acquired pneumonia
10. Fever with AKI
11. Fever with acute GI or hepatic involvement

12.  Suggestive epidemiological features:
One or more of the following within 14 days of the illness
1.Tick bite
2.Ticks on clothes or near homes or around playgrounds
3.Visit to an area which can serve as a habitat for ticks
4.Animal sheds in the proximity of the house
5.Contact with pet dogs infected with ticks
6. Visit to another geographical area endemic for rickettsial disease
7.Occurrence of similar illness simultaneously or sequentially in family
8.Exposure to rodents

13. Continued…
• Probable case : Suspected case having either eschar OR rapid (<48 hrs) defervescence
with anti-rickettsial therapy OR with suggestive laboratory features OR weil-felix test
positive with a titre > 1:80 OR a positive IgM ELISA for rickettsia ( OD >0.5)
• SUGGESTIVE LABORATORY FEATURES:
1. Normal to low TLC in the early stages with shift to left and later leucocytosis
2. Thrombocytopenia
3. Raised ESR and CRP
4. Hyponatremia
5. Elevated hepatic transaminases
6. Hypoalbuminemia
• Confirmed case: Suspected case having rickettsial DNA detected in whole blood or tissue
samples OR fourfold rise in antibody titres on acute and convalescent sera detected by
immunofluorescence assay (IFA) or immunoperoxidase assay (IPA).

15. DIFFERENTIAL DIAGNOSES
• Viral diseases : Enterovirus, Measles, Dengue, Chikunguniya, IM
• Bacterial diseases : Meningococcemia, Leptospirosis, Typhoid, Scarlet fever, Infective
endocarditis
• Protozoal : Malaria
• Vasculitis : Kawasaki disease, TTP
• Adverse drug reactions

16. LABORATORY INVESTIGATIONS FOR DIAGNOSES
• Collection of blood sample : To be dispatched immediately to lab at 2-8 degree celcius
temperature OR stored at 4 degrees. NO FREEZING.
• Isolation of virus : In BSL-3 level lab by 1. Embryonated chicken yolk sac culture
2. Cell culture : I.929 mouse fibroblast monoculture
3. Shell vial culture
• Serological Tests : 1. Weil Felix test
2.Complement Fixation test
3. Indirect Hemagglutination test
4. IgM and IgG ELISA
5. Immunoflourescence Assay
6. Immunoperoxidase Assay

17. IMAGING IN THE DIAGNOSIS OF SCRUB TYPHUS
Peribronchial
cuffing
Ground
glass
opacity
Ground
glass
opacity
Most common finding: Reticulonodular infiltrates and septal lines
Others: U/L or B/L hilar enlargement, ground glass opacity, rarely pleural effusion

18. USG Abdomen
GB wall
thickening and
Gb distension

19. CT ABDOMEN
Periportal areas of low
attenuation in liver
Common findings:
• Periportal areas of low
attenuation in the liver
• GB wall thickening
• Pericholecystic oedema
• Splenomegaly
• Splenic infarcts
• Lymphadenopathy
• Hepatic congestion and
periportal inflammation
Reduction in venous
flow,compression of portal
vein and peribiliary plexus
dilatation and increased
arterial flow
inhomogenous early phase
enhancement

20. CLINICAL PROFILE OF SCRUB TYPHUS IN INDIA

24. MANAGEMENT
IAP and ICMR guidelines:
Treatment should be instituted empirically in suspected cases without waiting for lab
confirmation.
 At PHC levels:
• Recognition of disease severity by physician and starting doxycycline before referral if
scrub typhus is suspected
• Referral to a higher centre in case of complications like ARDS, ARF, AES , MODS
• Starting drugs empirically in fever > 5 days when malaria and typhoid have been ruled
out
• Drugs : Oral doxycycline at 200 mg divided bd for people > 45 kg for 7 days or 4.5
mg/kg/day divided bd in children < 45 kg
OR
Oral Azithromycin 500 mg for 5 days or 10 mg/kg/day for 5 days OD

25. MANAGEMENT Continued….
 At secondary and tertiary care levels:
• Previous drug regimen in uncomplicated cases
• In complicated cases:
Inj Doxycycline 100 mg twice daily or 4.4 mg/kg/day bid in 100 ml NS infused over half an
hour initially for few days followed by oral therapy to complete 7 to 15 days of therapy
(ICMR) / for atleast 3 days after subsidence of fever to 7-10 days (IAP)
OR
Inj Azithromycin 500 mg iv or 10 mg/kg/day in 250 ml NS infused OD over 1 hour for 5 days
OR
Inj Chloramphenicol 50-100 mg/kg/day 6 hourly as infusion over 1 hour to complete 7-10
days of therapy.

26. POOR PROGNOSTIC FACTORS
 Younger age
 Short incubation period
 Sulphonamide therapy
 G6PD deficiency
 Absence of rash
 Diabetes mellitus
 Late institution of therapy

27. PREVENTION
• Vector control : 1. Control of rodents
2. Cutting and burning vegetations
3. Heavy spraying of insecticides like lindane
• Prevention of vector bites:1. Avoding areas infested with ticks
2. Wearing closed toe shoes and light coloured clothes (for tick
visibility)
3. Usage of permethrin based repellent on skin
4. Usage of 20-50 % DEET (N,N-diethyl-m-toluamide) on clothes
5. Hot water washing and hot drying of clothes to kill ticks
6. Pets should be periodically de-ticked and allowed tick collars
7. Regular tick checks
8. Prompt removal of attached ticks with tweezers and incineration
and cleaning affected area with soap-water/ iodine wash

28. PRE-EXPOSURE CHEMOPROPHYLLAXIS
• Recommended for high risk, short period exposure
• Use of Doxycycline 6 weeks before and after exposure ( IAP)
• Oral tetracycline (not in children ) or chloramphenicol can also be given once in 5 days
for 35 days

29. SCRUB TYPHUS VACCINES
 Several fruitless attempts to formulate vaccine since the British era like Formalin killed
Karp and Volner human trials, inactivated karp mouse trial (killed) , live vaccine trails
and irradiated vaccine trial ( WRAIR trial )
 Currently subunit trials are in practice:
 47 kd and 56 kd surface antigens used ( Sta- 47 and Sta- 56 respectively )
 47 kd prot found on OMP of O.tsutsugamushi, has strain specific and group reactive
epitopes
 56 kd plays a role in inciting CMI against O.tsutsugamushi and internalising it in host
cells
 Sta 47- 56 fusion product is looked upon as a suitable candidate for vaccine preparation

30. TAKE HOME MESSAGE
• Scrub typhus is one of the most under reported febrile illness in India
• The clinic-epidemiological profile is widely varied and necessitates further research
• A high index of clinical suspicion, prompt diagnosis and early institution of drug
therapy is necessary for prevention of mortality and morbidity
• Further prospects of research lie in formulating vaccines, preparation of proper and
rapid diagnostic kits and development of a robust surveillance and reporting system.

31. THANK YOU