Scrub typhus

SCRUB TYPHUS

1. Dr.Kumar Himanshu PGT-2 nd Year Department Of Community Medicine Katihar Medical College,Katihar

2. Scheme of Presentation Introduction Historical Perspective Epidemiology & Indian Scenario Pathogenesis Clinical features & Complications Approach to the Disease Management Prevention & Control

3. SCRUB TYPHUS - Introduction A lso known as - Japanese river fever known in Japanese folk to be associated with the jungle mite or chigger, termed ‘tsutsugamushi’ in Japanese . ( tsutsuga = disease,harm, noxious and mushi = bug ) is a zoonosis, with humans being accidental, dead end hosts .

4. Historical Perspective Rickettsial infection has been one of the great scourges of mankind, occurring in devastating epidemics during times of war and famine. Hippocrates in 460 bc used the term typhus , meaning ‘smoke’, to describe the ‘confused state of the intellect – a tendency to stupor’ associated with high fevers.

5. Napoleon’s retreat from Moscow was forced by rickettsial disease breaking out among his troops . Lenin is said to have remarked, in reference to rickettsial disease during Russian revolution,“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 Viet n am conflict .

7. The Rickettsial diseases Modern classification based on whole-genome analysis… T yp h us Group Epidemic Typhus - R.prowazek i i Endemic Typhus Scrub Typhus R.typhi O.tsutsugamushi Spot t ed F ever Gr o up O t h ers Indian tick typhus - R.conorii Rocky Mountain spotted fever – R.ricketsii Rickettsial pox - R.akari etc Q Fever - C oxiella brunetti Trench Fever - Rochalimaea Quintana

8. TsuTsugamushi Triangle South and Southeast Asia, the Asian Pacific rim, Northern Australia Geographic Distribution

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 u derdiagnosed (suspected ) cause of undifferentiated fever.

10. A g e n t of Scrub Typhus B u ddin g of O . ts u ts uga m u s h i on the cellular su rfa c e G ram-negative , rod-shaped (cocco-bacillus) bacterium Orientia (Rickettsia) tsutsugamushi. wide phenotypic and genotypic diversity 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 lacks lipopolysaccharide and peptidoglycan and does not have an outer slime layer

11. Vector - Primary Reservoir 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. 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

14. Incubation Period 7–21 days ( mean, 10–12 days)

15. Clinical Presentation – Eschar … a pathognomonic sign A painless 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 reddish erythema. Difficult to spot in darker individuals; moist intertriginous surfaces may be missed if not looked into carefully

16. Clinical Presentation -Eschars

17. 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

18. 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.

19. Clinical Features

20. Clinical Presentation - Complications More virulent strains of O. tsutsugamushi can cause Respiratory interstitial p ne um o nitis overwhelming pneumonia with ARDS Cardiac Toxic myocarditis Hematological Thrombocytopenia Pancytopenia disseminated intravascular coagulation ( DIC ) Neuropsychiatric Meningitis, Encephalitis Cochlear component of 8 th nerve involvement Transverse Myelitis Abdominal acute hepatic failure acute renal failure GI bleeding para-aortic, portahepatic and the splenic hilar lymphadenopathy

21. DD x – “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

22. APPROACH GUIDELINES

23. The Problems faced by us.. Diagnosis is greatly hampered by the lack of accurate and accessible laboratory diagnosis. Given the large populations of India and China, the numbers potentially exposed are enormous . With the growth of ecotourism in Asia, more travellers are returning to non-endemic areas with this disease.

24. LABORATORY DIAGNOSIS Weil-Felix test ELISA based tests, particularly immunoglobulin M (IgM) capture assays Molecular diagnosis by PCR Indirect Immunoperoxidase Assay ( IPA ) Immunofluorescence Assay (IFA) GOLD STANDARD

25. WEIL FELIX TEST Sharing of the antigens between rickettsia and proteus is the basis of this heterophile antibody test. Demonstrates agglutinins to Proteus vulgaris strain OX19 , OX 2 and Proteus mirabilis OX K . . 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.

26. 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.

27. Polymerase Chain Reaction (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.

28. 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

29. Immunoperoxidase Assay (IPA) is a modification of IFA technique that replaces the fluorochrome with peroxidase. Slide is observed using a bright-field microscope. Staining reaction is positive when O. tsutsugamushi particles stain light brown. Control Infected

30. Supportive laboratory Investigations Chest X-Ray showing infiltrates, mostly bilateral WBC count may become elevated to more than 11,000 / cu. mm. Thrombocytopenia (i.e. < 1,00,000/ cu.mm) is seen in majority of patients. Before admission Raised Transaminase levels are commonly observed After treatment

31. 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, ly mphadenopathy, multi-organ involvement like liver, lung and kidney involvement .

32. Probable case 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

33. 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.

34. Primary Health Centre Level Less severe cases..... A D U L T CH I L D REN IN PREGNA N CY 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.

35. Primary Health Centre Level 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.

36. 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.

37. P r op h yl a xis 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.

38. Vaccine against scrub typhus? T here 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 .

39. 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.

40. CONTROL STRATEGY Public Educati o n Rodent Control Habitat Modi f ic a t i on Case I dentif i c a ti o n & T r e at m ent

41. Public Educati o n 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 .

42. REFERENCES- Public Educati o n PARK’S TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE -23 RD EDITION COMMUNITY MEDICINE WITH RECENT ADVANCES BY A.H.SURYAKANTHA ; 4 TH EDITION HARRISON’S MANNUAL OF INTERNAL MEDICINE -19 TH EDITION Davidson’s principles and practice of medicine-21 st Edition Wikipedia and google for web references

43. Public Educati o n

44. Public Educati o n