Editorial

Diagnosis and Treatment of Scrub Typhus –

The Indian Scenario
AR Chogle

S crub Typhus, or tsutsugamushi disease is a febrile illness

caused by bacteria of the family Rickettsiaceae and
named Orientia tsutsugamushi. Scrub typhus is endemic to
specific, and this technique can be reliable for confirming the
diagnosis of scrub typhus. Also immunohistochemical staining
performed on skin lesions within 3 or 4 days of administration
a geographically distinct region, the so-called tsutsugamushi of antibiotics that are effective for Rickettsia, did not greatly
triangle, which includes Japan, Taiwan, China, and South influence diagnostic sensitivity.15
Korea.1 It also occurs in Nepal, Northern Pakistan, Papua New The diagnosis of a rickettsial illness has most often been
Guinea, and the Australian states of Queensland and Northern confirmed by serologic testing. The specific gold standard
New South Wales. 2 In India, the disease had occurred among techniques like the immunofluorescence antibody test (IFA), the
troops during World War II in Assam and West Bengal, and in indirect imunoperoxidase (IP) test, ELISA are not available in
the 1965 Indo-Pak war. There was a resurgence of the disease our country and the isolation of the organisms in animals or cell
in 1990 in a unit of an army deployed at the Pakistan border of culture is limited by the lack of containment facility as well as the
India.3 It is known to occur all over India, including Southern lack of expertise in handling these high risk group pathogens.16
India 4 and Northern India. 5 However, the reported number Many report of scrub typhus and other rickettsial diseases from
of cases of Scrub typhus from different parts of the country the Indian sub-continent are based on clinical findings and the
particularly from large tertiary care hospitals do not give a true relatively non-specific Weil-Felix test including the study by
picture of prevalence of scrub typhus in the country. As yet Vivekanandan M and co-workers.7
there are not many community based studies in our country.
Weil-Felix test has shown reasonably high specificity but a low
One such community based study involving several districts in
sensitivity for the diagnosis of Rocky mountain spotted fever,
Tamil Nadu showed that scrub typhus and rickettsial diseases
Mediterranean boutonneuse fever, murine typhus, epidemic
were widely distributed in the state.6
typhus and scrub typhus.16 Although a good correlation between
In this context the report of outbreak of scrub typhus the results of the Weil-Felix test and detection of IgM antibodies
in Pondicherry and in the current issue of the Journal 7 is by an IFA is often observed, with the development of techniques
meaningful. In this report the diverse clinical and laboratory that are used to grow rickettsiae, this test should be used only as
manifestations of scrub typhus are described. The diagnosis a first line of testing in rudimentary hospital laboratories. In spite
was based on the presence of eschar and/or positive Weil Felix of all the drawbacks associated with it, the Weil Felix test still
test with a titre of > 1:80. serves as a useful and cheapest available tool for the laboratory
In scrub typhus, an eschar approximately 5 to 20 mm in diagnosis of rickettsial diseases. A four-fold rise in agglutinin
diameter is formed at the site bitten by trombiculid mites, and titres in paired sera is diagnostic for infection with these febrile
this may be considered the most important clinical finding for the agents. However, with a single serum sample available, the
diagnosis of scrub typhus. The site bitten by chiggers is initially test is suggestive of infection only at a high cut-off titre (> 1 :
a papule followed by a blistered ulcer, and this is then covered 320) at which the positive predictive value and the specificity is
with a black crust; the border of the eschar is surrounded by reliable.16 Recently, commercial rapid detection kits like Dip-S-
reddish erythema. Such a typical eschar is formed at the time Ticks, scrub typhus RCT and scrub typhus IgM and IgG Rapid
when symptoms are manifested.8 Immunochromatographic Assay (PanBio, Brisbane, Australia)
In the past, the clinical diagnosis of scrub typhus was and Multies Dip-S-Ticks Scrub Recombinant Assay (Integrated
dependent on detecting eschar and rash and on the history Diagnostics, Baltimore, Maryland, USA) have appeared in the
of outdoor activity. 8-10 Nevertheless, under actual clinical market but are still far from the reach of most of the developing
conditions, only eschar without rash may be seen in some cases. countries due to their high cost.16
As was shown in one previous case report, for febrile patients Serious complications of scrub typhus are not uncommon
showing a lesion similar to eschar, distinguishing whether and may be fatal; they include pneumonia, myocarditis,
such an eschar-like lesion is actually a simple crust or eschar is meningoencephalitis, acute renal failure and gastrointestinal
required.11 Furthermore, eschars are also detected in rickettsial bleeding. Early diagnosis is important because there is usually an
pox, cutaneous anthrax, and other diseases, and travel and other excellent response to treatment and timely anti-microbial therapy
population migrations are currently often occurring. Scrub may help prevent complications. In developing countries with
typhus has been reported in Western countries. 12,13 Recently it limited diagnostic facilities, it is prudent to recommend empiric
has been shown that patients’ eschars can be used for detection therapy in patients with undifferentiated febrile illness having
and genetic characterization of Orientia tsutsugamushi during evidence of multiple system involvement. A clinical algorithm
the convalescent phase.14 Immunohistochemical staining of skin has been proposed for diagnosis of scrub typhus among patients
biopsy specimens, particularly that of eschars, is sensitive and hospitalized with febrile illness and to determine predictors
Hon.Physician, Kasturba Hospital for Infectious Diseases, Mumbai of bad prognosis. If a combination of elevated transamines,
400 008; Consultant Physician, Sir H.N.Hospital & Research Centre, thrombocytopenia and leukocytosis is used, the specificity
Mumbai 400 004. and positive predictive value for diagnosis of scrub typhus are

© JAPI • january 2010 • VOL. 58 11

about 80%.17 Regarding ancillary investigations in scrub typhus continued presence of human rickettsioses in southern India.
patients with multiorgan involvement, CT Scan findings of both Annals of Tropical Medicine and Parasitology 2001; 95 : 395-98.
chest and abdomen have been described in detail. Although these 5. Sharma A, Mahajan S, Gupta ML, Kanga A and Sharma V.
findings are non-specific they may facilitate accurate diagnosis.18 Investigation of an Outbreak of Scrub Typhus in the Himalayan
Region of India. Jpn J Infect Dis. 2005; 58 : 208-10.
A recent Cochrane review, on antibiotics for scrub typhus
prepared and published in Cochrane library 19 has made the 6. Kamarasu K, Mathan M. Rajagopal V, Subramaniam K et al.
Serological evidence for wide distribution of spotted fevers and
following observations :
scrub typhus fever in Tamil Nadu. Indian J Med Res 2007; 126 :
1. At present there is insufficient evidence from trials of 128-30.
comparative effects of different broad spectrum antibiotics 7. Vivekanandan M, Mani A, Priya YS, Singh AP, Jayakumar S, Purty
in scrub typhus. S. Out Break of Scrub Typhus in Pondicherry. J Assoc Physician
2. Doxycycline and tetracycline are similar drugs, both have India 2009; 57 : 802-806.
been used to treat this condition and both appeared to cure 8. Berman SJ, Kundin WD. Scrub typhus in South Vietnam : a study
the small number of patients studied. of 87 cases. Ann Intern Med. 1973; 79 : 26-30.

3. Rifampicin is seen to be more effective than doxycycline 9. Sayen JJ, Pond HS, Forrester JS , et al. Scrub typhus in Assam and
Burma : clinical study of 616 cases. Medicine (Baltimore) 1946; 25
in areas where scrub typhus appears to respond poorly to
: 155-214.
standard anti rickettsial drugs.
10. Blake FG, Maxcy KF, Sadusk JF Jr, et al. Studies on tsutsugamushi
4. Clinicians should monitor the progress of patients in the disease (scrub typhus, mite-borne typhus) in New Guinea and
light of reports of drug resistance. adjacent islands : epidemiology, clinical observations and etiology
5. Further research is required to evaluate antibiotics usage in the Dobadura. Am J Hyg 1945; 41 : 243-373.
in scrub typhus. Trials would be more easily interpreted if 11. Lee SH, Kim DM, Cho YS et al. Usefulness of eschar PCR for the
reliable diagnostic tests were available. Such research could diagnosis of scrub typhus. J Clin Microbiol 2006; 44 : 1169-71.
examine whether a single dose of doxycyline is as effective 12. Jensenius M, Fournier PE, Raoult D. Rickettsioses and the
as a three to five days course of treatment. international traveler. Clin Infect Dis 2004; 39 : 1493-99.
6. Regimens for severe disease need to be evaluated for 13. Jensenius M, Montelius R, Berild D, et al. Scrub typhus imported
to Scandinavia. Scand J Infect Dis 2006; 38 : 200-202.
example, comparing intravenous chloramphenicol with
intravenous tetracycline. 14. Liu YX, Cao WC, Gao Y, Zhang JL, Yang ZQ, ZHato ZT and Foley
JE. Orientia tsutsugamushi in Eschars from Scrub Typhus patients.
7. Studies are also needed to evaluate alternative antibiotics Emerging Infectious Diseases 2006; 12 : 1109-
(e.g. Azithromycin and Ciprofloxacin) particularly in areas
15. Kim DM, Park CJ, Lim SC, Park KH, Jang WJ and Lee SH. Diagnosis
where scrub typhus appears to response poorly to standard of Scrub Typhus by immunohistochemical staining of Orientia
anti-rickettsial drugs. tsutsugamushi in cutaneous lesions. Am J Clin Pathol 2008; 130
Clearly more research on scrub typhus in the Indian context : 543-51.
is required, particularly regarding epidemiology, pathogenesis, 16. Batra HV. Spotted fevers & typhus fever in Tamil Nadu. Indian J
diagnosis and treatment of this condition. Med Res 2007; 126 : 101-103.
17. Varghese GM, Abraham DC, Mathai D, Thomas K, Aaron R, Kavita
References ML, et al. Scrub typhus among hospitalized patients with febrile
illness in South India. Magnitude & Clinical Predictors. J Infect
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Korean Med Sci. 1995; 10 : 227-38.
18. Feong YJ, Kim S, Wook YD, Lee FW, Kim K-II, Lee SH. Scrub typhus
2. Mahajan SK. Scrub Typhus. J Assoc Physician India 2005; 53 : 954-58.
: Clinical, Pathologic, and Imaging findings. Radio Graphics 2007;
3. Singh P. Scrub typhus, a case report : military and regional 27 : 161-72.
significance. Med J Armed Forces India, 2004; 60 : 89-90.
19. Panpanich R, Garner P. Antibiotics for treating scrub typhus.
4. Mathai E, Lloyd G, Cherian E et al. Serological evidence for the Cochrane database Syste Reve 2002; 3 : CD002150.

Neurology For Practicing Physicians 2010

The 3rd edition of this annual weekend course will be conducted at Lonavala from Friday 26 th to Sunday 28th, February 2010 (please
note the changes of dates from the earlier announcement). Registration fees of Rs.2000/- will cover transport to and from Mumbai or
Pune, 2 nights (twin-sharing) stay with full board at a 3- or 4-star resort and course material. For brochures please contact:

Dr. Sudhir Kothari Dr. Roop Gursahani

1206 A/13, Shirole Road, Pune - 411004. 2101 Hinduja Clinic, Veer Savarkar Marg, Mahim,
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Limited seats. Advance Registrations will close 31st January, 2010

12 © JAPI • january 2010 • VOL. 58