|Year : 2013 | Volume
| Issue : 1 | Page : 72-74
Outbreak of scrub typhus in the North East Himalayan region-Sikkim: An emerging threat
S Gurung, J Pradhan, PY Bhutia
Department of Microbiology, Sir Thotub Namgyal Memorial Hospital, Gangtok, Sikkim, India
|Date of Submission||04-Aug-2012|
|Date of Acceptance||18-Oct-2012|
|Date of Web Publication||15-Mar-2013|
Department of Microbiology, Sir Thotub Namgyal Memorial Hospital, Gangtok, Sikkim
Source of Support: None, Conflict of Interest: None
Scrub typhus is an acute febrile illness that is known to be endemic in the South East Asian countries and the Western Pacific region. We here report an outbreak in the tiny Himalayan state of Sikkim. Patients with pyrexia of unknown origin were evaluated. They were screened by Weil-Felix test and the rapid immunochromatographic method. Samples that were positive by either Weil-Felix agglutination test or by rapid immunochromatography were confirmed by IgM enzyme-linked immunosorbent assay (ELISA). A total 204 samples were screened. Sixty-three patients were confirmed positive among which 42 were male and 21 were female. Effective management and early administration of antibiotics will help prevent the complications and mortality associated with scrub typhus.
Keywords: Doxycycline, fever, Leptotrombidium, Orientia. tsutsugamushi, pyrexia of unknown origin, scrub typhus, Sikkim
|How to cite this article:|
Gurung S, Pradhan J, Bhutia P Y. Outbreak of scrub typhus in the North East Himalayan region-Sikkim: An emerging threat. Indian J Med Microbiol 2013;31:72-4
|How to cite this URL:|
Gurung S, Pradhan J, Bhutia P Y. Outbreak of scrub typhus in the North East Himalayan region-Sikkim: An emerging threat. Indian J Med Microbiol [serial online] 2013 [cited 2019 Aug 20];31:72-4. Available from: http://www.ijmm.org/text.asp?2013/31/1/72/108729
| ~ Introduction|| |
Scrub typhus in humans results after the introduction of Orientia tsutsugamushi through the skin by the bite of a larval-stage (chigger) trombiculid mite.  It has been reported from various parts of the Indian subcontinent, , but cases from North East India have not been reported for the past three decades.
In 2004, 2008, and 2009, there was a cluster of patients predominantly pediatric who presented with pyrexia of unknown origin (PUO), some of who had the characteristic eschar and hepatosplenomegaly. They were negative for common causes of fever such as typhoid, dengue, malaria, and tuberculosis. Samples were sent to National Centre for Disease Control (NCDC), New Delhi, and they were found to be positive for scrub typhus. Weil-Felix test was performed for the samples sent in 2004 and IgM enzyme-linked immunosorbent assay (ELISA) for O. tsutsugamushi was done in 2008 and 2009. This disease is now recognized as prevalent in our state, but there is an urgent need to establish the true burden of this disease. The present study was undertaken to estimate the prevalence of the disease and correlate the demographic profile of the patients.
| ~ Materials and Methods|| |
Two hundred and four patients attending the medicine and pediatric departments during January 2011 to December 2011 diagnosed with PUO were evaluated. All samples were screened using Weil-Felix agglutination test containing a Proteus vulgaris antigen suspension OX19, OX2, and a Proteus mirabilis antigen suspension OXK (Tulip Diagnostics (P) Ltd. Verna, Goa, India), immunochromatography (ICT) test (Standard Diagnostics Inc., Kyonggi-do, Korea) containing a major surface protein 56-kDa antigen representative of O. tsutsugamushi (Karp, Kato, Gilliam). The ICT test detected IgA, IgM, and IgG. Samples with a titer of >320 or a positive ICT result were considered positive. Positive samples were further confirmed by indirect IgM ELISA (InBios International, Seattle, WA, USA) that used recombinant antigens to detect antibodies.
Blood culture, Widal test, peripheral smear for malarial parasite, and urine culture were done for all samples.
This study was conducted after institutional ethics committee clearance and approval of the Health Care, Human Services and Family Welfare Department, Government of Sikkim.
| ~ Results|| |
Two hundred and four samples were screened and scrub typhus was confirmed in 63 patients. There were 42 males and 21 females; 36 were adults patients (age above 13 years) and 27 were from the pediatric age group, the youngest being 2 years. The maximum number of patients was seen between the months of July and October. A total 26 patients presented with a duration of fever less than 1 week, 23 patients had a duration of 7-10 days, whereas 14 patients presented with fever of more than 2 weeks. The common clinical presentations are shown in [Table 1]. The clinical features among adults and children were analysed by χ2 -test. The difference was found to be statistically significant with a P value ≤0.05.The most common complication was acute renal failure seen in 4 adults and 7 children. Septicemia with multi-organ failure was encountered in 1 adult patient; encephalopathy was seen in 3 children; and pleural effusion in 1 child.
|Table 1: Clinical features at the time of presentation in adults and children|
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Weil-Felix test gave a titer of >320 in 51 patients; ICT was positive in 64 patients; and IgM ELISA was positive for 63 patients. All patients were treated with doxycycline except a 37-week pregnant female who was treated with azithromycin. The majority of the patients belonged to the East district (n0 = 30), followed by West ( n = 13), South ( n = 10), and North (n = 8).
| ~ Discussion|| |
Presence of eschar has been shown to be an important finding for diagnosis of rickettsial pox, scrub typhus, and other mite- or tick-borne rickettsiosis. Typical eschar is slightly raised erythema surrounding a black necrotic center,  and is commonly seen in the axilla, groin, neck, and perineal region. Eschar was seen in 10 pediatric patients and 2 adult patients in this study. Occurrence rate differs from region to region: Cases from Korea have reported a high number of eschar,  but those from Thailand and Taiwan have reported very low incidence. This may be due to variation in serotypes among the regions and also the eschar is usually painless and does not itch, so remains undetected.
Adult patients most commonly presented with headache, polyarthralgia, and vomiting, whereas facial puffiness, pedal edema, and rash were the chief complaints in the pediatric age group. This difference may be because diagnosis in children took a little longer as compared with the adults and thus progression of the disease to hepatomegaly (51.85%), splenomegaly (40.74), and pedal edema (55.56%).This difference in presentation was found to be statistically significant. Complications were encountered in only a few of the patients, the most common being acute renal failure (adults = 4, pediatric = 7) and encephalitis; other complications such as pneumonia were not encountered. Although the case fatality rate for scrub typhus reported has varied from 14% in India,  15-30% in Taiwan,  to 10% in Korea,  all patients in our study responded dramatically to antibiotic treatment except for one who developed septicemia with multi-organ failure and died. Studies have shown inter-strain variability in virulence,  and since serotyping and genotyping were not done, the authors are of the opinion that the strain type present in this region may be a less virulent one.
Transmission of disease occurs throughout the year in the tropical areas, whereas in the temperate zones transmission is seasonal.  A large number of cases in the present study were encountered during the period July to October, which receives the highest rainfall of 429-666 mm.  This seasonal phenomenon was also seen in a study done in Darjeeling district in the neighboring state of West Bengal.  Occurrence of Leptotrombidium deliense is influenced by rainfall, with more chiggers attached to the rodents in the wetter months of the year.  Risk of exposure to O. tsutsugamushi is greatest during the monsoon season,  which may be the reason for clustering of cases during the monsoons in our study.
Indirect immunofluorescence antibody (IFA) assay and indirect immunoperoxidase (IIP) test are the gold standard diagnostic tests for scrub typhus, but they require highly trained personnel and production of antigens may vary among different laboratories, leading to inconsistencies in the interpretation of results.  Weil-Felix test serves as a useful and affordable tool for laboratory diagnosis of rickettsial diseases in resource-poor countries. A four-fold rise in agglutinin titers in paired sera or a single serum sample with high titer of 320 is diagnostic for infection.  A total 51 patients were positive for scrub typhus with the OX K cut-off titers set at 320.
Primary infection produces a rapid rise in IgM antibodies within 8 days, whereas secondary or re-infection is characterized by a sharp rise in IgG levels, with a variable IgM response.  One patient sample, which was positive by Weil-Felix test and negative by IgM ELISA, gave positive result by rapid ICT. Since ICT also detects IgG antibodies, the patient may have had a secondary infection and thus the positive result. All screened samples were confirmed by IgM ELISA. Recombinant antigen-based ELISA has shown excellent performance and utilizes standardized commercially available antigens as compared with IFA and IIP. It has been suggested that recombinant antigen-based ELISA is suitable in moderately equipped laboratories in scrub typhus endemic regions.  Indirect IgM ELISA may give false-positive results due to presence of rheumatoid factor  and false-negative results may occur in secondary infection where there is a sharp rise in IgG levels.  These shortcomings could have been eliminated by using an IgM capture assay and including an IgG ELISA.
| ~ Conclusion|| |
Sikkim attracts thousands of domestic and foreign tourists every year. Good knowledge and global awareness of this disease as being prevalent in this Himalayan state will help in early diagnosis and effective therapy of travelers returning home with acute febrile illness.
| ~ Acknowledgments|| |
The authors wish to thank the following: Dr. Namgyal T Sherpa, Head of Department, Internal Medicine; Dr. Wangyal Barfungpa, Sr M.O., Department of Medicine; Dr. Ruth Yonzone, Consultant Paediatrician, STNM Hospital, for clinical evaluation of the patients; Dr. Kumar Bhandari, Secretary cum DGHS, Health Care, Human Services and Family Welfare Department, Govt. of Sikkim, for helping us procure the tests and kits required for the study; and Dr. Dechenla Tshering, Associate Professor, Department of Community Medicine, SMIMS, Gangtok, for statistical analysis of the table.
| ~ References|| |
|1.||Jeong YJ, Kim S, Wook YD, Lee JW, Kim KI, Lee SH. Scrub typhus: Clinical, pathologic, and imaging findings. RadioGraphics 2007;27:161-72. |
|2.||Vivekanandan M, Mani A, Priya YS, Singh AP, Jayakumar S, Purty S. Outbreak of scrub typhus in Pondicherry. J Assoc Physicians India 2010;58:24-8. |
|3.||Mahajan SK, Rolain JM, Kashyap R, Bakshi D, Sharma V, Prasher BS, et al. Scrub typhus in Himalayas. Emerg Infect Dis 2006;12:1590-2. |
|4.||Kim DM, Won KJ, Park CY, Yu KD, Kim HS, Yang TY, et al. Distribution of Eschars on the body of Scrub Typhus patients: A prospective study. Am J Trop Med Hyg 2007;76:806-9. |
|5.||Kim DM, Kim SW, Choi SH, Yun NR. Clinical and laboratory findings associated with scrub typhus. BMC Infect Dis 2010;10:108. |
|6.||Lai CH, Huang CK, Weng HC, Chung HC, Liang SH, Lin JN, et al. The difference in clinical characteristics between acute Q fever and scrub typhus in southern Taiwan. Int J Infect Dis 2009;13:387-93. |
|7.||Chang WH. Current status of Tsutsugamushi disease in Korea. J Korean Med Sci 1995;10:227-38. |
|8.||Available from: http://imdsikkim.gov.in/monthlymetparam.html [Last accessed on 2012 Oct 16]. |
|9.||Sharma PK, Ramakrishnan R, Hutin YJ, Barui AK, Manickam P, Kakkar M, et al. Scrub typhus in Darjeeling, India: Opportunities for simple, practical prevention measures. Trans R Soc Trop Med Hyg 2009;103:1153-8. |
|10.||Frances SP, Watcharapichat P, Phulsoksombati D, Tanskul P, Linthicum KJ. Seasonal occurrence of Leptotrombidium deliense (Acari: Trombiculidae) attached to sentinel rodents in an orchard near Bangkok, Thailand. J Med Entemol 1999;36:869-74. |
|11.||Kelly DJ, Fuerst PA, Ching WM, Richards AL. Scrub typhus: The geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 2009;48:203-30. |
|12.||Coleman RE, Sangkasuwan V, Suwanabun N, Eamsila C, Mungviriya S, Devine P, et al. Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand. Am J Trop Med Hyg 2002;67:497-503. |
|13.||Land MV, Ching W, Dasch GA, Zhang Z, Kelly DJ, Graves SR, et al. Evaluation of a commercially available recombinant-protein enzyme-linked immunosorbent assay for detection of antibodies produced in scrub typhus rickettsial infections. J Clin Microbiol 2000;38:2701-5. |
|14.||Jang W, Huh M, Park K, Choi M, Kim IS. Evaluation of immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of Orientia tsutsugamushi infection. Clin Diagn Lab Immunol 2003;10:394-8. |
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