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Molecular Epidemiology and Genetic Diversity of Orientia tsutsugamushi from Patients with Scrub Typhus in 3 Regions of India - Volume 21, Number 1—January 2015 - Emerging Infectious Disease journal - CDC

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Molecular Epidemiology and Genetic Diversity of Orientia tsutsugamushi from Patients with Scrub Typhus in 3 Regions of India - Volume 21, Number 1—January 2015 - Emerging Infectious Disease journal - CDC


Volume 21, Number 1—January 2015


Molecular Epidemiology and Genetic Diversity of Orientia tsutsugamushi from Patients with Scrub Typhus in 3 Regions of India

George M. VargheseComments to Author , Jeshina Janardhanan, Sanjay K. Mahajan, David Tariang, Paul Trowbridge, John A.J. Prakash, Thambu David, Sowmya Sathendra, and O.C. Abraham
Author affiliations: Christian Medical College, Vellore, India (G.M. Varghese, J. Janardhanan, J.A.J. Prakash, T. David, S. Sathendra, O.C. Abraham)Indira Gandhi Medical College, Shimla, India (S.K. Mahajan); Dr.H.Gordon Roberts Hospital, Jaiaw, Shillong, India (D. Tariang)Tufts Medical Center, Boston, Massachusetts, USA (P. Trowbridge)


Scrub typhus, an acute febrile illness that is widespread in the Asia-Pacific region, is caused by the bacteriumOrientia tsutsugamushi, which displays high levels of antigenic variation. We conducted an investigation to identify the circulating genotypes of O. tsutsugamushi in 3 scrub typhus–endemic geographic regions of India: South India, Northern India, and Northeast India. Eschar samples collected during September 2010–August 2012 from patients with scrub typhus were subjected to 56-kDa type-specific PCR and sequencing to identify their genotypes. Kato-like strains predominated (61.5%), especially in the South and Northeast, followed by Karp-like strains (27.7%) and Gilliam and Ikeda strains (2.3% each). Neimeng-65 genotype strains were also observed in the Northeast. Clarifying the genotypic diversity of O. tsutsugamushi in India enhances knowledge of the regional diversity among circulating strains and provides potential resources for future region-specific diagnostic studies and vaccine development.
Scrub typhus is a vector-borne, acute febrile illness caused by Orientia tsutsugamushi, an obligate intracellular, gram-negative bacterium. Scrub typhus is widespread in the Asia-Pacific region, known as the “tsutsugamushi triangle.” Mite larvae, or chiggers, of the genus Leptotrombidium transmit the causative bacteria to humans through their bite. The infection is maintained in nature through transovarial transmission in the vector and a reservoir in small mammals (1,2). Clinical signs and symptoms of scrub typhus in humans are largely nonspecific, and if infection is not treated promptly and appropriately, it carries a high mortality rate (3).
The Orientia genome has a high degree of plasticity and is considered to be the most highly repetitive bacterial genome sequenced (4). This diversity is a result of high numbers of intragenomic deletions, duplications, and rearrangements with transposable and conjugative elements. These recombinations and rearrangements are unlikely to occur in dead-end hosts, but the details of this process are unclear (5).
Clarifying the epidemiology and genetic diversity of O. tsutsugamushi strains is essential to the development of rapid diagnostics and vaccines in disease-endemic areas. These efforts would also help in the early recognition and treatment of the disease. Currently, the most widely used method for strain classification is sequence analysis of the 56-kDa type-specific antigen (TSA), an immunodominant outer membrane protein unique to O. tsutsugamushi. With an open reading frame (ORF) of ≈1,600 bp, the 56-kDa TSA contains 516–541 amino acids and is involved in host cell invasion through the binding of fibronectin (6). Four hypervariable domains in this region, variable domains (VD) I–IV, are responsible for the large degree of antigenic variation in this gene. The direct interaction with the host, uniqueness to O. tsutsugamushi, and high level of variability make this protein an attractive target for studying the genetic variation among strains. This region is also highly immunogenic, making it a potential candidate as a vaccine target.
The process of conventional serotyping was a complex procedure, requiring reference serum samples and antigens, and is of limited use today. Greater diversity among the strains has been revealed by using molecular genotyping methods. Antigenic variations in O. tsutsugamushi from patients and rodents in different scrub typhus–endemic regions have been reported by testing using the 56-kDa TSA, which has led to identification of several new subtypes (1), such as Japanese Gilliam, Japanese Karp, Kawasaki, Kuroki, and Shimokoshi, in addition to the previously described prototypes Karp, Kato, and Gilliam (7,8).
Given the broad endemicity of scrub typhus in the Asia-Pacific region and variations in clinical manifestations that may be attributable to strain variation, thorough investigation into the regional distribution of genotypes is warranted. This study was conducted to identify the circulating 56-kDa antigen genotypes in 3 scrub typhus–endemic geographic regions of India: South India, Northern India, and Northeast India.

Dr. Varghese is professor of infectious diseases at Christian Medical College, Vellore, India. His research includes the epidemiology (including molecular epidemiology), pathogenesis, early recognition, and management of rickettsial infections, particularly scrub typhus.


This work was supported by the Indian Council of Medical Research (no. 30/3/16/2008/ECD-II).


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Suggested citation for this article: Varghese GM, Janardhanan J, Mahajan SK, Tariang D, Trowbridge P, Prakash JAJ, et al. Molecular epidemiology and genetic diversity of Orientia tsutsugamushi from patients with scrub typhus in 3 regions of India. Emerg Infect Dis [Internet]. 2015 Jan [date cited].http://dx.doi.org/10.3201/eid2101.140580
DOI: 10.3201/eid2101.140580

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