Orientia tsutsugamushi, agent of scrub typhus, displays a single metapopulation with maintenance of ancestral haplotypes throughout continental South East Asia.

Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness in rural area of Asia-Pacific region. A multi-locus sequence typing (MLST) analysis was performed on strains isolated from human patients from 3 countries in Southeast Asia: Cambodia, Vietnam and Thailand. The phylogeny of the 56-kDa protein encoding gene was analyzed on the same strains and showed a structured topology with genetically distinct clusters. MLST analysis did not lead to the same conclusion. DNA polymorphism and phylogeny of individual gene loci indicated a significant level of recombination and genetic diversity whereas the ST distribution indicated the presence of isolated patches. No correlation was found with the geographic origin. This work suggests that weak divergence in core genome and ancestral haplotypes are maintained by permanent recombination in mites while the 56-kDa protein gene is diverging in higher speed due to selection by the mammalian immune system.

Broad-coverage molecular epidemiology of Orientia tsutsugamushi in Thailand.

Orientia tsutsugamushi, an obligate intracellular bacterium closely related to the genus Rickettsia, is the causative agent of scrub typhus, a major cause of febrile illness in rural areas of Asia-Pacific region. Scrub typhus is transmitted by the bite of infected mites of the genus Leptotrombidium. The region of the 56-kDa TSA gene spanning from variable domain I (VDI) to variable domain IV (VDIV) was sequenced and used for genotyping 77 O. tsutsugamushi samples from human patients confirmed with scrub typhus from 2001 to 2003 and 2009 to 2010 in different regions of Thailand. These sequences were also compared to previously published 56-kDa TSA sequences. Only 4 genotypes out of 8 previously reported in Thailand were identified, i.e. Karp, JG-v, TA763 and Kato, respectively. Two strains were not associated with known genotypes but were closely related to Taiwanese strains. The Karp genotype was confirmed as the predominant clade. The JG-v and TA763 genotypes, in contrast to other studies, also were found. The genotype TA716 was not found, except for one strain previously described.

Molecular epidemiology of Orientia tsutsugamushi in Cambodia and Central Vietnam reveals a broad region-wide genetic diversity.

Scrub typhus is an acute infectious disease caused by an obligate intracellular bacterium Orientia tsutsugamushi following the bite of infected trombiculid mites of the genus Leptotrombidium. This zoonotic disease is a major cause of febrile illness in the Asia-Pacific region, with a large spectrum of clinical manifestations from unapparent or mild disease to fatal disease. O. tsutsugamushi is characterized by a very high genomic plasticity and a large number of antigenic variants amongst strains. The 56-kDa type specific antigen (TSA) gene, encoding the major antigenic protein, was used as reference to investigate the genetic relationships between the strains and to genotype O. tsutsugamushi isolates. The open reading frame of the 56-kDa TSA gene of 41 sequences (28 Cambodian and 13 Vietnamese strains) from patient samples were sequenced and used for genotyping. The 28 Cambodian isolates clustered into 5 major groups, including Karp (43.5%), JG-v (25%), Kato/TA716 (21.5%), TA763 (3.5%) and Gilliam (3.5%). Karp (77%), TA763 (15.5%) and JG-v (7.5%) strains were identified amongst the 13 Vietnamese isolates. This is the first countrywide genotyping description in Cambodia and in Central Vietnam. These results demonstrate the considerable diversity of genotypes in co-circulation in both countries. The genotyping result might raise awareness amongst Cambodian and Vietnamese clinicians of the high genetic diversity of circulating O. tsutsugamushi strains and provides unique and beneficial data for serological and molecular diagnosis of scrub typhus infections as well as raw materials for future studies and vaccine development.