Abstract
BackgroundScrub typhus is a mite-borne febrile disease caused by O. tsutsugamushi infection. Recently, emergence of scrub typhus has attracted considerable attention in several endemic countries in Asia and the western Pacific. In addition, the antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine.Methodology/Principal findingsTo understand the evolutionary pathway of genotypic diversification of O. tsutsugamushi and the environmental factors associated with the epidemiological features of scrub typhus, we analyzed sequence data, including spatiotemporal information, of the tsa56 gene encoding a major outer membrane protein responsible for antigenic variation. A total of 324 tsa56 sequences covering more than 85% of its open reading frame were analyzed and classified into 17 genotypes based on phylogenetic relationship. Extensive sequence analysis of tsa56 genes using diverse informatics tools revealed multiple intragenic recombination events, as well as a substantially higher mutation rate than other house-keeping genes. This suggests that genetic diversification occurred via frequent point mutations and subsequent genetic recombination. Interestingly, more diverse bacterial genotypes and dominant vector species prevail in Taiwan compared to other endemic regions. Furthermore, the co-presence of identical and sub-identical clones of tsa56 gene in geographically distant areas implies potential spread of O. tsutsugamushi genotypes.Conclusions/SignificanceFluctuation and diversification of vector species harboring O. tsutsugamushi in local endemic areas may facilitate genetic recombination among diverse genotypes. Therefore, careful monitoring of dominant vector species, as well as the prevalence of O. tsutsugamushi genotypes may be advisable to enable proper anticipation of epidemiological changes of scrub typhus.
Highlights
Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection
Based on various informatics analyses, we found that genetic diversification of tsa56 might have been attained via frequent point mutations and subsequent genetic recombination among diverse genotypes
Continuous monitoring of dominant vector species and the associated O. tsutsugamushi genotypes might be required for developing better diagnostics and an effective vaccine for scrub typhus
Summary
Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection. The bacterium is an obligate intracellular pathogen maintained through transovarian and transtadial transmission in trombiculid mites that serve as vectors for the infectious disease [1,2]. It seems to an ancient infectious disease that has long been confined to its endemic area, several cases of suspected scrub typhus have been reported outside of the endemic region [4,5,6,7]. Given that vector mites maintain the intracellular pathogen, ecological changes of the vector species in local endemic regions could be the primary cause of the emergence of doi:10.1371/journal.pntd.0005408.g001 scrub typhus, as recently observed in South Korea [15,16]. The distribution of mite species associated with scrub typhus in the whole endemic region has been poorly monitored and the currently available vector map issued by the World Health Organization (WHO) is based on data before 1974 [18,19,20]. The antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine
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