The diversity and geographical structure of orientia tsutsugamushi strains from scrub typhus patients in Laos

Orientia tsutsugamushi is the causative agent of scrub typhus, a disease transmitted by Leptotrombidium mites which is responsible for a severe and under-reported public health burden throughout Southeast Asia. Here we use multilocus sequence typing (MLST) to characterize 74 clinical isolates from three geographic locations in the Lao PDR (Laos), and compare them with isolates described from Udon Thani, northeast Thailand. The data confirm high levels of diversity and recombination within the natural O. tsutsugamushi population, and a rate of mixed infection of ~8%. We compared the relationships and geographical structuring of the strains and populations using allele based approaches (eBURST), phylogenetic approaches, and by calculating F-statistics (FST). These analyses all point towards low levels of population differentiation between isolates from Vientiane and Udon Thani, cities which straddle the Mekong River which defines the Lao/Thai border, but with a very distinct population in Salavan, southern Laos. These data highlight how land use, as well as the movement of hosts and vectors, may impact on the epidemiology of zoonotic infections.Author Summary: Scrub typhus, caused by the pathogen Orientia tsutsugamushi, is endemic in Southeast Asia, including Laos, accounting for up to 15% of cases of undifferentiated fever in adult patients. Despite its public health importance, little is known about the genetics of the O. tsutsugamushi population in Laos—this information is important for optimizing diagnostics and epidemiological surveillance. We conducted a 4 year prospective study to examine the genetic diversity of O. tsutsugamushi causing scrub typhus in Lao patients and highlight the geographical differentiation that can occur even within a small country.