Research Article: A Dominant Clone of Leptospira interrogans Associated with an Outbreak of Human Leptospirosis in Thailand

Date Published: October 31, 2007

Publisher: Public Library of Science

Author(s): Janjira Thaipadungpanit, Vanaporn Wuthiekanun, Wirongrong Chierakul, Lee D. Smythe, Wimol Petkanchanapong, Roongrueng Limpaiboon, Apichat Apiwatanaporn, Andrew T. Slack, Yupin Suputtamongkol, Nicholas J. White, Edward J. Feil, Nicholas P. J. Day, Sharon J. Peacock, Mathieu Picardeau

Abstract: BackgroundA sustained outbreak of leptospirosis occurred in northeast Thailand between 1999 and 2003, the basis for which was unknown.Methods and FindingsA prospective study was conducted between 2000 and 2005 to identify patients with leptospirosis presenting to Udon Thani Hospital in northeast Thailand, and to isolate the causative organisms from blood. A multilocus sequence typing scheme was developed to genotype these pathogenic Leptospira. Additional typing was performed for Leptospira isolated from human cases in other Thai provinces over the same period, and from rodents captured in the northeast during 2004. Sequence types (STs) were compared with those of Leptospira drawn from a reference collection. Twelve STs were identified among 101 isolates from patients in Udon Thani. One of these (ST34) accounted for 77 (76%) of isolates. ST34 was Leptospira interrogans, serovar Autumnalis. 86% of human Leptospira isolates from Udon Thani corresponded to ST34 in 2000/2001, but this figure fell to 56% by 2005 as the outbreak waned (p = 0.01). ST34 represented 17/24 (71%) of human isolates from other Thai provinces, and 7/8 (88%) rodent isolates. By contrast, 59 STs were found among 76 reference strains, indicating a much more diverse population genetic structure; ST34 was not identified in this collection.ConclusionsDevelopment of an MLST scheme for Leptospira interrogans revealed that a single ecologically successful pathogenic clone of L. interrogans predominated in the rodent population, and was associated with a sustained outbreak of human leptospirosis in Thailand.

Partial Text: Leptospirosis is a zoonotic infection caused by pathogenic members of the genus Leptospira. Human disease is usually acquired following environmental exposure to Leptospira shed in the urine of an infected animal [1],[2]. Infection is acquired during occupational or recreational exposure to contaminated soil and water, organisms gaining entry to the accidental human host via abrasions or less commonly the conjunctiva [1]. Disease may also be acquired through direct contact with infected animals, and occurs in farmers, veterinarians and abattoir workers [1]. The disease has a worldwide distribution but is most common in tropical regions where incidence peaks during the rainy season [1],[2]. Clinical manifestations are broad ranging and follow a biphasic pattern in which a septicemic phase lasting around one week is followed by an immune phase during which antibodies are raised and organisms localize in tissues and appear in urine. Much disease is sub-clinical or mild, but patients reaching medical attention usually have an acute febrile illness associated with one or more of chills, headache, myalgia, conjunctival suffusion, and abdominal symptoms which can include nausea, vomiting and diarrhea [1]. Leptospirosis has been described as anicteric or icteric; the former represents 85–90% of cases and is associated with a good prognosis, while the latter may be associated with multisystem disease involving particularly the kidneys, lung and heart, with a reported mortality rate of 5–15% [1].

Human outbreaks of leptospirosis are well documented in the literature, as are clusters of cases linked by specific water-related activities or occupations [1],[2]. Outbreaks in Thailand and elsewhere are often linked to climatic events such as flooding and the concomitant increase in human exposure to environments contaminated by Leptospira. The precipitous increase in reported cases of leptospirosis in Thailand commencing in 1999, followed by the sustained incidence during the ensuing years, could not be explained by persistent climatic change or sequential episodes of regional flooding. Changes in reporting practice can lead to marked changes in the perceived disease incidence, although this does not explain the marked rise and fall in reported cases over time. An alternative explanation is that this was associated with the presence of a biologically successful clone of pathogenic Leptospira. In this study, we developed and applied robust typing methods to provide several lines of evidence in support of this hypothesis. This clone is likely to harbour an adaptive (competitive) advantage, albeit transiently. Possible explanations include a selective advantage for ST34 in the maintenance host (the bandicoot rat) leading to a higher bacterial load and higher shedding from urine, or a survival advantage once shed into environment, such as increased resistance to desiccation. Both possibilities are amenable to testing in the laboratory setting. Alternatively, ST34 may have a greater propensity to cause human disease compared with other circulating clones. Although difficult to test, the finding that ST34 co-existed in the environment with a large number of other STs but caused most disease would be supportive of this hypothesis. The virulence of ST34 as reflected by severity of human disease was not assessed in patients presenting to Udon Thani hospital, since the comparator group was small and caused by 11 other STs. The emergence of ST34 may have predated the outbreak, and this is difficult to refute since no strains were available from the period prior to the outbreak. However, the decline in frequency of ST34 as a cause of leptospirosis over time is consistent with the suggestion that there is a direct link between the clone and the outbreak.



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