Abstract
Scrub typhus, a chigger-borne febrile illness, occurs primarily in countries of the Asia-Pacific rim and islands of the Western Pacific. The etiologic agent is the obligate intracellular rickettsial bacterium Orientia tsutsugamushi. Research on O. tsutsugamushi has relied on the availability of several prototype strains, which were isolated from human cases of scrub typhus in the 1940s and 1950s. We review the history of the three original, and most important, prototype strains, Gilliam, Karp and Kato, including information on their isolation, their culture history, their clinical characteristics, their importance within the research literature on scrub typhus, and recent advances in elucidating their molecular genomics. The importance of these strains to the research and development of clinical tools related to scrub typhus is also considered. Finally, we examine whether the strains have been genetically stable since their isolation, and whether prototype strains maintained in separate laboratories are identical, based on pairwise comparisons of several sequences from four genes. By using genetic information archived in international DNA databases, we show that the prototype strains used by different laboratories are essentially identical, and that the strains have retained their genetic integrity at least since the 1950s. The three original prototype strains should remain a standard by which new diagnostic procedures are measured. Given their fundamental position in any comparative studies, they are likely to endure as a critical part of present and future research on scrub typhus and Orientia.
Highlights
Scrub typhus is a chigger-borne febrile illness of humans, caused by the rickettsia Orientia tsutsugamushi
In Crisis Fleeting [66], Records show continuous passages of the Gilliam strain at Walter Reed Army Institute of Research (WRAIR), together with the other two prototype strains (Karp and Kato), until 1988 when the entire rickettsial inventory was transferred to the Rickettsial Diseases Department, Naval Medical Research Institute (NMRI), the NMRC
When World War II (WWII) military operations began in the Southwest Pacific, medical officers were generally unaware of the disease that soon developed into a serious problem resulting in hundreds and later thousands of cases
Summary
Scrub typhus is a chigger-borne febrile illness of humans, caused by the rickettsia Orientia tsutsugamushi. At the end of the war, many of those medical officers continued their service and seized the opportunity to further investigate scrub typhus The efforts of those researchers, both during the war, and soon thereafter together with scientists in Japan, allowed the better diagnosis of cases, and led to the isolation and propagation of the obligate intracellular etiologic agent, currently named O. tsutsugamushi. Tools that emerged from the military medicine of WWII resulted in the development of procedures for the stable culture of strains of the agent of scrub typhus These included improvements to the serial passage in mouse, hamster and guinea pig, development of culture in embryonated chicken eggs and sample transfer on dry ice [19,54]. Scrub typhus remains a disease that can be successfully treated when identified early in its course by antibiotics such as tetracyclines, chloramphenicol and azithromycin ( other compounds such as cephalosporins and ciprofloxacin are not efficacious)
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