Origins, Importance and Genetic Stability of the Prototype Strains Gilliam, Karp and Kato of Orientia tsutsugamushi

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.

Keywords: Gilliam; Karp; Kato; O. tsutsugamushi; Orientia; comparative genomics; genetic stability; scrub typhus; serogroups.

Figure 1

Number of scientific publications within each decade-long period that mention terms “tsutsugamushi” or “scrub typhus”, together with one or more of the prototype strain names “Karp”, “Gilliam” or “Kato”.

Figure 2

Lt. Col. Alexander Gilliam, 1943—in Cairo (Photo courtesy of Laura and Sandy Gilliam).

Figure 3

Egg cultures of Gilliam strain (lower left) maintained at the US National Institutes of Health, Bethesda Maryland in Spring 1944. Note, other rickettsial strains in culture including Breinl and Wilmington strain of Rickettsia prowazekii and Rickettsia typhi, respectively, and Case #9, a New Guinea isolate from a scrub typhus patient. Picture appeared in Life Magazine, May 1, 1944, page 65.