The Effect of Mouse Age on the Determination of Rickettsia Tsutsugamushi Virulence

Abstract

SUMMARY: The effect of age on the susceptibility of ICR mice to lethal intraperitoneal (ip), Rickettsia tsutsugamushi infections was tested with five virulent strains -Karp, Kato, Gilliam, TA763, and TH1817-and three strains of reduced virulence-TA678, TA686, and TA716. Susceptibility differences were noted only in the ICR mice inoculated with two of the strains of reduced virulence, TA716 and TA678. With both strains, mice in the 12-weeks and younger age groups had lower death rates than did mice in the 21-weeks and older age groups. Also, CBA/CaJ mice of varying ages were inoculated intravenously with large doses of the Gilliam strain to determine the effect of age on susceptibility to acute death syndrome (ADS). A progressive increase in ADS resistance was seen in the 4-, 8-, 12-, and 16-week-old age groups. This study indicates that the age of mice used to test the virulence of R. tsutsugamushi strains may be an important consideration, especially when testing the ip lethality of strains of reduced virulence.The laboratory mouse is commonly used in the study of scrub typhus to isolate and characterize the causative agent, Rickettsia tsutsugamushi (Bell, Bennett and Whitman, 1946;Smadel, Jackson and Cruise, 1949;Elisberg and Bozeman, 1969;Shirai and Wisseman, 1975). Large studies often require that mice be accumulated over a period of several weeks, leading to a considerable disparity in their ages. Despite the extensive use of mice in scrub typhus research and the past interest in R. tsutsugamushi virulence for mice, specific information on the effect of age on mouse susceptibility to infection is lacking. Therefore, we tested the susceptibility of outbred mice of varying ages to intraperitoneal (ip) R. tsutsugamushi infection.Eight prototype strains were prepared, stored, and assessed for infectivity using methods reported previously (Groves and Osterman, 1978). ICR mice, ages 4, 8, 12, 21, 23, and 26 weeks, were infected intraperitoneally with 3, 10-fold varying dosages (5 mice/dose) of each rickettsial strain, and the total number of lethal infections within each age group recorded. Dosages for the virulent

Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

“…These methods assumed a model sensitivity sufficient to isolate human-virulent strains for propagation and analysis; however, virulence can vary dramatically both among the Orientia strains themselves and among the murine outbred or inbred strains used for isolation [48,75,[78][79][80][81][82][83]. Even the age of the mouse host can influence the apparent strain virulence and the capacity to isolate the agent in vivo [84]. Although very limited, there is evidence of strain differences indicated by variation in sensitivity to antibiotics or antibiograms, which is related to reports of antibiotic-refractory scrub typhus [62,85,86].…”