Risk Factors for Scrub Typhus, Murine Typhus, and Spotted Fever Seropositivity in Urban Areas, Rural Plains, and Peri-Forest Hill Villages in South India: A Cross-Sectional Study

Abstract

. Scrub typhus and spotted fever group rickettsioses are thought to be common causes of febrile illness in India, whereas they rarely test for murine typhus. This cross-sectional study explored the risk factors associated with scrub typhus, tick-borne spotted fever, and murine typhus seropositivity in three different geographical settings, urban, rural, and hill villages in Tamil Nadu, South India. We enrolled 1,353 participants living in 48 clusters. The study included a questionnaire survey and blood sampling. Blood was tested for Orientia tsutsugamushi (scrub typhus), Rickettsia typhi (murine typhus), and spotted fever group Rickettsia IgG using ELISA. The seroprevalence of scrub typhus, spotted fever, and murine typhus were 20.4%, 10.4%, and 5.4%, respectively. Scrub typhus had the highest prevalence in rural areas (28.1%), and spotted fever was most common in peri-forested areas (14.9%). Murine typhus was more common in rural (8.7%) than urban areas (5.4%) and absent in peri-forested hill areas. Agricultural workers had a higher relative risk for scrub typhus, especially in urban areas. For murine typhus, proximity to a waterbody and owning a dog were found to be major risk factors. The main risk factors for spotted fever were agricultural work and living in proximity to a forest. Urban, rural plains, and hill settings display distinct epidemiological pattern of Orientia and rickettsial infections. Although scrub typhus and spotted fever were associated with known risk factors in this study, the findings suggest a different ecology of murine typhus transmission compared with other studies conducted in Asia.

The burden of scrub typhus in India: A systematic review

“…The two community-based studies conducted during the period in this review (2016 and 2017, respectively) showed PLOS NEGLECTED TROPICAL DISEASES seroprevalences of 40.3% and 31.8% [17,18]. A recent study among urban areas, rural plains, and peri-forest hill villages in Tamil Nadu showed a seroprevalence of 28.1% [19]. The data so far suggests that the seroprevalence of scrub typhus in the community is about 30% which is comparable to endemic infections like tuberculosis in India, which has an estimated prevalence (latent tuberculosis) of 40% [20].…”

High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection

“…We have previously shown that the IgG response to scrub typhus infection in those with low initial IgG antibody levels was less pronounced and persistent compared to those with initially high IgG levels [ 14 ] ( Fig 1B ). This, together with the strong increase in IgG sero-positivity with age typically found in scrub typhus [ 11 , 12 ] ( Fig 1C ) suggests a gradual accumulation of IgG antibodies after multiple infections ( Fig 1D ). Similar dynamics have long been known for other infections, in particular Influenza [ 15 ].…”

“…Due to a small sample size in our previous study [ 14 ] we were unable to explore whether the observed effect was directly associated with IgG antibody levels or due to confounding by age. Older individuals are at a higher risk of severe scrub typhus [ 4 ] and are also known to have higher levels of scrub typhus IgG ( Fig 1C ) [ 11 , 12 ]. We therefore retrospectively enrolled additional scrub typhus cases to investigate the association between initial IgG antibody levels and severe infection.…”

“…Given the great strain diversity of O. tsutsugamushi, repeated infection with a variety of genetic variants may be a common phenomenon, possibly explaining some recent findings regarding the sero-epidemiology of scrub typhus. In cross-sectional surveys conducted in endemic areas in south India, IgG antibody levels against O. tsutsugamushi show a bimodal distribution with peaks at very low and very high levels (the latter are often regarded as "sero-positive") [11][12][13] (Fig 1A). This is in contrast to Rickettsia typhi and the spotted fever group Rickettsiae against which IgG antibody responses do not show a second peak at higher values in the general population [12].…”

“…In cross-sectional surveys conducted in endemic areas in south India, IgG antibody levels against O. tsutsugamushi show a bimodal distribution with peaks at very low and very high levels (the latter are often regarded as "sero-positive") [11][12][13] (Fig 1A). This is in contrast to Rickettsia typhi and the spotted fever group Rickettsiae against which IgG antibody responses do not show a second peak at higher values in the general population [12]. We have previously shown that the IgG response to scrub typhus infection in those with low initial IgG antibody levels was less pronounced and persistent compared to those with initially high IgG levels [14] (Fig 1B).…”