Hospitalisations and outpatient visits for undifferentiated fever attributable to scrub typhus in rural South India: Retrospective cohort and nested case-control study

Background The burden of scrub typhus in endemic areas is poorly understood. This study aimed at estimating the proportion of hospitalisations and outpatient visits for undifferentiated fever in the community that may be attributable to scrub typhus. Methodology and principal findings The study was a retrospective cohort with a nested case-control study conducted in the South Indian state of Tamil Nadu. We conducted house-to-house screening in 48 villages (42965 people, 11964 households) to identify hospitalised or outpatient cases due to undifferentiated fever during the preceding scrub typhus season. We used scrub typhus IgG to determine past infection. We calculated adjusted odds ratios for the association between IgG positivity and case status. Odds ratios were used to estimate population attributable fractions (PAF) indicating the proportion of hospitalised and outpatient fever cases attributable to scrub typhus. We identified 58 cases of hospitalisation and 236 outpatient treatments. 562 people were enrolled as control group to estimate the background IgG sero-prevalence. IgG prevalence was 20.3% in controls, 26.3% in outpatient cases and 43.1% in hospitalised cases. The PAFs suggested that 29.5% of hospitalisations and 6.1% of outpatient cases may have been due to scrub typhus. In villages with a high IgG prevalence (defined as ≥15% among controls), the corresponding PAFs were 43.4% for hospitalisations and 5.6% for outpatients. The estimated annual incidence of scrub typhus was 0.8/1000 people (0.3/1000 in low, and 1.3/1000 in high prevalence villages). Evidence for recall error suggested that the true incidences may be about twice as high as these figures. Conclusions The study suggests scrub typhus as an important cause for febrile hospitalisations in the community. The results confirm the adequacy of empirical treatment for scrub typhus in hospitalised cases with undifferentiated fever. Since scrub typhus may be rare among stable outpatients, the use of empirical treatment remains doubtful in these.
Author summary Scrub typhus is an important cause of fever in many Asian countries, including China, India, Vietnam and Japan. It is caused by the intra-cellular bacteria Orientia tsutsugamushi and is transmitted to humans by mite larvae (chiggers) which attach to the skin of the host. Scrub typhus is potentially life-threatening but treatable with relatively cheap antibiotics such as doxycycline. The incidence of scrub typhus in the community is not known as most studies were done at hospitals and health posts lacking a clearly defined source-population for patients seeking health care for fever. In this study, the proportion of fever cases due to scrub typhus and the incidence of the infection were estimated by retrospective case identification in a population of 42000 people living in 48 villages in the South Indian state of Tamil Nadu. We found that about 30% to 40% of hospitalisations for undifferentiated fever may be due to scrub typhus. In contrast, scrub typhus accounted for only about 5% of outpatient fever cases. Our findings confirm the need for large population-based cohort studies to better understand the epidemiology of scrub typhus in endemic settings.