Sero-Diagnosis of Scrub Typhus Infection in India: A Systematic Review and Meta-Analysis

Scrub typhus is a major yet often unrecognised cause of acute undifferentiated febrile illness (AUFI) in India. Delayed diagnosis contributes substantially to organ dysfunction and mortality, but accurate estimates of disease burden are limited by heterogeneous diagnostic practices. Understanding the proportion of clinically suspected cases attributable to scrub typhus is essential for improving early recognition and treatment.

We performed a systematic review and meta-analysis of studies reporting IgM enzyme-linked immunosorbent assay (ELISA) confirmed scrub typhus among patients presenting with acute febrile illness in India. Searches of major databases were conducted through August 2025. A random-effects model with DerSimonian-Laird estimator and Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate pooled prevalence. Freeman-Tukey double arcsine transformation was applied to stabilise variances. Study quality was assessed with the Joanna Briggs Institute checklist. Heterogeneity, publication bias and influence diagnostics were evaluated using both advanced and standard statistical tests and graphical tools.

A total of 44 studies involving 67,179 clinically suspected cases met eligibility criteria. The pooled prevalence of scrub typhus was 29.3% (95% CI: 22.3%-37.3%). Prevalence varied widely across regions (0.63%-93.10%). Sensitivity analyses demonstrated that no single study materially altered the pooled prevalence. Publication bias was minimal. The Doi plot showed minor asymmetry (LFK index, 1.47), whereas Egger's regression and Begg's test indicated no statistically significant publication bias.

This meta-analysis reveals that scrub typhus accounts for nearly one-third of suspected febrile illnesses in India (pooled prevalence: 29.3%). Clinicians in endemic regions should maintain a high index of suspicion and initiate timely therapy. Improved access to standardised diagnostics and molecular testing is essential to reduce morbidity and mortality.