The re-emerging shadow: A systematic review of scrub typhus in India

Abstract

Background: Scrub typhus, caused by Orientia tsutsugamushi and transmitted by larval trombiculid mites, has re-emerged as an important cause of acute febrile illness (AFI) in India. The disease is frequently underdiagnosed because of its non-specific clinical presentation, variable occurrence of eschar, and limited availability of reliable diagnostic facilities. Delayed diagnosis and treatment may result in severe complications and significant mortality.

Objectives: To systematically review the available literature on scrub typhus in India and to assess its epidemiology, pooled prevalence among patients with acute febrile illness, case fatality rate (CFR), clinical manifestations, diagnostic challenges, treatment outcomes, and emerging public health concerns.

Materials and methods: A systematic review of the published literature from 2013 to 2023 was conducted in accordance with the PRISMA 2020 guidelines. Electronic databases, including PubMed, Google Scholar, and Indian biomedical journals, were searched using predefined keywords related to scrub typhus and acute febrile illness. Two independent reviewers screened studies, extracted data, and assessed eligibility. Information regarding epidemiology, diagnostic methods, clinical features, prevalence, CFR, and treatment outcomes was synthesized. Heterogeneity among studies was assessed using the I² statistic, and sensitivity analysis was performed by excluding studies utilizing the Weil–Felix test.

Results: Scrub typhus has emerged as a major contributor to acute febrile illness across India, particularly in the Himalayan region, northeastern states, and southern India, with increasing reports from western and central regions. Pooled analyses indicate that approximately one-fourth of patients presenting with acute febrile illness are positive for scrub typhus. State-specific prevalence ranged from 15% to over 50%, while pooled CFR varied from <5% to over 20% depending on disease severity and healthcare setting. High heterogeneity was observed across studies (I² range: 32-71%), largely attributable to differences in diagnostic methods and study populations. Sensitivity analysis showed an increase in pooled prevalence from approximately 24% to 29% after excluding Weil-Felix-based studies, suggesting that less sensitive diagnostic methods underestimate the disease burden. Common clinical manifestations included high-grade fever, headache, myalgia, lymphadenopathy, and elevated live enzymes, whereas eschar was present in only 30-50% of patients. Severe complications included acute respiratory distress syndrome, meningoencephalitis, myocarditis, acute kidney injury, and shock. Doxycycline remained the cornerstone of therapy, although emerging reports of reduced treatment response have raised concerns regarding antimicrobial resistance.

Conclusion: Scrub typhus is a significant and growing public health challenge in India, accounting for a substantial proportion of acute febrile illness and preventable mortality. Early clinical suspicion, prompt initiation of appropriate antimicrobial therapy, improved access to reliable diagnostics, strengthened surveillance systems, and continued monitoring of circulating genotypes are essential for reducing disease burden and improving patient outcomes. Greater integration of clinical, laboratory, epidemiological, and One Health approaches is required to address the re-emergence of scrub typhus in India.