Acute respiratory distress syndrome in scrub typhus: a systematic review and meta-analysis

Abstract

PURPOSE: Acute respiratory distress syndrome (ARDS) is an important complication of scrub typhus and is associated with substantial mortality. The primary objective of this systematic review and meta-analysis was to estimate the proportion of hospitalised patients with microbiologically confirmed scrub typhus who developed ARDS. Secondary objectives were to estimate mortality among patients with scrub typhus-associated ARDS and to compare mortality between scrub typhus patients with and without ARDS. METHODS: This PROSPERO-registered systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, and Web of Science were searched from inception to April 2026 for studies reporting microbiologically confirmed hospitalised scrub typhus patients with extractable ARDS data. Pooled proportions and risk ratios (RRs) were estimated using random-effects models and reported with 95% confidence intervals (CIs). Prespecified subgroup analyses were performed for adult and paediatric populations. Methodological quality was assessed using design-specific Joanna Briggs Institute critical appraisal tools. RESULTS: Sixty-eight studies comprising 10,330 hospitalised patients with microbiologically confirmed scrub typhus were included. The pooled proportion of ARDS was 13% (95% CI 10%-16%; I² = 95.7%) across all age groups, with higher estimates among adults (15%, 95% CI 10%-21%) than paediatric patients (8%, 95% CI 6%-11%). Pooled mortality among patients with scrub typhus-associated ARDS was 21% (95% CI 13%-30%; I² = 76.5%), with higher estimates among adults (28%, 95% CI 13%-47%) than paediatric patients (16%, 95% CI 5%-29%). In 29 studies comprising 4,831 patients, mortality was substantially higher among patients with ARDS than among those without ARDS (RR 12.75, 95% CI 8.48-19.17; I² = 59.5%). CONCLUSION: ARDS occurs in a clinically important proportion of hospitalised patients with scrub typhus and is associated with a markedly increased observed risk of death. Estimates varied considerably across study settings, age groups, illness severity, and ARDS definitions. Early recognition of respiratory deterioration, timely anti-rickettsial therapy, and appropriate escalation of respiratory support are clinically important, but their specific impact on ARDS-related mortality remains to be further evaluated prospectively. REGISTRATION: The systematic review protocol was registered with PROSPERO (CRD420251058577).