Paediatric Dengue–Scrub Typhus Co-Infection in South Asia: A Systematic Review of Clinical and Immunopathogenic Features

Abstract

Dengue and scrub typhus are major causes of acute febrile illness in South Asia, particularly in India where both diseases demonstrate marked seasonal overlap. Paediatric populations represent a significant proportion of hospitalized cases. Coinfection with dengue virus (DENV) and Orientia tsutsugamushi is increasingly reported yet remains underrecognized due to overlapping clinical and laboratory features. This systematic review synthesizes available evidence on paediatric dengue–scrub typhus coinfection in South Asia, emphasizing epidemiology, molecular immunopathogenesis, clinical manifestations, diagnostic challenges, management strategies, and outcomes. A systematic search of PubMed, Scopus, Web of Science, Google Scholar, and regional databases was conducted for studies published between 2000 and February 2025. The last literature search was performed on 28 February 2025. Studies involving patients ≤18 years with laboratory-confirmed coinfection were included. Thirty-eight studies met inclusion criteria, comprising observational cohorts, case series, and case reports predominantly from India, with additional reports from Nepal and Sri Lanka. Quantitative meta-analysis was not performed due to heterogeneity in study design, diagnostic criteria, and outcome reporting. Coinfection prevalence ranged from 1.8% to 19.4% among hospitalized febrile children. A total of 38 clinical studies comprising 412 paediatric patients were included. Common features included persistent fever, severe thrombocytopenia, transaminitis, hepatosplenomegaly, hypoalbuminemia, capillary leak, and shock. Severe disease manifestations were reported in approximately 28–35% of cases, with mortality ranging from 3% to 8% across studies. Molecular mechanisms suggest synergistic endothelial injury mediated by cytokine amplification, complement activation, and macrophage hyperactivation. Early doxycycline administration significantly improved outcomes. The review highlights the need for routine dual screening during endemic seasons and underscores the immunopathogenic basis for increased severity in paediatric coinfection.