Chikungunya virus infection: A comprehensive review of pathogenesis, diagnosis and management

Abstract

Chikungunya fever (CHIKF), caused by the chikungunya virus (CHIKV), is an acute mosquito-borne viral disease that poses a rising global public health threat. To date, no specific antiviral therapies are available, and precise diagnosis is pivotal for optimal clinical management. This review systematically summarizes the latest evidence on CHIKV pathogenesis, diagnostic strategies, and clinical management based on English literature published between 2004 and 2025. Virus-host interactions dominate disease progression, including viral entry mediated by E1/E2 envelope proteins binding to host Mxra8 receptors and suppressed type I interferon responses via nsP2-mediated inhibition of the JAK-STAT pathway. The E1-A226V mutation greatly enhances viral transmissibility in Aedes albopictus, fueling the global spread of CHIKV. Clinically, persistent chronic arthropathy serves as the major long-term complication in 25%–40% of infected patients. Current diagnostic approaches consist of real-time RT-PCR as the early gold-standard test and serological antibody detection, whereas serological cross-reactivity with other arboviruses and inconsistent detection results frequently cause clinical misdiagnosis, and the confirmatory plaque reduction neutralization test (PRNT) is impractical for routine use. Clinical care for CHIKF remains predominantly supportive, relying on symptomatic treatment and close patient monitoring. Two FDA-approved vaccines have been licensed via accelerated approval based on immunogenicity surrogates, with solid clinical protective efficacy yet to be validated. This review highlights that in-depth elucidation of CHIKV pathogenic mechanisms, refinement of diagnostic accuracy, and development of targeted therapeutics are essential to improve the overall management of chikungunya fever.