Hantavirus disease: A review of global epidemiology, immunopathogenesis, clinical management, and future research priorities

Hantaviruses are rodent-borne zoonotic pathogens responsible for two major clinical syndromes: Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome/cardiopulmonary syndrome. Although significant progress has been achieved in hantavirus research over recent decades, major challenges remain in surveillance, diagnostics, therapeutics, and vaccine development. This review comprehensively synthesizes current evidence on hantavirus virology, taxonomy, reservoir ecology, transmission dynamics, global epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention, and One Health surveillance strategies. Particular emphasis is placed on the immunopathological mechanisms underlying endothelial dysfunction and vascular hyperpermeability, the hallmark features of severe disease. The review further explores how climate variability, land-use change, biodiversity loss, and rodent population dynamics shape spillover risk and geographic expansion. Current diagnostic approaches, including serology, RT-PCR, and next-generation sequencing, are critically evaluated alongside emerging point-of-care technologies. Therapeutic limitations are highlighted, particularly the absence of universally effective antivirals and globally approved vaccines. Key research gaps identified include inadequate surveillance in South Asia and Africa, insufficient understanding of Andes virus human-to-human transmission, limited validation of rapid diagnostics, and unresolved mechanisms of immune- mediated pathology. Adopting a One Health perspective, this review proposes priority research and public health directions to strengthen global preparedness, improve outbreak prediction, and accelerate development of effective diagnostics, therapeutics, and vaccines against hantavirus disease.