Human Orthohantavirus infections: From virology and clinical epidemiology to oral biological features and dental practice

Abstract Hantaviruses are rodent-borne zoonotic pathogens responsible for 2 severe clinical syndromes in humans: hemorrhagic fever with renal syndrome (HFRS), affecting an estimated 150,000 to 200,000 individuals annually worldwide, and hantavirus cardiopulmonary syndrome (HCPS), characterized by fulminant pulmonary edema with case fatality rates approaching 40%. Although the systemic manifestations of hantavirus disease are well described, the oral and salivary dimensions of infection have received comparatively little attention in the dental literature. This review synthesizes current evidence on the virology, global epidemiology, pathogenesis, clinical manifestations, oral complications, diagnostic approaches, treatment options, and dental practice implications of human hantavirus infections. A narrative review with a structured search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar was conducted, supplemented by hand-searching and by consultation of the World Health Organization and European Centre for Disease Prevention and Control outbreak reporting. Particular attention was directed toward primary research on salivary immunity, oral fluid diagnostics, and salivary gland tropism. Andes virus (ANDV) antigen has been detected in secretory cells of human salivary glands, and ANDV uniquely resists the antiviral capacity of human saliva, providing a biologically plausible mechanism for its person-to-person transmissibility. Infectious virus has since been recovered from saliva and gingival crevicular fluid during acute infection, although a salivary route of transmission remains an epidemiological association rather than proven. In a cohort of 69 confirmed ANDV-infected cases, salivary secretory immunoglobulin A (sIgA) was significantly elevated (4.846 vs. 0.333 mg/mL in exposed-uninfected contacts), whereas mucins MUC7 and MUC5B were more frequently detected in exposed-but-not-infected household contacts, a cross-sectional finding whose direction of causation is unresolved. Total salivary sIgA is a non-specific marker of mucosal immune activation and has no pathogen specificity. Oral fluid IgM assays for Hantaan virus achieved 96.7% sensitivity and 94.9% specificity against serum reference, supporting further evaluation of non-invasive salivary surveillance. Clinically, severe sore throat persisting for 2 to 3 weeks and oropharyngeal edema are documented as early features of hantavirus infection. Thrombocytopenia, which may be profound during the oliguric phase of HFRS, confers significant oral hemorrhagic risk. Human hantavirus infection presents with clinically significant oral and salivary manifestations that are directly relevant to dental practitioners. Dental teams should be aware of the hemorrhagic risk in patients with thrombocytopenia, the aerosol risk in patients with HCPS, the theoretical risk of ANDV transmission via oral contact in endemic regions, and the emerging utility of salivary diagnostics. Recommendations for dental practice are extrapolated from medical, virological, and general infection control evidence, rather than from dental clinical research, and are identified as precautionary where that is the case.