Understanding machupo virus: A neglected arenavirus with global health importance

Machupo virus (MACV), classified within the Mammarenavirus genus of the Arenaviridae family, serves as the causative agent of Bolivian hemorrhagic fever (BHF), a life-threatening zoonosis primarily confined to rural regions of Bolivia's Beni Department. First identified in 1959 during epidemics in San Joaquín, this bisegmented, ambisense, single-stranded RNA virus exhibits 20%-35% case-fatality rates, with highest lethality among children under 5 and adults over 55. The vesper mouse (Calomys callosus) acts as the principal reservoir, sustaining lifelong asymptomatic infections and shedding virus through excreta, facilitating human spillover via aerosol inhalation, contaminated food, or direct contact-predominant in agrarian settings. Clinically, BHF follows a 5-21 days incubation with initial nonspecific febrile prodrome (fever, myalgia, prostration) evolving into hemorrhagic diathesis (petechiae, mucosal bleeds), neurological signs (tremors, delirium), leukopenia/thrombocytopenia, and shock. Pathogenesis hinges on transferrin receptor 1-mediated endothelial tropism, type I interferon suppression (NP/Z), and cytokine storms, recapitulated in guinea pig/primate models. Designated Centers for Disease Control and Prevention Category A and biosafety level (BSL)-4, MACV constrains research; diagnostics demand reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, or isolation in maximum containment. Supportive therapy prevails, augmented by off-label ribavirin (preclinical efficacy) and convalescent plasma; Candid 1 (Junín-attenuated) cross-protects informally. This review details MACV's genomic organization (L/S segments encoding L/Z, NP/GPC), epidemiology, etiology, and advances: Reverse genetics for antivirals, GP-specific mAbs (100% guinea pig survival), multi-epitope vaccines, and high-throughput screening entry inhibitors. One health imperatives-rodent control, artificial intelligence surveillance, and Bolivian BSL-3 expansion-counter ecological drivers like deforestation. Amid climate, prioritizing global collaborations will forge resilient countermeasures, leveraging MACV as a sentinel for new world arenavirus threats.