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.