Introduction
Hantaviruses (Bunyaviricetes: Elliovirales: Hantaviridae: Mammantavirinae) are enveloped, single stranded, negative sense RNA viruses with three-segmented genome. The genomic segments consist of a small segment (S), a medium segment (M), and a large segment (L), which encode the nucleocapsid (N) protein, a nonstructural protein (NSs) in some species, surface glycoproteins (Gn and Gc), and an RNA-dependent RNA polymerase (RdRp), respectively [1]. Hantaviruses are distributed worldwide and are hosted by various vertebrate animal species. Pathogenic hantaviruses are primarily associated with rodents as natural reservoirs and are classified under the genus Orthohantavirus. These viruses establish seemingly asymptomatic and chronic infections in several rodent species. The risks of viral spillover have increased due to new farming practices, climate change, the expansion of rural human settlements, and disruptions to the zoonotic interface. Additionally, rural tourism has led to travel-related cases [2–4].
Several species of orthohantaviruses are responsible for Hantavirus Pulmonary Syndrome (HPS) in the Americas and Hemorrhagic Fever with Renal Syndrome (HFRS) in Asia and Europe. HPS, first described in 1993 in the US [5], is caused by at least 24 distinct viruses [6]. In Argentina, most HPS cases are caused by 7 viruses closely related to Andes virus (ANDV), species Orthohantavirus andesense. ANDV was the first hantavirus characterised in Argentina [7]. It was associated with the long-tailed pygmy rice rat Oligoryzomys longicaudatus in the Patagonian Andean region. After human infection, the signs and symptoms of the disease can manifest after a long period of up to 40 days [8,9]. Severe cases had progressive pulmonary edema, hypoxia and hypotension; fatal cases had a severe compromise in hemodynamic function. ANDV-HPS is associated with high case-lethality rates ranging from 21–50% [10,11].
Humans generally become infected through the inhalation of aerosolized rodent excreta. Before 1996, the route of orthohantavirus transmission was considered strictly zoonotic, resulting in “dead-end” human infections [7]. However, in 1996, an ANDV-caused HPS outbreak occurred in the small city of El Bolsón and then expanded to distant cities, such as Bariloche (121 km) and Buenos Aires (1700 km), involving 16 epidemiologically linked cases. This outbreak became a focal point for orthohantavirus research because molecular and epidemiological evidence suggested person-to-person (PTP) transmission [12,13]. A larger PTP transmission outbreak that began in 2018 and involved 34 cases and was curtailed by the implementation of strict quarantine measures. In this outbreak, several individuals were identified as superspreaders, predicting the high transmission potential of this strain [10].
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