Hantavirus pulmonary syndrome (HPS) is an American emerging disease caused by the rodent-borne virus genus Orthohantavirus (Family: Hantaviridae: Order: Elliovirales Class: Bunyaviricetes). In Argentina, almost half of the HPS infections occur in the northwestern endemic region. In this study, we monitored rodent abundance during 2022 and 2023 in three sites with different sampling methods (removal trapping, live trapping and hunted rodents by domestic cats) to evaluate their relationship with human infections. We found a similar pattern of variation in rodent abundance across time, and particularly a synchronous rise of rodent abundance that anticipated an HPS outbreak in 2023. Our dynamic regression models revealed a positive relationship between HPS cases and rodent abundance with a three-month lag, as well as rainfall with an eight-month lag. Our results provide a framework for the planning and implementation of public health prevention campaigns based on climatology and rodent monitoring. Domestic cats bringing rodents into houses can be an overlooked risk factor, particularly if viral shedding of infected rodents is magnified by stress. HPS is a disease of public health concern due to its high mortality rate, the lack of a specific therapeutic treatment and no vaccine. Thus, prevention of infections is of the utmost importance.

In this work, we performed the genetic characterization of a new variant of orthohantavirus associated with a fatal case of hantavirus pulmonary syndrome, outside the known endemic region, in northwestern Argentina. We first confirmed an orthohantavirus infection by ELISA, testing for the detection of IgM and IgG antibodies. Then, we extracted RNA from 100 microliters of serum, the only sample available, followed by RT-PCR. The amplicons were sequenced using Sanger and next-generation sequencing technology. We obtained partial sequences of 1253 bp, 799 bp and 1675 bp from the S-, M- and L-segments, respectively, showing low sequence identities with all the previously characterized hantaviruses (10.9%, 13.5% and 15.1% of the divergence, respectively). The phylogenetic analysis showed that this virus belongs to the Orthohantavirus andesense species (ANDV), and among the ANDV-like variants, it is more closely related to the Lechiguanas clade. Similar percentages of divergence were considered sufficient to distinguish AND-like variants in previous works. As the patient had no travel history before the onset of disease was reported, we conducted rodent surveys to confirm the presence of reservoirs. The rodent assemblage was compatible with the transitional zone among different ecoregions (Yungas, Chaco and Monte). Moreover, one of the species captured, Oligoryzomys flavescens, was previously described as a reservoir of hantavirus. This species may either host several variants across its range or encompass a species complex, as proposed by some authors.