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Hantavirus Pulmonary Syndrome (HPS), characterized by its high fatality rate, poses a significant public health concern in Argentina due to the increasing evidence of person-to-person transmission of Andes virus. Several orthohantaviruses were described in the country, but their phylogenetic relationships were inferred from partial genomic sequences. The objectives of this work were to assess the viral diversity of the most prevalent orthohantaviruses associated with HPS cases in the Central-East (CE) region of Argentina, elucidate the geographic patterns of distribution of each variant and reconstruct comprehensive phylogenetic relationships utilizing complete genomic sequencing. To accomplish this, a detailed analysis was conducted of the geographic distribution of reported cases within the most impacted province of the region. A representative sample of cases was then selected to generate a geographic map illustrating the distribution of viral variants. Complete viral genomes were obtained from HPS cases reported in the region, including some from epidemiologically linked cases. The phylogenetic analysis based on complete genomes defined two separate clades in Argentina: Andes virus in the Southwestern region and Andes-like viruses in other parts of the country. In the CE region, Buenos Aires virus and Lechiguanas virus clearly segregate in two subclades. Complete genomes were useful to distinguish person-to-person transmission from environmental co-exposure to rodent population. This study enhances the understanding of the genetic diversity, geographical spread, and transmission dynamics of orthohantaviruses in Central Argentina and prompt to consider the inclusion of Buenos Aires virus and Lechiguanas virus in the species Orthohantavirus andesense, as named viruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alonso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease caused by orthohantaviruses in the Americas. In Argentina, since 1995, several reservoirs and virus variants have been described, but the northeastern and central endemic zones in the country include an area without human or rodent infections, despite sharing rodent species with areas with that disease. The aim of this study was to search for orthohantavirus in rodent communities that inhabit this area, which borders two endemic areas of HPS. Small rodents were captured in June of 2022 through a total effort of 644 trap nights distributed in five grids located in the Iberá National Park, Corrientes, Northeastern Argentina. All rodents were sexed, weighed, and the species was recorded. Blood samples were extracted to detect ANDV-specific immunoglobulin G (IgG), and to extract the RNA virus. Trimmed sequences were mapped against reference sequences from GenBank. We captured a total of 36 Oligoryzomys flavescens and 15 Oxymycterus rufus. We detected the O. flavescens species infected with Lechiguanas orthohantavirus in the camping area of the National Park. A nucleotide comparison with previously published sequences shows a 98.34% similarity to the virus obtained from a human case of HPS reported in the adjacent Misiones province. This study demonstrated, for the first time, that O. flavescens is a host of the Lechiguanas orthohantavirus in this zone and contributes to closing information gaps on the distribution of orthohantavirus in Argentina. Additionally, the high similarity with the hantavirus found in the human case of Misiones suggests that the reservoir in that province would also be O. flavescens (not previously confirmed). This information permits us to focus on the preventive measurements to protect the human population., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Previous research conducted in central-east region of Argentina recorded potential orthohantavirus host rodents in diverse environments, but no research has focused particularly on islands, the environments that present the greatest risk to humans. For this reason, the aims of this research were to determine the orthohantavirus host in the rodent community focused on islands of Paraná River Delta, central-east region of Argentina, to identify temporal and spatial factors associated with orthohantavirus prevalence variations, to compare the functional traits of seropositive and seronegative rodents, and to explore the association between orthohantavirus prevalence and rodent community characteristics between August 2014 and May 2018. With a trapping effort of 14,600 trap-nights, a total of 348 sigmodontine rodent specimens belonging to seven species were captured 361 times. The overall antibody prevalence was 4.9%. Particularly, 14.9% of Oligoryzomys flavescens and 1.5% of Oxymycterus rufus, mainly reproductively active adult males, had antibodies against orthohantavirus. Even though O. flavescens inhabit all islands, our results suggest spatial heterogeneity in the viral distribution, with two months after periods of low temperature presenting increases in seroprevalence. This could be a response to the increased proportion of adults present in the rodent population. In addition, an association was found between the high seroprevalence and the diversity of the rodent assemblage. We also found 1.5% of O. rufus exposed to orthohantavirus, which shows us that further investigation of the ecology of the virus is needed to answer whether this species act as a spillover or a new competent host., (© 2023. EcoHealth Alliance.)

We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks., Competing Interests: The authors declare no conflict of interest.

We describe a patient in Argentina with severe acute respiratory syndrome coronavirus 2 infection and hantavirus pulmonary syndrome (HPS). Although both coronavirus disease and HPS can be fatal when not diagnosed and treated promptly, HPS is much more lethal. This case report may contribute to improved detection of co-infections in HPS-endemic regions.

Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8 + T cells are believed to be the central players involved in pathogenesis., Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed., Findings: High numbers of activated CD4 + and CD8 + T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level., Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response., Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) "Dr. Carlos Malbrán". Further details of fundings sources is included in the appendix., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease of the Americas. Eight native rodent species have been identified as HPS virus reservoirs in Argentina. The aim of this work was to detect the orthohantavirus genotypes present in a rodent community that inhabits a zone where a fatal HPS case occurred within an endemic locality of Central Argentina. We captured 27 rodents with a trapping effort of 723 trap nights. We detected 14.3% of infected Akodon azarae with the Pergamino genotype. This result expands the known distribution of this orthohantavirus. Although the Pergamino genotype has not been associated with human cases, the information about its distribution is relevant for risk assessment against potential changes in the virus infectivity., (Copyright © 2021 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Orthohantaviruses (genus Orthohantavirus, family Hantaviridae) are the etiologic agents of Hantavirus Pulmonary Syndrome in the Americas. In South America, orthohantaviruses are highly diverse and are hosted by sigmodontine rodents (subfamiliy Sigmodontinae, family Cricetidae), an also diverse group of rodents. The aims of this work were to (1) identify orthohantavirus hosts and (2) to study the spatial and temporal variations in the prevalence of infection and their associations with community, environmental and individual characteristics, in different environments of Misiones province, northeastern Argentina. Live-capture sessions were carried out during two years in different land uses, with a trapping effort of 31,653 trap nights. We captured 719 individuals from the species Akodon montensis, Rattus rattus, Mus musculus, Calomys tener, Thaptomys nigrita, Oligoryzomys nigripes, Euryoryzomys russatus, Oligoryzomys flavescens, Brucepattersonius sp., and Juliomys pictipes. Antibodies against orthohantavirus were detected in Akodon montensis in one natural protected and one periurban areas, and it was the most abundant species in almost every study sites. We observed the presence of spatial focality of orthohantavirus infection and a positive association with host abundance suggesting the existence of a threshold density. At the individual level, large, reproductively active, and male individuals were more likely to have antibodies against orthohantavirus. This is the first record of orthohantavirus infection in A. montensis in Argentina, which shows the importance of investigations about emerging diseases., (© 2021. EcoHealth Alliance.)

Background: From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions., Methods: Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events., Results: After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission., Conclusions: Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission. (Funded by the Ministerio de Salud y Desarrollo Social de la Nación Argentina and others.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%-50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors., Methodology and Main Findings: We compiled reported HPS cases in northwestern Argentina during the 1997-2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period., Conclusions/significance: This work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks., Competing Interests: The authors have declared that no competing interests exist.

Andes virus is unique among hantaviruses because it can be transmitted from person to person. This mechanism was previously supported by epidemiologic data and genetic evidence based only on partial sequences. We used full-length virus sequencing to confirm person-to-person transmission of this virus in a cluster of 3 cases in Argentina in 2014.

We describe the characterization of the viral genotype involved in the first case of hantavirus pulmonary syndrome reported in Tucumán, a Northwestern province of Argentina. A 23-year-old woman, with no record of travel history and previously diagnosed with an antiphospholipid syndrome, died after 11 days of severe cardiopulmonary insufficiency. Among the four endemic regions of hantavirus pulmonary syndrome in Argentina, the Northwest Region has the highest incidence, exceeding 50% of all reported cases in the country. Until now, only Salta and Jujuy (2 out of the 6 provinces composing the Northwest Region), reported cases of hantavirus pulmonary syndrome, all of which occurred in the Yungas Forest area. Remarkably, the viral genotype characterized in this case showed higher nucleotide identity with the Andes-BsAs genotype most prevalent in Buenos Aires province, located 1400 km apart from Tucumán, than with any of the commonly found genotypes in the Northwest Region. The Andes-BsAs genotype has been associated with 30% lethality and interhuman transmission in Buenos Aires province. Interhuman transmission cannot be ruled out in the present case.

Andes virus is the causative agent of hantavirus pulmonary syndrome (HPS) in Argentina and neighboring countries. In our country four different areas are affected: Northwest, Southwest, Central and Northeast, where distinct Andes virus genotypes were characterized. Three genotypes were described in Buenos Aires province (Central area): AND-Buenos Aires, AND-Lechiguanas and AND-Plata. In this work, we considered all HPS cases confirmed by ELISA and real time RT-PCR during the period 2009-2014 in Buenos Aires province. The annual distribution, fatality rate and geographic distribution were analyzed. We also analyzed the genotypes involved by RT-PCR and nucleotide sequencing. Finally we evaluated epidemiological data in order to establish the route of transmission. We analyzed 1386 suspect cases of hantavirus infection from Buenos Aires province and we confirmed 88 cases of Hantavirus Pulmonary Syndrome during 2009-2014. The overall average was 14.3 cases per year. The occurrence of a HPS outbreak was confirmed in Buenos Aires province during 2013, showing a 3 fold increase in case number compared to the annual average between 2009 and 2012, tending to normalize during 2014. The overall lethality was 25.6%, with a maximum value of 45.5% in 2011. Genotype analysis was performed in 30.7% of confirmed cases, AND-BsAs show the highest incidence, it was characterized in 72% of the studied cases. Epidemiological data and results of viral genome comparison strongly suggest person-to-person transmission in the three clusters of two cases described in our study.

Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary., (© 2015 Wiley Periodicals, Inc.)

We report a large case series of hantavirus pulmonary syndrome (HPS) in Argentina that was confirmed by laboratory results from 1995 through 2008. The geographic and temporal distribution of cases by age, sex, fatality rate, and risk factors for HPS was analyzed. A total of 710 cases were unequally distributed among 4 of the 5 Argentine regions. Different case-fatality rates were observed for each affected region, with a maximum rate of 40.5%. The male-to-female ratio for HPS case-patients was 3.7:1.0; the case-fatality rate was significantly higher for women. Agriculture-associated activities were most commonly reported as potential risk factors, especially among men of working age. Although HPS cases occurred predominantly in isolation, we identified 15 clusters in which strong relationships were observed between members, which suggests ongoing but limited person-to-person transmission.

After the Hantavirus Pulmonary Syndrome (HPS) outbreak occurred in Southern Argentina (Patagonia) in 1996, a new mechanism of hantavirus spread was described for Andes virus (AND): person-to-person transmission. Since then, this mode of transmission has been limited to the endemic area of AND Sout lineage. We report here an HPS case, patient A, with residence in Buenos Aires Province, whose unique epidemiological risk factor was to have shared a trip to Southern Argentina with an already ill person, later confirmed as an HPS case (patient I). A third case (patient B), with residence in Buenos Aires Province, developed HPS after several contact events with patient A, with no additional risk factors. Hantavirus infection was confirmed in all three patients by serological diagnosis and viral genetic characterization. The viral lineage characterized was AND Sout, being the same strain in the three cases. The clinical picture of patient A showed profound compromise, with gastrointestinal symptoms, with no clinical evidence of pulmonary involvement. In this work we present new evidence supporting person-to-person transmission for AND Sout lineage, where there was an only contact with the index case, occasional, prolonged and non-repeated, established out of the endemic area for AND Sout lineage.