Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study.

BACKGROUND: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated. METHODS: Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50). RESULTS: While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197. CONCLUSIONS: This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response. Clinical Trials Registration. NCT03682107.

Filling the gaps in the Argentinian distribution of orthohantavirus: First finding of Lechiguanas virus in rodents from Corrientes, Argentina.

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.

Hantavirus Pulmonary Syndrome Caused by Puumala Orthohantavirus-A Case Report and Literature Review.

In this article, we report on a rare case of acute respiratory distress syndrome (ARDS) caused by the Puumala orthohantavirus (PUUV), which is typically associated with hemorrhagic fever with renal syndrome (HFRS). This is the first documented case of PUUV-associated ARDS in Southeast Europe. The diagnosis was confirmed by serum RT-PCR and serology and corroborated by phylogenetic analysis and chemokine profiling. The patient was a 23-year-old male from Zagreb, Croatia, who had recently traveled throughout Europe. He presented with fever, headache, abdominal pain, and sudden onset of ARDS. Treatment involved high-flow nasal cannula oxygen therapy and glucocorticoids, which resulted in a full recovery. A systematic literature review identified 10 cases of hantavirus pulmonary syndrome (HPS) caused by PUUV in various European countries and Turkey between 2002 and 2023. The median age of patients was 53 years (range 24-73), and six of the patients were male. Most patients were treated in intensive care units, but none received antiviral therapy targeting PUUV. Eight patients survived hospitalization. The presented case highlights the importance of considering HPS in the differential diagnosis of ARDS, even in areas where HFRS is the dominant form of hantavirus infection.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Novel Ozark Orthohantavirus in Hispid Cotton Rats (Sigmodon hispidus), Arkansas, USA.

We report a novel orthohantavirus, putatively named Ozark orthohantavirus, in hispid cotton rats captured within the Ozark Plateau in Arkansas, USA. This virus phylogenetically clusters with other orthohantaviruses that cause severe human disease. Continued orthohantavirus surveillance and virus sequencing are needed to address the potential public health threat of this virus.

Detection of Hantavirus during the COVID-19 Pandemic, Arizona, USA, 2020.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

A Brief History of Bunyaviral Family Hantaviridae.

The discovery of Hantaan virus as an etiologic agent of hemorrhagic fever with renal syndrome in South Korea in 1978 led to identification of related pathogenic and nonpathogenic rodent-borne viruses in Asia and Europe. Their global distribution was recognized in 1993 after connecting newly discovered relatives of these viruses to hantavirus pulmonary syndrome in the Americas. The 1971 description of the shrew-infecting Hantaan-virus-like Thottapalayam virus was long considered an anomaly. Today, this virus and many others that infect eulipotyphlans, bats, fish, rodents, and reptiles are classified among several genera in the continuously expanding family Hantaviridae.

Acute Hantavirus Infection Presenting With Fever and Altered Mentation in the Absence of Pulmonary or Renal Manifestations.

Illness caused by hantaviruses is often severe and is typically characterized by diffuse pulmonary disease or renal insufficiency depending on the type of hantavirus. Here we report 2 cases of hantavirus infection that resulted in severe cognitive impairment but did not have any pulmonary or renal manifestations. These 2 cases may be indicative of previously underreported symptoms of hantavirus infection and might represent examples of hantavirus-related encephalopathy.

Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor.

Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hantavirus infection, and they also indicate the need for further research in vivo.

Factores pronósticos de síndrome cardio-pulmonar y muerte por hantavirus Andes Sur: estudio de cohorte en San Carlos de Bariloche y su zona de influencia sanitaria / Prognostic factors for cardio-pulmonary syndrome and death by hantavirus Andes Sur: cohort study in San Carlos de Bariloche and health influence área

Resumen Las infecciones por hantavirus, ocurren a través de la inhalación de aerosoles provenientes de excretas de roedores infectados. Estos virus causan síndrome cardiopulmonar en el caso de la variante Andes Sur, con una mortalidad que puede alcanzar el 50%. Se presenta como casos esporádicos o en pequeños conglomerados, en los que predomina el contagio interhumano. En este estudio observacional de tipo cohorte histórica, en personas infectadas con hantavirus Andes Sur durante los años 2009 a 2019 que fueron asistidas en el subsector público de salud de San Carlos de Bariloche(Argentina), se buscó identificar factores que pudieran predecir mala evolución (síndrome cardiopulmonar y muerte). Para ello se caracterizó el riesgo para cada una de las variables y, para obtener información clave sobre las relaciones entre las mismas, se aplicó además un análisis de correspondencias múltiples. Durante el período de estudio, 38 personas fueron incluidas. La edad media fue de 35 años. Se sospechó contagio de persona a persona en 10/38 (26.8%) casos. El 21.1% (8/28) tuvo al momento del diagnóstico un síndrome pulmonar por hantavirus. Mientras que, 55.3% (21/38) lo desarrolló durante su evolución y 44.7% (17/38) de los infectados fallecieron durante la internación. La edad mayor a 15 años y la plaquetopenia, se asociaron con un mayor riesgo de progresión clínica, mientras que las formas de leves o las personas asintomáticas, el contagio persona a persona o durante un brote epidemiológico, se asociaron con un menor riesgo de muerte.

Abstract Hantavirus infections occur through the inhalation of aerosols from the excreta of infected rodents. These viruses cause a cardiopulmonary syn drome in the case of the Andes Sur variant, with a mortality that can reach 50%. It occurs in sporadic cases or in small clusters, in which interhuman contagion predominates. In this historical cohort-type observational study, in people infected with Andes Sur hantavirus during the years 2009 to 2019 who was assisted in the public health subsector of San Carlos de Bariloche (Argentina), it was sought to identify factors that could predict poor evolution (cardiopulmonary syndrome and death). For this, the risk for each of the variables was characterized and, to obtain key information about the relationships between them, a multiple correspondence analysis was also applied. During the study period, 38 people were included. The mean age was 35 years. Person-to-person contagion was suspected in 10/38 (26.8%) cases. 21.1% (8/28) presented a hantavirus pulmonary syndrome at the time of diagnosis, while 55.3% (21/38) developed it during their evolution, and 44.7% (17/38) of those infected died during hospitalization. Age over 15 years and thrombocytopenia were associated with a higher risk of clinical progression, while mild forms or asymptomatic people, person-to-person transmission, or during an epidemiological outbreak, were associated with a lower risk of death.

[Prognostic factors for cardio-pulmonary syndrome and death by hantavirus Andes Sur: cohort study in San Carlos de Bariloche and health influence area]. / Factores pronósticos de síndrome cardiopulmonar y muerte por hantavirus Andes Sur: Estudio de cohorte en San Carlos de Bariloche y su zona de influencia sanitaria.

Hantavirus infections occur through the inhalation of aerosols from the excreta of infected rodents. These viruses cause a cardiopulmonary syndrome in the case of the Andes Sur variant, with a mortality that can reach 50%. It occurs in sporadic cases or in small clusters, in which interhuman contagion predominates. In this historical cohort-type observational study, in people infected with Andes Sur hantavirus during the years 2009 to 2019 who was assisted in the public health subsector of San Carlos de Bariloche (Argentina), it was sought to identify factors that could predict poor evolution (cardiopulmonary syndrome and death). For this, the risk for each of the variables was characterized and, to obtain key information about the relationships between them, a multiple correspondence analysis was also applied. During the study period, 38 people were included. The mean age was 35 years. Person-to-person contagion was suspected in 10/38 (26.8%) cases. 21.1% (8/28) presented a hantavirus pulmonary syndrome at the time of diagnosis, while 55.3% (21/38) developed it during their evolution, and 44.7% (17/38) of those infected died during hospitalization. Age over 15 years and thrombocytopenia were associated with a higher risk of clinical progression, while mild forms or asymptomatic people, person-to-person transmission, or during an epidemiological outbreak, were associated with a lower risk of death.

Las infecciones por hantavirus, ocurren a través de la inhalación de aerosoles provenientes de excretas de roedores infectados. Estos virus causan síndrome cardiopulmonar en el caso de la variante Andes Sur, con una mortalidad que puede alcanzar el 50%. Se presenta como casos esporádicos o en pequeños conglomerados, en los que predomina el contagio interhumano. En este estudio observacional de tipo cohorte histórica, en personas infectadas con hantavirus Andes Sur durante los años 2009 a 2019 que fueron asistidas en el subsector público de salud de San Carlos de Bariloche(Argentina), se buscó identificar factores que pudieran predecir mala evolución (síndrome cardiopulmonar y muerte). Para ello se caracterizó el riesgo para cada una de las variables y, para obtener información clave sobre las relaciones entre las mismas, se aplicó además un análisis de correspondencias múltiples. Durante el período de estudio, 38 personas fueron incluidas. La edad media fue de 35 años. Se sospechó contagio de persona a persona en 10/38 (26.8%) casos. El 21.1% (8/28) tuvo al momento del diagnóstico un síndrome pulmonar por hantavirus. Mientras que, 55.3% (21/38) lo desarrolló durante su evolución y 44.7% (17/38) de los infectados fallecieron durante la internación. La edad mayor a 15 años y la plaquetopenia, se asociaron con un mayor riesgo de progresión clínica, mientras que las formas de leves o las personas asintomáticas, el contagio persona a persona o durante un brote epidemiológico, se asociaron con un menor riesgo de muerte.

Expanded distribution of orthohantavirus Pergamino genotype: First record in Entre Rios province, Argentina / Ampliación de la distribución del Orthohantavirus genotipo Pergamino: Primer registro en la Provincia de Entre Ríos, Argentina

Abstract 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 commu-nity 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.

Resumen El síndrome pulmonar por hantavirus (SPH) es una enfermedad infecciosa emergente en América. Ocho especies de roedores nativos han sido identificadas como reservorios del virus causante del SPH en la Argentina. El objetivo de este trabajo fue detectar los genotipos de orthohantavirus presentes en una comunidad de roedores que habita en una zona donde ocurrió un caso fatal de SPH, en una localidad endémica de Argentina central. Se capturaron 27 individuos con un esfuerzo de 723 trampas-noche. Se detectó un 14,3% de Akodon azarae infectados con el genotipo pergamino. Este resultado amplía el conocido rango de distribución de este orthohantavirus. A pesar de que el genotipo pergamino no ha sido asociado con casos humanos hasta el momento, la información sobre su distribución es relevante para analizar el riesgo ante un potencial cambio en la infectividad del virus.

Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome.

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.

Evidence for Human-to-Human Transmission of Hantavirus: A Systematic Review.

BACKGROUND: Hantavirus is known to be transmitted from rodents to humans. However, some reports from Argentina and Chile have claimed that the hantavirus strain Andes virus (ANDV) can cause human-to-human transmission of the disease. The aim of this systematic review was to assess the evidence for human-to-human transmission of hantavirus. METHODS: We searched PubMed (inception to 28 February 2021), Cochrane Central, Embase, LILACS and SciELO (inception to 3 July 2020), and other sources. We included studies that assessed whether interpersonal contact with a person with laboratory-confirmed hantavirus infection led to human-to-human transmission. Two reviewers conducted screening, selection, data extraction, and risk of bias assessment. RESULTS: Twenty-two studies met the inclusion criteria. Meta-analysis was not possible due to heterogeneity. With the exception of 1 prospective cohort study of ANDV in Chile with serious risk of bias, evidence from comparative studies (strongest level of evidence available) does not support human-to-human transmission of hantavirus infection. Noncomparative studies with a critical risk of bias suggest that human-to-human transmission of ANDV may be possible. CONCLUSIONS: The balance of the evidence does not support the claim of human-to-human transmission of ANDV. Well-designed cohort and case-control studies that control for co-exposure to rodents are needed to inform public health recommendations.

Expanded distribution of orthohantavirus Pergamino genotype: First record in Entre Rios province, Argentina.

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.

Case Report: First Confirmed Case of Coinfection of SARS-CoV-2 With Choclo orthohantavirus.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a major international public health concern. The World Health Organization (WHO) declared the pandemic of coronavirus disease 2019 (COVID-19) on March 11, 2020. In Panama, the first SARS-CoV-2 infection was confirmed on March 9, 2020, and the first fatal case associated to COVID-19 was reported on March 10. This report presents the case of a 44-year-old female who arrived at the hospital with a respiratory failure, five days after the first fatal COVID-19 case, and who was living in a region where hantavirus pulmonary syndrome cases caused by Choclo orthohantavirus (CHOV), are prevalent. Thus, the clinical personnel set a differential diagnosis to determine a respiratory disease caused by the endemic CHOV or the new pandemic SARS-CoV-2. This case investigation describes the first coinfection by SARS-CoV-2 and CHOV worldwide. PCR detected both viruses during early stages of the disease and the genomic sequences were obtained. The presence of antibodies was determined during the patient's hospitalization. After 23 days at the intensive care unit, the patient survived with no sequelae, and antibodies against CHOV and SARS-CoV-2 were still detectable 12 months after the disease. The detection of the coinfection in this patient highlights the importance, during a pandemic, of complementing the testing and diagnosis of the emergent agent, SARS-CoV-2, with other common endemic respiratory pathogens and other zoonotic pathogens, like CHOV, in regions where they are of public health concern.

First Evidence of Akodon-Borne Orthohantavirus in Northeastern Argentina.

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.

Hantaviruses in Agricultural and Forestry Workers: Knowledge, Attitudes and Practices in Italian Physicians.

Hantaviruses are viral pathogens usually endemic in rodent populations. Human exposure follows inhalation of dusts contaminated with rodent excreta, and most individuals have been infected in occupational settings heavily contaminated with rodent droppings, such as agricultural and forestry. To date, knowledge, attitudes and practices of medical professionals, especially occupational physicians (OP), regarding hantavirus disease in at-risk workers have been scarcely investigated. We investigated these topics through a structured questionnaire administered through an online survey of 223 medical professionals (42.2% of them working as OP). Adequate general knowledge of hantavirus disease was found in 48.9% of respondents, with OP exhibiting a better understanding of clinical features of human hantavirus infections. OP aware of the endemic status of hantavirus in North-Eastern Italy exhibited higher risk perception for agricultural workers (odds ratio 21,193, 95% confidence interval 3.666-122.505). On the contrary, a better knowledge of hantaviruses was association with acknowledging an increased risk of hantavirus infection in forestry workers (odds ratio 5.880, 95% confidence interval 1.620-21.343). Hantavirus in Italy represent an often-overlooked biological risk in occupational settings. The lack of preventive immunization, the inappropriate risk perception and the unsatisfying awareness of hantavirus issues collectively stress the importance of appropriate information campaigns among health care providers.

The 1993 Hantavirus Pulmonary Syndrome Outbreak and Lessons for Today.

While grappling with the implications of the current COVID-19 pandemic, we have perhaps overlooked recent history dealing with previous outbreaks. In the spring of 1993, America was presented with an outbreak of Hantavirus Pulmonary Syndrome caused by the Sin Nombre virus. This article recounts the investigation into this disease and discusses the spectrum of issues that medical communities must face as it deals with a mysterious outbreak.