[Environmental factors and cardiopulmonary syndrome due to hanta virus in Chile]. / Factores ambientales y síndrome cardiopulmonar por virus hanta en Chile.

OBJECTIVE: Evaluate the relationship between ambient temperature, relative humidity and particulate matter 2,5 with the number of cases Hantavirus Cardiopulmonary Syndrome in Chile between 2015 and 2017. METHODS: Observational, cross-sectional study in 197 cases of Hantavirus Cardiopulmonary Syndrome reported and confirmed, occurring between 2015 and 2017 in Chile. RESULTS: Positive and significant relationship was identified between ambient temperature and number of cases of Hantavirus Cardiopulmonary Syndrome and a negative and significant relationship between the number of cases Hantavirus Cardiopulmonary Syndrome and the relative humidity. Also, ambient temperature together with particulate matter 2,5 was observed to increase significantly the number of cases of Hantavirus Cardiopulmonary Syndrome. CONCLUSIONS: Environmental factors are related to the number of cases Hantavirus Pulmonary Syndrome in Chile between the years 2015 to 2017.

OBJETIVO: Evaluar la relación entre la temperatura ambiente, humedad relativa y el material particulado ambiental 2,5 con el número de casos de síndrome cardiopulmonar por virus hanta en Chile durante el periodo 2015-2017. MÉTODOS: Estudio observacional transversal en 197 casos de síndrome cardiopulmonar por virus hanta notificados y confirmados, ocurridos entre los años 2015 y 2017 en Chile. Se realizó análisis bi- y multivariado entre variables de estudio. RESULTADOS: Se determinó una relación positiva y significativa entre temperatura ambiente y número de casos de Síndrome Cardiopulmonar por virus Hanta y una relación negativa y significativa entre el número de casos de Síndrome Cardiopulmonar por virus Hanta y la humedad relativa. Además se observó que la temperatura ambiental junto con material particulado 2,5 aumentan significativamente el número de casos de Síndrome Cardiopulmonar por virus Hanta. CONCLUSIONES: Los factores ambientales están relacionados con el número de casos de síndrome cardiopulmonar por virus Hanta en Chile entre los años 2015 y 2017.

Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain.

Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.

[Estimates of the spatial distribution of the relative risk of mortality of the main zoonoses in Chile: Chagas disease, hydatidosis, Hantavirus cardiopulmonary syndrome and leptospirosis]. / Estimaciones de la distribución espacial del riesgo relativo de mortalidad por las principales zoonosis en Chile: enfermedad de Chagas, hidatidosis, síndrome cardiopulmonar por hantavirus y leptospirosis.

BACKGROUND: Zoonoses are infections caused by all types of etiological transmissible agents from vertebrate animals to humans. During the last decades, the risk to health caused by different zoonoses has been a consequence of the natural distribution of the different etiological agents and by the emergence and reemergence of these diseases. AIM: To study the distribution of the risk of mortality of the four main zoonoses in continental Chile, based on national mortality data, with the objective of visualizing geographically where to focus the control efforts of these diseases. METHODS: Relative risk was estimated by means of Bayesian Statistics. RESULTS: The distribution in Chile of the main zoonoses was obtained. DISCUSSION/CONCLUSION: The risk maps obtained show a parasitic disease transmitted by high-risk vectors in the north, Chagas disease; a parasitic disease of biological communities in which man is an accidental host, associated with livestock areas, more prevalent in the south, hydatidosis; a bacterial disease transmitted by vertebrates, especially by rodents, where water is an important vehicle, dominant in the center, leptospirosis; and a viral disease transmitted by rodents, very dominant in the south, the hantavirus infection.

Estimaciones de la distribución espacial del riesgo relativo de mortalidad por las principales zoonosis en Chile: enfermedad de Chagas, hidatidosis, síndrome cardiopulmonar por hantavirus y leptospirosis / Estimates of the spatial distribution of the relative risk of mortality of the main zoonoses in Chile: Chagas disease, hydatidosis, Hantavirus cardiopulmonary syndrome and leptospirosis

Resumen Introducción: Las zoonosis son enfermedades o infecciones causadas por todo tipo de agentes etiológicos transmisibles desde animales vertebrados a humanos. Durante las últimas décadas, el riesgo para la salud ocasionado por diferentes zoonosis, ha sido generado por la distribución natural de los distintos agentes etiológicos y por la emergencia y reemergencia de estas enfermedades. Objetivo: Estudiar la distribución del riesgo de mortalidad de las cuatro principales zoonosis en Chile continental, basados en datos nacionales de mortalidad, con el objetivo de visualizar geográficamente donde focalizar los esfuerzos de control de estas enfermedades. Metodología: Se estima el riesgo relativo de las principales zoonosis en Chile, mediante estadística Bayesiana. Resultados: Se obtuvo la distribución de las cuatro principales zoonosis de Chile. Discusión/Conclusión: Se obtuvo la distribución de las cuatro principales zoonosis de Chile. Los mapas de riesgo obtenidos muestran una enfermedad parasitaria transmitida por vectores de alto riesgo en el norte, la enfermedad de Chagas; una enfermedad parasitaria de comunidades biológicas en que el hombre es un hospedero accidental, asociada a zonas ganaderas, prevalente en el sur, la hidatidosis; una enfermedad bacteriana transmitida por vertebrados, especialmente por roedores, donde el agua es un vehículo importante, dominante en el centro, la leptospirosis; y una enfermedad viral transmitida por roedores, muy dominante en el sur, la infección por hantavirus.

Background: Zoonoses are infections caused by all types of etiological transmissible agents from vertebrate animals to humans. During the last decades, the risk to health caused by different zoonoses has been a consequence of the natural distribution of the different etiological agents and by the emergence and reemergence of these diseases. Aim: To study the distribution of the risk of mortality of the four main zoonoses in continental Chile, based on national mortality data, with the objective of visualizing geographically where to focus the control efforts of these diseases. Methods: Relative risk was estimated by means of Bayesian Statistics. Results: The distribution in Chile of the main zoonoses was obtained. Discussion/Conclusion: The risk maps obtained show a parasitic disease transmitted by high-risk vectors in the north, Chagas disease; a parasitic disease of biological communities in which man is an accidental host, associated with livestock areas, more prevalent in the south, hydatidosis; a bacterial disease transmitted by vertebrates, especially by rodents, where water is an important vehicle, dominant in the center, leptospirosis; and a viral disease transmitted by rodents, very dominant in the south, the hantavirus infection.

Serological diagnosis of hantavirus pulmonary syndrome in a febrile patient in Colombia.

Hantavirus pulmonary syndrome (HPS) is an often fatal rodent-borne zoonosis caused by any of at least 20 hantavirus genotypes distributed throughout the Americas. Although HPS has been documented in several bordering countries, it has not been reported in Colombia. Here we report seroconversion to a hantavirus in paired samples from a hospitalized patient with symptoms compatible with HPS from Montería, Córdoba Department, north-western Colombia. Tests for regionally endemic agents including Plasmodium, Leptospira, Salmonella, dengue virus, Brucella, Rickettsia, human immunodeficiency virus and hepatitis viruses were negative. Because the patient was enrolled in a clinical trial for hemorrhagic fevers conducted by the University of Córdoba, serum samples were collected on admission and at discharge. Testing using Sin Nombre virus ELISA showed IgG and IgM seroconversion between samples. The eventual finding of this first clinical case of hantavirus infection in Colombia is consistent with the high prevalence of hantavirus antibodies in humans in the region and the likely exposure of the patient to rodents. The clinical presentation was similar to that found in neighbouring Panama.

Hantavirus regulation of endothelial cell functions.

Hantaviruses cause two vascular permeability-based diseases and primarily infect endothelial cells which form the primary fluid barrier of the vasculature. Since hantavirus infections are not lytic, the mechanisms by which hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) or Hantavirus Pulmonary Syndrome (HPS) are indeterminate. HPS is associated with acute pulmonary oedema and HFRS with moderate haemorrhage and renal sequelae, perhaps reflecting the location of vast microvascular beds and endothelial cell reservoirs available for hantavirus infection. Endothelial cells regulate capillary integrity, and hantavirus infection provides a primary means for altering vascular permeability that contributes to pathogenesis. The central importance of endothelial cells in regulating oedema, vascular repair, angiogenesis, immune cell recruitment, platelet deposition as well as gas exchange and solute delivery suggest that a multitude of inputs and cellular responses may be influenced by hantavirus infection and contribute to pathogenic changes in vascular permeability. Here we focus on understanding hantavirus interactions with endothelial cells which are linked to vascular permeability, and provide insight into the contribution of endothelial cell responses in hantavirus pathogenesis.

Atualização de conhecimentos sobre a patogênese da síndrome pulmonar e cardiovascular por hantavírus / Updating knowledge about hantavirus cardiopulmonary syndrome pathogenesis

A Síndrome Pulmonar e Cardiovascular por Hantavírus (SPCVH) é uma doença grave e com elevada taxa de letalidade. Decorrente da infecção humana por hantavírus, ela vem ocorrendo em número crescente de casos em diversos países das Américas, inclusive no Brasil. A pneumonite intersticial, o edema pulmonar e o choque cardiogênico, que caracterizam a doença, ocorrem, em grande parte, em virtude da ativação da resposta imune, especialmente linfócitos T CD8(mais) e macrófagos, ambos produtores de citocinas inflamatórias. Embora as células endoteliais, alvos da infecção viral, produzam uma resposta antiviral de interferon, muitas espécies de hantavírus podem inibir ou retardar ativamente tais respostas. Além disso, os hantavírus exercem efeito inibidor sobre receptores celulares responsáveis pela manutenção da integridade vascular. Quadros clínicos de maior gravidade também têm sido associados a elevadas cargas virais. Inversamente, anticorpos neutralizantes parecem exercer um efeito protetor contra as formas graves. Neste artigo são tratados, de forma detalhada, aspectos relevantes da patogênese da SPCVH.

Two cases of hantavirus pulmonary syndrome in Randolph County, West Virginia: a coincidence of time and place?

Hantavirus pulmonary syndrome (HPS) is caused by an infection with viruses of the genus Hantavirus in the western hemisphere. Rodent hosts of hantaviruses are present throughout the United States. In July 2004, two HPS case-patients were identified in Randolph County, WV: a wildlife science graduate student working locally and a Randolph County resident. We interviewed family members and colleagues, reviewed medical records, and conducted environmental studies at likely exposure sites. Small mammals were trapped, and blood, urine, and tissue samples were submitted to the Centers for Disease Control and Prevention for laboratory analyses. These analyses confirmed that both patients were infected with Monongahela virus, a Sin Nombre hantavirus variant hosted by the Cloudland deer mouse, Peromyscus maniculatus nubiterrae. Other than one retrospectively diagnosed case in 1981, these are the first HPS cases reported in West Virginia. These cases emphasize the need to educate the public throughout the United States regarding risks and prevention measures for hantavirus infection.

Corticosteroids combined with continuous veno-venous hemodiafiltration for treatment of hantavirus pulmonary syndrome caused by Puumala virus infection.

Reported here are two cases of hantavirus pulmonary syndrome caused by Puumala virus infection, which rapidly resolved after initiation of corticosteroid treatment combined with continuous veno-venous hemodiafiltration. These cases emphasize the role of the inflammatory response in the pathogenesis of hantavirus pulmonary syndrome.

Bidirectional virus secretion and nonciliated cell tropism following Andes virus infection of primary airway epithelial cell cultures.

Hantavirus pulmonary syndrome (HPS) is an acute disease resulting from infection with any one of a number of New World hantaviruses. HPS has a mortality rate of 40% and, unlike many other severe respiratory diseases, often occurs in young, healthy adults. Infection is usually initiated after inhalation of rodent excreta containing virus particles, but human-to-human transmission has been documented. Postmortem tissue samples show high levels of viral antigen within the respiratory endothelium, but it is not clear how the virus can traverse the respiratory epithelium in order to initiate infection in the microvasculature. We have utilized Andes virus infection of primary, differentiated airway epithelial cells to investigate the ability of the virus to interact with and cross the respiratory epithelium. Andes virus infects the Clara and goblet cell populations but not the ciliated cells, and this infection pattern corresponds to the expression of beta(3) integrin, the viral receptor. The virus can infect via the apical or basolateral membrane, and progeny virus particles are secreted bidirectionally. There is no obvious cytopathology associated with infection, and beta(3) integrins do not appear to be critical for respiratory epithelial cell monolayer integrity. Our data suggest that hantavirus infection of the respiratory epithelium may play an important role in the early or prodrome phase of disease as well as serving as a source of virus involved in transmission.

Hantavirus pulmonary syndrome in northwestern Argentina: circulation of Laguna Negra virus associated with Calomys callosus.

The purpose of this study was to characterize the hantaviruses circulating in northwestern Argentina. Human and rodent studies were conducted in Yuto, where most cases of hantavirus pulmonary syndrome (HPS) occur. Partial virus genome sequences were obtained from the blood of 12 cases of HPS, and from the lungs of 4 Calomys callosus and 1 Akodon simulator. Phylogenetic analysis showed that three genotypes associated with HPS circulate in Yuto. Laguna Negra (LN) virus, associated with C. laucha in Paraguay, was identified for the first time in Argentina; it was recovered from human cases and from C. callosus samples. The high sequence identity between human and rodent samples implicated C. callosus as the primary rodent reservoir for LN virus in Yuto. The genetic analysis showed that the Argentinian LN virus variant differed 16.8% at the nucleotide level and 2.9% at the protein level relative to the Paraguayan LN virus. The other two hantavirus lineages identified were the previously known Bermejo and Oran viruses.

Frecuencia de mycloplasma pneumoniae y chlamydia pneumoniae en pacientes con distress respiratorio y serología negativa para hantavirus / Mycoplasma pneumoniae and chlamydia pneumoniae frequency in respiratory distress syndrome with negative serology for hantavirus

Se realizó un estudio retrospectivo por medio de IFI, para detectar anticuerpos IgG anti Chlamydia pneumoiae y Mycoplasma pneumoniae, en pacientes seronegativos para hantavirus, con sintomatología de neumonia atípica y distress respiratorio. Chlamydia pneumoniae alcanzó una prevalencia de 8,6 por ciento y M. pneumoniae de 17,1 por ciento en los pacientes estudiados. Se enfatiza la importancia que estos agentes tienen en nuestro medio y la necesidad de contar con técnicas de laboratorio rápida, que permitan un diagnóstico diferencial oportuno entre el síndrome pulmonar por hantavirus y otras patologías que producen cuadros similares, principalmente con neumonía atípica

Exposure to rodents and rodent-borne viruses among persons with elevated occupational risk.

Persons who have frequent contact with rodents as part of their occupation may be at increased risk of exposure to rodent-borne viruses such as Sin Nombre virus (SNV), the agent of hantavirus pulmonary syndrome, and Whitewater Arroyo virus (WWA), a New World arenavirus. Eighty-one persons with possible occupational exposure to rodents completed questionnaires and provided specimens for serologic testing. Seventy-two participants reported handling rodents as part of their job. The mean total number of rodents handled during participants' careers was approximately 2200. IgG antibody to lymphocytic choriomeningitis virus was detected in serum from one (1.2%) participant. IgG antibody to SNV, WWA, and Amapari viruses was not detected in any of the serum specimens. Despite considerable exposure to rodents, participants did not have significant serological evidence of exposure to rodent-borne viruses.

Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses.

Hantaviruses cause two human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantaviruses infect human endothelial cells but cause little or no damage to the infected endothelium. We analyzed with Affymetrix DNA Arrays (Santa Clara, CA) the endothelial cell transcriptional responses directed by hantaviruses associated with HPS [New York-1 virus (NY-1V)], HFRS [Hantaan virus (HTNV)], or by a hantavirus not associated with human disease [Prospect Hill virus (PHV)]. Hantavirus infections induced 117 cellular genes and repressed 25 genes by >3-fold, 4 days postinfection (p.i.). Although >80% of cells were infected by each virus 1 day p.i., PHV induced or repressed 67 genes at this early time compared with three genes altered by HTNV or NY-1V. The early high-level induction of 24 IFN-stimulated genes by PHV (4- to 229-fold) represents a fundamental difference in the temporal regulation of cellular responses by pathogenic and nonpathogenic hantaviruses. Because all hantaviruses induced >23 IFN-stimulated genes at late times p.i., pathogenic hantaviruses appear to suppress early cellular IFN responses that are activated by nonpathogenic hantaviruses. At late times p.i., 13 genes were commonly induced by HTNV and NY-1V that were not induced by PHV. In contrast to NY-1V, HTNV uniquely induced a variety of chemokines and cell adhesion molecules (i.e., IL-8, IL-6, GRO-beta, ICAM), as well as two complement cascade-associated factors that may contribute to immune components of HFRS disease. NY-1V failed to induce most cellular chemokines directed by HTNV (3/14) or genes primarily activated by NF-kappaB. However, NY-1V uniquely induced beta3 integrin-linked potassium channels, which could play a role in HPS-associated vascular permeability. These studies provide a basic understanding of hantavirus-directed cellular responses that are likely to differentiate pathogenic and nonpathogenic hantaviruses, contribute to HFRS and HPS pathogenesis, and provide insight into disease mechanisms and potential therapeutic interventions.

Hantavirus pulmonary syndrome: a zebra worth knowing.

Hantavirus pulmonary syndrome (HPS) is a severe cardiopulmonary illness most often caused by the Sin Nombre virus, which is transmitted to humans by inhalation of aerosolized particles of rodent excreta or direct rodent contact. Although HPS is more common in the western United States, cases have been identified in 31 states. The illness begins as a nonspecific febrile prodrome, sharing many of its initial symptoms with other more common viral infections. Patients then quickly develop noncardiogenic pulmonary edema, respiratory failure, and shock. Characteristic laboratory findings include thrombocytopenia, a left-shifted leukocytosis, hemoconcentration, and presence of immunoblasts. The overall case fatality rate of HPS is approximately 40 percent. Diagnosis is confirmed by serologic identification of IgM and IgG antibodies to Sin Nombre virus. There is no specific therapy, but early recognition of HPS during the prodromal phase can expedite initiating cardiopulmonary support in an intensive care unit, which is associated with improved survival rates. Prevention of HPS involves avoiding contact with rodents and rodent habitats.

Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndrome.

Hantavirus cardiopulmonary syndrome (HCPS) is a life-threatening respiratory disease characterized by profound pulmonary edema and myocardial depression. Most cases of HCPS in North America are caused by Sin Nombre virus (SNV), which is carried asymptomatically by deer mice (Peromyscus maniculatus). The underlying pathophysiology of HCPS is poorly understood. We hypothesized that pathogenic SNV infection results in increased generation of reactive oxygen/nitrogen species (RONS), which contribute to the morbidity and mortality of HCPS. Human disease following infection with SNV or Andes virus was associated with increased nitrotyrosine (NT) adduct formation in the lungs, heart, and plasma and increased expression of inducible nitric oxide synthase (iNOS) in the lungs compared to the results obtained for normal human volunteers. In contrast, NT formation was not increased in the lungs or cardiac tissue from SNV-infected deer mice, even at the time of peak viral antigen expression. In a murine (Mus musculus) model of HCPS (infection of NZB/BLNJ mice with lymphocytic choriomeningitis virus clone 13), HCPS-like disease was associated with elevated expression of iNOS in the lungs and NT formation in plasma, cardiac tissue, and the lungs. In this model, intraperitoneal injection of 1400W, a specific iNOS inhibitor, every 12 h during infection significantly improved survival without affecting intrapulmonary fluid accumulation or viral replication, suggesting that cardiac damage may instead be the cause of mortality. These data indicate that elevated production of RONS is a feature of pathogenic New World hantavirus infection and that pharmacologic blockade of iNOS activity may be of therapeutic benefit in HCPS cases, possibly by ameliorating the myocardial suppressant effects of RONS.

Hantavirus pulmonary syndrome--Vermont, 2000.

In 1993, an outbreak of an unexplained pulmonary illness occurred in the southwestern United States. This outbreak led to the first description of hantavirus pulmonary syndrome (HPS), a rodentborne hantaviral infection. Hantaviruses have been found in rodents in rural areas throughout the United States, but most infection has occurred in the southwest. This report describes the first HPS case in Vermont and underscores the importance of preventing exposure to peridomestic rodents and recognizing the signs and symptoms of HPS.