Caracterización y evolución temporal de la mortalidad por zoonosis bajo declaración obligatoria, entre los años 1997 y 2018 / Characterization and temporal evolution of mortality due to zoonoses under mandatory declaration, between the years 1997 and 2018

INTRODUCCIÓN: Las zoonosis son enfermedades transmitidas desde un hospedador animal al ser humano o viceversa. En Chile, las zoonosis de Notificación Obligatoria (NO) son: brucelosis, carbunco, triquinosis, hidatidosis, leptospirosis, dengue, enfermedad de Chagas, hantavirosis y rabia. OBJETIVO: Evaluar la tendencia y caracterizar la mortalidad por zoonosis de NO en Chile entre 1997-2018. METODOLOGÍA: Estudio ecológico de la mortalidad por zoonosis de NO. Se utilizaron bases de mortalidad y población oficiales. Se describió la mortalidad relativa, general y específica, según variables sociodemográficas. Se calcularon tasas de mortalidad anuales brutas (TMb) y ajustadas (TMa, método directo). Se evaluó la tendencia temporal con modelos de regresión de Prais-Winsten. Resultados: Entre 1997 y 2018 la mortalidad por zoonosis de NO correspondió al 0,12% (2.359 muertes) de la mortalidad total, siendo las principales causas la enfermedad de Chagas (59,8%), hidatidosis (23,9%) y hantavirosis (13,8%). La TMa general disminuyó significativamente (B: -0,017; IC95%: -0,024; -0,009) al igual que hidatidosis (B: -0,011; IC95%: -0,013; -0,008), sólo hantavirosis mostró un aumento (no significativo). CONCLUSIÓN: La mortalidad por zoonosis de NO disminuyó durante el período estudiado; solo la hantavirosis mostró un aumento en su tendencia. Se sugiere enfocar estrategias para prevenir la transmisibilidad y mortalidad por hanta, así como mejorar el acceso a tratamiento para las otras zoonosis.

BACKGROUND: Zoonoses are diseases transmitted from an animal host to humans or vice versa. In Chile, the zoonoses of mandatory notification are brucellosis, anthrax, trichinosis, hydatidosis, leptospirosis, dengue, Chagas disease, hantavirosis and rabies. AIM: To assess the trend and characterize the mortality from zoonoses of mandatory notification in Chile between 1997-2018. METHODS: An official mortality and population data were used. Relative, general and specific mortality rates were described according to sociodemographic variables. Crude and adjusted annual mortality rates (direct method) were calculated. Temporal trend was evaluated with the Prais-Winsten regression model. RESULTS: Between 1997 and 2018, the mortality rate due to zoonosis of mandatory notification corresponded to 0.13% (2152 deaths) of the total mortality, being Chagas disease (59.2%), hydatidosis (24.6%) and hantavirosis (13.5%) the main causes. The general adjusted mortality rate decreased significantly (B: -0.017; IC95%: -0.024; -0.009) as did hydatidosis (B: -0.011; IC95%: -0.013; -0.008), and only hantavirosis showed an increase trend (not significant). CONCLUSION: Mortality due to zoonoses decreased during the period; only hantavirosis showed an increasing trend. It is suggested to focus on strategies to prevent contagion and mortality by hantavirosis, as well as to improve access to treatment for the other zoonoses.

Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection.

New World hantaviruses (NWHs) are endemic in North and South America and cause hantavirus cardiopulmonary syndrome (HCPS), with a case fatality rate of up to 40%. Knowledge of the natural humoral immune response to NWH infection is limited. Here, we describe human monoclonal antibodies (mAbs) isolated from individuals previously infected with Sin Nombre virus (SNV) or Andes virus (ANDV). Most SNV-reactive antibodies show broad recognition and cross-neutralization of both New and Old World hantaviruses, while many ANDV-reactive antibodies show activity for ANDV only. mAbs ANDV-44 and SNV-53 compete for binding to a distinct site on the ANDV surface glycoprotein and show potently neutralizing activity to New and Old World hantaviruses. Four mAbs show therapeutic efficacy at clinically relevant doses in hamsters. These studies reveal a convergent and potently neutralizing human antibody response to NWHs and suggest therapeutic potential for human mAbs against HCPS.

[Survival of persons with hantavirus infection diagnosed in Paraná State, Brazil]. / Sobrevida de pessoas com hantavirose diagnosticadas no Estado do Paraná, Brasil.

Hantavirus infection is an emerging disease with public health impact. Since the signs and symptoms are nonspecific and easily confused with those of other diseases, the prognosis could be improved by knowledge of the factors potentially contributing to the outcome. The study aimed to identify the factors associated with survival time in persons with hantavirus infection. This was a study of confirmed cases of hantavirus infection from January 1992 to June 2016 in Paraná State, Brazil. Each case presented two possible competitive outcomes: death or cure. Survival analysis used a competitive risks model and outcome probabilities estimated by the Aalen-Johansen estimator. The measure of association was the hazards ratio (HR) with 95% confidence interval (95%CI). Of the 280 individuals with hantavirus infection, 107 (38.21%) evolved to death, 161 (57.5%) to cure, and 12 (4.29%) were censored. The final survival model consisted of the use of mechanical ventilation for death (HR = 2.86; 95%CI: 1.76-4.64; p = 0.00002), hemorrhagic signs for death (HR = 2.86; 95%CI: 1.69-4.84; p = 0.00009) and for cure (HR = 0.66; 95%CI: 0.45-0.95; p = 0.03), headache for cure (HR = 1.99; 95%CI: 1.12-3.54; p = 0.02), and age under 20 years for cure (HR = 1.73; 95%CI: 1.05-2.84; p = 0.03). Hemorrhagic signs and use of mechanical ventilation are factors associated with the severity of cases and do not allow sufficient time to reverse the outcome. However, these signs of severity corroborate the argument of the importance of timely suspicion, allowing adequate clinical management to reduce case-fatality.

Hantavirose é uma doença emergente e com impacto na saúde pública. Por apresentar sinais e sintomas inespecíficos e facilmente confundidos com outras doenças, seu prognóstico poderia ser melhorado por meio do conhecimento de fatores que pudessem contribuir para seu desfecho. O estudo objetivou identificar os fatores associados ao tempo de sobrevivência em pessoas com hantavirose. Trata-se de um estudo com casos confirmados de hantavirose de janeiro/1992 a junho/2016 do Estado do Paraná, Brasil. Cada caso apresentou dois desfechos competitivos possíveis: óbito ou cura. Para a análise de sobrevivência foi utilizado um modelo de riscos competitivos e as probabilidades dos desfechos estimadas pelo estimador de Aalen-Johansen. A medida de associação foi a razão de riscos (RzRiscos), com respectivos intervalos de 95% de confiança (IC95%). Dos 280 indivíduos com hantavirose, 107 (38,21%) evoluíram para o óbito, 161 (57,5%) para a cura e 12 (4,29%) foram censurados. O modelo final de sobrevivência foi composto por uso de respirador mecânico para o óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), sinais hemorrágicos para o óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) e para a cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefaleia para a cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) e menor de 20 anos para a cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Sinais hemorrágicos e uso de respirador mecânico são fatores relacionados com a gravidade dos casos e não oportunizam tempo suficiente para reverter o desfecho. No entanto, esses sinais de gravidade corroboram o argumento da importância da suspeição oportuna, permitindo um manejo clínico adequado a fim de reduzir a letalidade.

El hantavirus es una enfermedad emergente y con impacto en la salud pública. Por presentar señales y síntomas inespecíficos, y fácilmente confundidos con otras enfermedades, su pronóstico podría ser mejor gracias al conocimiento de factores que pudiesen contribuir a su resultado. El estudio tuvo como objetivo identificar los factores asociados al tiempo de supervivencia en personas con hantavirus. Se trata de un estudio con casos confirmados de hantavirus de enero/1992 a junio/2016 del estado de Paraná, Brasil. Cada caso presentó dos desenlaces competitivos posibles: óbito o cura. Para el análisis de supervivencia se utilizó un modelo de riesgos competitivos y las probabilidades de los resultados se estimaron mediante el estimador de Aalen-Johansen. La medida de asociación fue la razón de riesgos (RzRiscos), con sus respectivos intervalos de 95% de confianza (IC95%). De los 280 individuos con hantavirus, 107 (38,21%) evolucionaron hacia el óbito, 161 (57,5%) hacia la cura y 12 (4,29%) fueron censurados. El modelo final de supervivencia estuvo compuesto por el uso de respirador mecánico para el óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), señales hemorrágicas para el óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) y para la cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefalea para la cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) y menor de 20 años para la cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Las señales hemorrágicas y uso de respirador mecánico son factores relacionados con la gravedad de los casos y no destinar tiempo suficiente para revertir el desenlace. No obstante, estas señales de gravedad corroboran el argumento de la importancia de la sospecha oportuna, permitiendo un manejo clínico adecuado, con el fin de reducir la letalidad.

Sobrevida de pessoas com hantavirose diagnosticadas no Estado do Paraná, Brasil / Survival of persons with hantavirus infection diagnosed in Paraná State, Brazil / Supervivencia de personas con hantavirus diagnosticadas en el estado de Paraná, Brasil

Resumo: Hantavirose é uma doença emergente e com impacto na saúde pública. Por apresentar sinais e sintomas inespecíficos e facilmente confundidos com outras doenças, seu prognóstico poderia ser melhorado por meio do conhecimento de fatores que pudessem contribuir para seu desfecho. O estudo objetivou identificar os fatores associados ao tempo de sobrevivência em pessoas com hantavirose. Trata-se de um estudo com casos confirmados de hantavirose de janeiro/1992 a junho/2016 do Estado do Paraná, Brasil. Cada caso apresentou dois desfechos competitivos possíveis: óbito ou cura. Para a análise de sobrevivência foi utilizado um modelo de riscos competitivos e as probabilidades dos desfechos estimadas pelo estimador de Aalen-Johansen. A medida de associação foi a razão de riscos (RzRiscos), com respectivos intervalos de 95% de confiança (IC95%). Dos 280 indivíduos com hantavirose, 107 (38,21%) evoluíram para o óbito, 161 (57,5%) para a cura e 12 (4,29%) foram censurados. O modelo final de sobrevivência foi composto por uso de respirador mecânico para o óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), sinais hemorrágicos para o óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) e para a cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefaleia para a cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) e menor de 20 anos para a cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Sinais hemorrágicos e uso de respirador mecânico são fatores relacionados com a gravidade dos casos e não oportunizam tempo suficiente para reverter o desfecho. No entanto, esses sinais de gravidade corroboram o argumento da importância da suspeição oportuna, permitindo um manejo clínico adequado a fim de reduzir a letalidade.

Abstract: Hantavirus infection is an emerging disease with public health impact. Since the signs and symptoms are nonspecific and easily confused with those of other diseases, the prognosis could be improved by knowledge of the factors potentially contributing to the outcome. The study aimed to identify the factors associated with survival time in persons with hantavirus infection. This was a study of confirmed cases of hantavirus infection from January 1992 to June 2016 in Paraná State, Brazil. Each case presented two possible competitive outcomes: death or cure. Survival analysis used a competitive risks model and outcome probabilities estimated by the Aalen-Johansen estimator. The measure of association was the hazards ratio (HR) with 95% confidence interval (95%CI). Of the 280 individuals with hantavirus infection, 107 (38.21%) evolved to death, 161 (57.5%) to cure, and 12 (4.29%) were censored. The final survival model consisted of the use of mechanical ventilation for death (HR = 2.86; 95%CI: 1.76-4.64; p = 0.00002), hemorrhagic signs for death (HR = 2.86; 95%CI: 1.69-4.84; p = 0.00009) and for cure (HR = 0.66; 95%CI: 0.45-0.95; p = 0.03), headache for cure (HR = 1.99; 95%CI: 1.12-3.54; p = 0.02), and age under 20 years for cure (HR = 1.73; 95%CI: 1.05-2.84; p = 0.03). Hemorrhagic signs and use of mechanical ventilation are factors associated with the severity of cases and do not allow sufficient time to reverse the outcome. However, these signs of severity corroborate the argument of the importance of timely suspicion, allowing adequate clinical management to reduce case-fatality.

Resumen: El hantavirus es una enfermedad emergente y con impacto en la salud pública. Por presentar señales y síntomas inespecíficos, y fácilmente confundidos con otras enfermedades, su pronóstico podría ser mejor gracias al conocimiento de factores que pudiesen contribuir a su resultado. El estudio tuvo como objetivo identificar los factores asociados al tiempo de supervivencia en personas con hantavirus. Se trata de un estudio con casos confirmados de hantavirus de enero/1992 a junio/2016 del estado de Paraná, Brasil. Cada caso presentó dos desenlaces competitivos posibles: óbito o cura. Para el análisis de supervivencia se utilizó un modelo de riesgos competitivos y las probabilidades de los resultados se estimaron mediante el estimador de Aalen-Johansen. La medida de asociación fue la razón de riesgos (RzRiscos), con sus respectivos intervalos de 95% de confianza (IC95%). De los 280 individuos con hantavirus, 107 (38,21%) evolucionaron hacia el óbito, 161 (57,5%) hacia la cura y 12 (4,29%) fueron censurados. El modelo final de supervivencia estuvo compuesto por el uso de respirador mecánico para el óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), señales hemorrágicas para el óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) y para la cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefalea para la cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) y menor de 20 años para la cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Las señales hemorrágicas y uso de respirador mecánico son factores relacionados con la gravedad de los casos y no destinar tiempo suficiente para revertir el desenlace. No obstante, estas señales de gravedad corroboran el argumento de la importancia de la sospecha oportuna, permitiendo un manejo clínico adecuado, con el fin de reducir la letalidad.

Magnitude and distribution of deaths due to hantavirus in Brazil, 2007-2015. / Magnitude e distribuição dos óbitos por hantavirose no Brasil, 2007-2015.

OBJECTIVE: to describe the magnitude and temporal and spatial distribution of hantavirus cases and deaths in Brazil between 2007 and 2015. METHODS: descriptive study with data from the Notifiable Diseases Information System (SINAN). RESULTS: 1,060 cases and 410 deaths were reported in the period; hantavirus lethality was 39.0%, varying according to month (from 28.6% in November to 50.7% in December), sex (37.4% in males and 42.6% in females), age (higher lethality in the elderly and children) and Brazilian regions (46.2% in the North, 32.9% in the South); most of the individuals who died lived in urban areas (58.3%) and were infected in rural area (70.2%). CONCLUSION: high lethality in certain population groups, months of the year and regions of Brazil point to low clinical suspicion of the disease in groups with low exposure, which may compromise proper case management.

Cross-sectional study on case fatality rate due to hantavirus infection in Goiás State, Brazil, 2007-2013. / Estudo transversal da letalidade da hantavirose no estado de Goiás, 2007-2013.

OBJECTIVE: to describe the epidemiological and clinical profile of hantavirus infection and to analyze factors associated with case-fatality in Goiás, Brazil. METHODS: this was a cross-sectional study on case fatality due to hantavirus infection from 2007 to 2013 using data from the Notifiable Diseases Information System (SINAN) for Goiás State. Logistic regression analysis was performed to estimate odds ratios (OR) with 95% confidence intervals (95%CI). RESULTS: 1,171 suspected cases were reported, of which 73 (6.2%) were confirmed. Among the confirmed cases, greater frequency was found among males (n=50), fever was the most common symptom (n=70), and there was a high proportion of hospitalization (n=68). The case-fatality rate was 57.5% . The following factors were associated with death: acute respiratory failure (ARF) (OR=3.6; 95%CI 1.2;10.6), hemoconcentration (OR=3.3; 95%CI 1.1;7.9) and not using a mechanical ventilator (OR=3.4; 95%CI 1.3;9.1). After adjustment, the ARF was still associated with death (OR=3.4; 95%CI 1.0;11.6). CONCLUSION: the case-fatality rate was high, primarily associated with respiratory failure.

Estudo transversal da letalidade da hantavirose no estado de Goiás, 2007-2013 / Estudio transversal de la letalidad de la infección por hantavirus en el estado de Goiás, Brasil, 2007-2013 / Cross-sectional study on case fatality rate due to hantavirus infection in Goiás State, Brazil, 2007-2013

OBJETIVO: descrever o perfil epidemiológico e clínico da hantavirose e analisar fatores associados à letalidade em Goiás, Brasil. MÉTODOS: foi conduzido um estudo transversal com dados do Sistema de Informação de Agravos de Notificação (Sinan), referentes ao período de 2007 a 2013, no estado de Goiás. Regressão logística foi empregada para estimar razões de chances (OR) com intervalos de confiança de 95% (IC95%). RESULTADOS: foram notificados 1.171 casos suspeitos de hantavirose e 73 (6,2%) confirmados. Entre os confirmados, observou-se maior frequência entre homens (n=50), febre como sintoma mais frequente (n=70) e elevada proporção de hospitalizações (n=68). A taxa de letalidade foi de 57,5%. Foram fatores associados ao óbito: insuficiência respiratória aguda (IRpA) (OR=3,6; IC95%1,2;10,6), hemoconcentração (OR=3,3; IC95%1,1;7,9) e não uso do respirador mecânico (OR=3,4; IC95%1,3;9,1). Após ajuste, a IRpA permaneceu associada ao óbito (OR=3,4; IC95%1,0;11,6). CONCLUSÃO: foi identificada alta taxa de letalidade, associada principalmente com insuficiência respiratória.

OBJETIVO: evaluar el perfil clínico y epidemiológico del hantavirus y los factores asociados con su letalidad en Goiás, Brasil. MÉTODOS: estudio transversal usando datos del Sistema de Información de Enfermedades de Declaración Obligatoria (Sinan), referentes al periodo 2007-2013, en el estado de Goias. Usamos regresión logística para calcular odds ratio (OR) con intervalos de confianza al 95%. RESULTADOS: fueron reportados 1.171 casos sospechosos de hantavirus 73 fueron confirmados (6,2%). Entre los confirmados la frecuencia fue mayor entre hombres (n=50), fiebre fue síntoma más común (n=70), 68 fueron hospitalizados, la tasa de letalidad fue 57,5%. Variables asociadas con letalidad: insuficiencia respiratoria aguda (IRpA) (OR=3,6 IC95% 1,2; 10,6), hemoconcentración (OR=3.3 IC95% 1,1; 7,9) y no usar respirador mecánico (OR=3,4 IC95% 1,3; 9,1). Sólo IRpA se mantuvo asociado en modelos multivariados (OR=3,4 IC95% 1,0; 11,6). CONCLUSIÓN: identificamos una alta tasa de letalidad asociada principalmente con insuficiencia respiratoria.

OBJECTIVE: to describe the epidemiological and clinical profile of hantavirus infection and to analyze factors associated with case-fatality in Goiás, Brazil. METHODS: this was a cross-sectional study on case fatality due to hantavirus infection from 2007 to 2013 using data from the Notifiable Diseases Information System (SINAN) for Goiás State. Logistic regression analysis was performed to estimate odds ratios (OR) with 95% confidence intervals (95%CI). RESULTS: 1,171 suspected cases were reported, of which 73 (6.2%) were confirmed. Among the confirmed cases, greater frequency was found among males (n=50), fever was the most common symptom (n=70), and there was a high proportion of hospitalization (n=68). The case-fatality rate was 57.5% . The following factors were associated with death: acute respiratory failure (ARF) (OR=3.6; 95%CI 1.2;10.6), hemoconcentration (OR=3.3; 95%CI 1.1;7.9) and not using a mechanical ventilator (OR=3.4; 95%CI 1.3;9.1). After adjustment, the ARF was still associated with death (OR=3.4; 95%CI 1.0;11.6). CONCLUSION: the case-fatality rate was high, primarily associated with respiratory failure.

A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus.

BACKGROUND: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.

[Prognostic factors in hantavirus infections]. / Hantavirus enfeksiyonlarinda prognostik faktörler.

The hantaviruses classified in Hantavirus genus of Bunyaviridae family, may cause two different types of clinical conditions, namely hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Mortality may reach up to 40% in these infections. Hantavirus subtypes (Sin Nombre, Hantaan, Seoul, Puumala, Dobrava, etc) with different virulences represent one of the most significant factors affecting the mortality. Additionally, many other factors including age, gender, humoral immune response, genetic factors, patient's clinical and laboratory findings, transfusion, mechanical ventilation requirement, antiviral treatment and immunotherapy administered to the patient are prognostically important. Increasing age had an unfavorable effect on mortality. While the disease is commonly observed in the male gender, mortality rate is higher in the female gender. The higher the emergent neutralizing antibody response, the virus spread, the number of the infected cells and the cytotoxic T lymphocyte-mediated injury will be lower. The requirement for dialysis is reported to be higher with a poorer prognosis in individuals with HLA-B8, -DR3, -DQ2 alleles, and those with HLA-B27 allele usually experience a milder clinical course. Clinically, the risk of mortality increases in patients with multiple, central nervous system hemorrhage, sepsis, disseminated intravascular coagulation (DIC) and secondary infection. The presence of adult respiratory distress syndrome (ARDS), the requirement for mechanical ventilation, the presence of dyspnea and hemoconcentration in HPS are reported to be the most important prognostic factors associated with death. The correlation of severity and the transfusion requirement with mortality was demonstrated. High serum levels of white blood cells, blood urea nitrogen (BUN), creatinine phophokinase (CPK), C-reactive protein (CRP), prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer and INR (International normalized ratio) are prognostic factors that increase the mortality risk. Hemodialysis support is particularly important in cases infected with Hantaan and Dobrava viruses. Respiratory support and mechanical ventilation can be life-saving in HPS cases. Extracorporeal membrane oxygenation support has been demonstrated to have a favorable contribution to the patient survival in HPS. While there are some human and animal trials showing that ribavirin reduces the severity of HFRS, hemodialysis requirement and mortality, its efficacy for HPS has not yet been demonstrated. As a result, a proper evaluation of the prognostic factors will provide physicians a perspective with respect to the disease course and the necessary treatment approach.

Análise do perfil epidemiológico da hantavirose no Brasil no período de 2007 a 2012 / Analysis of the epidemiological profile of hanavirus in Brazil for the period 2007 to 2012

As hantaviroses são zoonoses que causam doenças humanas graves como a síndrome cardiopulmonar por hantavírus (SCPH) registrada no continente americano. No Brasil a SCPH é doença de notificação obrigatória aos serviços de saúde por apresentar elevada letalidade e incipiente conhecimento da sua epidemiologia. O presente estudo descreve o perfil epidemiológico da SCPH no Brasil para o período de 2007 a 2012. Foi realizado um estudo descritivo dos registros do Sistema Nacional de Agravos de Notificação, foram analisadas as fichas de notificação e investigação e os dados foram avaliados quanto a completitude da informação, oportunidade e perfil dos casos registrados. Os resultados são apresentados em números brutos, medidas de proporção e tendência central e as analises foram desenvolvidas pelos softwares Excel 2010, Tabwin 32 e TerraView. No período estudado foram notificados 8.456 casos de SCPH, com confirmação de 9 porcento (756/8.456), preferencialmente pelo critério laboratorial 91,1 porcento (689/756). O coeficiente de letalidade médio para o período foi de 38,2 porcento, as maiores incidências da doença foram nos estados do Mato Grosso, Santa Catarina e Distrito Federal e as maiores letalidades no Amazonas, Mato Grosso e São Paulo. Quanto à sazonalidade foram observados casos em todos os meses do ano; os óbitos foram mais frequentes em homens 72,3 porcento (209/289) e maior letalidade 42,3 porcento (80/189) foi observada em mulheres. Os casos acometeram principalmente pessoas que exerciam atividades relacionadas à agricultura 18,8 porcento (90/478) que se expuseram ao ambiente com roedores 36,9 porcento (279/756)...

Hantaviruses are zoonoses that cause serious human diseases in the Americas such as hantavirus pulmonary syndrome (HPS). In Brazil HPS is a notifiable disease to health services due to its high lethality and incipient knowledge of its epidemiology. The present study describes the epidemiology of HPS in Brazil for the period 2007-2012. We conducted a descriptive study of the records of the National Notifiable Diseases System, analyzed the reporting forms and research, and the data were evaluated for completeness of information, opportunity and profile of registered cases. The results are presented as raw numbers, measures of central tendency and proportion and analyses developed using Excel 2010 software, and 32 Tabwin terraView. In the study period 8,456 cases of HPS were reported, with confirmation of 9 percent (756/8,456), ideally by laboratory testing 91.1 percent (689/756). The average coefficient of lethality for the period was 38.2 percent, whilst the highest incidences of the disease were in the states of Mato Grosso, Santa Catarina and the Federal District and the greatest lethalities were in Amazonas, Mato Grosso and São Paulo. Regarding seasonality, cases were observed in all months of the year. Deaths were more frequent in males 72.3 percent (209/289) and high mortality was observed in women 42.3 percent (80/189). The cases were mainly people who conducted activities related to agriculture 18.8 percent (90/478) who were exposed to the rodent environment, 36.9 percent (279/756)...

Hantaviruses as zoonotic pathogens in Germany.

BACKGROUND: Hantavirus disease is a zoonosis of increasing clinical importance. A new incidence peak was reached in Germany in 2012, with more than 2800 reported cases. These viruses are transmitted from small mammals to human beings. The disease begins with high fever and non-pathognomonic manifestations that can end in shock and organ failure. METHODS: This article is based on a selective literature search, on the authors' experiences at the National Referral Laboratory for Hantavirus Infections (Nationales Konsiliarlaboratorium für Hantaviren), and on published recommendations from Germany and abroad. RESULTS: Two hantavirus species cause clinically relevant infections in Germany. Puumala virus, which is transmitted by bank voles, causes large outbreaks of disease every 2 to 3 years in the southwestern and western regions of Germany and in the Bavarian Forest. Dobrava-Belgrad virus, transmitted by striped field mice, causes infections in the north and east of the country. Serological tests are available for primary and confirmatory diagnosis; moreover, viral nucleic acids can be amplified in the early phase of illness and compared with the viral nucleic acids from the reservoir hosts of the corresponding type of infection. Infections with American types of hantavirus have ca. 35% case fatality, and hantaviruses from southeastern Europe and Asia are also highly pathogenic; in contrast, the febrile illnesses caused by hantaviruses in Germany are usually relatively mild. CONCLUSION: When persons living in high-risk areas present with fever of unknown origin or with renal dysfunction of unknown origin, physicians should consider the possibility of a hantavirus infection and should initiate the appropriate diagnostic evaluation.

Induction of protective immunity in a Syrian hamster model against a cytopathogenic strain of Andes virus.

Andes virus (ANDV) is responsible for the Hantavirus Pulmonary Syndrome cases in Argentina and neighboring countries, with moderate to high case-fatality rates. ANDV has some particular features, which make it unique among other members of the Hantavirus genus such as person-to-person transmission and causing a disease similar to Hantavirus Pulmonary Syndrome in the hamster as an animal model. The kinetics of replication in Vero E6 cells of an ANDV strain isolated in Argentina, called Andes/ARG, was studied. Cytopathic effect and the formation of clear plaques were observed and therefore Andes/ARG could be quantified by classic plaque assay. The Andes/ARG strain was found to be highly lethal in Syrian hamsters allowing experiments to demonstrate the protective potential of vaccines. A recombinant nucleocapsid protein of ANDV induced a long lasting antibody response and protective immunity against a homologous challenge, but to a lower extent against heterologous challenge by the Seoul virus.

Perfil clínico epidemiológico de infección por hantavirus en la Provincia de Buenos Aires, Argentina, periodo 1996 – 2009 / Clinical epidemiological profile hantavirus infection the Buenos Aires province, Argentina, during 1996-2009

Introducción: La infección denominada hantavirus es considerada una zoonosis viral. Se han identificado más de 21 especies en todo el mundo, transmitidas por diferentes roedores, que son su reservorio natural. Argentina hasta el año 2004 fue el país con mayor incidencia en América del Sur siendo Buenos Aires una de las provincias de mayor incidencia del país. Objetivo: El objetivo del presente trabajo fue analizar las variables clínico-epidemiológicas de la enfermedad en la Provincia de Buenos Aires analizando la serie histórica de 14 años (1996-2009). Material y método: Se analizaron 704 fichas de notificación clínica-epidemiológica. La detección serológica de anticuerpos se realizó mediante Elisa. Las variables estudiadas fueron sexo, edad, residencia según partido y región sanitaria, semana epidemiológica (SE), tasa de incidencia y letalidad, evolución clínica y la presencia de diferentes síndromes. Resultados: 622 casos (88.3 por ciento) presentaron estudio de laboratorio serológico, siendo 291 los casos (46.8 por ciento) positivos o confirmados con IgM. Analizando la evolución clínica, (194 pacientes con dato, 67 por ciento) 112 pacientes curaron y 79 fallecieron. La edad promedio de pacientes fallecidos fue de 33 años. La letalidad para cada síndrome fue: gripal 39.9 por ciento, respiratorio 42.1 por ciento con el, renal 43.9 por ciento, hepático 38.5 por ciento, neurológico 57.1 por ciento y hematológico 40 por ciento. El estudio resulta un aporte al conocimiento de la prevalencia del perfil clínico epidemiológico del hantavirus en la Provincia de Buenos Aires, Argentina.

Introduction: Hantavirus infection is considered a viral zoonosis. More than 21 species have been indentified throughout the world, transmitted by different rodents, which are its natural reservoir. Until 2004, Argentina was the country with the highest incidence in South America, Buenos Aires being one of the provinces with the highest incidence in the country. Objective: The objective of this study was to analyze the clinical and epidemiological variables of the disease in the Buenos Aires Province, analyzing 14 years of historical trends (1996-2009). Materials and methods: 704 clinical-epidemiological notifications were analyzed. Serological detection of antibodies was carried out using ELISA. The variables studied were sex, age, residence according to health system district, epidemiological week (EW), incidence rate, lethality, clinical evolution, and the presence of different syndromes. Results: 622 cases (88.3 percent) had a laboratory serological report, 291 (46.8 percent) of those being positive cases or those confirmed with IgM. Analyzing clinical evolution, (194 patients included this data, 67 percent) 112 patients were cured y 79 died. The average age of deceased patients was 33 years. Lethality for each syndrome was: influenza 39.9 percent, respiratory 42.1 percent, renal 43.9 percent, hepatic 38.5 per cent, neurological 57.1 percent y hematological 40 per cent. This study contributes to knowledge of the clinical epidemiological profile of hantavirus in Buenos Aires Province, Argentina.

Ecology of hantavirus in a changing world.

Hantavirus is a genus of virus represented by 45 different species and is hosted by small mammals, predominantly rats and mice. Roughly, half of all hantaviruses cause diseases in humans that vary in morbidity from mild to severe. The natural and anthropogenic changes occurring in the environment appear to be impacting the ecology of hantaviruses and their natural hosts as well as the incidence of hantaviral diseases in humans. Although such studies are limited at this time, there is evidence that natural climate cycles such as El Niño as well as anthropogenic climate change enhance hantavirus prevalence when host population dynamics are driven by food availability. Climate appears to have less of an effect on hantavirus when host populations are controlled by predators. Human alteration to the landscape also appears to enhance hantavirus prevalence when the disturbance regime enriches the environment for the host, for example, agriculture. More long-term studies on multiple species of hantavirus are needed to accurately predict the outcome of changing environmental conditions on prevalence in hosts as well as disease incidence in humans.

Avaliação e análise dos casos de hantavirose na 2ª e 5ª Coordenadorias Regionais de Saúde no período de 1998 a 2005 / Evaluation and analysis of the cases of hantavirose in 2ª and 5ª Regional Coordenadorias of Health in the period of 1998 the 2005

O presente trabalho teve como objetivo realizar os levantamentos dos registros do agravo Hantavirose, constantes no Sistema Nacional de Agravos e Notificação (SINAN/MS), provenientes dos 48 municípios pertencentes à 5ª Coordenadoria Regional da Saúde/Caxias do Sul (RS), e 41 municípios pertencentes à 2ª Coordenadoria Regional da Saúde/Porto Alegre (RS), no período de 1998 a 2005. Os dados analisados e encontrados foram: 1. Números de municípios que notificaram Hantavirose no período: 07/41 (17%) na 2ª CRS e 10/48 (20,83%) na 5ª CRS; 2. Número de casos de Hantavirose notificados e confirmados sorologicamente: 06/77 (07,6%) na 2ª CRS e 06/43 (13,95%) na 5ª CRS; 3. Casos notificados, confirmados óbitos, letalidade e municípios por ano de ocorrência: 118 casos notificados, 12 confirmados sorologicamente, 06 óbitos, taxa de letalidade 50%...

Hantavirus / Hantavirus infection

Esta enfermedad tiene actualmente una presentación endémica con brotes estacionales y localizados en algunas regiones del país. La incidencia más alta desde que la enfermedad apareció en el país ocurrió en el año 2001, observándose posteriormente una estabilización. En el año 2004 alcanzó a 0,35 x 100.000 hab., similar a lo observado el año anterior. La tasa de mortalidad se ha mantenido estable en los últimos 3 años, con cifras entre 0,12 a 0,11 muertes por cien mil hab. Durante el año 2004 se notificaron 269 casos sospechosos de infección por Hantavirus, confirmándose 56 casos de Síndrome Cardiopulmonar por Hantavirus (SCPH) y 1 caso de Enfermedad Leve (sin compromiso pulmonar), cifra que se encuentra dentro de los rangos habituales. Como es propio de esta enfermedad, el aumento estacional se inició a fines de 2003 manteniéndose hasta marzo de 2004. En el resto de los meses se observó un número de casos bajo lo esperado, con excepción de octubre. Como en años anteriores, el 74 por ciento de los enfermos de SCPH correspondió a hombres. Esta distribución se ha mantenido a través del tiempo, lo que se relaciona principalmente con los riesgos de la actividad laboral. La edad promedio fue de 33 años (rango de < 1 año y 66 años). El 14 por ciento de los casos de SCPH tiene una edad inferior a 15 años (8 casos). Destaca en 2004, la ocurrencia de un caso en un lactante de 1 mes y medio, residente en una localidad rural de la provincia de Osorno, X Región, que evolucionó con daño cerebral. El riesgo de enfermar por Hantavirus aumenta en los grupos de edades productivas: las tasas de incidencia más altas se encuentran en los grupos de 30-39 y 20-29 años (0,63 y 0,49 por cien mil hab., respectivamente). La letalidad en el año 2004 alcanzó a un 32 por ciento (18 fallecidos), levemente superior a lo observado en 2003 (30 por ciento).

Hantavirus / Hantavirus infections

A partir de 1995, en que se detectaron los primeros casos de Síndrome Cardiopulmonar por Hantavirus (SCPH) en nuestro país, esta enfermedad ha variado presentándose desde 1997 como una endemia con casos esporádicos y brotes estacionales desde noviembre a abril. Durante el año 2005 la tendencia estacional observada en los años anteriores se mantuvo. Las tasas de incidencia más elevadas ocurrieron en los años 2001 y 2002, probablemente como consecuencia de la mejoría de los sistemas de notificación. Se observa un leve aumento en la incidencia durante el año 2005 (0,42 por 100.000 hab.), lo que coincide con la presentación de un mayor número de agrupaciones de casos, superior a lo observado el año 2004 (0,35 por 100.000 hab.). La mortalidad es el resultado de la expresión más grave de la enfermedad, las tasas de mortalidad más elevadas ocurrieron en los años 1997, 1998 y 2001, años epidémicos, a partir de entonces se ha mantenido estable en los últimos años con una tasa de 0,12 por 100.000 habitantes en el año 2005. Durante el año 2005, se confirmaron 67 casos de SCPH y 7 de enfermedad leve, cifra superior a mediana para este mismo período (60 casos). En el año 2005 fallecieron 21 personas, con una letalidad global de 30 por ciento. Esta se ha mantenido en condiciones similares en los años anteriores y desde el inicio de la endemia se ha observado una mayor letalidad en las mujeres, situación que no ha variado hasta el momento (37 por ciento en mujeres).

Effects of internal fluctuations on the spreading of Hantavirus.

We study the spread of Hantavirus over a host population of deer mice using a population dynamics model. We show that taking into account the internal fluctuations in the mouse population due to its discrete character strongly alters the behavior of the system. In addition to the familiar transition present in the deterministic model, the inclusion of internal fluctuations leads to the emergence of an additional deterministically hidden transition. We determine parameter values that lead to maximal propagation of the disease and discuss some implications for disease prevention policies.