Controversias sobre el uso de corticoides en el síndrome cardiopulmonar por hantavirus / Controversies on corticosteroid therapy in hantavirus cardiopulmonary syndrome

Resumen El síndrome cardiopulmonar por hantavirus es una zoonosis emergente en la Argentina, que presenta baja incidencia, pero elevada mortalidad. No existe tratamiento farmacológico especifico y la única alternativa actual es la terapia de apoyo. En este artículo se expone la patogenia del síndrome cardiopulmonar por hantavirus a través de la revisión de las experiencias clínicas de otros países de Sudamérica, en particular Chile, y la adquirida en el Hospital de Infecciosas Francisco Javier Muñiz de Buenos Aires, Argentina. Se discute sobre la administración temprana de corticoides en este síndrome, teniendo en cuenta que la evidencia a favor de su uso es insuficiente.

Abstract Hantavirus cardiopulmonary syndrome is an emerging zoonosis in Argentina, which has low incidence but high death rates. No specific pharmacological therapy is available and symptomatic therapy is the only current alterna tive. This article presents the pathogenesis of hantavirus cardiopulmonary syndrome through a review of clinical experiences in neighbor South American countries, mainly Chile, and the experience acquired at the Infectious Diseases Hospital Francisco Javier Muñiz, Buenos Aires, Argentina. The role of early corticosteroid therapy is discussed taking into account that there is insufficient evidence favoring its use in the hantavirus cardiopulmonary syndrome.

Criterios de laboratorio clínico y su utilidad como predictores del diagnóstico de síndrome cardiopulmonar por hantavirus / Clinical laboratory criteria and its utility as predictive of diagnosis of the cardiopulmonary syndrome by hantavirus

Resumen Introducción: La infección por hantavirus es una zoonosis emergente, endémica en Chile, generando el síndrome cardiopulmonar por hantavirus (SCPH), caracterizado por disfunción cardiopulmonar con falla respiratoria rápidamente progresiva y altamente letal. Para una orientación clínica precoz del SCPH, debido a su poca especificidad en síntomas y ayudar al diagnóstico diferencial, se han estudiado algunos parámetros de laboratorio que puedan ser de utilidad. Objetivo: Identificar criterios del laboratorio como factores predictores del diagnóstico de SCPH en pacientes con sospecha de enfermedad por hantavirus. Metodología. Estudio de cohorte retrospectiva de 71 pacientes que ingresaron a Urgencia del Hospital Guillermo Grant Benavente. Se determinó la capacidad discriminativa de parámetros de laboratorio al momento de ingreso: recuento de plaquetas, hematocrito, inmunoblastos, TTPa y GOT. Resultados: Se encontraron diferencias significativas en los parámetros estudiados entre pacientes confirmados (n: 22) con respecto a los no confirmados (n: 49). Hematocrito, inmunoblastos, GOT y TTPa tuvieron un OR > 1 y las plaquetas un OR < 1. La mejor combinación para predecir SCPH fue hematocrito, plaquetas y GOT con sensibilidad 90,9% y especificidad 81,6%. Conclusión: Los cinco parámetros estudiados son buenos predictores de SCPH en pacientes con sospecha del mismo y podrían ser útiles en hospitales de baja complejidad para rápido traslado a centro que cuente con unidad de pacientes crítico.

Background. The hantavirus infection is an emerging zoonotic disease, endemic in Chile, generating the hantavirus cardiopulmonary syndrome (HCPS), characterized by cardiopulmonary dysfunction with rapidly progressive respiratory failure and high lethality. For an early clinical orientation of HCPS, due to its non-specificity in symptoms and to help the differential diagnosis, some laboratory parameter that may be useful have been studied. Aim: To identify laboratory criteria as predictive factors of HCPS in patients with suspected hantavirus infection. Methodology: Retrospective cohort study of 71 patients admitted to the Hospital Guillermo Grant Benavente Emergency. We determined discriminative capacity of laboratory's parameters at the time of admission: platelets recount, hematocrit, inmunoblasts, activated partial thromboplastin time (aPTT) and aspartate aminotransferase (AST/GOT). Results: Were found significant differences in all parameters studied between confirmed patients (22) with respect to unconfirmed (49). Hematocrit, inmunoblasts, AST/GOT and aPTT had a OR > 1 and platelets count had a OR < 1. The best combination for predict HCPS was hematocrit, platelets count and AST/GOT with 90,01% sensibility and 81,63% specificity. Conclusion: The five parameters studied are good predictors of HCS in suspicious patients and they would may be useful in low complexity hospitals for quick transfer a center with critical care units.

Hantavirus: descripción de dos décadas de endemia y su letalidad / Hantavirus: description of two decades of endemia and its lethality

Introducción: la infección por hantavirus es una zoonosis endémica en Chile. En dos décadas la letalidad ha descendido a una cifra estable de alrededor de un 30 por ciento, pese a importantes esfuerzos por disminuirla. Objetivos: describir los eventos que ocurren antes de la hospitalización y analizar la relación entre estas variables y la letalidad, con el objetivo de identificar momentos de intervención para mejorar la sobrevida de los pacientes. Material y Métodos: se analizaron retrospectivamente todos los casos notificados a través del Boletín Notificación Enfermedades de Declaración Obligatoria (ENO), la Encuesta Epidemiológica de Investigación Ambiental de los casos de Hantavirus del Ministerio de Salud de Chile. Resultados: existieron diferencias significativas en la letalidad por HV determinada por zona geográfica, tipo de trabajo y hospital donde se atendió primariamente el caso. Conclusiones: Hantavirus, por su rápida evolución hacia una condición catastrófica debe tenerse siempre presente en el diagnóstico diferencial y proceder en consecuencia para tener un diagnóstico precoz y acceso a un centro hospitalario con experiencia en manejo de esta patología.(AU)

Introduction: Hantavirus infection is an endemic zoonosis in Chile. In two decades, lethality decreased to 30 percent and has remained stable,despite significant efforts to reduce it. Objectives: to describe the events occurred previous the hospitalization and to analyze the relationship between these variables and the lethality, in order to identify moments of intervention to improve patient's survival. Methods: we analyzed all the cases reported through the mandatory declaration diseases forms of the Ministry of Health of Chile. Results: There were significant differences in HV lethality determined by patient´s geographic area of residence, type of work and hospital category at admission. Conclusions: due to the rapid progress of hantavirus infection to HCPS, this infection must always be present in the differential diagnosis and proceed in order to have an early diagnosis and the opportunity to send the patient to a center with the best resources to manage the patient.(AU)

Seropositivity diagnosis for hantavirus in Jataí, Goiás State, Brazil

Abstract INTRODUCTION: Emerging diseases are of great interest, especially those associated with high mortality rates such as hantaviruses. We aimed to conduct a seroepidemiological survey to determine the levels of hantavirus infection. METHODS: In-house enzyme-linked immunosorbent assay (ELISA) was used to detect specific antibodies. RESULTS: Of the 429 samples collected, seropositivity of 3.9% to anti-hantavirus immunoglobulin G (IgG) was observed (CI 95%: 2.3-5.7). Moreover, in three cases, immunoglobulin M (IgM) was detected, of which two were diagnosed as hantavirus cardiopulmonary syndrome (HCPS). CONCLUSIONS: Our data indicate the considerable occurrence of previous hantavirus infections, highlighting occurrences from sub-clinical cases to HCPS.

Correlación entre criterios clínicos y de laboratorio de casos notificados por sospecha de hantavirosis y el resultado de la técnica de referencia / Correlation between clinical and laboratory criteria of suspected Hantavirus cases and the results of the reference diagnostic technique

Antecedentes: Actualmente en Chile, debido a la elevada sospecha clínica de enfermedad por hantavirus y el alto impacto en salud pública que esto provoca, se hace necesario reforzar al equipo de salud, los criterios de sospecha clínica y epidemiológica de hantavirosis. Objetivo: Analizar la información contenida en las notificaciones de sospecha de infección por hantavirus versus la técnica de referencia para el diagnóstico confirmatorio de casos sospechosos, ELISA IgM de captura anti-hantavirus. Material y Método: Mediante cálculo de precisión diagnóstica se analizó la correlación que existe entre la información entregada en las notificaciones versus el resultado de la confirmación mediante la técnica de referencia. Resultados: De 1.566 pacientes estudiados 3,4% (53 casos) fue confirmado para SCPH. De las notificaciones analizadas 58,6% estaban con datos incompletos. Los porcentajes de positividad de la técnica de referencia asociada a fiebre, mialgia y cefalea, fueron de 80-85%. Destaca que la presencia de inmunoblastos (> 10%), presenta: S: 25%, E: 98%, VPP: 37%, VPN: 97%. Paratrombocitopenia se obtuvo: S: 98%, E: 74%, VPP: 16%, VPN: 100%. Conclusión: Se hace necesario reiterar a nivel del sistema sanitario chileno la importancia de contar con datos completos en los formularios de notificación. La presencia de trombocitopenia e inmunoblastos (> 10%) fue altamente sensible y especifica, respectivamente, en la detección de pacientes con SCPH. Con el fin de optimizar la sospecha de infección por hantavirus, según la definición de caso sospechoso, se plantea la necesidad de desarrollar programas de capacitación para la sospecha clínica y lectura de parámetros de laboratorio, tales como presencia de inmunoblastos en el hemograma, así como incluir un algoritmo con el fin de optimizar la sospecha y el uso adecuado de los recursos sanitarios.

Background: Currently in Chile, due to the frequent clinical suspicion of Hantavirus disease and the high public health impact that this causes, it is necessary to strengthen the criteria for clinical and epidemiological suspicion in the health team. Objective: To analyze the information contained in the reports of suspected Hantavirus infection versus the confirmatory diagnosis with the reference technique, IgM capture ELISA anti-hantavirus. Material andMethods: Correlation between the information provided in notifications versus the result of confirmation was analyzed by calculating diagnostic accuracy. Results: 3.4% of 1,566 patients studied (53 cases) was confirmed as SCPH. 58.6% of the analyzed notifications was incomplete. The percentage of positivity of the reference technique associated with fever, myalgia and headache was 80-85%. The presence of immunoblasts (> 10%) showed 25% sensitivity, 98% specificity, 37% PPV, 97% NPV. Thrombocytopenia exhibited 98% sensitivity, 74% specificity, 16% PPV, 100% NPV. Conclusion: It is necessary to reinforce the importance of comprehensive data reporting at the health system level. The presence of thrombocytopenia and immunoblasts (> 10%) is highly sensitive and specific, respectively, for detecting patients with SCPH. There is a need to develop training programs in order to optimize the suspicion of Hantavirus infection and appropriate use of health resources.

Hallazgos morfológicos en casos fatales de síndrome cardiopulmonar por hantavirus: Estudio de 7 autopsias / Morphological findings in fatal cases of hantavirus cardiopulmonary syndrome: Report of 7 autopsies

Introducción: El síndrome cardiopulmonar por hantavirus (SCPH) es una enfermedad infecciosa aguda, caracterizada por insuficiencia cardio-respiratoria súbita y alta mortalidad, causada por un virus ARN del género Hantavirus, familia Bunyaviridae. Un 15 por ciento de los casos chilenos ha sido pesquisado en la Araucanía. Objetivo: Conocer en casos fatales de SCPH, sus características clínicas y morfológicas. Material y Método: Estudio descriptivo-retrospectivo de siete casos fatales con examen postmortem, de SCPH, atendidos entre 1997 y 2009 en el Hospital Regional de Temuco. Resultados: Los casos fueron principalmente pacientes jóvenes, rurales, con un cuadro de compromiso respiratorio progresivo, con leucocitosis, trombopenia e infiltrado pulmonar intersticial bilateral. Los principales hallazgos histopatológicos fueron un acentuado edema pulmonar intra-alveolar e intersticial, con escaso daño epitelial e infiltrado mono-nuclear y leve edema miocárdico con infiltrado mononu-clear. Conclusiones: Los antecedentes epidemiológicos, clínicos y laboratorio permiten sospechar SCPH. En los casos fatales la autopsia permite diferenciar el SCPH de otras patologías similares y aporta tejidos para confirmar el diagnóstico.

Introduction: Hantavirus cardiopulmonary syndrome (HCPS) is an acute infectious disease characterized by sudden cardiorespiratory failure and high mortality, caused by a RNA virus of the genus Hantavirus, family Bunyaviridae, 15 percent of Chilean cases have been detected in the Araucania Region. Objective: To determine in fatal cases of HCPS, clinical and morphological characteristics. Materials and Methods: Descriptive-retrospective analysis of seven fatal cases with postmortem study of HCPS, attended between 1997 and 2009 at the Hospital of Temuco, Chile. Results: Cases were young patients from rural areas, and presented as an illness of progressive respiratory failure, with leukocytosis, thrombocytopenia and bilateral interstitial pulmonary infiltrates. Main morphological findings were marked intersticial and intraalveolar pulmonary edema, with minimal epithelial injury and mononuclear cell intersticial infiltrate and mild edematous intersticial inflamatory process. Conclusions: Epidemiological, clinical and laboratory background allow to suspect HCPS. In fatal cases, the autopsy makes possible to discard other similar pathologies and provide tissue for confirmation of the disease.

Síndrome pulmonar por hantavírus com disfunção de múltiplos órgãos: relato de caso / Hantavirus pulmonary syndrome with multiple organ dysfunctions: case report

JUSTIFICATIVA E OBJETIVOS: A hantavirose é uma zoonose que apresenta distribuição mundial e sua transmissão está relacionada com o íntimo contato com roedores. Causa dois tipos de doença: a febre hemorrágica com síndrome renal (FHSR), endêmica na Ásia e Europa e a síndrome pulmonar por hantavírus (SPH), encontrada no continente americano, inclusive no Brasil, com elevadas taxas de mortalidade. O objetivo deste estudo foi relatar um caso de SPH com disfunção de múltiplos órgãos, que recebeu tratamento intensivo precoce e reanimação guiada por parâmetros de fluxo e de perfusão tecidual. RELATO DO CASO: Paciente do sexo masculino, 36 anos, iniciou quadro febril inespecífico, dispnéia progressiva, hipóxia grave e insuficiência respiratória aguda. Apresentava infiltrado interstício-alveolar difuso na radiografia de tórax. Evoluiu com disfunção de múltiplos órgãos (pulmonar, renal, hematológica, cardiovascular e metabólica). Recebeu tratamento e monitorização hemodinâmica invasiva precoces. As alterações laboratoriais mais importantes foram plaquetopenia, elevação dos níveis de hematócrito e hemoglobina, leucocitose, elevação de transaminases, de lactado desidrogenase e sorologia positiva para hantavírus (ELISA IgM positivo). O paciente apresentou reversão das disfunções orgânicas, recebendo alta hospitalar após 21 dias de hospitalização. CONCLUSÕES: A reanimação precoce e agressiva dirigida por metas levou à reversão da síndrome de falência de múltiplos órgãos e a um desfecho clínico favorável, apesar da gravidade da doença.

BACKGROUND AND OBJECTIVES: Hantavirus infection is a zoonose with worldwide distribution. The transmission is related to the intimal contact with rodents. It causes two syndromes: hemorrhagic fever with renal syndrome (HFRS), endemic in Asia and Europe and the Hantavirus pulmonary syndrome (HPS), found in the American continent, including Brazil, with high mortality rates. The aim of this study is to report a case of HPS with multiple organ failure, managed with early goal-directed therapy guided by flow and tissue perfusion parameters. CASE REPORT: A 36 year-old male had fever with progressive dispnea, severe hypoxia and acute respiratory failure. Diffuse interstitial alveolar infiltrates were seen in the chest X-Ray. He developed multiple organ dysfunction syndromes (pulmonary, renal, coagulation, cardiovascular and metabolic). Treatment and invasive hemodynamic monitoring with pulmonary artery catheter was early instituted. The most important laboratory findings were thrombocytopenia, elevated hematocrit and hemoglobin concentrations, elevated liver enzymes, elevated lactate dehydrogenase and a positive sorology for Hantavirus (ELISA IgM positive). Organ dysfunctions reverted to normal and he was discharged after 21 days in hospital. CONCLUSIONS: An early and adequate resuscitation with goal-directed therapy enabled the reversion of the multiple organ failure syndromes and a favorable outcome, despite the severity of the disease.

Susceptibilidad genética a hantavirus Andes: Asociación entre la expresión clínica de la infección y alelos del sistema HLA en pacientes chilenos / Genetic susceptibility to Andes Hantavirus: Association between severity of disease and HLA alíeles in Chilean patients

En Chile, la infección por hantavirus Andes (ANDV) tiene una expresión clínica variable, reconociéndose diversos grados de severidad. El presente estudio se realizó con el objeto de analizar la posible asociación entre la constitución genética de pacientes chilenos para el sistema HLA y la expresión clínica de la infección por ANDV. Se analizaron los alelos HLA A, B, DRB1 y DQB1, en dos grupos de pacientes con infección por ANDV: 41 pacientes con evolución clínica leve (sin insuficiencia respiratoria severa y sin requerimientos de ventilación mecánica) y 46 pacientes con evolución clínica grave (con insuficiencia respiratoria grave y/o shock). La determinación molecular del sistema HLA se realizó mediante SSP-PCR. El alelo HLA DRB1 * 15, se encontró en una frecuencia significativamente más alta en los pacientes leves (p = 0,007). Por lo tanto, el alelo DRB 1*15 se asociaría al curso clínico leve de la enfermedad. El alelo HLA-B*08, se encontró en una frecuencia mayor en los pacientes graves, la diferencia alcanzó una significación estadística marginal (p = 0,06). Así, el alelo HLA-B*08, podría estar asociado al curso clínico grave de síndrome cardiopulmonar ocasionado por hantavirus Andes.

Andes hantavirus (ANDV) infection in Chile has a variable clinical expression, and infected individuals may present with different grades of disease severity. This study aimed to determine if clinical expression of ANDV infection in Chilean patients is associated with the HLA system. HLA alíeles A, B, DRB1 and DQB1, were studied in two groups of patients with confirmed ANDV infection: 41 patients with a mild disease course (without respiratory failure and cardiovascular shock) and 46 patients with a severe disease course (with respiratory failure and shock). Molecular typing of HLA system was performed by SSP-PCR. The HLA-DRB 1*15 alíele, was significantly more common in the group of patients with mild disease (p = 0,007) and thus for possibly associated with a protective effect against ANDV infection. Conversely, HLA-B*08 was more common in patients with severe disease (p = 0,06). Although the association was marginally significant, alíele HLA-B*08 may be linked to an increased susceptibility to the severe clinical course of HCPS by ANDV.

Síndrome cardiopulmonar por hantavírus no Triângulo Mineiro e Alto Paranaíba, Minas Gerais, 1998-2005: aspectos clínico-epidemiológicos de 23 casos / Hantavirus cardiopulmonary syndrome in the Triângulo Mineiro and Alto Paranaíba regions, State of Minas Gerais, 1998-2005: clinical-epidemiological aspects of 23 cases

Foram analisados os achados epidemiológicos, clínicos, laboratoriais e terapêuticos de 23 casos de síndrome cardiopulmonar por hantavírus, identificados sorologicamente ou por imunohistoquímica em hospitais do município de Uberlândia, Minas Gerais. Febre (100 por cento), dispnéia (100 por cento) e mialgias (78 por cento) foram os sintomas mais frequentemente observados nesta casuística. Os sinais físicos mais prevalentes foram hipotensão (65 por cento) e taquicardia (65 por cento). Achados laboratoriais mais comuns incluíram trombocitopenia (96 por cento), hemoconcentração (83 por cento) e leucocitose (74 por cento). Valores anormais de enzimas hepáticas foram encontrados em todos os pacientes testados e alterações em radiografias de tórax foram muito (95,6 por cento) freqüentes. Em 55,5 por cento dos pacientes, foi necessário intubação orotraqueal e suporte hemodinâmico. O presente estudo confirmou o padrão sazonal da síndrome cardiopulmonar por hantavírus na região de Uberlândia e o envolvimento, no ciclo de transmissão da doença, de grupos profissionais considerados de baixo risco de infecção. A alta (39 por cento) taxa de letalidade e a gravidade da doença observadas neste estudo podem estar associadas ao atendimento tardio dos pacientes.

The epidemiological, clinical, laboratory and treatment findings from 23 cases of hantavirus cardiopulmonary syndrome were analyzed. These cases were identified either serologically or immunohistochemically in hospitals in the municipality of Uberlândia, State of Minas Gerais. Fever (100 percent), dyspnea (100 percent) and myalgia (78 percent) were the symptoms most frequently observed in this sample. The most prevalent physical signs were hypotension (65 percent) and tachycardia (65 percent). The most common laboratory findings included thrombocytopenia (96 percent), hemoconcentration (83 percent) and leukocytosis (74 percent). Abnormal values for liver enzymes were found in all the patients tested and abnormalities in chest radiography were very frequent (95.6 percent). In 55.5 percent of the patients, orotracheal intubation and hemodynamic support were required. The present study confirmed the seasonal pattern of hantavirus cardiopulmonary syndrome in the Uberlândia region and the involvement of professional groups who are considered to be at low risk of infection, in the transmission cycle of the disease. The high lethality rate (39 percent) and the severity of the disease observed in this study may be related to attending to these patients at a late stage.

Síndrome pulmonar e cardiovascular por Hantavirus: aspectos epidemiológicos, clínicos, do diagnóstico laboratorial e do tratamento / Hantavirus pulmonary and cardiovascular syndrome: epidemiology, clinical presentation, laboratory diagnosis and treatment

The Hantavirus pulmonary and cardiovascular syndrome (HPCVS) is an emerging disease in Brazil. In this study, eight confirmed cases of HPCVS were studied. All the patients presented fever and dyspnea as well as thrombocytopenia and hypoxemia. Tachycardia, malaise, hypotension and lung rales occurred in 75 to 87.5% of the cases. Hemoconcentration, blood cell count increased and immature neutrophils, and high levels of creatinine were observed in 75 to 87.5%. Intravenous liquid infusion, the use of drugs for increasing systemic vascular resistance and inotropism, and mechanic ventilation were used for the patients. Mechanical ventilation and volume administration should be started precociously, preferable in intensive care units employing recommended universal and respiratory precautions. Careful volume administration should be limited if signs of pulmonary edema develop. Mortality (50%) is high and probably related to the severity of the disease as well as to a delayed attending of the patients for intensive management. It is important to report hantaviruses and HPCVS to the Brazilian medical community considering that many cases could be undiagnosed.

A síndrome pulmonar e cardiovascular por Hantavirus (SPCVH), é doença emergente com descrição crescente de casos no Brasil. Neste trabalho, estudou-se 8 casos confirmados da doença. Todos apresentaram febre e dispnéia. Taquicardia, astenia, hipotensão e estertoração pulmonar ocorreram em 75 a 87,5% dos casos. Plaquetopenia e hipoxemia ocorreram em 100% dos casos, hemoconcentração, leucocitose com desvio à esquerda e elevação de uréia e creatinina séricas em 75 a 87,5%. Assistência respiratória, hidratação endovenosa e utilização de aminas vasoativas foram as medidas utilizadas nos pacientes. Ressalta-se que o suporte ventilatório e cardiovascular deve ser precocemente instituído, preferencialmente em unidades de terapia intensiva, com precauções universais e respiratórias de isolamento. Deve-se ter cuidados com infusão excessiva de líquidos para não agravar o edema pulmonar. A mortalidade observada, de 50%, é elevada, deveu-se à gravidade da doença e ao comparecimento tardio para tratamento intensivo. Deve-se informar sobre a SPCVH aos profissionais de saúde, considerando que casos de SPCVH, provavelmente, vêm passando desapercebidos.