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.

Síndrome cardiopulmonar por Hantavirus luego del brote de Epuyén, Argentina: la necesidad de investigar nuevas formas de intervención terapéutica / Cardiopulmonary syndrome due to Hantavirus after the outbreak in Epuyén, Argentina: the need to investigate new forms of therapeutic intervention / Síndrome cardiopulmonar por Hantavírus depois do surto de Epuyén, Argentina: a necessidade de investigar novas formas de intervenção terapêutica

Los Hantavirus son virus con ARN de cadena simple pertenecientes a la familia Bunyaviridae. A diferencia de otros virus de la familia, no tienen artrópodos como vectores; sus hospederos en la naturaleza son roedores y algunos mamíferos pequeños. La transmisión al hombre ocurre por la inhalación de excretas de los animales infectados, rara vez por mordeduras y se ha documentado la posibilidad de transmisión persona a persona. Existen dos formas clínicas de la enfermedad: fiebre hemorrágica con síndrome renal (FHSR) distribuida en Europa y Asia, y síndrome cardiopulmonar por Hantavirus (SCPH), en las Américas. El SCPH se presenta clinicamente en cuatro fases: incubación, prodrómica, cardiopulmonar y convalescencia. En el laboratorio es frecuente el hallazgo de trombocitopenia, junto con otros cambios hematológicos y bioquímicos. El diagnóstico se realiza por la detección de anticuerpos o PCR. Recientemente en Epuyén, Provincia de Chubut, Argentina, ocurrió un brote que afectó a 34 personas con 12 muertes asociado a la transmisión interpersonal. Se revisa la situación actual con respecto al tratamiento y las posibilidades futuras de intervención. Aunque se trate de una enfermedad con una baja prevalencia, la alta tasa de letalidad y el alto impacto emocional y económico que sufren las localidades afectadas hacen necesario seguir investigando la búsqueda de nuevas alternativas de tratamiento.

Hantaviruses are single-stranded RNA viruses that belong to the Bunyaviridae family. Unlike other viruses in the family, they do not have arthropods as vectors; their hosts in the wild are rodents and some small mammals. Human transmission takes place through inhalation of excreta from infected animals, rarely from bites, and the possibility of person-to-person transmission has been documented. There are two clinical forms of the disease: hemorrhagic fever with renal syndrome (HFRS) distributed in Europe and Asia, and cardiopulmonary Hantavirus syndrome (HCPS) distributed in the Americas. The HCPS presents clinically in four phases: incubation, prodromal, cardiopulmonary and convalescence. In the laboratory, a thrombocytopenia is common, together with other hematological and biochemical changes. Diagnosis is made through the detection of antibodies or PCR. Recently, in Epuyén, Province of Chubut, Argentina, an outbreak occurred, affecting 34 people with 12 deaths associated with interpersonal transmission. The current situation is reviewed with respect to the treatment and the future possibilities of intervention. Although it is a disease with a low prevalence, the high rate of lethality and the high emotional and economic impact suffered by the affected areas make it necessary to continue investigating in search of new treatment alternatives.

Os Hantavírus são vírus RNA de cadeia simples pertencentes à família Bunyaviridae. Diferente de outros vírus da família, não têm artrópodes como vetores; seus anfitrões na natureza são roedores e alguns mamíferos pequenos. A transmissão para o homem acontece através da inalação de excrementos dos animais infectados, raras vezes por mordeduras e foi documentada a possibilidade de transmissão de pessoa para pessoa. Existem duas formas clínicas da doença: febre hemorrágica com síndrome renal (FHSR) distribuída na Europa e Ásia, e síndrome cardiopulmonar por Hantavírus (SCPH), nas Américas. O SCPH apresenta-se clinicamente em quatro fases: incubação, prodrômica, cardiopulmonar e convalescença. No laboratório é frequente o achado de trombocitopenia, junto a outras mudanças hematológicas e bioquímicas. O diagnóstico é realizado pela detecção de anticorpos ou PCR. Recentemente em Epuyén, Província de Chubut, Argentina, houve um surto que afetou 34 pessoas com 12 mortes associado à transmissão interpessoal. Revê-se a situação atual relativa ao tratamento e às possibilidades futuras de intervenção. Embora se trate de uma doença com uma baixa prevalência, a alta taxa de letalidade e o alto impacto emocional e econômico que sofrem as localidades afetadas tornam necessário continuar investigando em busca de novas alternativas de tratamento.

Brote de síndrome pulmonar por hantavirus, Tucumán, Argentina / Outbreak of hantavirus pulmonary syndrome in Tucumán, Argentina

Se describe un brote de síndrome pulmonar por hantavirus en el departamento de Burruyacú, provincia de Tucumán. La detección en 2016 de un caso de hantavirosis en una joven de 23 años -en ese momento considerado el primero ocurrido en dicha provincia- promovió un estudio epidemiológico exhaustivo, que permitió detectar retrospectivamente otro caso ocurrido en un niño de 5 años, un mes antes, en el mismo departamento. La infección fue confirmada por serología en ambos casos (caso 1 en muestras de 4 y 7 días de evolución, caso 2 en muestra a los 4 días). En ambos casos el genotipo viral fue caracterizado como HU39694 y los contactos fueron serológicamente negativos. En las áreas fueron identificados roedores pertenecientes a los géneros Akodon y Calomys y a la especie Mus musculus, pero no a Oligoryzomys, el reservorio habitual del genotipo HU39694. Tampoco se detectaron anticuerpos anti-hantavirus en suero de los roedores capturados. La ausencia de registro de viajes a área endémica de este genotipo y los hábitos recreacionales de los pacientes, sumados a los resultados serológicos negativos para hantavirus en los contactos, permiten inferir la posible exposición de los pacientes a fluidos de roedores infectados durante actividades recreativas o sociales al aire libre en sus respectivas áreas de residencia. En conclusión, se demuestra la circulación en Tucumán del genotipo viral HU39694, hasta ahora considerado restringido a la región pampeana central. Se extiende así a Tucumán el área endémica de hantavirosis, pero no se identificó el reservorio en el área.

We describe an outbreak of hantavirus pulmonary syndrome in the Burruyacú Department, Province of Tucumán. The detection in 2016 of a case of hantavirosis affecting a 23-year-old woman, considered at that time to be the first case occurred in that province, promoted a thorough epidemiological study. The investigation allowed the retrospective detection of another case occurred one month earlier in a 5-year-old child in the same Department. In both cases, the infection was confirmed by serology (case 1 at days 4 and 7 of disease onset, case 2 at day 4) and the viral genotype was characterized as HU39694. The contacts of both cases were serologically negative for hantavirus. The rodents captured in the area belonged to genus Akodon, genus Calomys and species Mus musculus. Oligoryzomys, the known reservoir for this viral genotype, was not found. Specific anti-hantavirus antibodies were not detected in the captured rodents. Given that the patients had not visited hantavirus endemic areas and their contacts were negative for hantavirus, we infer that the patients were locally exposed to fluids of infected rodents during their usual social or recreational outdoor activities. In conclusion, we demonstrate that hantavirus HU39694 -a genotype until now considered to be restricted to the Central Pampas of the country- is circulating in the North Western province of Tucumán. The endemic area of hantavirosis is thus expanded to this province but the viral reservoir in the area has not yet been identified.

Hantavirus pulmonary syndrome in Tucumán province associated to an unexpected viral genotype

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

Se describe la caracterización del genotipo viral del primer caso de síndrome pulmonar por hantavirus reportado en la Provincia de Tucumán. Una mujer de 23 años, con diagnóstico previo de síndrome antifosfolipídico y sin antecedente de viaje reciente, falleció tras 11 días de enfermedad. De las cuatro regiones endémicas para este síndrome, la región Noroeste es la de mayor incidencia del país, concentrando más del 50% de los casos informados en Argentina. Hasta el momento, solamente dos de las seis provincias que componen la región Noroeste, Salta y Jujuy, habían registrado síndrome pulmonar por hantavirus con casos en áreas pertenecientes a la Selva de las Yungas. Desde ahora, se suma a dicha región la provincia de Tucumán. Llamativamente, el genotipo viral caracterizado en este caso mostró mayor identidad con el genotipo más prevalente en la provincia de Buenos Aires llamado Andes-BsAs, y no como se esperaba, con los genotipos comúnmente encontrados en la región Noroeste. El genotipo Andes-BsAs se ha asociado a letalidad próxima al 30% y también a transmisión interhumana en la provincia de Buenos Aires. No se puede descartar transmisión interhumana en el presente caso.

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.

Development of a novel plaque reduction neutralisation test for hantavirus infection

In the Americas, hantaviruses cause severe cardiopulmonary syndrome (HCPS) with a high fatality rate. Hantavirus infection is commonly diagnosed using serologic techniques and reverse transcription-polymerase chain reaction. This paper presents a novel plaque reduction neutralisation test (PRNT) for detecting antibodies to Brazilian hantavirus. Using PRNT, plaque detection was enhanced by adding 0.6% of dimethyl sulfoxide into the overlay culture medium of the infected cells. This procedure facilitated clear visualisation of small plaques under the microscope and provided for easy and accurate plaque counting. The sera from 37 HCPS patients from the city of Ribeirão Preto, Brazil was evaluated for the Rio Mamoré virus (RIOMV) using PRNT. Six samples exhibited neutralising antibodies; these antibodies exhibited a low titre. The low level of seropositive samples may be due to fewer cross-reactions between two different hantavirus species; the patients were likely infected by Araraquara virus (a virus that has not been isolated) and RIOMV was used for the test. This assay offers a new approach to evaluating and measuring neutralising antibodies produced during hantavirus infections and it can be adapted to other hantaviruses, including viruses that will be isolated in the future.

Avaliação da infecção por Hantavirus em amostras humanas e de roedores silvestres e sinantrópicos no Estado do Rio de Janeiro / Assessment for hantavirus infection in human specimens and wild and synanthropic rodents in Rio de Janeiro

A síndrome pulmonar por hantavírus (SPH) tem sido registrada no Brasil desde1993 e a transmissão para o homem ocorre através da inalação de partículas viraispresentes em aerossóis de excretas de roedores infectados. No Brasil, nove genótiposvirais caracterizados a partir de roedores e/ou humanos foram descritos, sendo seiscomprovadamente patogênicos. Desde os primeiros registros, mais de 1600 casoshumanos foram confirmados, com ampla distribuição entre a maioria dos estadosbrasileiros e alta taxa de letalidade. A SPH apresenta-se como doença febril agudacaracterizada pelo grave comprometimento cardiovascular e respiratório. Os pacientespodem exibir uma ampla variedade de manifestações clínicas, onde os sinais e sintomaspodem ser confundidos com os de outras doenças. Assim é necessário o diagnósticodiferencial separando casos de SPH de outros agravos com manifestações clínicassemelhantes, como é o caso da dengue. Embora não existam relatos de casos humanosno estado do Rio de Janeiro, foram encontradas evidências sorológicas em humanos econfirmação de circulação de hantavírus patogênico entre roedores silvestres, maisespecificamente, na espécie Oligoryzomys nigripes, no Parque Nacional da Serra dosÓrgãos, em Teresópolis. Neste cenário, este estudo teve como objetivos avaliar ainfecção por hantavírus em amostras humanas e em amostras de roedores silvestres esinantrópicos provenientes de diversos municípios fluminenses. Um total de 497amostras de soro de pacientes negativos para dengue pelos testes sorológicos, cedidaspelo LACEN/RJ, provenientes de 25 municípios, e de 235 amostras de roedoresprovenientes de sete municípios, foram analisadas através do ensaio imunoenzimáticopara detecção de anticorpos anti-hantavírus da classe IgM e IgG (ELISA IgM e IgG) ede testes moleculares...

Hantavirus pulmonary syndrome (HPS) has been registered in Brazil since 1993and transmission to humans occurs through inhalation of viral particles present inaerosols from excreta of infected rodents. In Brazil, nine viral genotypes characterizedfrom rodents and/or humans have been described, six of them pathogenic. Over 1.600human cases were confirmed, with wide distribution among most Brazilian states andhigh lethality. Hantavirus pulmonary syndrome presents as an acute febrile illnesscharacterized by severe cardiovascular and respiratory compromise. Patients mayexhibit a wide variety of clinical manifestations, where signs and symptoms can beconfused with other diseases. Thus the differential diagnosis of HPS is necessary fromother illnesses with similar clinical manifestations, such as dengue. There are no reportsof human cases in Rio de Janeiro state, until now, but serologic evidence in humans andconfirmation of circulating pathogenic hantavirus among wild rodents in ParqueNacional da Serra dos Órgãos in Teresopolis, related to the rodent Oligoryzomysnigripes were found. In this scenario, this study aimed to evaluate hantavirus infectionin human, wild and synanthropic rodents samples from different municipalities in Riode Janeiro state. Serum samples from 497 dengue fever seronegative patients, from 25municipalities provided by the LACEN/RJ, and 235 serum samples from rodents, fromseven municipalities, were analyzed by enzyme-linked immunosorbent assay fordetection of anti-hantavirus antibodies of IgM and IgG (IgM and IgG ELISA) andmolecular tests. Five human samples, from Valença, Vassouras and Nova Friburgomunicipalities, presented IgM antibodies against hantavirus...

Síndrome pulmonar por Hantavirus (Virus Río Mamoré) en la Amazonía Peruana / Hantavirus pulmonary syndrome (Rio Mamore Virus) in the Peruvian Amazon region

La hantavirosis es una infección viral zoonótica transmitida por roedores cuya forma clínica más letal es el síndrome pulmonar por Hantavirus (SPH). La variante río Mamoré es autóctona de Sudamérica y fue descrita en roedores sin asociarla a enfermedad en humanos. Se presenta dos casos de SPH causados por hantavirus río Mamoré en la Amazonía peruana en noviembre de 2011. En ambos casos, el diagnóstico confirmatorio fue molecular, efectuados en el Instituto Nacional de Salud de Perú. Se realizó análisis filogenético del fragmento de genoma viral y la evaluación histopatológica. Ambos pacientes evolucionaron a síndrome de distrés respiratorio del adulto y estado de choque refractario. Un paciente falleció y el otro se recuperó a los doce días.

Hantavirus infection is a viral zoonotic infection borne by rodents which most letal form clinical is the Hantavirus Pulmonary Syndrome (SPH, Spanish abbreviation). The Mamore River variant originates in South America and was found in rodents without any association to human diseases. Two cases of SPH were identified in the Peruvian Amazon region in November 2011. In both cases, a molecular diagnostic testing was conducted by the Instituto Nacional de Salud from Peru. A phylogenetic analysis of a viral genome fragment and a histopathological evaluation were conducted. Both patients developed adult respiratory distress syndrome and refractory shock. A patient died and another one recovered 12 days later.

Síndrome cardiopulmonar por hantavirus: a propósito de un caso: [revisión] / Hantavirus pulmonary syndrome: a case report: [review]

El Hantavirus es un patógeno de aparición relativamente nueva. El año 1996 fue publicado el primer en Chile y un año antes se habla establecido el primer diagnostico de síndrome cardiopulmonar (SCPH) en nuestro país. En Chile el tipo de Hantavirus es el Andes cuyo reservorio es el ratón de cola larga (Oligoryzomys longicaudatus). Se puede presentar como infección inaparente, como una enfermedad leve por Hantavirus o como su expresión más grave que es el SCPH. En general se manifiesta como un cuadro rápidamente progresivo, que tiene 3 etapas, la prodrómica, la cardiopulmonar y la de convalecencia. Comienza como si fuera un cuadro gripal, con fiebre y mialgias o como un cuadro gastrointestinal, seguido por aparición súbita de insuficiencia respiratoria con o sin aparición de inestabilidad hemodinámica que puede progresar en algunos casos hasta edema agudo de pulmón, shock y muerte. En Chile se han confirmado casos de SCPH desde la ciudad de Valparaíso hasta Aysén, siendo esta última la de mayor incidencia en el país. A la fecha, durante el 2010 se han confirmado 30 casos. La letalidad alcanza a un 33 por ciento El objetivo de este trabajo es comunicar un caso de SCPH de rápida regresión y revisar la literatura respecto al tema.

Diagnosis of hantavirus infection in humans and rodents in Ribeirão Preto, State of São Paulo, Brazil / Diagnóstico de infecção por hantavírus em humanos e roedores em Ribeirão Preto, Estado de São Paulo

INTRODUCTION: Hantavirus pulmonary and cardiovascular syndrome (HPCS) is an emerging serious disease in the Americas. Hantaviruses (Bunyaviridae) are the causative agents of this syndrome and are mainly transmitted through inhalation of aerosols containing the excreta of wild rodents. In the Ribeirão Preto region (state of São Paulo, Brazil), HPCS has been reported since 1998, caused by the Araraquara virus (ARAV), for which Necromys lasiurus is the rodent reservoir. This study aimed to show diagnostic results relating to infection in humans and rodents, obtained at the Virology Research Center of the Ribeirão Preto School of Medicine, University of São Paulo, between 2005 and 2008. METHODS: HPCS was diagnosed by means of ELISA and/or RT-PCR in 11 (21.2 percent) out of 52 suspected cases, and 54.4 percent of these were fatal. Furthermore, 595 wild rodents (Necromys lasiurus, Akodon sp, Calomys tener and Oligoryzomys sp) were caught between 2005 and 2008. RESULTS: Fifteen (2.5 percent) of these rodents presented antibodies for hantavirus, as follows: Necromys lasiurus (4 percent), Calomys tener (1.9 percent) and Akodon sp (1.5 percent). Nucleotide sequences obtained through RT-PCR from one HPCS patient and one Calomys tener rodent were compared with hantavirus sequences from GenBank, which showed that both were homologous with ARAV. CONCLUSIONS: This work corroborates previous studies showing that ARAV is the hantavirus causing HPCS in the Ribeirão Preto region. It also shows that rodents infected with hantavirus represent a constant risk of transmission of this virus to man.

INTRODUÇÃO: A síndrome pulmonar e cardiovascular por hantavírus é uma doença grave emergente nas Américas. Os hantavírus, Bunyaviridae, são os agentes causadores desta síndrome, causadas, principalmente, pela inalação de aerossóis dos dejetos de roedores silvestres. Na região de Ribeirão Preto, a SPCVH, causada pelo vírus Araraquara, tem sido diagnosticada, desde 1998. O roedor-reservatório do ARAV é o Necromys lasiurus. Este tem como objetivo mostrar os resultados de diagnósticos da infecção de humanos e roedores obtidos no Centro de Pesquisa em Virologia da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, durante o período de 2005 a 2008. MÉTODOS: A síndrome pulmonar e cardiovascular por hantavírus foi diagnosticada, por ELISA e/ou RT-PCR, em 11 (21,2 por cento) dos 52 casos suspeitos e destes, 54,4 por cento foram casos fatais. Além disso, também, de 2005 a 2008, foram capturados 595 roedores silvestres, Necromys lasiurus, Akodon sp, Calomys tener e Oligoryzomys sp. RESULTADOS: Quinze (2,5 por cento) destes roedores apresentaram anticorpos para hantavírus. As soropositividades intraespécie ou gênero foram 4 por cento para Necromys lasiurus, 1,9 por cento para Calomys tener e 1,5 por cento para Akodon sp. Sequências nucleotídicas, obtidas pela RT-PCR de um paciente com SPCVH e de um roedor Calomys tener, foram comparadas com sequências de hantavírus do GenBank, o que mostrou que ambas tinham homologia com o ARAV. CONCLUSÕES: Este trabalho corrobora outros estudos que mostram que o ARAV é o hantavírus causador da SPCVH, na região de Ribeirão Preto, além de mostrar que roedores infectados por hantavírus representam um risco constante de transmissão desses vírus para o homem.

Síndrome pulmonar e cardiovascular por hantavírus: aspectos clínicos de uma doença emergente no sudeste brasileiro / Pulmonary and cardiovascular syndrome due to hantavirus: clinical aspects of an emerging disease in southeastern Brazil

A síndrome pulmonar e cardiovascular por hantavírus é doença causada pela aspiração de aerossóis dos dejetos de roedores silvestres contaminados por vírus da família Bunyaviridae. Estudamos manifestações clínicas e laboratoriais de 70 casos ocorridos de 1998 a 2007 na região de Ribeirão Preto, SP. A freqüência de sintomas foi dispnéia (87 por cento), febre (81 por cento), tosse (44 por cento), cefaléia (34 por cento), taquicardia (81 por cento), hipotensão arterial (56 por cento), hipóxia (49 por cento), acidose metabólica (57 por cento), linfocitopenia (51 por cento), hematócrito >45 por cento (70 por cento), leucocitose com desvio à esquerda (67 por cento), creatinina (51 por cento) e uréia (42 por cento) séricas elevadas. A letalidade (54,3 por cento) ocorreu principalmente no 4o dia. Insuficiência respiratória, hipotensão arterial e choque ocorreu 24-48 horas; o hematócrito elevado e a plaquetopenia são sinais fortemente sugestivos da doença. A hipótese diagnóstica de pneumonia atípica associada a bom prognóstico (p:0,0136); a infusão hídrica >2.000ml e hipotensão arterial associadas a mau prognóstico (p:0,0286 e p:0,0453).

Pulmonary and cardiovascular syndrome due to hantavirus is a disease caused by inhalation of aerosols from the excreta of wild rodents contaminated by viruses of the Bunyaviridae family. We studied the clinical and laboratory manifestations of 70 cases that occurred in the region of Ribeirão Preto, SP, Brazil, between 1998 and 2007. The frequency of symptoms was as follows: dyspnea (87 percent), fever (81 percent), coughing (44 percent), headache (34 percent), tachycardia (81 percent), low arterial blood pressure (56 percent), metabolic acidosis (57 percent), lymphocytopenia (51 percent), hematocrit > 45 percent (70 percent), leukocytosis with left deviation (67 percent), creatinine (51 percent) and urea (42 percent). Mortality (54.3 percent) occurred mainly on the fourth day. Respiratory insufficiency, low arterial blood pressure and shock occurred after 24 to 48 hours. High hematocrit and decreased platelet levels were signs strongly suggestive of the disease. The diagnostic hypothesis of atypical pneumonia was associated with a good prognosis (p = 0.0136). Fluid infusion greater than 2,000 ml and arterial hypotension were associated with a poor prognosis (p = 0.0286 and p = 0.0453).

Los hantavirus causantes de la fiebre hemorrágica con síndrome renal y del síndrome pulmonar / The hantaviruses causing hemorrhagic fever with renal syndrome and pulmonary syndrome

Este trabajo de revisión se enfoca en el análisis de la información básica sobre los hantavirus, agentes causales de dos enfermedades importantes en salud pública: la fiebre hemorrágica con síndrome renal (FHSR) y el síndrome pulmonar por hantavirus (SPH), dos zoonosis distribuidas en Asia/Europa y el continente americano, respectivamente. Los hantavirus se transmiten al hombre a través de la manipulación y contacto directos de roedores infectados o tejidos y secreciones (orina, heces y saliva). La FHSR y el SPH comparten algunas características clínicas, aunque las hemorragias y la afectación renal son propias de la FHSR,y los problemas respiratorios del SPH. Se aportan algunos datos sobre estudios realizados en México sobre hantavirus y se mencionan las condiciones ecológicas vinculadas con la distribución de los virus y sus reservorios naturales, así como algunas medidas para evitar o reducir el riesgo de infección.

The goal of this review is to provide basic information on hantaviruses as causative agents of Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS), two zoonotic diseases widely distributed in Asia/Europe, and the American continent, respectively. Hantaviruses are rodent-borne and transmitted to humans by direct contact with infected rodents or their secretions (urine, feces and saliva). Both, HFRS and HPS share some clinical aspects, however, hemorrhage and renal failure are the hallmark of HFRS, while respiratory problems are distinctive signs and symptoms of patients with HPS. Studies on hantavirus infection in rodents from Mexico are included, some recomendations to prevent or avoid contact with rodents are mentioned, and some determinant ecologic factors of hantaviruses distribution and their natural rodents, are also included.

Expression of a hantavirus N protein and its efficacy as antigen in immune assays

Hantavirus cardiopulmonary syndrome (HCPS) has been recognized as an important public heath problem. Five hantaviruses associated with HCPS are currently known in Brazil: Juquitiba, Araraquara, Laguna Negra-like, Castelo dos Sonhos, and Anajatuba viruses. The laboratory diagnosis of HCPS is routinely carried out by the detection of anti-hantavirus IgM and/or IgG antibodies. The present study describes the expression of the N protein of a hantavirus detected in the blood sample of an HCPS patient. The entire S segment of the virus was amplified and found to be 1858 nucleotides long, with an open reading frame of 1287 nucleotides that encodes a protein of 429 amino acids. The nucleotide sequence described here showed a high identity with the N protein gene of Araraquara virus. The entire N protein was expressed using the vector pET200D and the Escherichia coli BL21 strain. The expression of the recombinant protein was confirmed by the detection of a 52-kDa protein by Western blot using a pool of human sera obtained from HCPS patients, and by specific IgG detection in five serum samples of HCPS patients tested by ELISA. These results suggest that the recombinant N protein could be used as an antigen for the serological screening of hantavirus infection.

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.

Febres hemorrágicas por vírus no Brasil / Viral hemorrhagic fevers in Brazil

Chamando a atencão para as febres hemorrágicas por vírus, que em sua maioria tem escassa informacão divulgada e provavelmente são subnotificadas, mostra-se neste artigo casos clínicos das 4 doencas deste tipo que ocorrem no Brasil: febre amarela, dengue hemorrágico/síndrome de choque do dengue, febre hemorrágica por arenavírus e síndrome pulmonar e cardiovascular por hantavírus. Também, relevantes aspectos clínicos, laboratoriais e epidemiológicos destas viroses são aqui abordados. São doencas que têm alta letalidade e induzem extravasamento capilar e coagulopatia, que podem ser evidenciados pela elevacão do hematócrito e plaquetopenia. A suspeita clínica e o tratamento precoce são fundamentais à sobrevida dos pacientes.