Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. METHODS: We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if VA ECMO was avoided and HVHF-nonresponders if VA ECMO support was needed despite HVHF. A targeted-HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients. RESULTS: Patients had maximum serum lactate of 8.8 (8.7-12.8) mmol/L and a lowest cardiac index of 1.8 (1.8-1.9) L/min/m2 . The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF-responders who received targeted-HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication. CONCLUSION: HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted-HVHF may increase the chance of success.

Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35-40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. METHODS: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. RESULTS: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34-58) vs. 83 (64-177) K/mm3, p < 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78-1.0) p < 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. CONCLUSIONS: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers.

Síndrome cardiopulmonar por hantavirus / Hanta syndromevirus cardiopulmonary

Introducción: En el ámbito mundial las enfermedades infecciosas son la segunda causa de muerte en el presente siglo. La epidemiología de las enfermedades infecciosas emergentes y reemergentes plantean desafíos a la clínica y a la salud pública en general, tal es el caso del síndrome cardiopulmonar por hantavirus. Objetivo: Actualizar los conocimientos sobre la vigilancia epidemiológica del microorganismo responsable y documentar a los profesionales de la salud. Métodos: Revisión de artículos de investigación referentes al síndrome cardiopulmonar por hantavirus en el presente siglo. Se realizaron búsquedas en las fuentes de indexación Scopus, SciELO, Medline, Latindex, Bireme, Google. Lilacs, PubMed sobre el microorganismo, patogenia, manifestaciones clínicas, diagnóstico y tratamiento. Conclusiones: La emergencia y reemergencia de este síndrome con alta letalidad debe ser de dominio de clínicos, pediatras, intensivistas, epidemiólogos y los médicos de la atención primaria para su prevención, diagnóstico precoz y conducta oportuna. La vigilancia epidemiológica es fundamental(AU)

Introduction: Infectious diseases are globally the second cause of death in this century. The epidemiology of emerging and reemerging infectious diseases poses clinical and public health challenges in general; such is the home of Hantavirus cardiopulmonary syndrome. Objective: Updating information on the epidemiological surveillance of the causing microorganism and provide said knowledge to health professionals. Methods: Reviewing research articles related to cardiopulmonary syndrome by Hantavirus conducted in the present century. Researches were carried out about the microorganism, pathogenesis, clinical manifestations, diagnosis and treatment in the indexing sources Scopus, SciELO, Medline, Latindex, Bireme, Google, Lilacs and PubMed. Conclusions: The emergence and reemergence of this highly lethal syndrome should be known by clinicians, pediatricians, intensive care staff, epidemiologists and primary care physicians for prevention, early diagnosis and timely treatment. Epidemiological surveillance is essential(AU)

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.

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.

Etiología y caracterización epidemiológica del síndrome febril no palúdico en tres municipios del Urabá antioqueño, Colombia / Etiology and epidemiological characterization of non-malarial febrile syndrome in three municipalities of Urabá (Antioquia), Colombia

Introducción. La región de Urabá es endémica para varias enfermedades febriles agudas de origen infeccioso. Sin embargo, solo los pacientes con malaria pueden acceder a un diagnóstico oportuno y rápido, motivo por el cual muchos síndromes febriles no palúdicos quedan sin diagnóstico etiológico claro. Objetivo. Establecer la etiología, describir las manifestaciones clínicas y explorar algunos posibles factores de riesgo relacionados con los síndromes febriles agudos no palúdicos en pacientes procedentes de los municipios de Necoclí, Turbo y Apartadó. Materiales y métodos. Se tomaron muestras de suero en fase aguda y de convalecencia de 220 pacientes febriles negativos para malaria, provenientes de zonas rurales y urbanas de Necoclí, Turbo y Apartadó en los años 2007 y 2008. Se practicaron pruebas para diagnóstico de dengue (detección de anticuerpos IgM por ELISA), leptospirosis (detección de anticuerpos IgM e IgG por IFI), rickettsiosis (detección de anticuerpos IgG por IFI), hantavirus y arenavirus (detección de anticuerpos IgG por ELISA). Resultados. Se encontraron frecuencias de dengue, leptospirosis, rickettsiosis y arenavirus de 37,3 %, 14,1 %, 2,7 % y 0,5 %, respectivamente. Se presentaron 12 casos de coinfección de leptospirosis-dengue y uno de leptospirosis-rickettsiosis-dengue. El sexo masculino y la humedad relativa media, fueron factores de riesgo para dengue. El inicio de signos clínicos en febrero de 2008, se asoció tanto con la infección por dengue como por leptospirosis. Conclusión. Se reafirma la importancia del virus del dengue, Rickettsia spp. y Leptospira spp., como agentes causantes del síndrome febril en la región del Urabá.

Introduction: Urabá, a region on the northern coast of Colombia, is endemic to several acute febrile illnesses of infectious origin; however, only patients with malaria may have access to quick and effective diagnosis. For this reason, many non-malarial febrile patients go without a clear etiologic diagnosis. Aim: To establish the etiology and clinical signs of acute febrile non-malaria syndromes and explore some of the likely risk factors in patients originating in the municipalities of Necocli, Turbo and Apartado who exhibit these symptoms. Materials and methods: We obtained acute and convalescent sera from 220 non-malarial febrile patients from the rural and urban zones of Necocli, Turbo and Apartado during 2007 and 2008. Serologic tests for dengue (IgM by ELISA), leptospirosis (IgM and IgG by IFA), rickettsiosis (IgG by IFI), hanta and arenavirus (IgG by ELISA) were performed. Results: We found that the frequency of infection for dengue, leptospirosis, rickettsiosis and arenavirus, was 37.3%; 14.1%; 2.7% and 0.5%, respectively. There were 12 co-infection cases of leptospirosis-dengue and one of leptospirosis-rickettsiosis-dengue. Male gender and relative humidity were considered risk factors for dengue, and the beginning of clinical signs in February of 2008 was associated with the infection of dengue and leptospirosis. Conclusion: This study confirms previous records that underline the importance of Rickettsia spp, dengue virus and Leptospira spp as causal agents of febrile syndrome in this region of Colombia.

[Etiology and epidemiological characterization of non-malarial febrile syndrome in three municipalities of Urabá (Antioquia), Colombia]. / Etiología y caracterización epidemiológica del síndrome febril no palúdico en tres municipios del Urabá antioqueño, Colombia.

INTRODUCTION: Urabá, a region on the northern coast of Colombia, is endemic to several acute febrile illnesses of infectious origin; however, only patients with malaria may have access to quick and effective diagnosis. For this reason, many non-malarial febrile patients go without a clear etiologic diagnosis. AIM: To establish the etiology and clinical signs of acute febrile non-malaria syndromes and explore some of the likely risk factors in patients originating in the municipalities of Necocli, Turbo and Apartado who exhibit these symptoms. MATERIALS AND METHODS: We obtained acute and convalescent sera from 220 non-malarial febrile patients from the rural and urban zones of Necocli, Turbo and Apartado during 2007 and 2008. Serologic tests for dengue (IgM by ELISA), leptospirosis (IgM and IgG by IFA), rickettsiosis (IgG by IFI), hanta and arenavirus (IgG by ELISA) were performed. RESULTS: We found that the frequency of infection for dengue, leptospirosis, rickettsiosis and arenavirus, was 37.3%; 14.1%; 2.7% and 0.5%, respectively. There were 12 co-infection cases of leptospirosis-dengue and one of leptospirosis-rickettsiosis-dengue. Male gender and relative humidity were considered risk factors for dengue, and the beginning of clinical signs in February of 2008 was associated with the infection of dengue and leptospirosis. CONCLUSION: This study confirms previous records that underline the importance of Rickettsia spp, dengue virus and Leptospira spp as causal agents of febrile syndrome in this region of Colombia.

[Purpura fulminans, cerebral infarcts and multiorganic dysfunction due to hantavirus infection. Review and case report]. / Púrpura fulminante, infartos cerebrales y disfunción multiorgánica debido a infección por hantavirus. Revisión del tema y comunicación de un caso.

Multiorganic failure is a rare manifestation of hantavirus infection but it should be included among differential diagnoses of multiorganic failure in the pediatric age. Currently, there is no effective therapy for this infection. A high suspicion index and early referral to a pediatric intensive care unit with extracorporeal membrane oxygenation may lead to a favourable impact in the outcome. We report a fatal case of hantavirus infection in a 9-year-old girl with a severe disease refractory to hemodynamic supportive measures, and characterized by purpura fulminans, cerebral infarcts, cardiopulmonary failure, and acute renal failure. Commentaries and review about these infrequent clinical manifestations are made.

Púrpura fulminante, infartos cerebrales y disfunción multiorgánica debido a infección por hantavirus. Revisión del tema y comunicación de un caso / Purpura fulminans, cerebral infarcts and multiorganic dysfunction due to hantavirus infection. Review and case report

El fallo multiorgánico es raro en la infección por hantavirus y debería ser incluido dentro de los diagnósticos diferenciales de disfunción ultiorgánica en la edad pediátrica. Actualmente, no existe terapia eficaz para esta infección. Un alto índice de sospecha y la derivación temprana a una unidad de cuidados intensivos con disponibilidad de oxigenación con membrana extracorpórea pueden mejorar el pronóstico. Con motivo de un caso fatal de una niña de 9 años infectada por hantavirus, que exhibió una enfermedad caracterizada por púrpura fulminante, infartos cerebrales, fallo cardiopulmonar e insuficiencia renal aguda, refractaria a todas las medidas de apoyo, decidimos comentar el cuadro clínico y hacer una revisión del tema.

Púrpura fulminante, infartos cerebrales y disfunción multiorgánica debido a infección por hantavirus. Revisión del tema y comunicación de un caso / Purpura fulminans, cerebral infarcts and multiorganic dysfunction due to hantavirus infection. Review and case report

El fallo multiorgánico es raro en la infección por hantavirus y debería ser incluido dentro de los diagnósticos diferenciales de disfunción ultiorgánica en la edad pediátrica. Actualmente, no existe terapia eficaz para esta infección. Un alto índice de sospecha y la derivación temprana a una unidad de cuidados intensivos con disponibilidad de oxigenación con membrana extracorpórea pueden mejorar el pronóstico. Con motivo de un caso fatal de una niña de 9 años infectada por hantavirus, que exhibió una enfermedad caracterizada por púrpura fulminante, infartos cerebrales, fallo cardiopulmonar e insuficiencia renal aguda, refractaria a todas las medidas de apoyo, decidimos comentar el cuadro clínico y hacer una revisión del tema.(AU)

Hantavirus infection induces a typical myocarditis that may be responsible for myocardial depression and shock in hantavirus pulmonary syndrome.

Despite clinical evidence of myocardial dysfunction, there is no pathological evidence of myocardial injury in hantavirus pulmonary syndrome (HPS). The dominant opinion is that the primary cardiac lesion is functional rather than structural. The present study describes hantaviral antigen and particles in the cardiac endothelium and interstitial macrophages in association with a typical myocarditis in HPS. Human hearts from 14 individuals who died of HPS were compared with hearts from 14 individuals who died of acute necrotizing pancreatitis associated with acute lung injury and 4 individuals who died accidental deaths without thoracic injury (as controls); all cases were selected from autopsies. Transmural blocks of myocardial tissue were excised from the middle portion of the left-ventricular free wall and fixed in formalin. Small samples of myocardial tissue from 4 HPS cases and 4 non-HPS controls were fixed in glutaraldehyde for electron microscopic study. Histomorphometric, immunohistochemical, and ultrastructural methods were employed to detect the presence of hantavirus in the myocardium and to evaluate interstitial edema and the minor diameter of myocytes, to characterize the immunophenotype, and to estimate the number of inflammatory cells and in situ cytokine-producing cells and the T helper cell subset 1 and 2 immune responses (tumor necrosis factor [TNF]-alpha, interferon-gamma, interleukin [IL]-10, and IL-4). Cardiac remodeling; hantaviral antigen and particles in the endothelium and macrophages; scattered foci of myofiber necrosis; greater interstitial cellular infiltration, mainly composed of macrophages and memory T lymphocytes and a significant number of T helper and B lymphocytes; and TNF-alpha protein expression in macrophage-type cells and cardiomyocytes were observed to a greater extent in HPS myocardium than in normal and acute pancreatitis control myocardium. These findings give support to the opinion that structural changes could be responsible for myocardial depression and shock in HPS, and it should be properly named as "hantavirus cardiopulmonary syndrome" (HCPS).

Síndrome pulmonar por hantavirus ¿Cómo la peste? / Hantavirus pulmonary syndrome

La enfermedad grave por Hantavirus se caracteriza por fiebre hemorrágica y rápido progreso, en menos de 24 horas al shock, con grave compromiso cardiopulmonar.Presentamos una paciente que ingresó a la UCIP proveniente del Gran Buenos Aires y destacamos los elementos clínicos y bioquímicos que deben sugerir la sospecha diagnóstica especialmente cuando provenga de zonas endémicas.Se trataba de una niña de 11 años de edad, previamente sana, que había comenzado con síndrome febril progresivo 4 días antes de su ingreso, a lo que se agregaron vómitos y diarrea.Frente a la rápida descompensación respiratoria y hemodinámica ingresó a UCIP, donde se diagnosticóshock hipovolémico hemorrágico, edema pulmonar agudo e insuficiencia respiratoria aguda, que requirieron altos parámetros de asistencia respiratoria mecánica y elevadas dosis de inotrópicos.Debido a las características referidas de evolución hiperaguda, la extracción de abundante líquido por tubo endotraqueal, la hipoalbuminemia y el marcado aumento de LDH en una niña previamente sana, se sospechó etiología infecciosa de origen no habitualdescartándose leptospirosis, Mycoplasma pneumoniaey gérmenes comunes. Se confirmó el diagnóstico de Hantavirus tipo Andes a través de Ig G y M.Presentó estado crítico los primeros 3 días y luego tuvo buena evolución a pesar de manifestar parámetrosde mal pronóstico. En la actualidad se encuentra libre de secuelas

Síndrome pulmonar por hantavirus ¿Cómo la peste? / Hantavirus pulmonary syndrome

La enfermedad grave por Hantavirus se caracteriza por fiebre hemorrágica y rápido progreso, en menos de 24 horas al shock, con grave compromiso cardiopulmonar.Presentamos una paciente que ingresó a la UCIP proveniente del Gran Buenos Aires y destacamos los elementos clínicos y bioquímicos que deben sugerir la sospecha diagnóstica especialmente cuando provenga de zonas endémicas.Se trataba de una niña de 11 años de edad, previamente sana, que había comenzado con síndrome febril progresivo 4 días antes de su ingreso, a lo que se agregaron vómitos y diarrea.Frente a la rápida descompensación respiratoria y hemodinámica ingresó a UCIP, donde se diagnosticóshock hipovolémico hemorrágico, edema pulmonar agudo e insuficiencia respiratoria aguda, que requirieron altos parámetros de asistencia respiratoria mecánica y elevadas dosis de inotrópicos.Debido a las características referidas de evolución hiperaguda, la extracción de abundante líquido por tubo endotraqueal, la hipoalbuminemia y el marcado aumento de LDH en una niña previamente sana, se sospechó etiología infecciosa de origen no habitualdescartándose leptospirosis, Mycoplasma pneumoniaey gérmenes comunes. Se confirmó el diagnóstico de Hantavirus tipo Andes a través de Ig G y M.Presentó estado crítico los primeros 3 días y luego tuvo buena evolución a pesar de manifestar parámetrosde mal pronóstico. En la actualidad se encuentra libre de secuelas(AU)