Frequency of histopathological changes in Howler monkeys ( Alouatta sp. ) naturally infected with yellow fever virus in Brazil

Abstract: INTRODUCTION: Due to the importance that Howler monkeys have on the yellow fever (YF) epidemiological sylvatic cycle in Brazil, more accurate morphological diagnostic criteria needs to be established, especially considering the differences that may exist between the genera of Brazilian non-human primates (NHPs) involved in yellow fever virus (YFV) epizootics. METHODS: Records of YF epizootics in NHPs in Brazil between 2007 and 2009 were obtained from the Brazilian Ministry of Health database to select YF positive (n=98) Howler monkeys (Alouatta sp.) for this study. The changes described in the histopathological reports were categorized by organ and their frequencies calculated. RESULTS: The most frequent lesions observed in the animals with YF were hepatocyte apoptosis (Councilman body formation), midzonal hepatocyte necrosis, steatosis, liver hemorrhage, inflammatory mononuclear cell infiltration of the liver, renal acute tubular necrosis and interstitial nephritis. Midzonal hepatocyte necrosis, steatosis and hemorrhage presented positive correlations with apoptosis of hepatocytes, suggesting strong YFV pathogenic effect association; they were also the main histopathological changes in the Alouatta sp. A pronounced negative correlation between apoptosis of hepatocytes and hepatic mononuclear cell infiltration pointed to significant histopathological differences between YFV infection in Howler monkeys and humans. CONCLUSIONS: The results warn that NHPs may exhibit different response patterns following YFV infection and require a more careful diagnosis. Presumptive diagnosis based on primate histopathological lesions may contribute to public health service control.

Seroprevalence of flaviviruses antibodies in water buffaloes (Bubalus bubalis) in Brazilian Amazon

The state of Pará encompasses 26% of Brazilian Amazon where an enormous diversity of arboviruses has been found. This study aimed to assess the prevalence and distribution of hemagglutination-inhibition antibodies against antigens of six Flavivirus (yellow fever virus, Ilheus virus, Saint Louis encephalitis virus, Cacipacore virus, Bussuquara virus and Rocio virus) in water buffaloes in Pará state, Brazil. The prevalence of antibodies in these farm animals is important to determine the circulating arboviruses.

Seroprevalence of flaviviruses antibodies in water buffaloes (Bubalus bubalis) in Brazilian Amazon

The state of Pará encompasses 26% of Brazilian Amazon where an enormous diversity of arboviruses has been found. This study aimed to assess the prevalence and distribution of hemagglutination-inhibition antibodies against antigens of six Flavivirus (yellow fever virus, Ilheus virus, Saint Louis encephalitis virus, Cacipacore virus, Bussuquara virus and Rocio virus) in water buffaloes in Pará state, Brazil. The prevalence of antibodies in these farm animals is important to determine the circulating arboviruses.

Arboviroses da Amazônia: estudo do mecanismo de morte celular e da resposta fenotípica do hospedeiro na febre amarela / Arboviruses of the Amazonia: study of the cell death mechanism of cell death and the fenotipic host response in the yellow fever[

Os eventos histológicos no fígado foram quantificados, usando técnica de imunomarcação para avaliar 53 amostras hepáticas provenientes de viscerotomia de pacientes vitimados por febre amarela silvestre. A análise quantitativa dos eventos demonstrou amplo predomínio do componente apoptótico sobre a necrose. O infiltrado inflamatório é desproporcional em intensidade à morte dos hepatócitos. Houve predomínio de linfócitos TCD4+, ocorrendo em menor proporção linfócitos TCD8+, linfócitos B, células NK e apresentadoras de antígenos (S100). A expressão citocínica foi de perfil Th1, com expressão de TNF-a, IFN-g e acompanhada de intensa imunomarcação para TGF-b. Frente aos achados acreditamos que a predileção pela localização médio zonal das lesões do fígado poderia decorrer de fenômenos de hipóxia por hipofluxo secundária à vasculopatia sistêmica e associada ao efeito citopático viral.In this work, the histological events in the liver were quantified, using a immunomarking technique to evaluate 53 hepatic samples from the viscerotomy of patients with the sylvatic form of yellow fever. Quantitative analysis of the events demonstrated an ample prevalence of an apoptotic component in the necrosis. The intensity of the inflammatory infiltration is disproportionate to the death of the hepatocytes. There is a prevalence of TCD4+ lymphocytes, with a smaller proportion of TCD8+ lymphocytes, B lymphocytes, NK cells and antigen-presenting cells (S100). The cytokine expression presented a profile of Th1, with expression of TNF-a, IFN-g and accompanied by intense immunomarking by TGF-b. Faced with these findings, we consider that the predilection for the midzonal location of the lesions in the liver could arise from the phenomena of hypoxia secondary to systemic vasculopathy associated to the viral cytopathic effect...

Vacunación en la fiebre amarilla / Vaccination in the yellow fever

Actualmente, la vacuna contra la fiebre amarilla es preparada exclusivamente con la cepa 17D del virus atenuado. Esta vacuna tiene un excelente registro de inocuidad y su poder inmunogénico es elevado. En el pasado se utilizó ampliamente en Africa la cepa "French neurotropic", desarrollada por el Instituto Pasteur de Dakar, a través de múltiples pases en cerebro de ratón. Entre 1940 y 1960 se aplicaron más de 80 millones de dosis por medio de escarificación; sin embargo, se comprobó que la vacuna ocasionaba encefalitis en una proporción pequeña, pero importante, de niños menores de 12 años. Esto dió por resultado que al inicio de la década de los 80 se interrumpiera su producción. Producción mundial de la vacuna: una encuesta realizada en la década de los años ochenta indicó que la producción mundial de la vacuna contra la fiebre amarilla se acercaba a los 19 millones de dosis por año, de las cuales aproximadamente 12 millones fueron producidas por la Fundación Oswaldo Cruz, Brasil. También se estimó que la reserva mundial de la vacuna era de 4.5 millones de dosis, cantidad considerada insuficiente para combatir epidemias extensas, o prevenir la propagación de las mismas a otras áreas. Actualmente hay once laboratorios aprobados por la OMS para la producción de vacunas contra la fiebre amarilla, dos de los cuales están situados en países del Continente Americano

A clinico-pathological study of yellow fever with demonstration of the virus in the human liver

The clinical histopathological and serological findings in three patients who developed yellow fever after entering the Guayaguayare forest in south-east Trinidad in January and February 1979 are described in this report. The patients were all previously healthy young males and the clinical features of the disease varied from fulminant viral hepatitis with hepato-renal failure to a self-limiting anicteric viral illness. The first patient died, and histopathological examination of the liver was done post-mortem. Needle biopsy of the liver was done on case 2 which presented with the clinical picture of infective hepatitis, and on case 3 with the features of an anicteric viral illness. The histopathological hallmarks of midzonal necrosis, granular eosinophilic degeneration (Councilman bodies) and fatty change in the parenchymal cells of the liver were seen in three cases. The electron microscopic study demonstrated the presence of the yellow fever virus in the liver of the patient who died.