Challenges in research and management of hepatitis E virus infection in Cuba, Mexico, and Uruguay / Retos en la investigación y el tratamiento de la infección por el virus de la hepatitis E en Cuba, México y Uruguay / Desafios em pesquisa e tratamento da infecção pelo vírus da hepatite E em Cuba, ­México e ­Uruguai

ABSTRACT The symposium "Epidemiology of Hepatitis E virus (HEV) Infection and Associated Immune Response" was held at the Universidad de Guadalajara, Mexico, on 14 June 2017, to define the status of research on HEV infection in three countries in Latin America and the Caribbean (LAC)—Cuba, Mexico, and Uruguay—compared to the situation in Germany. Scientists identified specific research gaps in understanding HEV transmission and the resulting impact on development of disease in the three abovementioned LAC countries. Specific recommendations for implementing standardized serologic and molecular diagnostic methods and epidemiologic, basic, and applied research aimed to develop prevention and handling strategies for this infection, along with the associated comorbidities in the three LAC countries, were also discussed. Given similar demographic, sanitary, and economic conditions in other LAC countries that could predispose them to be at high risk for HEV transmission and infection, these research gaps and recommendations might apply to the entire LAC region. This report was ­prepared by meeting participants based on 1) symposium presentations, 2) literature reviews, and 3) group discussions.

RESUMEN El 14 de junio del 2017 se realizó en la Universidad de Guadalajara (México) un simposio sobre las características epidemiológicas de la infección por el virus de la hepatitis E (VHE) y la respuesta inmunitaria asociada. El objetivo fue definir el estado de las investigaciones sobre la infección por el VHE en tres países de América Latina y el Caribe —Cuba, México y Uruguay— en comparación con la situación en Alemania. Los científicos señalaron que para comprender la transmisión del VHE y la consiguiente repercusión en el avance de la infección en estos tres países latinoamericanos aún faltan investigaciones sobre ciertos temas específicos. También analizaron recomendaciones concretas para poner en práctica métodos estandarizados de diagnóstico serológico y molecular, y realizar investigaciones epidemiológicas, básicas y aplicadas a fin de elaborar estrategias de prevención y tratamiento de esta infección y las comorbilidades asociadas en los tres países antes mencionados. Considerando que otros países de América Latina y el Caribe presentan condiciones demográficas, sanitarias y económicas similares que podrían implicar una predisposición a un riesgo alto de transmisión del VHE y de infección por este virus, este análisis sobre las brechas y recomendaciones en el ámbito de la investigación podría aplicarse en toda la subregión. El presente informe fue elaborado por los participantes del simposio sobre la base de: 1) presentaciones del simposio; 2) revisiones bibliográficas; y 3) debates en grupos.

RESUMO O simpósio Epidemiologia da infecção pelo vírus da hepatite E (HEV) e ­resposta imune associada foi realizado na Universidade de Guadalajara, no México, em 14 de junho de 2017, para determinar a situação da pesquisa em HEV em três países da América Latina e Caribe (ALC) - Cuba, México e Uruguai - em comparação à Alemanha. Os especialistas identificaram lacunas específicas nas pesquisas no que se refere ao entendimento da transmissão do HEV e ao impacto resultante do surgimento da doença nos três países da ALC mencionados. Também foram debatidas recomendações aos três países da ALC, especificamente implementar métodos sorológicos e moleculares padronizados de diagnóstico e realizar pesquisa epidemiológica, básica e aplicada visando elaborar estratégias de prevenção e de enfrentamento da infecção e das comorbidades associadas. Diante da semelhança das condições demográficas, econômicas e de saúde que poderia predispor outros países da ALC a um maior risco de transmissão e infecção de HEV, as lacunas em pesquisa e recomendações provavelmente se aplicam à toda a Região da ALC. Este relatório foi preparado pelos participantes do encontro embasado nas apresentações do simpósio, revisão da literatura científica e discussões em grupo.

High Prevalence of ITPA Alleles Associated with Ribavirin-Induced Hemolytic Anemia Among Mexican Population

ABSTRACT Background. The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. Material and methods. In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. Results. The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients. Conclusion. A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.

High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

Epidemiología de las hepatitis virales en México / Epidemiology of viral hepatitis in Mexico

Las hepatitis virales son una de las causas principales de daño hepático en México. En este estudio se analiza el estado actual de las hepatitis virales en México. La Secretaría de Salud informa un total de 192 588 casos de hepatitis virales entre 2000 y 2007. De éstos, 79 por ciento corresponden aVHA, 3.3 por ciento aVHB, 6 por ciento a VHC y 11.7 por ciento a casos sin agente etiológico descrito. No obstante, el VHB se podría estar subdiagnosticando, ya que hay zonas de alta endemia en poblaciones indígenas, existen limitaciones en la sensibilidad y especificidad de las pruebas inmunológicas y podría ser común la hepatitis B oculta. ElVHE podría ser uno de los agentes etiológicos de aquellos casos que carecen de un agente etiológico conocido. Se proponen estrategias específicas para el control de las hepatitis virales tendientes a disminuir el número de casos.

The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79 percent HAV, 3.3 percent HBV, 6 percent HCV, and 12 percent without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed.

Pensamentos automáticos e ansiedade num grupo de jogadores de futebol de campo / Automatics thoughts and anxiety in soccer team

O atleta de futebol experiencia situações estressoras, que interpretadas como ameaçadoras, podem desencadear respostas de ansiedade. A ansiedade exacerbada existe nos jogadores com crenças muito rígidas, as quais afetam substancialmente sua percepção das situações esportivas. O presente estudo tem o objetivo de avaliar a ansiedade no esporte em equipes de futebol e identificar as crenças e os pensamentos disfuncionais mais comuns apresentados por esses jogadores. Foram investigadas três equipes de futebol amador. Utilizaram-se os instrumentos: Inventário de Depressão de Beck (BDI) e Inventário de Ansiedade de Beck (BAI). Verificaram-se 61 por cento de sintomas de ansiedade e 39 por cento de depressão. Os pensamentos automáticos disfuncionais relatados pelos atletas concentram-se nas concepções sobre o erro, perfeccionismo e na estrutura do trabalho. Com um plano de atendimento baseado na abordagem cognitiva comportamental, a Psicologia do Esporte pode ganhar tempo e dinâmica, auxiliando o atleta a transformar seus pensamentos disfuncionais em pensamentos racionais que levem a comportamentos mais satisfatórios a ele, à equipe e à torcida

Enfermedad trofoblástica gestacional: análisis de 15 casos servicio de gineco-obstetricia Hospital General Dr. Pastor Oropeza.I.V.S.S Barquisimeto 1983-1985 / Gestational trophoblastic disease: analysis of 15 cases gyneco-obstetric service General Hospital Dr. Pastor Oropeza I.V.S.S. Barquisimeto 1983-1985

Se observaron 15 casos de Enfermedad Trofoblástica Gestacional en el Servicio de Gineco-Obstetricia del Hospital General "Dr. Pastor Oropeza" de Barquisimeto, en el lapso comprendido entre 1983-1985. Se analizó incidencia, procedencia, relación con la edad gestacional, paridad, abortos, se correlacionó el diagnóstico clínico histológico y persistencia de enfermedad, se correlacionó los títulos iniciales de gonadotrofinas, fracción Beta, con el diagnóstico histológico. Se analizó la respuesta el tratamiento profiláctico y se analizó en forma general el patrón de seguimiento observado. Se recomienda un control cuidadoso en todos los casos con diagnóstico de Mola Hidatiforme, en una consulta especial, para su seguimiento y tratamiento adecuado