The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination

Abstract Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p = 0.598) and the total of negative samples for the remaining viruses tested (p = 0.614). There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030) as well as condition 2 (p = 0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal distribution. These data indicate the significant involvement of HAdV-F type 41 in the etiology of ADD in Minas Gerais, which demonstrates the importance of other viral agents in the development of the disease after the introduction of rotavirus vaccine immunization.

Epidemiologia das rotaviroses antes e após a introdução da vacina / Rotavirus epidemiology before and after vaccine introduction

OBJETIVOS: Avaliar a prevalência e a circulação dos genótipos de rotavírus, antes e após a introdução da vacina oral contra rotavírus humano, bem como verificar uma possível mudança na faixa etária de ocorrência da infecção pelo RV-A. MÉTODOS: Trata-se de um estudo transversal realizado no período de 2002 a 2011, em Juiz de Fora, MG. Foram avaliados 1.144 espécimes fecais diarreicos, obtidos de crianças de 0 a cinco anos não hospitalizadas, que foram analisadas por PAGE e RT-PCR. Os dados relativos à prevalência e distribuição etária dos casos de rotavirose foram analisados pelo teste χ2 (p < 0,05), utilizando-se o programa SPSS, versão 13.0. RESULTADOS: Infecções por rotavírus foram detectadas em 9,35% (107/1.144) das amostras, com prevalências variando de 11,12% (90/809) no período pré-vacinal a 5,07% (17/335) no pós-vacinal (p = 0,001). Dentre as amostras caracterizadas, os genótipos mais frequentemente detectados foram G1P[6] (6/33 = 18,2%) no período 2002-2005 e G2P[4] no ano de 2006 (11/33 = 33,3%) e no período 2007-2011 (5/33 = 15,2%). Observou-se, ainda, uma redução significativa no número de casos de rotavirose em crianças de 0 a 36 meses, após a introdução da vacina. CONCLUSÕES: O estudo revelou queda significativa na prevalência de rotavírus, principalmente na faixa etária de 0 a 36 meses, no período 2007-2011, bem como redução na circulação do genótipo G1.

OBJECTIVES: To evaluate the prevalence and circulation of rotavirus genotypes before and after the introduction of oral vaccine against human rotavirus (OVHR), and to check for a possible change in the age of occurence of the infection by RV-A. METHODS: This was a cross-sectional study conducted between 2002-2011, in the city of Juiz de Fora, state of Minas Gerais, Brazil. A total of 1,144 diarrheal stool specimens were obtained from nonhospitalized children aged between 0 and 5 years, and analyzed by polyacrylamide gel electrophoresis and reverse-transcription polymerase chain reaction for genotype characterization. Data on prevalence and age distribution of rotavirus cases were analyzed through the chi-squared test (p < 0.05), using SPSS, release 13.0. RESULTS: Rotavirus infection was detected in 9.35% (107/1,144) samples, with prevalence rates ranging from 11.12% (90/809) in the pre-vaccine to 5.07% (17/335) in the post-vaccine period (p = 0.001). Among the samples tested, the most frequently detected genotypes were G1P[6] (6/33 = 18.2%) in the period between 2002 and 2005 and G2P[4] in 2006 (11/33 = 33.3%) and in the period between 2007 and 2011 (5/33 = 15.2%). There was also a significant reduction in the number of cases of rotavirus disease in children aged between 0 and 36 months after the vaccine introduction. CONCLUSIONS: The study evidenced a significant decrease in the prevalence of rotavirus, mainly in children aged between 0 and 36 months in the 2007-2011 period, as well as a reduction in G1 genotype circulation.

Acute diarrhea in hospitalized children of the municipality of juiz de fora, MG, Brazil: prevalence and risk factors associated with disease severity / Diarreia aguda em crianças hospitalizadas no município de Juiz de Fora, MG: prevalência e fatores de risco associados à gravidade da doença

CONTEXT: Acute diarrhea is a common cause of hospitalization among children under 5 years of age. Knowing the prevalence and risk factors associated with the severity of acute diarrhea is essential to control morbidity and mortality. OBJECTIVE: Describe the prevalence of demographic, epidemiologic and clinical features of children under 6 years of age hospitalized for acute diarrhea, and investigate the association between these determinants and the severity of the diarrheic episode. METHOD: Retrospective, cross-sectional study, during the period from January, 2005 through December, 2008, in the municipality of Juiz de Fora, MG, Brazil. Files from 6,201 children from 0 to 6 years of age, hospitalized in two public teaching institutions (which account for 84% of all the hospitalizations in the municipality), were assessed. Acute diarrhea was defined as the presence of at least three evacuations of liquid or loose stools, within 24 hours, for a maximum period of 14 days. The patients with acute diarrhea were divided in two groups, according to disease severity, severe diarrhea being considered whenever hospitalization lasted for at least 4 days. Epidemiologic and clinical data were assessed and compared through the application of the chi-squared test and the binomial logistic regression model. RESULTS: The prevalence rate for admission due to acute diarrhea was 8.4%. The factors significantly associated with the severity of the diarrheic episode were: age under 6 months (P = 0.01, OR = 2.762); disease onset during fall (P = 0.033, OR = 1.742), presence of fever (P = 0.017, OR = 1.715) and antibiotic use during hospitalization (P = 0.000, OR = 3.872). CONCLUSIONS: Diarrhea is the third most common cause of hospitalization among children under 6 years of age in Juiz de Fora. Young age (under or equal to 6 months), fever, antibiotic use during hospitalization and disease onset during fall are risk factors associated with longer hospital stay.

CONTEXTO: Diarreia aguda é uma causa frequente de internação em crianças menores de 5 anos. O conhecimento da prevalência e dos fatores de risco associados à gravidade da diarreia aguda é fundamental no controle da morbimortalidade. OBJETIVO: Descrever a prevalência das características demográficas, epidemiológicas e clínicas de pacientes menores de 6 anos hospitalizados por diarreia aguda e investigar a associação entre esses determinantes e a gravidade do episódio diarreico. MÉTODO: Estudo transversal, retrospectivo, realizado no período de janeiro de 2005 a dezembro de 2008, no município de Juiz de Fora, MG. Foram avaliados 6.201 prontuários das crianças de 0 a 6 anos de idade hospitalizadas em duas instituições públicas de ensino que respondem juntas por 84% das internações no município. Diarreia aguda foi definida como presença de pelo menos três evacuações líquidas ou de consistência amolecida em 24 horas por no máximo 14 dias. Os pacientes com diarreia aguda foram divididos em dois grupos, de acordo com a gravidade do quadro e foi considerado diarreia grave o período de hospitalização maior ou igual a 4 dias. Os dados epidemiológicos e clínicos dos pacientes foram avaliados e comparados através da aplicação do teste do qui ao quadrado e do modelo de regressão logística binomial. RESULTADOS: A prevalência de internações por diarreia aguda foi de 8,4%. Os fatores que mostraram associação significativa com gravidade do episódio diarreico foram: idade inferior a 6 meses (P = 0,01, OR = 2,762); início da doença no outono (P = 0,033, OR = 1,742), presença de febre (P = 0,017, OR = 1,715) e uso de antibioticoterapia durante a internação (P = 0,000, OR = 3,872). CONCLUSÕES: Diarreia é a terceira causa de internação em crianças abaixo dos 6 anos em Juiz de Fora. Baixa idade (inferior ou igual a 6 meses), febre, uso de antibiótico na internação e início do episódio diarreico no outono são fatores de risco associados ao maior tempo de hospitalização.

Acute diarrhea in hospitalized children of the municipality of Juiz de Fora, MG, Brazil: prevalence and risk factors associated with disease severity.

CONTEXT: Acute diarrhea is a common cause of hospitalization among children under 5 years of age. Knowing the prevalence and risk factors associated with the severity of acute diarrhea is essential to control morbidity and mortality. OBJECTIVE: Describe the prevalence of demographic, epidemiologic and clinical features of children under 6 years of age hospitalized for acute diarrhea, and investigate the association between these determinants and the severity of the diarrheic episode. METHOD: Retrospective, cross-sectional study, during the period from January, 2005 through December, 2008, in the municipality of Juiz de Fora, MG, Brazil. Files from 6,201 children from 0 to 6 years of age, hospitalized in two public teaching institutions (which account for 84% of all the hospitalizations in the municipality), were assessed. Acute diarrhea was defined as the presence of at least three evacuations of liquid or loose stools, within 24 hours, for a maximum period of 14 days. The patients with acute diarrhea were divided in two groups, according to disease severity, severe diarrhea being considered whenever hospitalization lasted for at least 4 days. Epidemiologic and clinical data were assessed and compared through the application of the chi-squared test and the binomial logistic regression model. RESULTS: The prevalence rate for admission due to acute diarrhea was 8.4%. The factors significantly associated with the severity of the diarrheic episode were: age under 6 months (P = 0.01, OR = 2.762); disease onset during fall (P = 0.033, OR = 1.742), presence of fever (P = 0.017, OR = 1.715) and antibiotic use during hospitalization (P = 0.000, OR = 3.872). CONCLUSIONS: Diarrhea is the third most common cause of hospitalization among children under 6 years of age in Juiz de Fora. Young age (under or equal to 6 months), fever, antibiotic use during hospitalization and disease onset during fall are risk factors associated with longer hospital stay.

Study of the dynamic of rotavirus circulation by identification of their electropherotypes / Estudo da dinâmica de circulação de rotavírus através da identificação de seus eletroferótipos eletroferótipos

An electrophoretical study of rotavirus strains was carried out to determine the RNA migration pattern sand to follow the dynamics of virus circulation. Fifty five positive fecal samples for rotavirus, obtained from 0-5 year old children during 2005 and 2006, were subjected to the Polyacrylamide Gel Electrophoresis. It was possible to define the RNA migration pattern of 37 (62%) rotavirus strains, displaying eight distinct profiles, all of them compatible with group A rotavirus. All rotavirus were detected from May to September showing an outstanding seasonality. In 2005 were detected only rotavirus strains presenting long migration patterns (100%=15/15), named L1, L2, L3 or L4. The L2 profile was predominant. However, in 2006, a few rotavirus strains displaying long migration patterns (L1 and L2) were detected (14%=3/22) from May to June, although rotavirus strains presenting short migration patterns (S1, S2, S3 or S4) were detected between Julyand August. These viruses of short RNA migration patterns were the most predominant strains (86%=19/22). The variability of RNA migration patterns detected showed a great genomic heterogeneity of rotavirus strains. By monitoring viral nucleic acid electrophoretic characteristics was possible to follow the dynamics of rotavirus circulation between 2005 and 2006.

Foi realizado um estudo eletroforético de amostras de rotavírus, visando determinar os perfis de migração do RNA viral, bem como acompanhar a dinâmica da circulação dos mesmos. Para tanto, 55 amostras fecais diarréicas, positivas para rotavírus, obtidas de crianças de 0-5 anos, durante os anos de 2005 e 2006, foram submetidas à técnica de eletroforese em gel de poliacrilamida. Foi possível definir o perfil eletroforético de 37 (62%) delas, tendo sido observados oito perfis distintos, todos compatíveis com rotavírus do grupo A. Todas as amostras de rotavírus foram detectadas de maio a setembro, indicando uma sazonalidade na ocorrência destas infecções em Juiz de Fora. Em 2005 todas as amostras apresentaram perfis longos (100%=15/15), denominados de L1 a L4, com predominância de amostras de perfil L2. Em 2006, poucas amostras de perfil longo (14%=3/22) foram detectadas nos meses de maio e junho, tendo sido substituídas pelas amostras de perfil curto (C1-C4), que emergiram em julho, predominando neste ano (86%=19/22). A variabilidade dos perfis eletroforéticos detectados mostrou uma grande heterogeneidade genômica e através do monitoramento foi possível acompanhar a dinâmica de circulação das amostras de rotavírus entre 2005 e 2006.