RESUMO
Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis, a Gram-negative bacterium described over a century ago. Despite broad vaccine coverage and treatment options, the disease is remerging as a public health problem especially in infants and older children. Recent data indicate re-emergence of the disease is related to bacterial resistance to immune defences and decreased vaccine effectiveness, which obviously suggests the need of new effective vaccines and drugs. In an attempt to contribute with solutions to this great challenge, bioinformatics tools were used to genetically comprehend the species of these bacteria and predict new vaccines and drug targets. In fact, approaches were used to analysis genomic plasticity, gene synteny and species similarities between the 20 genomes of Bordetella pertussis already available. Furthermore, it was conducted reverse vaccinology and docking analysis to identify proteins with potential to become vaccine and drug targets, respectively. The analyses showed the 20 genomes belongs to a homogeneous group that has preserved most of the genes over time. Besides that, were found genomics islands and good proteins to be candidates for vaccine and drugs. Taken together, these results suggests new possibilities that may be useful to develop new vaccines and drugs that will help the prevention and treatment strategies of pertussis disease caused by these Bordetella strains. Communicated by Ramaswamy H. Sarma.
Assuntos
Bordetella pertussis , Coqueluche , Criança , Humanos , Adolescente , Bordetella pertussis/genética , Coqueluche/prevenção & controle , Coqueluche/microbiologia , Vacina contra Coqueluche/farmacologia , GenômicaRESUMO
A coqueluche, doença infectocontagiosa, atualmente vem apresentando um perfil reemergente. Fatores como diminuição da imunidade, anos após a vacinação, mudanças no genótipo da bactéria e maior susceptibilidade entre jovens e adultos são considerados como contribuintes para o aumento da taxa da incidência da doença. Assim, esse estudo teve como objetivos verificar a distribuição espacial dos casos confirmados de coqueluche entre o período de 2007 a 2015; identificar o comportamento da série histórica da taxa de incidência da coqueluche durante o período de 2001 a 2015 no Brasil e verificar a associação da vacina contra coqueluche e a ocorrência da doença no estado do Rio Grande do Norte. Dessa forma, o caminho metodológico da pesquisa foi dividido em três partes. A análise da distribuição espacial considerou como unidade de análise as 482 Regiões Imediatas de Articulação Urbana e utilizou o software Terraview para construção dos mapas temáticos. Para se verificar a tendência da série optamos por utilizar o ajuste de uma função polinomial no tempo, utilizando-se assim modelos de regressão polinomial. Em relação a associação foi estabelecido como critério de inclusão a confirmação do caso de acordo com os critérios estabelecidos pelo Ministério da Saúde, sendo excluídos aqueles cujas fichas não encontravam-se devidamente preenchidas ou que estivessem com algum tipo de dúvida que comprometesse a coleta dos dados. Os resultados demonstraram que a doença apresentou uma distribuição espacial democrática em todo território nacional, formando pequenos clusters com altas taxas de incidência nas regiões de articulação urbana presentes nas regiões sul e sudeste. Identificamos também que houve, na série histórica, uma tendência crescente da doença ao longo de 15 anos. E por fim, os resultados apontam que independentemente do estado vacinal os indivíduos estão adoecendo por coqueluche, o que não gerou evidência científica suficiente para medir a efetividade da vacina. Os achados sugerem que aspectos relacionados a vacinação precisam ser melhor investigados para que se possa garantir o controle da doença. É necessário também que ocorram melhorias nas ações de vigilância, o que pode garantir uma representação epidemiológica fidedigna da doença (AU).
Pertussis, an infectious-contagious disease, is currently presenting a reemerging profile. Factors such as decreased immunity years after vaccination, changes in the genotype of the bacteria and increased susceptibility among young and adults are considered to have contributed to increase the disease incidence rate. Therefore, this study aimed to verify the spatial distribution of confirmed pertussis cases between 2007 and 2015; to identify the patterns in the time-series of pertussis incidence rates during the period 2001 to 2015 in Brazil and to verify the association of pertussis vaccine with the occurrence of the disease in the state of Rio Grande do Norte. Thus, the methodological path of the research was divided into three parts. The analysis of the spatial distribution considered the 482 Regions Immediate Urban Articulation as unit of analysis and used the Terraview software to construct the thematic maps. In order to verify the trend in the series we chose to use the adjustment of a polynomial function in time, using polynomial regression models. Regarding the association, the confirmation of the case was established as inclusion criteria in accordance with the criteria established by the Ministry of Health, being excluded those files that were not properly filled or had any uncertainties that could compromise the data collection. The results suggests that the disease has a democratic spatial distribution throughout the country, forming small clusters with high incidence rates in the urban articulation present in the South and Southeast regions. It was also identified in the time-series an increasing tendency of the disease over a period of 15 years. Finally, the results indicate that regardless of vaccination status individuals are being infected with pertussis, which did not generate enough scientific evidence to measure the effectiveness of the vaccine. The findings suggest that aspects related to vaccination need further investigation in order to guarantee disease control. There is also a need for improvements in surveillance actions, which can ensure a reliable epidemiological representation of the disease (AU).
Assuntos
Humanos , Pré-Escolar , Criança , Vacina contra Coqueluche/farmacologia , Coqueluche/epidemiologia , Doenças Transmissíveis/imunologia , Pessoal de Saúde , Brasil/epidemiologia , Vacina contra Coqueluche/imunologia , Modelos Lineares , Imunização , Estudos Ecológicos , Estudos de Avaliação como Assunto , Análise EspacialRESUMO
The incidence of the highly infectious respiratory disease named pertussis or whooping cough has been increasing for the past two decades in different countries, as in much of the highly vaccinated world. A decrease in vaccine effectiveness over time, especially when acellular vaccines were used for primary doses and boosters, and pathogen adaptation to the immunity conferred by vaccines have been proposed as possible causes of the resurgence. The contributions of these factors are not expected to be the same in different communities, and this could lead to different epidemiological trends. In fact, differences in the magnitude and dynamics of pertussis outbreaks as well as in the distribution of notified cases by age have been reported in various regions. Using an age-structured mathematical model designed by us, we evaluated how the changes in some of the parameters that could be related to the above proposed causes of disease resurgence - vaccine effectiveness and effective transmission rates - may impact on pertussis transmission. When a linear decrease in vaccine effectiveness (VE) was assayed, a sustained increase in pertussis incidence was detected mainly in infants and children. On the other hand, when changes in effective transmission rates (ßij) were made, a dynamic effect evidenced by the presence of large peaks followed by deep valleys was detected. In this case, greater incidence in adolescents than in children was observed. These different trends in the disease dynamics due to modifications in VE or ßij were verified in 18 possible scenarios that represent different epidemiological situations. Interestingly we found that both incidence trends produced by the model and their age distribution resemble the profiles obtained from data reported in several regions. The implications of these correlations are discussed.
Assuntos
Doenças Transmissíveis Emergentes/etiologia , Vacina contra Coqueluche/farmacologia , Vacinas Acelulares/farmacologia , Coqueluche/prevenção & controle , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Humanos , Incidência , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Modelos Biológicos , Vacina contra Coqueluche/administração & dosagem , Estados Unidos/epidemiologia , Vacinas Acelulares/administração & dosagem , Coqueluche/epidemiologia , Coqueluche/transmissão , Adulto JovemRESUMO
A coqueluche é uma doença respiratória, causada pela bactéria Bordetella pertussis. Atualmente, estima-se a ocorrência anual de 50 milhões de casos e mais de 300 mil mortes anuais em todo mundo. A transmissão ocorre, principalmente, pelo contato direto de uma pessoa doente com uma pessoa suscetível, através de gotículas de secreção da orofaringe eliminada por tosse ou espirro. O estudo realizado objetivou a caracterização da coqueluche como doença re-emergente, visando a análise epidemiológica da doença no Estado do Rio de Janeiro, valorizando também a percepção da Biossegurança pelos profissionais da área da saúde. Os resultados alcançados revelaram indicadores da ressurgência da doença no Brasil. As análises foram objeto de reflexões propostas em quatro artigos científicos, que explicitaram as metodologias utilizadas, os resultados encontrados e as discussões pertinentes à pesquisa. Os artigos intitulam-se: (1) An overview of reemerging Pertussis and evidence of ressurgence in Brazil, (2); A re-emergência da coqueluche; Da rotina dos atendimentos ao imperativo da Biossegurança (3); Fórum itinerante de ciência e saúde. Programa de capacitação para as doenças negligenciadas e re-emergentes e (4) Identification of linear B epitopes of pertactin of Bordetella pertussis induced by immunization with whole and acellular vaccine.
Whooping cough is a respiratory disease caused by the bacteria Bordetellapertussis. Today there is an estimate of fifty million cases a year and about three hundred thousand deaths worldwide. Transmission takes place mainly through direct contact of asick to a susceptible person and spreads by oropharynx fluid droplets released bycoughing or sneezing. The present study aimed at defining whooping cough as a reemergent disease, taking the epidemiologic analysis of the disease in the state of Rio de Janeiro as base and also surveying perception and compliance to biosafety proceduresamong health workers. Results obtained strongly indicated resurgence of the disease in Brazil and data has been presented in scientific paper format , into four propositions thatdiscussed methodology used, main results and thoughts pertaining to the investigation: The papers are entitled (1) An overview of re-emerging pertussis and evidence ofresurgence in Brazil, (2) Re-emergence of whooping cough : from routine clinical evaluation to the demand of biosafety, (3) Mobile fora for science and health : a capacitybuildingprogram for neglected and re-emergent diseases and (4) Identification of linear B epitopes of pertactin of Bordetella pertussis induced by immunization with whole and acellular vaccine.
Assuntos
Coqueluche/epidemiologia , Pessoal de Saúde , Vacina contra Coqueluche/farmacologia , Vacina contra Coqueluche/históriaRESUMO
Bordetella pertussis was transmitted from an immunized boy to his father and possibly to other family members. This case report demonstrates that although unusual, acute adult B. pertussis infection can occur. B. pertussis immunization may not prevent infection but can reduce the severity. B. pertussis was detected in sputum from the adult by direct-fluorescent antibody staining and was grown on Regan-Lowe medium. Serology tests confirmed the infection in the adult.
Assuntos
Coqueluche/diagnóstico , Doença Aguda , Anticorpos Antibacterianos/sangue , Bordetella pertussis/crescimento & desenvolvimento , Bordetella pertussis/imunologia , Bordetella pertussis/isolamento & purificação , Criança , Família , Técnica Direta de Fluorescência para Anticorpo , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Vacina contra Coqueluche/farmacologia , Escarro/microbiologia , Coqueluche/imunologia , Coqueluche/transmissãoRESUMO
A toxoid vaccine, composed of purified pertussis toxin inactivated with H2O2 (NICHD-Ptxd), was developed on the basis of evidence that serum neutralizing antibodies (antitoxin) would confer immunity to pertussis. In vivo and in vitro assays of NICHD-Ptxd showed only trace or nondetectable levels of pyrogenic, adenosine diphosphate-ribosyltransferase, binding and pharmacologic activities. Nevertheless, about 40% of the antigenicity of pertussis toxin was retained. Adult volunteers were injected, two times 6 weeks apart, with either 10 (n = 21), 50 (n = 25), or 75 (n = 30) micrograms/dose of one lot, Ptx-06, adsorbed onto AI(OH)3. Neither fever nor changes in the levels of leukocytes, lymphocytes, fasting blood glucose, or insulin were observed in the volunteers. The optimal immunizing dose, 50 micrograms, induced levels of antitoxin (geometric mean (GM) 302 U) comparable to those found in eight adults convalescent from pertussis (GM 269 U) and greater than those found in 18-month-old children after their fourth dose of diphtheria and tetanus toxoids and pertussis vaccine (GM 20.0 U, p less than 0.001). These data indicate that NICHD-Ptxd is safe and immunogenic in adults, and they justify its evaluation in infants and children.