Challenges to global pertussis prevention and control / 中华流行病学杂志

Pertussis is an acute, highly infectious respiratory disease caused by Bordetella pertussis, and is one of the leading causes of infant disease and death worldwide. The pertussis vaccine has been used in the expanded program on immunization globally since 1974 and the vaccination coverage remains high. In recent years, the pertussis incidence rate increased, even pertussis outbreaks occurred, in more and more countries or areas after years with low incidence level. The disease burden of pertussis has been seriously underestimated, and the prevention and control of pertussis is facing many challenges. This article reviews the epidemic status of pertussis worldwide, the factors affecting the reemergence of pertussis, and the challenges in the prevention and control to provide a reference for prevention and control of pertussis.

Estandarización de un ELISA para la cuantificación de anticuerpos IgG humanos contra células enteras de Bordetella pertussis / Standardization of an ELISA for the quantification of human IgG antibodies against whole cells of Bordetella pertussis

Bordetella pertussis es un patógeno exclusivo de humanos que causa la tos ferina, enfermedad respiratoria aguda que afecta principalmente a la población pediátrica. Existen dos tipos de vacunas comercializadas contra este patógeno: celulares y acelulares. Las vacunas celulares han sido extensamente utilizadas y siguen teniendo gran relevancia. El presente trabajo tuvo como objetivo la estandarización de un ELISA para la cuantificación de anticuerpos IgG contra células enteras de Bordetella pertussis. Para ello se determinó la concentración de recubrimiento, el rango lineal de la curva, los parámetros de precisión intra e interensayo, la especificidad, el valor de corte y el límite de detección. Se determinó como concentración de recubrimiento 0,5 UO/mL de células enteras. La curva estándar utilizando un suero de referencia internacional presentó un buen ajuste a una función polinómica en un intervalo entre las diluciones 1/100 y 1/24.300 con un coeficiente de correlación R2≥0,98. Los coeficientes de variación en los ensayos de precisión intra e interensayo estuvieron en los intervalos establecidos para cada uno (≤10 por ciento, ≤20 por ciento respectivamente). Los resultados obtenidos avalan el empleo de este ELISA cuantitativo para la evaluación de la respuesta a células enteras de Bordetella pertussis en ensayos clínicos(AU)

Bordetella pertussis is a pathogen exclusive to humans that causes pertussis, an acute respiratory disease that mainly affects the pediatric population. There are two types of vaccines commercially available against this pathogen: cellular and acellular. Cellular vaccines have been widely used and continue to be of great relevance. The aim of the present work was to standardize an ELISA for the quantification of IgG antibodies against whole cells of Bordetella pertussis. For this purpose, the coating concentration, the linear range of the curve, the intra- and inter-assay precision parameters, the specificity, the cut-off value and the detection limit were determined. The coating concentration was determined as 0.5 UO/mL of whole cells. The standard curve using an international reference serum presented a good fit to a polynomial function in a range between dilutions 1/100 and 1/24,300 with a correlation coefficient R2≥0.98. The coefficients of variation in the intra- and inter-assay precision tests were in the intervals established for each (≤10percent, ≤20percent respectively). The results obtained support the use of this quantitative ELISA for the evaluation of whole-cell response to Bordetella pertussis in clinical trials(AU)

Amplificación directa de ADN de Bordetella pertussis purificado de hisopados nasofaríngeos por un método de bajo costo, rápido (60-segundos) y libre de equipos / Direct amplification of Bordetella pertussis DNA purified from nasopharyngeal swabs by a low-cost, fast (60-second), and equipment-free method

RESUMEN Objetivo. Desarrollar y evaluar un método de bajo costo basado en celulosa para la purificación rápida y amplificación directa de ADN de Bordetella pertussis de hisopados nasofaríngeos. Materiales y métodos. Se prepararon discos de celulosa y se evaluaron diferentes parámetros (buffers de lisis/lavado, número de discos y elución de ADN). El método se acopló a una amplificación directa por PCR en tiempo real (qPCR) y se estimó el rendimiento utilizando hisopados nasofaríngeos que fueron positivos (n=100) y negativos (n=50) para ADN B. pertussis por qPCR, comparado con el método basado en columnas de sílice. Se calculó el grado de concordancia, sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN). Se evaluó la factibilidad del método rápido para ser acoplado a un ensayo colorimétrico de amplificación isotérmica mediada por lazo (LAMP). Resultados. El método rápido con un disco de celulosa y buffer de lisis y lavado conteniendo PVP-40 y Tween 20, respectivamente, mostró una mayor capacidad para purificar ADN amplificable de B. pertussis. El método tuvo una sensibilidad de 89,0% (IC95%, 80,2%-94,9%) y una especificidad de 98,5% (IC95%, 92,1%-100,0%), con un buen grado de concordancia (Kappa=0,867; IC95% 0,788 - 0,946), respecto al método referencial. Los VPP y VPN fueron 98,6% (IC95%, 92,7,2%-100,0%) y 88,2% (IC95%, 78,7%-94,4%), respectivamente. Se evidenció una amplificación exitosa por LAMP, y se obtuvieron resultados comparables con el método por columnas de sílice. Conclusión. El método desarrollado es simple, de bajo costo y libre de equipos para la obtención rápida (60 segundos) de ADN en el punto de atención, y puede ser implementado en diversas técnicas moleculares orientados al diagnóstico oportuno y al estudio epidemiológico de tos ferina.

ABSTRACT Objective. To develop and evaluate a low-cost cellulose-based method for rapid purification and direct amplification of Bordetella pertussis DNA from nasopharyngeal swabs. Materials and methods. We prepared cellulose discs and evaluated different parameters (lysis/wash buffers, number of discs and DNA elution). The method was coupled to a direct real-time PCR (qPCR) amplification and the performance was estimated using nasopharyngeal swabs that were positive (n=100) and negative (n=50) for B. pertussis DNA by qPCR, compared to the silica column-based method. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and the degree of agreement. The feasibility of the rapid method to be coupled to a loop-mediated isothermal amplification colorimetric assay (LAMP) was evaluated. Results. The rapid method, with a cellulose disk and lysis and wash buffer containing PVP-40 and Tween 20, respectively, showed a greater capacity to purify amplifiable DNA from B. pertussis. The method had a sensitivity of 89.0% (95%CI: 80.2%-94.9%) and a specificity of 98.5% (95%CI: 92.1%-100.0%), with a good degree of agreement (Kappa=0.867; 95%CI: 0.788 - 0.946), compared to the reference method. The PPV and NPV were 98.6% (95%CI: 92.7.2%-100.0%) and 88.2% (95%CI: 78.7%-94.4%), respectively. Successful amplification by LAMP was evident, and comparable results were obtained with the silica column method. Conclusion. The developed method is simple, low-cost and equipment-free for rapid (60 seconds) DNA collection at the point of care, and can be implemented in various molecular techniques aimed at the timely diagnosis and epidemiological study of pertussis.

Cambios epidemiológicos y actualidades sobre vacunación contra Bordetella pertussis en Latinoamérica / Epidemiologic changes and novelties on vaccination against Bordetella pertussis in Latin America

Resumen A pesar de que la tosferina (coqueluche) es una enfermedad prevenible por vacunas (EPV), la epidemiología latinoamericana muestra que hay persistencia de brotes en la región. Esta persistencia se debe, al menos en parte, a factores tales como la cobertura vacunal, la presencia de movimientos anti vacunas, la diversidad de los sistemas locales de vigilancia y la falta de una definición de caso unificada para la región. Dada la importancia de la tosferina en Latinoamérica y los cambios ocurridos en las recomendaciones para la vacunación, este manuscrito tiene como objetivo revisar los datos epidemiológicos y los cambios recientes en los calendarios de vacunación y su impacto sobre la enfermedad pediátrica por Bordetella pertussis en Latinoamérica. Los datos epidemiológicos más recientes muestran que entre regiones, países, y segmentos dentro de cada país hay heterogeneidad en la cobertura vacunal, con distintos rebrotes. Esfuerzos en la región han tratado de mejorar esta situación al introducir vacunas acelulares (aP), menos reactogénicas que las vacunas de células enteras (wP) en los calendarios vacunales. Además, algunos países han mejorado la definición de caso confirmado, al introducir la reacción de polimerasa en cadena (RPC) como criterio diagnóstico. En respuesta a las heterogeneidades de cada país y a la epidemiología actual de la región, un Comité de Expertos de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE) y la Asociación Latinoamericana de Pediatría (ALAPE) propone una definición unificada de caso y recomendaciones para mejorar la cobertura vacunal y reducir los brotes de tosferina en Latinoamérica.

Abstract Although whooping cough is a vaccine-preventable disease (VPD), its epidemiologic characteristics in Latin America shows persistence of outbreaks in the region. This persistence is due, at least in part, to the presence of antivaccine movements, the diversity of the surveillance systems, and the lack of a uniform case definition for the region. Given the importance of whooping cough in Latin America and the changes in vaccine recommendations, this manuscript aims to review epidemiologic data and recent changes in the vaccination calendars and their impact on the pediatric disease by Bordetella pertussis in Latin America. Recent epidemiological data reveal that between regions, countries, and administrative units within each country there is a marked heterogeneity of vaccine coverage, with different outbreak patterns. Efforts in the region have tried to improve this situation by introducing acellular pertussis vaccines (aP) in the vaccine calendars, which are less reactogenic than whole-cell pertussis vaccines (wP). Moreover, some countries have improved the case definition. Some countries have implemented a confirmed case definition by introducing polymerase chain reaction (PCR) as a diagnostic criterion. As a response to the heterogeneities observed within and between countries and the regional epidemiologic profiles, a Steering Committee from the Latin American Society for Pediatric Infectiology (SLIPE) and the Latin American Association of Pediatrics (ALAPE) propose a unified case definition and recommendations to improve vaccine coverage and reduce the outbreaks of whooping cough in Latin America.

A comparative analysis of the Chinese and English descriptions of typical pertussis manifestations and recommendations for the diagnosis of pertussis-like or pertussis syndrome / 中国当代儿科杂志

The Chinese and English names of pertussis or whooping cough show the important clinical features of the disease in terms of its course and cough characteristics respectively. In the clinical description of typical pertussis, the meanings of the Chinese and English words are not completely consistent, such as spastic cough versus paroxysmal cough, spasmodic stage/phase versus paroxysmal stage/phase, and "back-hook" versus whoop, and some descriptions in English are not seen in Chinese. This article aims to provide more comprehensive information for the understanding of pertussis by comparing the descriptions of typical clinical manifestations of pertussis in Chinese and English literatures and to put forward suggestions for the diagnosis of pertussis syndrome based on typical clinical manifestations.

Clinical value of cleaved lymphocytes in assisting the diagnosis of pertussis in children / 中国当代儿科杂志

OBJECTIVE@#To study the value of cleaved lymphocytes in peripheral blood smear in assisting the early diagnosis of pertussis.@*METHODS@#Nasopharyngeal swabs and peripheral blood samples were collected from 107 children with pertussis-like disease. PCR-flow fluorescent hybridization was used to detect the nucleic acids of Bordetella pertussis. Based on the detection results, the children were divided into two groups: pertussis (n=52) and non-pertussis (n=55). According to age, the pertussis group was divided into two subgroups: 0.05).@*CONCLUSIONS@#The detection of cleaved lymphocytes combined with peripheral blood cell counts provides a new option for the early diagnosis of pertussis in children.

Knowledge, Attitude and Practice Regarding Pertussis among a Public University Students in Malaysia

Abstract Objective: To study the knowledge, attitude, and practice (KAP) regarding pertussis among students in a public university in Malaysia. Material and Methods: This study was a cross-sectional study using convenience sampling to recruit 171 respondents. The data was collected using a self-administered questionnaire comprised of four different parts: the socio-demographic data, the knowledge, the attitude and the practice towards the prevention of pertussis. The data were analyzed using correlation, independent t-test, and ANOVA according to the different study objectives and types of data. Results: More than half of the respondents (67.8%) indicated that they had heard about pertussis. The school or university (59.6%) was the most common source of information, followed by Internet (46.2%). The most of the respondents (43.9%) possessed moderate knowledge regarding pertussis and knew that Bordetella pertussis is the causative agent of pertussis (76.0%). A significant positive correlation between knowledge regarding pertussis with age (p=0.023) was observed, however, there was no association between age with attitude and practice (p=0.272 and 0.131, respectively). Gender and marital status did not influence the KAP regarding pertussis; nevertheless, significantly different between different faculties. Conclusion: Students from the Faculty of Medicine had the highest knowledge scores, while the students from the Faculty of Nursing had the most top attitude and practice scores compared to students from another faculty. The students from the public university generally had a good level of KAP regarding pertussis.

Situação epidemiológica da coqueluche no Distrito Federal entre 2007 e 2016 / Epidemiological situation of pertussis in the Federal District between 2007 and 2016 / Situación epidemiológica de tos ferina en el Distrito Federal entre 2007 y 2016

Resumo A vigilância da coqueluche intensificou-se no Brasil com o aumento de casos a partir de 2012. Em 2015, a quantidade de notificações no Distrito Federal diminuiu, possivelmente devido à introdução da vacina adsorvida difteria, tétano e pertussis acelular para gestantes em novembro de 2014 no país. Trata-se de estudo descritivo, baseado na revisão das notificações compulsórias de coqueluche no Sistema de Notificação Nacional entre 2007 e 2016. Constatou-se que a doença atinge principalmente crianças menores de 1 ano com esquemas vacinais incompletos. A administração dessa vacina para gestantes mostrou-se importante ferramenta para proteger bebês menores de 6 meses.

Abstract Pertussis monitoring intensified in Brazil with the increase of cases since 2012. In 2015, the number of notifications in the Federal District decreased, possibly due to the introduction of diphtheria, tetanus and acellular pertussis vaccine for pregnant women in November 2014 in the country. This is a descriptive study based on the review of compulsory pertussis reporting in the National Notification System between 2007 and 2016. It was found that the disease mainly affects children under one year of age with incomplete vaccination regimens. The administration of this vaccine to pregnant women has proved to be an important tool to protect babies under six months.

Resumen La vigilancia de la tos ferina se intensificó en Brasil con el aumento de casos a partir de 2012. En 2015, la cantidad de notificaciones en el Distrito Federal disminuyó, posiblemente debido a la introducción de la vacuna contra la difteria, el tétanos y la pertussis acelular para gestantes, en noviembre de 2014, en el país. Se trata de un estudio descriptivo, basado en la revisión de las notificaciones obligatorias de tos ferina en el Sistema de Notificación Nacional, entre 2007 y 2016. Se constató que la enfermedad afecta principalmente a niños menores de 1 año con regímenes de vacunación incompletos. La administración de esta vacuna a mujeres embarazadas se mostró como una importante herramienta para proteger a los bebés menores de 6 meses.

Pertussis, historia, hechos y situación actual / Pertussis, history, facts, and current situation / Pertussis, história, fatos e situação atual

Pertussis, tos convulsa o coqueluche son términos que se emplean como sinónimos para referirse a una infección respiratoria inmunoprevenible grave causada por la bacteria gram negativa denominada Bordetella pertussis. La mejor manera de prevenir la enfermedad es a través de la vacunación. Las primeras experimentaciones con vacunas comenzaron después de que Jules Bordet y Octave Gengou del Instituto Pasteur de Bruselas identificaran el agente etiológico en 1906. Estas primeras vacunas se hicieron a partir de células enteras del agente causal muertas por calor. La historia de las vacunas contra la enfermedad continuó desde aquel entonces con vacunas combinadas y luego con vacunas de componentes o acelulares. Su uso masivo desde los años 50 permitió una reducción muy marcada de la morbimortalidad asociada a la enfermedad. Sin embargo en el año 2008, se estimó que en el mundo se producen por año 16 millones de casos de los cuales 195.000 resultan ser fatales. Para el año 2014 esta estimación sobre el número de casos creció a 24,1 millones de casos en el año. El incremento del número de casos detectado en los últimos 20 años ha estado dirigiendo la mirada de la comunidad sanitaria y científica hacia la identificación de causas de esta nueva situación epidemiológica de pertussis para revisar e implementar estrategias de control más efectivas. Se ha logrado así un mejor reconocimiento de la enfermedad no solo entre los lactantes y los niños, sino también en los adolescentes y adultos. El mayor reconocimiento de que los niños mayores, los adolescentes y los adultos están en riesgo de contraer la enfermedad y que pueden transmitirla a los más vulnerables ha resaltado la necesidad de comprender mejor la inmunidad inducida por las vacunas y su duración. El rol de las vacunas y en particular de las vacunas acelulares constituidas por pocos inmunógenos en altas dosis sobre la selección de geno/fenotipos bacterianos más resistentes a la inmunidad inducida por las vacunas ha comenzado a visualizarse más claramente. La investigación en curso que utiliza herramientas novedosas sin dudas ha mejorado el conocimiento en general sobre esta patología, sin embargo la investigación debe continuar de forma de lograr una vigilancia más oportuna con terapias y vacunas de nueva generación más eficaces.

Pertussis or whooping cough is a preventable respiratory infectious disease caused by the gram-negative microorganism known as Bordetella pertussis. The best strategy to prevent pertussis is to get vaccinated. Vaccine development began just after Jules Bordet and Octave Gengou at Pasteur Institute from Brussels identified the etiologic agent of the disease in 1906. The first vaccine was formulated with heat-killed B. pertussis bacteria, which was later combined with tetanus and diphtheria toxoids (DTP). The second generation of pertussis vaccine was the acellular vaccine consisting in a few purified B. pertussis immunogens. The massive use of these vaccines since the 50s reduced the morbidity and mortality associated with the disease. However, in 2008 it was estimated that 16 million cases occurred by year with 195,000 deaths worldwide. For 2014, this estimation rised to 24.1 million cases per year. The increase in the number of cases detected in the last 20 years has been directing the attention of the health and scientific community towards the identification of causes of this new epidemiological situation of pertussis to review and implement more effective control strategies. This has achieved a better recognition of the disease not only among infants and children but also in adolescents and adults. The awareness that older children, adolescents and adults are at risk of contracting the disease and that they can transmit pertussis to the most vulnerable highlighted the need to better understand the immunity induced by pertussis vaccination and also the duration of such immunity. Another aspect that needs to be understood is that related to the selection pressure that the vaccines would be exerting (in particular the acellular vaccines) on the circulating bacterial population. In this sense, an increase in the prevalence of strains of B. pertussis that are more resistant to the immunity conferred by the vaccines has been detected. The ongoing research using innovative tools has undoubtedly improved the knowledge on pertussis; however research should continue to achieve a more timely surveillance with more effective new generation therapies and vaccines.

Pertussis, tosse convulsa ou coqueluche são termos que se utilizam como sinônimos para fazer referência a uma infecção respiratória imunoprevenível grave provocada pela bactéria gram negativa denominada Bordetella pertussis. A melhor forma de prevenir a doença é através da vacinação. As primeiras experimentações com vacinas começaram depois de que Jules Bordet e Octave Gengou do Instituto Pasteur de Bruxelas identificassem o agente etiológico em 1906. Estas primeiras vacinas foram feitas a partir de células inteiras do agente causal mortas por calor. A história das vacinas contra a doença continuou a partir de então com vacinas combinadas e depois com vacinas de componentes ou acelulares. O uso generalizado delas desde os anos 50 permitiu uma redução muito importante da morbimortalidade associada à doença. Entretanto, no ano 2008, a estimativa foi de 16 milhões de casos produzidos no mundo por ano dos quais 195.000 resultaram fatais. Para o ano 2014, essa estimativa sobre o número de casos cresceu a 24,1 milhões de casos no ano. O aumento do número de casos detectado nos últimos 20 anos dirigiu e dirige o foco da comunidade sanitária e científica para a identificação de causas dessa nova situação epidemiológica de coqueluche de forma de revisar e implementar estratégias de controle mais efetivas. Um melhor reconhecimento da doença foi assim possível, não só entre bebês e meninos, mas também nos adolescentes e adultos. O maior reconhecimento de que as crianças mais velhas, os adolescentes e os adultos estão em risco de contrair a doença e que pode transmiti-la aos mais vulneráveis tem salientado a necessidade de compreender melhor a imunidade induzida pelas vacinas e a duração delas. O papel das vacinas e, em particular, das vacinas acelulares constituídas por poucos imunógenos em altas doses sobre a seleção de genótipos/fenótipos bacterianos mais resistentes à imunidade induzida pelas vacinas tem começado a ser visualizado mais claramente. A pesquisa em andamento que utiliza ferramentas novas, sem dúvidas, tem melhorado o conhecimento em geral sobre essa patologia, contudo a pesquisa deve continuar de maneira de alcançar uma vigilância mais oportuna com terapias e vacinas de nova geração mais eficazes.

Serosurveillance for vaccine-preventable diseases: A look inside the pertussis experience / Serovigilancia de enfermedades prevenibles por vacunación: una mirada desde la experiencia con la tosferina

Abstract Introduction: Serological surveillance (serosurveillance) provides the most direct measure of herd immunity of vaccine-preventable diseases. Little is known about the opportunities and challenges of serosurveillance experiences, particularly pertussis. Objective: To describe the process of serosurveillance for vaccine-preventable diseases with an emphasis on the experience of pertussis in the metropolitan area of Antioquia (Valle de Aburrá) in 2015 and 2016 and analyze the contributions and challenges for its sustainability. Materials and methods: We described the planning and conduction of serosurveillance of pertussis antibodies of mothers and in the umbilical cord at the time of delivery in eight hospitals based on random sampling and their capacity to advance the serosurveillance periodically. We compared the contributions and the challenges of this experience with other probabilistic and non-probabilistic programs. Results: We achieved the participation of hospitals and mothers respecting the delivery care process. We established a serum bank following ethical and technical guidelines. This program based on the random selection of hospitals and mothers has enabled the estimation of antibodies prevalence in mothers and in the umbilical cord, which has been possible given the high coverage of hospital care during childbirth at a lower cost and fewer risks than a population-based survey in conflictive areas. The main challenges for the sustainability of this program are the creation of stable jobs and access to funding and legal and methodological long-term frameworks. Conclusions: Hospital serosurveillance as described is an option to monitor the impact of vaccination on the population. Our experience could be reproduced in other regions under similar conditions if the above-mentioned challenges are solved.

Resumen Introducción. La vigilancia serológica es la forma más directa de medir la inmunidad de rebaño frente a las enfermedades prevenibles por vacunación. Poco se sabe acerca de las oportunidades y los desafíos de las experiencias de serovigilancia, en general y, específicamente, la de la tosferina. Objetivo. Describir el proceso de serovigilancia de enfermedades prevenibles por vacunación con énfasis en la experiencia en el caso de la tosferina en el área metropolitana de Antioquia (Valle de Aburrá) en el 2015 y el 2016 y analizar lo que dicha experiencia ha aportado y los desafíos que persisten para su sostenibilidad. Materiales y métodos. Se describió el proceso de planeación y el desarrollo de la serovigilancia de tosferina en el momento del parto en ocho hospitales seleccionados al azar, así como la capacidad para adelantar el programa de manera periódica. Se compararon los aportes y los desafíos en el curso de esta experiencia con los de otros programas poblacionales probabilistas e institucionales no probabilistas. Resultados. Se logró la participación de los hospitales y de las madres con pleno respeto del proceso de atención del parto, y se conformó un banco de sueros siguiendo lineamientos éticos y técnicos. El programa permitió estimar la prevalencia de anticuerpos en la madre y en el cordón umbilical, lo que se facilitó por la alta cobertura de atención hospitalaria del parto, a un menor costo y menos riesgos que los programas poblacionales en zonas conflictivas. Los principales desafíos para la sostenibilidad del programa son la estabilidad laboral del personal de salud, así como normas y una financiación de largo plazo. Conclusiones. La serovigilancia hospitalaria es una opción para monitorizar el impacto poblacional de la vacunación. Esta experiencia se podría extender a otras regiones en condiciones similares si se resuelven los retos mencionados.

Seroprevalencia de Bordetella pertussis en el personal de enfermería y médicos residentes del Hospital Infantil de México Federico Gómez / Seroprevalence of Bordetella pertussis in pediatric healthcare workers at the Hospital Infantil de México Federico Gómez

Resumen Introducción Bordetella pertussis es el agente causal de la tosferina, una enfermedad de alta letalidad, especialmente en menores de 6 meses, pero prevenible mediante la vacunación. Los reportes en hospitales de brotes de tosferina muestran que el caso índice suelen ser personas adultas. En adultos, la enfermedad se manifiesta principalmente con tos persistente. El propósito de este estudio fue conocer la seroprevalencia de B. pertussis en el personal de salud de un hospital pediátrico en un país donde aún no se considera la vacunación obligatoria para los empleados. Métodos Participaron personal de enfermería y médicos residentes en trato directo con pacientes hospitalizados. A cada participante se le realizó detección de anticuerpos inmunoglobulina G, antitoxina de pertussis (anti-TP) y se le aplicó un cuestionario para datos clínicos y demográficos. Resultados Se incluyeron 93 individuos, el 85% de personal de enfermería con mediana de edad de 35 años (rango intercuartil: 29-42.5). El 21.5% de los participantes laboraban en el Servicio de Urgencias, el 8.6%, en la Unidad de Terapia Intensiva Pediátrica, el 6.5%, en la Unidad de Cuidados Intensivos Neonatales. Se encontraron títulos detectables de anticuerpos anti-TP en el 18.3%, de los cuales, el 53% presentaron títulos de infección reciente y solamente el 23.5%, historia de tos de más de dos semanas de evolución. Conclusiones El personal de salud está en riesgo de sufrir la enfermedad y de transmitirla a los lactantes, quienes pueden fallecer por esta causa. Este estudio sugiere que las políticas actuales de vacunación en personal de salud se deben de modificar para determinar obligatoriedad de la vacuna, especialmente en quienes atienden a la población pediátrica.

Abstract Background Bordetella pertussis is the causative agent of pertussis, a disease that is preventable by vaccination but has a high mortality, particularly in children < 6 months. Reports of pertussis outbreaks in hospitals show that the index case is usually an adult. In adults, the disease manifests mainly with persistent cough. The purpose of this study was to determine the seroprevalence of B. pertussis in the health personnel of a pediatric hospital in a country where vaccination of this staff is not considered mandatory. Methods Nursing staff and resident doctors who were involved in direct treatment with hospitalized patients participated in the study. Each participant was screened for immunoglobulin G anti-pertussis toxin antibodies (anti-PT), and a questionnaire was applied for clinical and demographic data. Results Ninety-three individuals were included, of which 85% were nurses, median age 35 years (interquartile range: 29-42.5). The participants worked in the emergency department (21.5%), in the Pediatric Intensive Care Unit (8.6%), and in the Neonatal Intensive Care Unit (6.5%). Detectable titers of anti-TP antibodies were found in 18.3%, of which 53% presented titles suggestive of recent infection and only 23.5% cough > 2 weeks of duration. Conclusions Health personnel are at risk of suffering from the disease and be potential transmitters to infants, who may die from this cause. This study suggests that the current vaccination policies in health personnel should be modified to determine the compulsory nature of the vaccination, especially in those individuals in charge of the care of the pediatric population.

Mecanismos efetores da resposta imune na infecção por Bordetella pertussis / Immune response effector mechanisms to Bordetella pertussis infection

A coqueluche é uma doença infecciosa aguda, transmissível, com predileção pelo trato respiratório, caracterizada por paroxismos de tosse seca e considerada uma importante causa de morbidade e mortalidade infantil. A resposta imunológica humoral e celular do hospedeiro promove a contenção da infecção, pois essas respostas se caracterizam como importantes linhas de defesa durante a infecção e colonização da bactéria. Dessa forma, esta revisão bibliográfica procurou descrever os mecanismos mais eficazes de resposta imune contra Bordetella pertussis e abordar os mecanismos de evasão utilizados pelo patógeno.

Pertussis is a transmissible infectious disease with a predilection for the respiratory tract characterized by paroxysms of dry cough. It is considered an important cause of child morbidity and mortality. The humoral and cellular immune responses of the host promote the containment of the infection, and these responses are characterized as important lines of defense during infection and colonization of the bacterium. Thus, this literature review sought to describe the most effective immune response mechanisms against Bordetella pertussis and to address the avoidance mechanisms used by the pathogen.

Prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features / 中国当代儿科杂志

OBJECTIVE@#To investigate the prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features.@*METHODS@#A total of 106 children who were treated at the outpatient service or hospitalized from January 1, 2016 to May 31, 2017 were enrolled. Their nasopharyngeal swabs and venous blood samples were collected for Bordetella pertussis culture, multiple PCR and serum anti-pertussis toxin antibody detection. According to these results, the children were divided into pertussis group with 26 children and control group with 80 children, and clinical features were analyzed for both groups. E-test stripes were used to determine the sensitivity of Bordetella pertussis strains to erythromycin, azithromycin, doxycycline, levofloxacin, sulfamethoxazole/trimethoprim and amoxicillin.@*RESULTS@#Of the 106 children with chronic cough, 26 (24.5%) were found to have Bordetella pertussis infection. There were no significant differences in the incidence rates of typical symptoms of pertussis between the pertussis and control groups (P>0.05). E-test showed that erythromycin and azithromycin had a minimal inhibitory concentration (MIC) of >256 mg/L against five Bordetella pertussis strains, while amoxicillin had an MIC of 0.5-1 mg/L.@*CONCLUSIONS@#The presence of Bordetella pertussis infection in children with chronic cough should be taken seriously by clinicians, and children with chronic cough and Bordetella pertussis infection may not have the typical symptoms of pertussis and are mainly manifested as chronic cough. Amoxicillin may be an alternative drug for macrolide-resistant Bordetella pertussis infection.

Antimicrobial susceptibility and antigen genotypes of Bordetella pertussis strains isolated from neonates / 中国当代儿科杂志

OBJECTIVE@#To investigate the alternative antimicrobial drugs for the treatment of neonatal pertussis and the antigen genotypes of Bordetella pertussis (B. pertussis) strains.@*METHODS@#A total of 32 B. pertussis strains isolated from neonates between May 2013 and July 2018 were used in this study. E-test stripes were used to measure the minimal inhibitory concentration (MIC) of 18 antimicrobial drugs including erythromycin, sulfamethoxazole-trimethoprim (SMZ) and ampicillin. The 23S rRNA gene of isolated strains was amplified and sequenced to identify the mutation site of erythromycin resistance gene, and the seven antigen genotypes of B. pertussis strains (ptxA, ptxC, ptxP, prn, fim2, fim3 and tcfA2) were analyzed.@*RESULTS@#Of the 32 B. pertussis strains, 25 (78%) were resistant to erythromycin, azithromycin, clarithromycin and clindamycin, with an MIC of >256 mg/L, and A2047G mutation was observed in the 23S rRNA gene. All strains had an MIC of ≤0.064 mg/L for SMZ. The MIC of ampicillin, amoxicillin, amoxicillin-clavulanic acid and ceftriaxone ranged from 0.032 to 1 mg/L. The strains resistant to macrolide antibiotics had an antigen genotype of ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2.@*CONCLUSIONS@#B. pertussis strains from neonates are often resistant to macrolides, and the in vitro test shows that off-label use of sulfonamides is a reliable regimen for the treatment of neonates with macrolide-resistant pertussis. The prevalence of drug-resistant strains further emphasizes the importance of immunoprophylaxis.

Enzyme-linked immunosorbent assay for detecting anti-pertussis toxin antibody in mouse

PURPOSE: Although the DTaP and Tdap vaccines used to prevent pertussis have been used for a long time, there is no standard method for measuring pertussis antigens. Therefore, this preliminary study was conducted to develop an enzyme-linked immunosorbent assay method using an animal model for measuring antibodies against pertussis toxin, the most important pertussis pathogenic antigen, in the sera of vaccinated mice. MATERIALS AND METHODS: Bordetella pertussis Tohama phase I was cultured for 24–30 hours, and then pertussis toxin was purified from the culture medium by chromatography. Purified pertussis toxin was diluted in phosphate-buffered saline-coating buffer, and 100 µL of diluted pertussis toxin was added to each well and reacted at room temperature for 4 hours. Positive serum was diluted to 1/1,250–1/80,000 and negative serum was diluted to 1/50 to determine the coating concentration with the optimal signal/noise ratio. Optimal test conditions were confirmed from the dilution factors of the secondary antibody and streptavidin horseradish peroxidase (SA-HRP). RESULTS: Optimal conditions were as follows: 4 µg/mL for coating antigen; 1/40,000 for secondary antibody; and 1/1,000 for the SA-HRP dilution factor. Comparison of the sera obtained from mice treated with a developing vaccine and commercial vaccine with National Institute for Biological Standard and Control standard serum under the established conditions showed the following results: 1,300.62, 534.94, and 34.85, respectively. CONCLUSION: The method developed in this study is suitable for measuring anti-pertussis toxin antibodies and may be applicable for clinical sample analysis or indirect diagnosis of pertussis.

Pertussis outbreak investigation in Janamora district, Amhara Regional State, Ethiopia: a case-control study

Introduction: on April 17/2017 Janamora district, Amhara regional state health officials reported an increasing number of people with a cough. The objectives of this study was to investigate the outbreak, describe risk factors and implement control measures.Methods: we conducted a community based unmatched 1:1 case-control study April 22-May 10, 2017. We used a probable case definition (≥2 weeks cough with vomiting, apnea, or inspiratory whoop) to identify suspected pertussis cases. Neighbors of cases were considered as controls. We conducted a door-to-door active case search and reviewed medical records, assessed vaccination status by parental interview or vaccination card. We implemented multivariable logistic regression to identify independent factors associated with the outbreak.Results: we investigated 60 cases and 60 controls. Most (68.3%) of the cases were under the age of 15. The majority (86.6%) of pertussis suspected cases, and 83.4% controls had not received any pertussis vaccine. The overall attack rate was 0.13% and the case fatality rate was 3.3%. The age-specific attack rate for under-five children was 0.33%. Females were more likely to have pertussis (AOR: 2.91; 95% CI: 1.17-7.22), contact with pertussis suspected person (AOR: 6.29; 95% CI: 2.53-15.62) and living in a relatively poorly ventilated house (AOR: 3.01; 95% CI: 1.17-7.70) were also significant risk factors of pertussis.Conclusion: weak supplementary immunization activities might have contributed to the outbreak. Treating household contacts and integration of diagnostic laboratory test of pertussis into the local health system is of paramount importance to detect outbreaks early on

A survey of the domestic epidemiological characteristics and clinical manifestations of pertussis

PURPOSE: This report describes the results of a survey of the characteristics of pertussis in children from a single institution and compares it to data from the Korea Centers of Disease Control (KCDC). METHODS: We retrospectively evaluated the medical records of 17 and 6 patients diagnosed with pertussis and parapertussis, respectively, at Soonchunhyang University Bucheon Hospital from January 2005 to January 2017. RESULTS: Of the 17 patients with pertussis, 9 were under 1 year of age (52.9%), 3 were aged between 1 and 10 years (17.6%), and 5 were over 10 years of age (29.4%). Seven patients (41.2%) had never received diphtheria-tetanus-acellular pertussis vaccines, of which 5 were infants below 2 months of age and 2 were 10 years old and lived in China. Four patients showed the initial symptoms of cough in China. The sources of infection were the parents (2 cases) and the siblings (8 cases). All patients showed prolonged severe cough and the average duration of cough was 26 days. Severe symptoms, including dyspnea, cyanosis, apnea, and seizures, were observed in the children under 2 months of age. According to the recent 10-year KCDC data, the highest rate of pertussis diagnosis was noted in infants (47.8%), followed by adolescents (18.7%). Six patients with parapertussis also presented with prolonged severe cough without any other severe symptoms. Lymphocytosis was not found, unlike the patients with pertussis. CONCLUSION: The possibility of pertussis and parapertussis should be considered among patients with prolonged severe cough, especially in infants and adolescents.

Clinical features and risk factors of pertussis in children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and risk factors of pertussis in children.@*METHODS@#A retrospective analysis was performed for the clinical data and laboratory markers for immune function of 253 hospitalized children with pertussis. A total of 314 hospitalized children with cough were used as the control group. Quantitative real-time PCR was used to detect Bordetella pertussis DNA. The clinical data of both groups were collected to analyze the risk factors for pertussis.@*RESULTS@#A total of 23 typical clinical parameters were compared between the pertussis and control groups, and there were significant differences in only 10 clinical parameters between the two groups (P<0.01). As for the complications observed in the two groups, the pertussis group had a significantly lower incidence rate of myocarditis than the control group (P<0.05). The pertussis group had significantly lower levels of serum globulin and IgM than the control group (P<0.05). Compared with the control group, the pertussis group had a significantly higher proportion of children with a lack of diphtheria-pertussis-tetanus immunization or timely immunization and a contact history of suspected pertussis patients (P<0.05). A lack of vaccine immunization or timely immunization and a contact history of suspected pertussis patients were risk factors for pertussis (P<0.05).@*CONCLUSIONS@#The clinical features are not typical in children with pertussis. Quantitative real-time PCR for detecting Bordetella pertussis DNA helps with the early diagnosis of atypical pertussis. Infants/toddlers should be immunized in time and be isolated from suspected pertussis patients to reduce the incidence of pertussis.