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.

Maternal vaccination: A narrative review

Background: Vaccinations in general are considered to be one of the greatest achievements in medicine, saving millions of lives globally. Aim: This narrative review highlights issues related to vaccination in pregnancy and provides information on those vaccines registered for use in pregnancy. Method: Published articles on vaccinations in pregnancy are included in this review. The search engines used included PubMed, Medline, Google Scholar, and ScienceDirect. Results: Vaccinations during pregnancy are more likely to be administered in high income countries (HICs) compared to low-income countries (LICs) due to easier access to healthcare services and better communicable disease awareness. Maternal and perinatal morbidity and mortality rates associated with infectious diseases are higher in LICs with access to maternal care services, infrastructure and hospital equipment lacking in these settings. Conclusion: Suitable vaccinations are recommended for use in pregnancy to prevent harm to women, their foetuses and newborns from some communicable diseases, and they have resulted in declines in maternal and infant morbidity and mortality. Furthermore, this review has shown that vaccination during pregnancy is not only safe for both the woman and her foetus but also effective. Therefore, health professionals and national governments should strongly consider approved vaccinations prior to or during pregnancy.

Factores que influyen en la adherencia a la vacuna contra la tosferina en mujeres embarazadas en Uruguay / Factors that influence the uptake of pertussis vaccine in pregnant women in Uruguay

INTRODUCCIÓN: Desde 2015 se ofrece la vacunación contra tosferina de modo universal y gratuito a mujeres embarazadas del Uruguay. Si bien es obligatoria, la cobertura vacunal, aún no es completa. OBJETIVOS: Conocer la prevalencia de mujeres embarazadas de dos hospitales públicos de Uruguay que recibieron vacuna dpaT en 2017 y determinar posibles factores que influyen en la adherencia a vacunarse. MÉTODOS: Estudio observacional, transversal, descriptivo, mediante encuestas a pacientes cursando puerperio inmediato. RESULTADOS: Se analizaron 884 encuestas (edad promedio 25,2 años; 16% adolescentes; la mayoría en pareja y educación secundaria incompleta). Se vacunaron 317 mujeres (36%). Dentro de los factores que se asociaron a la no vacunación se destacan: adolescencia (OR 1,88; IC 95% 1,24-2,85), no tener pareja (OR 1,40; IC 95% 1,04-1,85), no conocer la obligatoriedad de la vacuna (OR 9,44; IC 95% 6,63-13,45), no haber sido informada sobre los beneficios de la vacuna (OR 4; IC 95% 2,43-6,41) y no creer en el beneficio de las vacunas en el embarazo (OR 6,37; IC 95% 4,61-8,78). DISCUSIÓN: La mayoría de las mujeres embarazadas no recibieron la vacuna dpaT ni tuvieron indicación médica. La falta de información sobre la obligatoriedad y su beneficio, y las creencias con respecto a la vacunación se asociaron a una disminución en la adherencia a la misma. Los profesionales de la salud que atienden mujeres gestantes deben recomendar e informar sobre el beneficio de la vacunación para ellas y el neonato y generar la percepción de riesgo necesaria, como una de las medidas para mejorar la cobertura vacunal.

BACKGROUND: Since 2015, pertussis vaccine has been offered universally and free of charge to pregnant women in Uruguay. Although it is mandatory, vaccination coverage is not yet complete. AIM: To study the pertussis vaccination coverage in 2017 in pregnant women in two state hospitals and to search for barriere for uptaking the vaccine. METHODS: We conducted an observational, descriptive and transversal study, using a survey in patients undergoing immediate postpartum period. RESULTS: 884 surveys were analyzed (mean age 25.2 years; 16% teenagers, most of them in a relationship and incomplete high school). 317 women (36%) were vaccinated. Main barriere for uptaking Tdap vaccine were: teenage and being single were associated with a greater risk for the uptake. Not being aware of the vaccine mandatoriness and not being informed about its benefits were associated with 9,44 and 4 higher risks for not uptaking the vaccine (IC 95% 6.63-13.45 and IC 95% 2.43-6.41, respectively). Not believing in the benefits of pertussis vaccine during pregnancy was associated with 6.37 higher risk (OR 6.37; IC 95% 4.61-8.78). DISCUSSION: Most pregnant women in this study during 2017 did not uptake pertussis vaccine and did not have medical indication for it. The lack of information about the obligation and benefits, and also patients' beliefs about the vaccination were identified as barriere. Health professionals who treat pregnant women should recommend and inform about the benefits of pertussis vaccine for women and the infant, and create the necessary perception of risk, in order to improve the vaccination coverage.

Factores que influyen en la adherencia a la vacuna contra la tosferina en mujeres embarazadas en Uruguay / Factors that influence the uptake of pertussis vaccine in pregnant women in Uruguay

Introducción: desde 2015 se ofrece la vacunación contra tosferina de modo universal y gratuito a mujeres embarazadas del Uruguay. Si bien es obligatoria, la cobertura vacunal, aún no es completa. Objetivos: conocer la prevalencia de mujeres embarazadas de dos hospitales públicos de Uruguay que recibieron vacuna dpaT en 2017 y determinar posibles factores que influyen en la adherencia a vacunarse. Métodos: estudio observacional, transversal, descriptivo, mediante encuestas a pacientes cursando puerperio inmediato. Resultados: se analizaron 884 encuestas (edad promedio 25,2 años; 16% adolescentes; la mayoría en pareja y educación secundaria incompleta). Se vacunaron 317 mujeres (36%). Dentro de los factores que se asociaron a la no vacunación se destacan: adolescencia (OR 1,88; IC 95% 1,24-2,85), no tener pareja (OR 1,40; IC 95% 1,04-1,85), no conocer la obligatoriedad de la vacuna (OR 9,44; IC 95% 6,63-13,45), no haber sido informada sobre los beneficios de la vacuna (OR 4; IC 95% 2,43-6,41) y no creer en el beneficio de las vacunas en el embarazo (OR 6,37; IC 95% 4,61-8,78). Discusión: la mayoría de las mujeres embarazadas no recibieron la vacuna dpaT ni tuvieron indicación médica. La falta de información sobre la obligatoriedad y su beneficio, y las creencias con respecto a la vacunación se asociaron a una disminución en la adherencia a la misma. Los profesionales de la salud que atienden mujeres gestantes deben recomendar e informar sobre el beneficio de la vacunación para ellas y el neonato y generar la percepción de riesgo necesaria, como una de las medidas para mejorar la cobertura vacunal.

Background: since 2015, pertussis vaccine has been offered universally and free of charge to pregnant women in Uruguay. Although it is mandatory, vaccination coverage is not yet complete. Aim: to study the pertussis vaccination coverage in 2017 in pregnant women in two state hospitals and to search for barriere for uptaking the vaccine. Methods: we conducted an observational, descriptive and transversal study, using a survey in patients undergoing immediate postpartum period. Results: 884 surveys were analyzed (mean age 25.2 years; 16% teenagers, most of them in a relationship and incomplete high school). 317 women (36%) were vaccinated. Main barriere for uptaking Tdap vaccine were: teenage and being single were associated with a greater risk for the uptake. Not being aware of the vaccine mandatoriness and not being informed about its benefits were associated with 9,44 and 4 higher risks for not uptaking the vaccine (IC 95% 6.63-13.45 and IC 95% 2.43-6.41, respectively). Not believing in the benefits of pertussis vaccine during pregnancy was associated with 6.37 higher risk (OR 6.37; IC 95% 4.61-8.78). Discussion: most pregnant women in this study during 2017 did not uptake pertussis vaccine and did not have medical indication for it. The lack of information about the obligation and benefits, and also patients' beliefs about the vaccination were identified as barriere. Health professionals who treat pregnant women should recommend and inform about the benefits of pertussis vaccine for women and the infant, and create the necessary perception of risk, in order to improve the vaccination coverage.

Caracterización de la hipotonía-hiporrespuesta post vacuna pentavalente y tamizaje del neurodesarrollo en niños bajo 6 años de edad, 2013-2018, Uruguay / Characterization of hypotonia-hyporesponsiveness after pentavalent vaccine and neurodevelopmental screening in children under 6 years of age, 2013-2018, Uruguay

INTRODUCCIÓN: La hipotonía-hiporrespuesta (HHR) es uno de los efectos adversos supuestamente atribuibles a la vacunación e inmunización de tipo neurológico más notificados. El impacto a largo plazo a nivel del neurodesarrollo no es completamente conocida. OBJETIVO: Caracterizar los eventos de HHR post vacuna pentavalente notificados entre 2014 y 2018 al Ministerio de Salud Pública (MSP) de Uruguay. Realizar el tamizaje del neurodesarrollo de los que al momento de la evaluación tenían menos de 6 años de edad. METODOLOGÍA: Estudio descriptivo de las notificaciones al Sistema Nacional de Farmacovigilancia del MSP. Se realizó el tamizaje del neurodesarrollo con la Guía Nacional para la Vigilancia del Desarrollo. RESULTADOS: 30 casos, la mayoría de breve duración, en las primeras horas post primera dosis y con recuperación espontánea. Requirieron hospitalización 29. Se realizó el tamizaje del neurodesarrollo en 16. La media de tiempo entre el evento y esta evaluación fue 2 años y 2 meses. Fue normal la prueba de tamizaje en 15. En uno se detectó un retraso del lenguaje. CONCLUSIONES: Los episodios de HHR se presentaron con características similares a las descritas en la bibliografía. A pesar de las limitaciones del estudio, no se encontraron retrasos ni desvíos del desarrollo en los niños evaluados.

BACKGROUND: Hypotonic-hyporesponsive episodes (HHE) is one frequently reported neurologic adverse effect supposedly attributable to vaccination and immunization. Its long-term impact on neurodevelopment is not completely known. AIM: To characterize the post-pentavalent vaccine HHE events reported to the Uruguayan Ministry of Health (M of H) between 2014 and 2018. To perform neurodevelopment screening of those who were under 6 years of age at the time of evaluation. METHODS: Descriptive study of the reports made to the National Farmacosurveillance System of the M of H. Neurodevelopment screening was performed using the National Guidelines for Developmental Surveillance. RESULTS: 30 cases were studied. Most cases occurred after the first doses, were of short duration and during the first hours after vaccination, with spontaneous recovery. Median time between the event and this evaluation was 2 years and 2 months. Screening tests were normal in 15. Delay in the language area was detected in one case. CONCLUSIONS: HHE events had similar characteristics to those described in the literature, with no severe short-term complications. Despite the limitations of the present study, no delays nor deviations were found in the development of the children who were evaluated.

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.

Reactogenicity of Bordetella pertussis vaccines formulations using aluminum adjuvants in Sprague Dawley rats / Reactogenicidad de formulaciones de vacunas de Bordetella pertussis utilizando adyuvantes de aluminio en ratas Sprague Dawley

Combined vaccines for childhood are a strategy in the prevention of several diseases. These can maximize protection and decrease immunization schedules in children. New candidates are getting closer to being able to meet these needs, but they raise numerous strategic questions related to formulation and regulatory aspects. In addition to being immunogenic and protective must have low reactogenicity when combined with other antigens. Adjuvants are important components in achieving these combinations. Therefore, a reactogenicity study was designed for two Bordetella pertussis formulations containing hydroxide or aluminum phosphate in Sprague Dawley rats. Both formulations dose were administered in 0.2 mL intramuscularly. Clinical evaluations, body weight, water consumption, food, temperature, muscle volume, dermal irritability and pathological studies with special interest at the inoculation site were carried out. Only differences in body temperature and muscle volume were found with a slight increase in values with return to normal. The macroscopic study showed lesions at the site of inoculation, consid­ered characteristics of aluminum adjuvants, such as granulomatous abscesses and the increase in regional lymph nodes near the inoculation site. As conclusion, there are no differences between the formulations of B. pertussis with hydroxide or aluminum phosphate resulted in low reactogenicity.

Las vacunas combinadas resultan una estrategia importante en la obtención de vacunas múltiples para la infancia y el uso de adyuvantes es un componente de gran valor en lograr estas combinaciones, además de ser inmunogénicas y protectoras deben tener baja reactogenicidad, cuando se combinan con diferentes antígenos. Por esta razón, se diseñó un estudio de reactogenicidad a dos formulaciones que contenían hidróxido y fosfato de aluminio con antígenos de Bordetella pertussis en ratas Sprague Dawley. Se administró a cada grupo de ensayo una dosis correspondiente de ambas formulaciones en 0,2 mL por vía intramuscular. Se realizaron observaciones clínicas, comportamiento del peso corporal, consumo de agua, alimentos, temperatura corporal, volumen muscular, irritabilidad dérmica y estudios anatomopatológicos macroscópicos, con especial interés en el sitio de inoculación. No se observaron síntomas, ni muertes en los animales durante el estudio. Tampoco se encontraron diferencias entre los grupos experimentales en cuanto al peso corporal, el consumo de agua y de alimentos; los estudios de temperatura corporal y volumetría muscular evidenciaron un ligero incremento en los valores, los cuales involucionaron rápidamente a la normalidad. En el estudio anatomopatológico macroscópico se observaron lesiones a nivel del punto de inoculación, consideradas propias de los adyuvantes que contienen aluminio, tales como formaciones abscedadas de tipo granulomatosas y el aumento de los ganglios linfáticos regionales cercanos al punto de inoculación. Se concluye que las formulaciones en hidróxido y fosfato de aluminio con antígenos de B.pertussis resultaron ser de baja reactogenicidad.

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.

Características clínicas y epidemiológicas de tos ferina en pacientes hospitalizados en un hospital de tercer nivel de Perú / Clinical and epidemiological characteristics of whooping cough in hospitalized patients of a tertiary care hospital in Peru

RESUMEN Objetivo: Describir las características clínicas y epidemiológicas de los pacientes menores de 2 años hospitalizados con el diagnóstico de tos ferina en un hospital pediátrico de tercer nivel de Perú. Métodos: Serie de casos de pacientes menores de 2 años hospitalizados con diagnóstico de tos ferina durante el año 2012. Resultados: Fueron hospitalizados 121 pacientes. Se realizaron pruebas para confirmar el diagnóstico (inmunofluorescencia directa, reacción en cadena de la polimerasa, cultivo) al 53,72%. El 23,15% (n = 28) fueron casos confirmados, todos menores de 10 meses, ninguno había recibido 3 dosis de la vacuna contra pertussis, el 96,43% (n = 27) de ellos fueron menores de 6 meses y 42,86% (n = 12) menores de 3 meses; un 10,71% (n = 3) ingresaron a unidad de cuidados intensivos, todos menores de 2 meses, uno de los cuales falleció. Los síntomas más frecuentes en los casos confirmados fueron tos (96,43%), rubicundez facial (96,43%), tos paroxística (92,86%) y cianosis asociada a la tos (78,57%); el contacto epidemiológico probable más frecuente fue la madre (17,86%) y la mayoría de casos se presentaron en verano (46,43%). Conclusión: La tos ferina es causa de morbimortalidad sobre todo en los menores de 6 meses de edad y en los no inmunizados o parcialmente inmunizados. Se deben mejorar las tasas de vacunación y fomentar la confirmación de casos para no contribuir al infradiagnóstico de esta enfermedad.

ABSTRACT Objective: Describe the clinical and epidemiological characteristics of patients under 2 years of age hospitalized with whooping cough in a tertiary care children's hospital in Peru. Methods: This was a case series of patients under 2 years of age who were hospitalized with a diagnosis of whooping cough in 2012. Results: A total of 121 patients were hospitalized. Diagnostic testing (direct immunofluorescence, polymerase chain reaction, culture) was carried out in 53.72% of patients. Overall, 23.15% (n = 28) were confirmed cases, all of whom were patients less than 10 months old, and none of whom had received 3 doses of whooping cough vaccine. A total of 96.43% (n = 27) of cases were under 6 months of age, 42.86% (n = 12) were younger than 3 months, and 10.71% (n = 3) were admitted to the intensive care unit. Of these cases, all were younger than 2 months old, and one patient died. The most common symptoms in the confirmed cases were coughing (96.43%), facial redness (96.43%), paroxysmal coughing (92.86%), and coughing-related cyanosis (78.57%). The most frequent probable epidemiological contact was the mother (17.86%), and the majority of cases occurred in the summer (46.43%). Conclusion: Whooping cough is a cause of morbidity and mortality, especially in those younger than 6 months of age and in those who are not immunized or only partially immunized. Vaccination rates should be improved and case confirmation encouraged to prevent the underdiagnosis of this disease.

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.

Introduction of pertussis surveillance system and evaluation of its operational effect in Tianjin / 中国当代儿科杂志

The pertussis surveillance system has been established since 2009 in Tianjin, and continuously improved over the past 10 years. This system determines the definition and classification of pertussis, establishes simple and feasible sampling methods and laboratory detection methods in clinical practice, standardizes the report management of pertussis cases and the treatment of epidemic situations. After the implementation of the surveillance system, the number of reported pertussis cases increased from 26 in 2009 to 802 in 2017, the number of diagnosed cases increased from 19 in 2009 to 662 in 2017, the reported incidence rate of pertussis increased from 0.16/100 000 in 2009 to 4.28/100 000 in 2017, and the number of medical institutions of reporting perutssis cases increased from 2 in 2009 to 53 in 2017. The specimen collection rate of the reported cases reached up to 93.66%. These results show that the sensitivity of pertussis surveillance has been improved and show that the data from the surveillance system may reflect more precisely the epidemical characteristics of perutssis in Tianjin.

Development and implementation of standardized method for detecting immunogenicity of acellular pertussis vaccines in Korea

PURPOSE: There is no standard method for confirming the immunogenicity of acellular pertussis vaccines. We tried to develop a local standard method for evaluating the immunogenicity of the three-component of acellular pertussis vaccines which was developed by a Korean local company. MATERIALS AND METHODS: The developed pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) were evaluated by in-house enzyme-linked immunosorbent assay (ELISA) using 189 negative sera, 25 positive sera, and 73 paired sera (pre- and post-Tdap [tetanus, diphtheria, and acellular pertussis] vaccinated sera). ELISA units were calculated by the reference line method, compared with World Health Organization reference sera, and the cut-off value was calculated using negative sera. RESULTS: When compared to National Institute for Biological Standards and Control control antigen (NIBSC) control antigens, the developed pertussis toxin (PT) and filamentous haemagglutinin (FHA) antigens were 203.48 and 61.60 IU/µg, respectively. Each in-house ELISA was established by validating the coefficients of variation % (PT, 11.53%; FHA, 8.60%; pertactin [PRN], 9.86%) obtained from the results of inter- and intra-assay variation. Also, the cut-off values of PT, FHA, and PRN were 11.65, 38.95, and 5.66 EU/mL, respectively. The distributions of antibody levels in paired showed that 93.15% (68/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were higher than a 100% increase after vaccination. Additionally, the values of 89.04% (65/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were below each cut-off point. CONCLUSION: We established an in-house ELISA method using self-developed antigens, and these immunoassays have provided a way to standardize measuring the immunogenicity of newly developed vaccines, through single- and dual-serology.

Seroprevalence of Pertussis in Healthcare Workers without Adult Pertussis Vaccine Use at a University Hospital in Korea

BACKGROUND: Pertussis is highly contagious respiratory disease. Healthcare workers (HCWs) can be an important mediator of the disease. A seroprevalence of pertussis was investigated in HCWs to determine the immune status against pertussis and to detect the unidentified pertussis. METHODS: This study was conducted for HCWs at a hospital located in Korea in 2011. After obtaining written informed consent for HCWs voluntarily participating in the study, 10 mL of blood was collected from each subject. Demographic and medical data were collected using questionnaire. Data on the underlying disease and vaccination history were reviewed again through medical records. The presence of anti-pertussis toxin (anti-PT) immunoglobulin G (IgG), and immunoglobulin A (IgA) was detected by quantitative analysis using a commercially available ELISA kit (EUROIMMUN, Lübeck, Germany). RESULTS: A total of 412 HCW participated in the study. Among them, 14 were excluded due to the inadequate sample amount or medical history not secured. Of the 398 HCWs analyzed, 16.6% (66/398) were men and the mean age was 33.82 ± 9.10 years (range, 21–67). The mean anti-PT IgG titer was 8.32 ± 20.40 IU/mL (range, 0.4–287.5 IU/mL). The overall seroprevalence (rate of anti-PT IgG antibody [Ab] titer > 5 IU/mL) was 33.7%. Three (0.8%) HCWs had the Ab level > 100 IU/mL indicated acute infection. There was no statistically significant difference in the seroprevalence and mean titer of anti-PT IgG Ab according to age group, type of occupation, patient-facing position, or working in the pediatric department. CONCLUSION: The seroprevalence of pertussis of the HCWs of a university hospital in Korea was low, and there were some unrecognized acute infections. Therefore, booster immunization of pertussis to HCWs should be actively considered.

Episodios de Hipotonía Hiporrespuesta (EHH) postvacunación: reporte de una serie de casos / Post-vaccination hypotonic-hyporesponsive episodes: report of a series of cases

Objetivo: Describir características clínicas, antecedentes de vacunación, recursos médicos utilizados y continuidad del esquema de vacunación de los casos de Episodio de Hipotonía Hiporrespuesta (EHH) que consultaron al Vacunatorio del Hospital de Niños Ricardo Gutiérrez (HNRG). Materiales y métodos: Estudio descriptivo de serie de casos. Se incluyeron los niños con diagnóstico de EHH, según los Criterios de Brighton, que consultaron entre Enero 2010 y Agosto 2017. Resultados: Se registraron 14 casos, 1 se descartó por datos insuficientes (n= 13). La media de edad fue 5 meses, sin predominio de sexo. Diez casos se presentaron luego de la 1° dosis y todos antes de las 24hs. Recibieron quíntuple celular 12 pacientes, hexavalente 1; recibieron otras vacunas 11 casos. Síntomas concomitantes más frecuentes: fiebre e irritabilidad. Realizaron consulta médica 12 y se internaron 9. Doce tuvieron recuperación total, de 1 no hay datos. Ocho continuaron el esquema con vacuna acelular, uno con celular y ninguno presentó complicaciones. Conclusiones: Todos presentaron el EHH dentro de las 24hs post vacunación con componente pertussis, con recuperación completa. La mayoría luego de la primera dosis. Más del 80% requirió consulta médica y casi el 70% internación. La continuidad del esquema no se asoció con complicaciones

Objective: To describe the clinical manifestations, vaccination history, medical resources used and the continuity of the vaccination schedule in all the cases of hypotonic-hyporesponsive episodes (HHE) seen in the immunization center of Ricardo Gutierrez Children´s Hospital. Materials and methods: Descriptive study of a retrospective case series. All children diagnosed with HHE according to the Brighton Criteria, who were seen between January 2010 and August 2017, were included. Results: There were 14 cases, one of which was dismissed due to insufficient data (n= 13). The mean age was 5 months, with no predominance of sex. Ten of the episodes occurred after the 1st dose and all of them within 24 hs. Twelve patients received pentavalent whole-cell vaccines, one received the hexavalent vaccine and eleven received other vaccines. The most frequent concomitant symptoms were fever and irritability. Twelve required medical consultation and nine, hospitalization. Evolution: 12 recovered completely and data were missing from 1. Eight of the patients who were followed up continued with acellular vaccines, one with pentavalent whole-cell vaccine. None presented complications. Conclusions: All patients presented the HHE within 24 hours after the administration of pertussis component vaccines, recovering completely HHE has been observed mainly after the first dose More than 80% required medical consultation and almost 70%, hospitalization. The continuity of the schedule was not associated with complications

Pertussis: enfermedad reemergente / Pertussis: reemerging disease / Pertussis: doença reemergente

RESUMEN Introducción: Actualmente a pesar de las estrategias de vacunación a nivel mundial, B. pertussis se ha convertido en un problema de salud pública, sigue siendo una de las enfermedades menos prevenibles por vacunación en todo el mundo, aún en países desarrollados con amplia cobertura de vacunación. Objetivo: Describir los principales mecanismos de virulencia asociados a la infección mediante los cuales la bacteria logra evadir la respuesta inmune, además de dar a conocer un panorama actual del estado de inmunización contra la tos ferina y la problemática de su reemergencia a nivel mundial. Métodos: Se realizó una revisión mediante búsqueda electrónica de literatura; entre las estrategias de búsqueda se destaca el empleo de las bases de datos como PubMed, ScienceDirect, SciELO, Redalyc; y búsqueda en portales de salud; sobre aspectos generales de la enfermedad y su agente causal, además de últimas actualizaciones sobre el tema. Resultados: Como lo confirman recientes estudios, el incremento del riesgo de infección por B. pertussis sigue presentándose en adolescentes y adultos debido a la disminución en la respuesta inmune inducida por la vacunación y la infección natural, por ende, la información actual indica que está reemergiendo la tos ferina en todo el mundo, situación que es necesario conocer para un oportuno diagnóstico y tratamiento. Conclusiones: Análisis de la literatura demuestra la necesidad de ampliar el uso de técnicas moleculares; llevar a cabo la modificación de los programas de vacunación, con la administración de dosis de refuerzo entre adolescentes y adultos; además programas de monitoreo epidemiológico eficaces de recolección de casos con tos ferina y sistemas adecuados de notificación para lograr la reducción equitativa y sustentable de la morbilidad y mortalidad de ésta enfermedad.

ABSTRACT Introduction: Currently despite vaccination strategies worldwide, B. pertussis has become a public health problem, it remains one of the least vaccine preventable diseases in the world, even in developed countries with extensive coverage of vaccination. Objective: To describe the main mechanisms of virulence associated with the infection through which the bacterium manages to evade the immune response, as well as to present a current picture of the state of immunization against pertussis and the problem of its reemergence worldwide. Methods: Electronic literature search was performed; among the search strategies we highlight the use of databases such as PubMed, ScienceDirect, SciELO, Redalyc; and search in health portals; on general aspects of the disease and its causal agent, in addition to the latest updates on the subject. Results: As confirmed by recent studies, the increased risk of B. pertussis infection continues to occur in adolescents and adult's due to the decrease in the immune response induced by vaccination and natural infection, therefore, current information indicates that reemerging whooping cough around the world, a situation that is necessary to know for a timely diagnosis and treatment. Conclusions: Analysis of the literature demonstrates the need to expand the use of molecular techniques; to carry out the modification of the vaccination programs, with the administration of doses of reinforcement between adolescents and adults; In addition to effective epidemiological monitoring programs for the collection of pertussis cases and adequate notification systems to achieve an equitable and sustainable reduction in the morbidity and mortality of this disease.

RESUMO Introdução: Atualmente, apesar das estratégias de vacinação em todo o mundo, B. pertussis tornou-se um problema de saúde pública, continua a ser uma das doenças menos evitáveis pela vacina no mundo, mesmo em países desenvolvidos com ampla cobertura de vacinação. Objetivo: Descrever os principais mecanismos de virulência associados à infecção através dos quais a bactéria consegue evadir a resposta imune, bem como apresentar uma imagem atual do estado da imunização contra a tosse convulsa e o problema da ressurgência em todo o mundo. Métodos: Pesquisa eletrônica de literatura foi realizadantre as estratégias de Investigação, destacamos o uso de bancos de dados como PubMed, ScienceDirect, SciELO, Redalyc; e investigação em portais de saúde; sobre aspectos gerais da doença e seu agente causal, além das atualizações mais recentes sobre o assunto. Resultados: Conforme confirmado por estudos recentes, o aumento do risco de infecção por B. pertussis continua a ocorrer em adolescentes e adultos devido à diminuição da resposta imune induzida por vacinação e infecção natural, portanto, informações atuais indicam que a ressurreição de tosse convulsa ao redor do mundo, uma situação que é necessário conhecer para um diagnóstico e tratamento oportunos. Conclusões: A análise da literatura demonstra a necessidade de ampliar o uso de técnicas moleculares; para realizar a modificação dos programas de vacinação, com a administração de doses de reforço entre adolescentes e adultos; além de programas efetivos de monitoramento epidemiológico para a coleta de casos de tosse convulsa e sistemas de notificação adequados para alcançar uma redução sustentável e equitativa na morbidade e mortalidade desta doença.

Vacunación con pertussis en el embarazo: una estrategia segura y efectiva para proteger al lactante menor / Pertussis vaccination in pregnancy: Security and effectiveness in the protection of the infant

El coqueluche es una enfermedad inmunoprevenible que puede amenazar la vida. A pesar de la vacunación en lactantes desde los 2 meses de edad, se siguen presentando casos y brotes a nivel nacional y mundial, con un alto riesgo de morbimortalidad en los menores de 6 meses. Se ha planteado que la vacunación antenatal con componente pertussis acelular (Tdpa) sería útil, segura y efectiva, dado que transfiere una alta tasa de anticuerpos al niño, disminuyendo en 85% la incidencia de coqueluche en este grupo. No se ha encontrado mayor incidencia de efectos adversos en embarazadas con esta vacuna. Esta estrategia ha sido implementada en varios países desarrollados y de Latinoamérica. El objetivo del presente manuscrito es revisar y discutir los beneficios de la vacunación antenatal con Tdpa. Se concluye que se debiera promover la inmunización materna con vacuna Tdpa para prevenir la infección y mortalidad asociada en el menor de 6 meses de vida por Bordetella pertussis.

Whooping cough is an immune preventable disease that can be life threatening. Despite infant immunization starting at 2 month of age, there are many cases and outbreaks in our country and also around the world, with a high risk of mortality specially in infants under 6 month of age. It has been proposed that antenatal vaccination with acellular pertussis component (Tdap) would be useful, safe and effective since it transfers a high antibody rate to the child, reducing the incidence of pertussis in this group by 85%. No higher incidence of adverse effects has been found in pregnant women with this vaccine. This strategy has been implemented in several developed and Latin American countries. The purpose of this manuscript is to review and discuss the benefits of antenatal vaccination with Tdap. It was concluded that maternal immunization with Tdap vaccine should be promoted to prevent infection and associated mortality in the less than 6 months of age by Bordetella pertussis.

Tetanus–diphtheria–acellular pertussis vaccination for adults: an update

Although tetanus and diphtheria have become rare in developed countries, pertussis is still endemic in some developed countries. These are vaccine-preventable diseases and vaccination for adults is important to prevent the outbreak of disease. Strategies for tetanus, diphtheria, and pertussis vaccines vary from country to country. Each country needs to monitor consistently epidemiology of the diseases and changes vaccination policies accordingly. Recent studies showed that tetanus–diphtheria–acellular pertussis vaccine for adults is effective and safe to prevent pertussis disease in infants. However, vaccine coverage still remains low than expected and seroprevalence of protective antibodies levels for tetanus, diphtheria, and pertussis decline with aging. The importance of tetanus–diphtheria–acellular pertussis vaccine administration should be emphasized for the protection of young adult and elderly people also, not limited to children.