Características clínicas y epidemiológicas de los pacientes con infección por Bordetella pertussis hospitalizados

Introducción: La tosferina causada por la bacteria Bordetella pertussis, es una de las principales enfermedades prevenibles por vacunas en el mundo. En Panamá es una causa importante de morbimortalidad en la población infantil. A nivel nacional se registraron 20 casos en el 2018 y 108 en el 2019. El objetivo es describir el comportamiento clínico y epidemiológico de la infección en la población pediátrica. Materiales y métodos: Es un estudio descriptivo, retrospectivo y observacional. Se incluyeron pacientes de 0 a 14 años con diagnóstico de infección por B. pertussis. Las variables: edad, sexo, procedencia, comorbilidades, signos, síntomas, vacuna contra               B. pertussis, hemograma, complicaciones, defunción. Resultados: La tasa hospitalaria fue de 5 casos por cada 10 000 hospitalizados.  El sexo presentó una razón de 2:1. El grupo etario más afectado fue el de 2 a 3 meses. La tos fue la manifestación más frecuente. La comorbilidad que se observó con mayor frecuencia fue la desnutrición. El 56% de los pacientes no contaban con vacuna contra B. pertussis. La leucocitosis se observó en 66% de los casos, la linfocitosis en 16% y la trombocitosis en 34%. Tasa de mortalidad hospitalaria, por enfermedad específica de 1,4 casos por 10 000 hospitalizados. Tasa de letalidad, de 25 por cada 100 casos.  Conclusiones: Se encontró predisposición en el sexo femenino. Los lactantes menores son el grupo más afectado. La mayoría de los pacientes y sus madres, no habían recibido vacunación contra B. pertussis. La letalidad observada fue mayor a la descrita en la literatura. (provisto por Infomedic International)

Introduction: Whooping cough caused by the Bordetella pertussis bacterium is one of the main vaccine-preventable diseases in the world. In Panama it is an important cause of morbidity and mortality in the child population. At the national level, 20 cases were registered in 2018 and 108 in 2019. The objective is to describe the clinical and epidemiological behavior of the infection in the pediatric population. Materials and methods: It's a descriptive, retrospective and observational study. Patients from 0 to 14 years old with a diagnosis of B. pertussis infection were included. The variables: age, sex, origin, comorbidities, signs, symptoms, vaccine against B. pertussis, blood count, complications, death. Results: The hospital rate was 5 cases per 10,000 hospitalized. Sex presented a ratio of 2:1. The most affected age group was 2 to 3 months. Cough was the most frequent manifestation. The most frequently observed comorbidity was malnutrition. 56% of the patients didn´t have a vaccine against B. pertussis. Leukocytosis was observed in 66% of cases, lymphocytosis in 16%, and thrombocytosis in 34%. Hospital mortality rate, by specific disease of 1.4 cases per 10,000 hospitalized. Fatality rate, 25 per 100 cases. Conclusions: A predisposition was found in the female sex. Younger infants are the most affected group. Most of the patients and their mothers had not received vaccination against B. pertussis. The observed lethality was higher than that described in the literature. (provided by Infomedic International)

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)

Epidemiological characteristics of pertussis in Huzhou City from 2012 to 2022 / 预防医学

Objective@#To analyze the epidemiological characteristics of pertussis in Huzhou City, Zhejiang Province from 2012 to 2022, so as to provide insights into formulation of pertussis control measures.@*Methods@#The data of reported pertussis cases in Huzhou City from 2012 to 2022 were collected through the Infectious Disease Report Information System of Chinese Disease Prevention and Control Information System. The temporal, spatial and population distributions of pertussis cases in Huzhou City from 2012 to 2022 were analyzed using a descriptive epidemiological method.@*Results@#A total of 499 pertussis patients were reported in Huzhou City from 2012 to 2022, with mean annual reported incidence of 1.508/105, and no death was reported. The reported incidence of pertussis remained at a low level in Huzhou City from 2012 to 2021, all below 1/105, and increased to 12.625/105 in 2022. The reported incidence of pertussis appeared an overall tendency towards a rise in Huzhou City from 2012 to 2021 (Z=-29.261, P<0.001). The incidence of pertussis peaked from June to July, and a relatively higher incidence rate of pertussis was reported in Deqing (6.359/105) and Anji counties (1.725/105), while higher incidence was found among children at ages of <1 year (30.566/105), 4 years (31.896/105) and 5 years (29.485/105). @*Conclusion@#The reported incidence of pertussis was at a low level in Huzhou City from 2012 to 2021, and increased sharply in 2022. The incidence of pertussis peaked from June to July, was concentrated in Deqing and Anji counties and higher among infants under one year of age and preschool children at ages of 4 to 5 years.

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.

Opinión de un panel de expertos sobre la protección contra la tos ferina en México: el papel de las vacunas acelulares y de células enteras / An expert panel opinion on protection against pertussis in Mexico: The role of acellular and whole-cell vaccines

Resumen La tos ferina es una enfermedad causada por Bordetella pertussis. Aunque es altamente contagiosa, puede ser prevenible por vacunación. Existen dos tipos de vacunas: las de células enteras y las acelulares. La tos ferina ha resurgido en algunos países debido a que su control a escala mundial es heterogéneo. Esta reemergencia se ha relacionado con diversos factores: mayor sensibilidad hacia la infección, mejor detección de la enfermedad, problemas para obtener adecuadas coberturas de vacunación, incremento en los sujetos susceptibles (especialmente menores de 6 meses), pérdida de la inmunidad en los adolescentes y adultos jóvenes, y probables cambios genéticos y adaptativos de B. pertussis. En este documento se analizan las características, las ventajas y las desventajas de las vacunas de células enteras y de las vacunas acelulares. Se presentan las recomendaciones internacionales y se ofrece el posicionamiento de los participantes con respecto a la influencia del uso de vacunas acelulares y las desventajas potenciales de volver a utilizar vacunas de células enteras, en especial por su reactogenicidad. Por último, se analizan las estrategias para lograr un mejor control de la tos ferina en México.

Abstract Pertussis is a highly contagious disease caused by Bordetella pertussis, which may be preventable by vaccination. There are two types of vaccines: whole-cell vaccines and acellular vaccines. Since pertussis control worldwide is heterogeneous, re-emergence of whooping cough has been observed in some countries. This re-emergence has been related to several factors: increased susceptibility to infection, better detection of disease, problems in obtaining adequate vaccination coverage, increase in susceptible subjects (mainly under 6 months of age), loss of immunity in adolescents and young adults, and likely genetic and adaptive B. pertussis changes. This paper discusses whole-cell and acellular vaccines' characteristics, advantages, and disadvantages. International recommendations are presented, and the participants' position is offered regarding the influence of the use of acellular vaccines and the potential disadvantages of reintroducing whole-cell vaccines, mainly due to their reactogenicity. Finally, strategies to achieve better control of pertussis in Mexico are discussed.

Síndrome coqueluchoide y tosferina

RESUMEN Introducción: El síndrome coqueluchoide es una causa frecuente de ingreso y no siempre se descarta a la Bordetella pertussis como su origen. Objetivo: Identificar la etiología infecciosa en niños ingresados con síndrome coqueluchoide/coqueluche y su relación con el estado de la vacunación. Métodos: Estudio descriptivo, transversal, en 120 niños hasta 10 años de edad con diagnóstico de síndrome coqueluchoide ingresados en el Servicio de Neumología del Hospital Pediátrico "Juan Manuel Márquez", entre enero 2010 y septiembre 2012. Se evaluó la edad, sexo, evolución, resultados de reacción en cadena de la polimerasa y cultivo para virus, bacterias y micoplasmas en muestras obtenidas al ingreso, procesadas en el Instituto de Medicina Tropical, además, cumplimiento de vacunación antipertussis. Las variables cualitativas se describieron mediante frecuencias absolutas y porcentajes; para evaluar la relación tos ferina e incumplimiento de la vacunación se empleó la prueba Ji cuadrada con un nivel de significación de p≤ 0,05. Resultados: Predominaron los menores de un año (69,2 %) y el sexo femenino (55%). Bordetella pertussis se aisló en 71 casos (59,2 %); más frecuente en menores de 6 meses (59,7 %) y en niños con vacunación incompleta (80 %), pero no fue significativa la diferencia con los casos no pertussis (p=0,214).Existió coinfección con virus y micoplasmas (54-76 %). La etiología viral predominó en los restantes 49; rinovirus fue el más representado en general. Falleció una recién nacida con neumonía por B pertussis. Conclusiones: Ante un síndrome coqueluchoide debemos siempre tener presente la posibilidad de tos ferina, sobre todo en niños pequeños con vacunación incompleta.

ABSTRACT Introduction: Coqueluchoid syndrome is a frequent cause of admission and Bordetella pertussis is not always ruled out as its origin. Objective: Identify the infectious etiology in children admitted with coqueluchoid/coqueluche syndrome and its relationship with vaccination status. Methods: A descriptive, cross-sectional study was conducted in 120 children up to 10 years of age diagnosed with coqueluchoid syndrome admitted to the Pulmonology Service of "Juan Manuel Márquez" Children's Hospital between January 2010 and September 2012. Age, sex, evolution, polymerase chain reaction results and culture for viruses, bacteria and mycoplasmas were evaluated in samples obtained at admission, processed at the Institute of Tropical Medicine ; in addition to the compliance with anti-pertussis vaccination. Qualitative variables were described by absolute frequencies and percentages; to evaluate the ratio of whooping cough and non-compliance with vaccination, the Ji square test was used with a significance level of p≤ 0.05. Results: Children under one year of age (69.2%) and female sex (55%) predominated. Bordetella pertussis was isolated in 71 cases (59.2%); it was more frequent in children under 6 months (59.7%) and in children with incomplete vaccination (80%), but the difference with non-pertussis cases was not significant (p= 0.214). There was co-infection with viruses and mycoplasmas (54-76%). Viral etiology predominated in the remaining 49; rhinovirus was the most represented overall. A newborn died with B. pertussis pneumonia. Conclusions: In the face of a coqueluchoid syndrome we must always keep in mind the possibility of whooping cough, especially in young children with incomplete vaccination.

Advance in the immunologic mechanism and mucosal immunity of Bordetella pertussis / 国际儿科学杂志

Pertussis, or whooping cough, is a highly contagious respiratory disease.Despite the implementation of the universal immunization program, pertussis remains a significant public health problem.Existing pertussis vaccines have a poorly controlled effect, and new vaccines are needed to protect against pertussis disease, as well as to prevent infection and transmission of Bordetella pertussis.The development of new pertussis vaccines requires an in-depth study of pertussis′s pathogenesis and immune mechanism, especially the protective immune mechanism.With the further understanding of the protective immune mechanism, the mucosal vaccine has been paid more attention, and new approaches, such as nasal immunization, outer membrane vesicles, and live attenuated vaccine have been adopted.This paper summarizes pertussis′s immune mechanism and mucosal immunity to provide ideas for the research and development of new pertussis vaccines.

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.

Genetic diversity and molecular epidemiology of Bordetella pertussis isolates / 中华微生物学和免疫学杂志

Objective:To investigate the genetic diversity and molecular epidemiology of Bordetella pertussis in Shaanxi province, and analyze the possible reasons of resurgence in this region. Methods:We characterized clinical isolates collected during 2012-2017 using multilocus antigen sequence typing (MAST) and multilocus variable-number tandem repeat analysis (MLVA).Results:The circulating strains and vaccine strains were different in molecular characteristics. The majority (95%) of the isolates were typed as prn1/ ptxP1/ ptxA1/ fim3-1/ fim2-1. In addition, eight MLVA types (MTs) and eight PFGE profiles were identified, respectively. MT195, MT55 and MT104 were dominant and MT195 continually increased annually. Conclusions:The genetic characteristics of the current strains in Shaanxi province were different from those of the vaccine strain. The evolution through genetic variation might be one of the reasons for the recurrence of pertussis in this region.

Macrolide resistance, molecular characteristics and PFGE types of Bordetella pertussis strains / 中华微生物学和免疫学杂志

Objective:To analysis the macrolide resistance, molecular characteristics and plused-field gel electrophoresis(PFGE) type of Bordetella pertussis ( Bp), explore the possible resistance mechanism and the relationship between PFGE types and macrolide resistance profiles. Methods:Erythromycin, azithromycin and clarithromycin susceptibility of clinical isolates during 2016 to 2018 was determined by E-test. PCR was used to detect the drug-resistant genes and mutation sites. PFGE were employed to do molecular typing for the strains.Results:Thirty-five strains were isolated, of which 27 strains were resistant to all three antibiotics, two strains were resistant to erythromycin and azithromycin, and six strains were sensitive to all three antibiotics. Partial macrolide resistant strains carried the methylase gene ermA (27.6%, 8/29) and ermB (31.0%, 9/29); A2047G site mutation was detected in macrolide-resistant strains, while no drug-resistant genes or mutation sites were found in sensitive strains. Resistant strains were classified into BPSR23 and BPFINR9 types, while sensitive strains were other profiles. Conclusions:The clinical isolated Bp were seriously resistant to erythromy and showed signs of resistance to other macrolides. The acquisition of methylase gene and mutation of A2047G site might be the main mechanism of resistance. The macrolide resistance might have has a certain correlation with PFGE profile.

Nigella sativa Derived Phytochemicals against Cough

Nigella sativa plant extract is traditionally used to cure cough. It is caused by Bordetella pertussis. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that p-cymene can effectively deactivate the adenylate cyclase thereby interrupting the life cycle of the organism

Michelia champaca L. Derived Phytochemicals against Peptidase Do of Bordetella pertussis Causing Cough

Phytochemicals from Michelia champaca L. plant extract are traditionally used to cure cough. Cough can be caused by many reasons. Caugh can be caused by the infection of Bordetella pertussis. The objective of the study is to identify the phytochemical of Michelia champaca capable of curing cough. Molecular docking method applied using “Biovia Discovery Studio”. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that magnoflorine can effectively deactivate the peptidase Do enzyme which will interrupt the life cycle of the microorganism and inhibit the multiplication

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.

Caracterización de la infección por Bordetella pertussis en el Hospital Metropolitano de Quito / Characterization of Bordetella pertussis infection at the Metropolitan Hospital of Quito

Abstract: Introduction: Whooping cough continues to be a public health problem. The objective of the study was to characterize the hospital discharge diagnosed with pertussis confirmed by Multiplex PCR in respiratory samples with Bordetella pertussis isolation in the Hospital Metropolitano Quito, 2015-2018 period. Materials and methods: Retrospective descriptive study of confirmed cases with Bordetella pertussis by Multiplex PCR in respiratory samples, period 2015-2018. Results and discussion: During 4 years, it was suspected in 19 cases of which 10 were confirmed, by PCR in respiratory samples, 1 case had positive confirmation by culture for Bordetella pertussis in the National Health Institute of Public Health Research. 80% (8) corresponded to younger infants. 20% (2) presented respiratory failure and 50% (5) entered the ICU, 3 of them required mechanical ventilation. In 40% (4) more than one microorganism was isolated in the respiratory panel, where Rhinovirus 1, 2, 3, 4 were prevalent. 100% (10) was dependent on supplemental oxygen and 50% (5) was discharged with home oxygen. 60% (6) presented incomplete vaccination for age. The average hospitalization was 8 days. 50% (5) received antibiotic therapy prior to admission. The hospital treatment was clarithromycin. All cases had family contact with respiratory infection. No mortality was recorded. Bordetella pertussis is an important causal agent of hospital admission in infants. It is imperative to maintain adequate vaccination strategies and achieve an adequate herd effect.

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.

Low tetanus-diphtheria-acellular pertussis (Tdap) vaccine coverage among healthcare workers in a quaternary university hospital in São Paulo, Brazil: need for continuous surveillance and implementation of active strategies

Abstract Introduction: Vaccination with tetanus-diphtheria-acellular pertussis (Tdap) has been recommended for healthcare workers (HCWs) by Brazilian Ministry of Health since November 2014. Objective: To describe the strategies implemented to improve Tdap uptake, cumulative vaccine coverage after each intervention, variables associated to Tdap vaccination, and reasons for non-vaccination among HCWs of the main building of a quaternary hospital attached to the Sao Paulo University Medical School. Methods: A list of HCWs eligible for pertussis vaccination was generated. From April to December 2015, the following interventions were implemented: note on intern journal reminding the importance of pertussis vaccination; email to the head nurses strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians of Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. Vaccine coverage was accessed at the end of each month. Multivariate Poisson regression model with a robust error variance was used to evaluate variables associated with Tdap vaccination. Reasons for non-vaccination were evaluated from January to May 2017 through phone calls for HCWs who had not received Tdap. Results: The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.8% to 41.2%. In the multivariate analysis, occupation (physician), working place (obstetrics or anesthesiology) and influenza vaccination in 2015 were independently associated to Tdap vaccination. The main reason for non-vaccination was unawareness of Tdap recommendations. Conclusions: Tdap uptake among HCWs was low in our hospital. Providing vaccination at convenient places/times for HCW seems to be the most efficient strategy to increase vaccine uptake.

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.

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.