Present situation and prospect of development and vaccination of acellular pertussis vaccine / 中国生物制品学杂志

@#Whooping cough(pertussis)is a highly contagious respiratory disease,which mainly affects infants and young children.Vaccination is an effective measure to prevent pertussis infection.Due to the fewer side effects,acellular pertussis vaccines(aPVs)have replaced whole-cell pertussis vaccine(wPVs)in many countries.Despite vaccination coverage is high,the short immunity induced by aPVs is considered to be significant reason for the re-emergence of pertussis.For improving pertussis vaccine,genetically detoxified vaccine and live attenuated vaccine have showed obvious clinical results and other strategies including using novel adjuvants in aPVs,increasing antigen or packaging aPVs with nanoparticles also have good prospects.This paper reviews the antigen composition and protective effects of aPVs,vaccination programs in different countries,potential candidate components of pertussis vaccine and new strategies for prevention of pertussis.

Present situation and prospect of development and vaccination of acellular pertussis vaccine / 中国生物制品学杂志

@#Whooping cough(pertussis)is a highly contagious respiratory disease,which mainly affects infants and young children.Vaccination is an effective measure to prevent pertussis infection.Due to the fewer side effects,acellular pertussis vaccines(aPVs)have replaced whole-cell pertussis vaccine(wPVs)in many countries.Despite vaccination coverage is high,the short immunity induced by aPVs is considered to be significant reason for the re-emergence of pertussis.For improving pertussis vaccine,genetically detoxified vaccine and live attenuated vaccine have showed obvious clinical results and other strategies including using novel adjuvants in aPVs,increasing antigen or packaging aPVs with nanoparticles also have good prospects.This paper reviews the antigen composition and protective effects of aPVs,vaccination programs in different countries,potential candidate components of pertussis vaccine and new strategies for prevention of pertussis.

Applicability verification of Lowry2 method for protein content determination of intermediate products of component pertussis vaccine / 中国生物制品学杂志

@#Objective To verify the applicability of Lowry2 method[the second method of Folin-phenol method of Chinese Pharmacopoeia(VolumeⅢ,2020 edition)]for the determination of protein content of intermediate products of component pertussis vaccine.Methods The standard and sample were precipitated and pretreated with deoxycholate and trichloroacetic acid to remove impurities,and then reacted with Folin-phenol,and the absorbance was measured at 750 nm wavelength.The standard curve was drawn with the concentration and absorbance of the standard,and the sample concentration was calculated. The method was verified for the specificity,linearity,accuracy and precision,and used to detect the protein content of intermediate products of three batches of component pertussis vaccine.Results There was no significant difference between the protein content in background buffer of intermediate product detected by this method and that in ultrapure water(t = 0. 277～1. 178,P = 0. 304～0. 795);The linear relationship of standard curve was good at the protein concentration of 0～50 μg/mL,each R~2> 0. 98;The spike recovery of accuracy verification was in the range of 90%～110%;The RSDs of repeatability and intermediate precision verification were both less than 3%. The detection results of protein content in the intermediate products of three batches of component pertussis vaccine all met the requirements of internal manufacturing and verification regulations.Conclusion Lowry2 method has good specificity,accuracy and precision,and can be used to determine the protein content of component pertussis intermediate products,which provides a basis for the applicability of Lowry2 method.

Research progress on combined vaccines based on diphtheria-tetanus and acellular pertussis vaccine / 中国生物制品学杂志

@#Combined vaccine is a single vaccine preparation made by mixing two or more different organism or purified antigens by physical methods.The use of combined vaccine can reduce the number of immunization shots and improve the compliance of children and acceptance of parents;reduce the costs of transportation,storage and management;avoid missing vaccination and improve vaccination rate.At present,a variety of combined vaccines have been licensed abroad,which have good safety and immunogenicity;some combined vaccines have been put on the market in China,and many combined vaccines are in clinical trials.In recent years,with the successful development of component pertussis vaccine and inactivated poliovirus vaccines of Sabin strain Ⅰ,Ⅱ and Ⅲ in China,the combined vaccines based on diphtheria-tetanus-acellular pertussis vaccine(DTaP) have been greatly developed.In this paper,the research progress on combined vaccines based on DTaP,which have been licensed and in clinical trials at home and abroad,was reviewed,in order to provide ideas for the development of related combined vaccines in China.

Tétanos generalizado en un niño parcialmente inmunizado

Resumen El tétanos continúa siendo un problema de salud pública, y que afecta a todas las edades. La mortalidad aumenta por bajas coberturas de vacunación y escasez de recursos para un tratamiento temprano. Es causado por la toxina de Clostridium tetani (tetanoespasmina) el cual ingresa al organismo a través de heridas contaminadas por cuerpos extraños. La clínica más frecuente del tétanos es del tipo generalizado y se caracteriza por la contracción tónica de músculos esqueléticos, espasmos musculares intensos, dolorosos, e hiperactividad autonómica. El diagnóstico es principalmente clínico. Se presenta el caso clínico de un tétanos generalizado en un niño con vacunación incompleta. Se discute la importancia de la vacunación y el diagnóstico y tratamiento precoz para mejorar el pronóstico de la enfermedad.

Abstract Tetanus continues to be a public health problem, which affects all age groups. Mortality increases when immunization programs have low coverage and there is a lack of resources for early treatment. This disease is caused by the toxin of Clostridium tetani (tetanospasmin) which enters the body via wounds contaminated by foreign bodies. The most common symptoms of tetanus are of the generalized type and are characterized by tonic contraction of skeletal muscles, intense, painful muscle spasms, and autonomic hyperactivity. The diagnosis is clinical and the previous vaccination history becomes important. We report the case of generalized tetanus in a child with incomplete immunizations. Highlight the importance of vaccination and early diagnosis and treatment.

Protective effect of exclusive breastfeeding and effectiveness of maternal vaccination in reducing pertussis-like illness

Abstract Objective: To assess the protective effect of exclusive breastfeeding and the effectiveness of maternal vaccination in reducing pertussis-like illness. Method: This was a case-control study conducted in sentinel hospitals for pertussis in Recife between July 2016 and July 2018. Cases included children aged under six months with symptoms compatible with pertussis (pertussis-like illness). Controls included children aged under six months, living in the metropolitan region of Recife with no diagnosis of pertussis-like illness and matched by the same hospital and birth date. Results: Seventy-three cases and 194 controls were included. The diagnosis of pertussis-like illness was predominantly clinical (97,2%). Amongst the main symptoms, paroxysmal cough was observed in 95.89% of cases and vomiting in 53.4%. There were 29 hospitalized cases and no deaths. Out of the 73 cases, 47 were born to mothers vaccinated against pertussis during pregnancy, and the mothers of 144 of the 194 controls had been vaccinated. The protective effect of breastfeeding was of 74% (95% CI;38%, 89%). Children younger than six months, who were exclusively breastfed and with mothers vaccinated against pertussis during pregnancy were 5 times less likely to develop pertussis-like illness, corresponding to a protection of 79% (95% CI;31%, 94%). The effectiveness of maternal vaccination against pertussis-like illness in children under six months was low (27%) and not statistically significant (CI 95%; −34% a 60%). Conclusions: Exclusive breastfeeding protects children under six months from pertussis-like illness and may be enhanced when associated with maternal vaccination. These strategies should be encouraged because they also protect against pertussis-like illnesses.

Hospitalização por coqueluche em crianças no período pré e pós-implantação da vacina dTpa para gestantes / Hospitalization due to pertussis in children in the pre- and post-implantation periods of the DTaP vaccine for pregnant women

Resumo Introdução A imunização da gestante parece proteger o bebê por meio da transferência passiva de anticorpos e ter um impacto na prevenção da doença em bebês que ainda não iniciaram a vacinação contra coqueluche. Objetivo Analisar o comportamento dos registros de hospitalizações por coqueluche em crianças menores de 1 ano de idade, conforme a cobertura da vacina dTpa para gestantes. Método Trata-se de um estudo ecológico de caráter observacional e quantitativo dos registros de hospitalizações por coqueluche, em crianças menores de 1 ano de idade, no Sul do Brasil, durante o período de 2007 a 2017. Os dados foram obtidos por meio do Sistema de Informação Hospitalar no DATASUS. Resultados No período analisado, foram registradas 342.139 hospitalizações por doenças respiratórias em crianças menores de 1 ano, sendo que 3.062 foram por coqueluche. No período pré-vacinal, a média anual foi de 102,2/100.000/ano e, no período pós-vacinal, foi de 46,8/100.000/ano, representando uma queda de 54,2% no número de registros, variando de 27,8/100.000/ano em 2007 a 139/100.000/ano em 2013, caindo para 47,9/100.000/ano em 2017. Conclusão Houve uma redução no número de registros de hospitalizações por coqueluche após a introdução da vacina dTpa, mesmo com uma cobertura vacinal abaixo de 50%.

Abstract Background Immunization of pregnant women seems to protect infants through passive antibody transfer, and have an impact on disease prevention in infants who have not yet started vaccination for pertussis. Objective Analyze the behavior of hospitalization records for pertussis in children under 1 year of age according to the coverage of the Diphtheria, Tetanus and acellular Pertussis (DTaP) vaccine for pregnant women. Methods This is an ecological, observational, quantitative study conducted with records of hospitalization due to pertussis in children under 1 year of age in southern Brazil from 2007 to 2017. Data were obtained from the hospital information system at DATASUS. Results In the analyzed period, 342.139 children aged ≤1 year were hospitalized as a result of respiratory diseases, and 3.062 of these hospitalizations were due to pertussis. In the pre-vaccination period, the annual average was 102.2/100,000 and, in the post-vaccination period, it was 46.8/100.000, representing a 54.2% decrease in the number of records, varying from 27.8/100.000/year in 2007 to 139.0/100.000/year in 2013, and reducing to 47.9/100.000/year in 2017. Conclusion There was a reduction in the number of hospitalizations due to pertussis after the introduction of the DTaP vaccine, even with vaccination coverage <50%.

Análisis económico de las vacunas del primer año de vida con componente pertussis en el contexto de la ini-ciativa mundial de erradicación de la poliomielitis en Argentina / Vaccination in children under 1 year with pertussis component in the context of the global initiative for the eradication of poliomyelitis in Argentina: economic analysis

INTRODUCCIÓN: La Iniciativa Mundial de Erradicación de la Polio promueve la introducción de vacuna de polio inactivada (IPV) en sus programas, con la posterior retirada de Sabin (bOPV). OBJETIVO: Construir un modelo de económico que compare diferentes esquemas de vacunación para la prevención de polio y tosferina en el primer año de vida. Material y MÉTODOS: Análisis de cuatro escenarios de vacunación del esquema primario para Argentina, en base a los precios de las vacunas, costos del programa y reactogenicidad de vacuna celular o acelular para Bordetella pertussis: - Escenario 1 (caso base): dos dosis de IPV, una dosis de bOPV y tres dosis de vacuna pentavalente (DTwP-HB-Hib); - Escenario 2: tres dosis IPV y de pentavalente; - Escenario 3: tres dosis de hexavalente (DTaP-HepB-IPV-Hib); - Escenario 4: dos dosis de hexavalente más una dosis de pentavalente más IPV. RESULTADOS: El costo incremental en base al escenario 1 fue de USD 3.716.671; 19.696.668 y 14.383.341 para los escenarios 2, 3 y 4, respectivamente. Para la reactogenicidad, la diferencia fue de USD -14.178.240 comparado el caso base con el escenario 3. DISCUSIÓN: La inversión de incorporación de full IPV y costos asociados se modifica según tipo de vacuna y reactogenicidad asociada al componente B. pertussis.

BACKGROUND: Global Polio Eradication Initiative promotes the introduction of inactivated polio vaccine (IPV) in its programs, with withdrawal of Sabin (bOPV). There is no an economic analysis of the investment related to the incorporation of IPV vaccines together with a whole cell Bordetella pertussis vaccine or combined with acellular hexavalent. AIM: An economic model that compares different vaccination schemes for the prevention of polio and pertussis in the first year of life was carried out. METHODS: Four vaccination scenarios for the primary scheme based on Argentina demographic and costs data were developed: - Scenario 1 (base case): two doses of IPV, one dose of bOPV and three doses of pentavalent (DTwP-HepB-Hib) vaccine; - Scenario 2: three doses of IPV plus three doses of pentavalent; - Scenario 3: three doses of hexavalent; - Scenario 4: two doses of hexavalent plus one dose of pentavalent plus IPV. RESULTS: The incremental cost based on scenario 1 was USD 3.716.671; 19.696.668 and 14.383.341 for scenarios 2, 3 and 4 respectively. In terms of reactogenicity savings was -14.178.240 compared base case with scenario 3. DISCUSSION: Full IPV introduction investment and costs associated were modified according to the type of vaccine and reactogenicity related with the B. pertussis component.

Risk Perceptions and Acceptance Towards the Uptake of Pertussis Vaccine Amongst the Healthcare Workers in Sabah and Sarawak

@#Introduction: The incidence of pertussis is increasing amongst adolescents and adults. Therefore, adults require booster vaccination for protection against pertussis infection. Vaccination among healthcare workers (HCW) should be prioritized when a country implements an adult vaccine. However, the coverage of pertussis vaccination is still deficient among HCW due to low-risk perception. Method: This was a cross-sectional study using Survey Monkey (online). A total of 920 HCWs comprising of doctors, assistant medical officers (AMO), nurses, and environmental health officers (EHO) working at the hospitals and district health offices in Sabah and Sarawak were selected to partake in the study using a multistage sampling method. The website containing the questionnaire was given to the participants using either email or WhatsApp. Results: A total of 853 responders of whom 22.2% were doctors, 58.1% were nurses, 10.1% were medical assistants, and 9.6% were environmental health officers responded to the questionnaire. Most of the respondents (81.5%) are willing to receive the pertussis vaccine. The Protection Motivation score was significantly different between those willing and those not willing to take the vaccine (p-value<0.001). Robust path analysis showed that sociodemographic factors (age, the institution of working and prior pertussis vaccination) (p=0.004), threat (p<0.001) and coping pathway (p<0.001) were linked with the willingness to uptake vaccine. Conclusion: The sociodemographic factors of the HCW can affect the willingness of the HCW to uptake the pertussis vaccine directly and indirectly through their risk perception towards pertussis.

Vacuna hexavalente en el Perú. Hacia la cobertura segura y sostenida de la vacunación en la infancia. Consenso de expertos / Hexavalent vaccine in Peru. Towards safe and sustained coverage of childhood immunization. Expert consensus

Objetivo. La inmunización es una de las intervenciones más importantes para prevenir la morbimortalidad en la población mundial. No obstante, aún persisten brechas para alcanzar coberturas ideales de vacunación. Además, las múltiples dosis y vacunas dificultan alcanzar las metas mínimas establecidas. Por ello, se desarrollan vacunas combinadas y fraccionadas para reducir el número de inyecciones, errores programáticos, reactogenicidad y mejorar la adherencia. En tres días distintos, durante 9 horas, se reunieron 6 médicos pediatras expertos en vacunas en el Perú siguiendo el método RAND/UCLA, con el objeto de elaborar un consenso de opinión y actualización de la vacuna combinada hexavalente [DTaP+Haemophilus influenzae tipo b (Hib)+Hepatitis B (HVB)+antipolio inactivada (IPV)] y su eventual uso en el Programa ampliado de inmunizaciones (PAI). Las recomendaciones del consenso son: reemplazar las vacunas, antipolio oral (OPV) por IPV, pertussis de células enteras por vacunas acelulares y DTP de los 4 años por dTap entre los 4 y 6 años; usar la vacuna hexavalente para la serie primaria (2, 4 y 6 meses); usar 4 dosis de vacuna contra Hib (2, 4, 6 y 18 meses); incorporar la vacuna hexavalente en el PAI; no usar la IPV fraccionada (fIPV) y administrar solo 4 dosis de IPV.

Objetive. Immunization is one of the most important interventions to prevent morbidity and mortality in the world population. However, gaps persist to achieve ideal vaccination coverage. In addition, the multiple vaccines and necessary doses make it difficult to reach the minimum established goals. On this scenario, combined and fractionated vaccines are being developed with the aim of reducing the injections number, programmatic errors, reactogenicity and improving adherence. On three different days, for 9 hours, 6 pediatricians experts in vaccines in Peru met following the RAND/UCLA method in order to develop a consensus opinion and update of the combined hexavalent vaccine [DTaP+Haemophilus influenzae type b (Hib)+Hepatitis B (HVB)+Inactivated Polio Vaccine (IPV)] and its eventual use in the Extended Immunization Program (EPI). The consensus recommendation are: replace the vaccines, Oral Polio Vaccine (OPV) by IPV, pertussis of whole cells by acellular vaccines and DTP of 4 years old by dTap between 4 and 6 years old; use the hexavalent vaccine for the primary series (2, 4 and 6 months); use 4 doses of Hib vaccine (2, 4, 6 and 18 months); incorporate the hexavalent vaccine in the EPI; do not use fractionated IPV (fIPV) and only administer 4 doses of IPV.

Episodio de hipotonía-hiporreactividad como evento supuestamente atribuido a la vacunación e inmunización. Reporte de un caso / Case study of a hypotonic-hyporesponsive episode from an alleged adverse effect following vaccination and immunization / Relato de caso de episódio hipotônico hiporresponsivo supostamente atribuído a um evento adverso pós-vacinação e imunização

Resumen: El desarrollo de la vacunación a nivel mundial ha permitido el control de algunas enfermedades infecciosas, constituyéndose en una poderosa herramienta de salud pública. Asimismo, se han identificado algunos efectos secundarios neurológicos, como el denominado episodio de hipotonía-hiporreactividad, evento supuestamente atribuido a la vacunación e inmunización. Si bien es poco frecuente, se considera un efecto adverso severo. El objetivo de este artículo es reportar un caso y revisar la literatura sobre el tema. Se presenta una lactante de 2 meses que luego de tres horas de recibir la primera dosis de la vacuna combinada pentavalente, presenta episodio de hipotonía con cianosis de segundos de duración. Este episodio se caracteriza por presentarse horas después de la administración de la vacuna con un inicio súbito de hipotonía generalizada, hiporreactividad y palidez cutánea o cianosis. El diagnóstico es de exclusión, ya que se presenta en lactante de aspecto grave. La mayoría de los episodios se han relacionado con el componente pertussis, ya sea celular o acelular. La vigilancia de los ESAVI es un pilar fundamental para desarrollar esquemas de vacunación eficaces y seguros para toda la población.

Summary: The global development of vaccines has enabled us to control some infectious diseases and has become a powerful public health tool. Despite this, vaccines have some neurological side effects, such as the so-called Hypotonic-Hyporesponsive Episode (HHE), an adverse event following vaccination and immunization (AEFI). Even though it is rare, it is considered to be a severe adverse effect. The objective of this article is to report about a HHE case and to review the literature on the subject. The case is of a 2-month-old infant who, after 3 hours of receiving the first dose of the combined pentavalent vaccine, developed a hypotonic episode with cyanosis of seconds of duration. HHE usually happens hours after the vaccine is administered and it shows a sudden onset of generalized hypotonia, hyporesponsiveness, pale skin or cyanosis. A diagnosis of exclusion was made, since the symptoms looked serious on the infant. Most episodes have been linked to cellular or acellular pertussis. It is essential to carry out AEFI surveillance in order to develop effective and safe vaccination schedules for the entire population.

Resumo: O desenvolvimento global de vacinas há permitido controlar algumas doenças infeccionas tornando-se uma poderosa ferramenta de saúde pública. Apesar disso, elas têm alguns efeitos colaterais neurológicos, como o chamado Episódio Hipotônico-Hiporresponsivo (EHH), um evento adverso pós-vacinação e imunização (EAPV). Embora seja raro, é considerado um efeito adverso grave. O objetivo deste artigo é relatar um caso de EHH e revisar a literatura sobre o assunto. O relato de caso é de uma criança de 2 meses de idade quem, após 3 horas de recebimento da primeira dose da vacina pentavalente combinada, desenvolveu um episódio hipotônico com cianose de segundos de duração. O EHH geralmente ocorre horas após a administração da vacina e mostra um início repentino de hipotonia generalizada, hiporresponsividade, pele pálida ou cianose. O diagnóstico foi de exclusão, pois os sintomas no bebê eram sérios. A maioria dos episódios foi associada à pertussis celular ou acelular. É essencial realizar a vigilância da EAPV para desenvolver cronogramas de vacinação eficazes e seguros para toda a população.

Protection Motivation Theory-Based Questionnaire Validation to Predict Acceptance of Healthcare Workers towards Uptake of Pertussis Vaccine

@#Introduction: Pertussis is known to cause infection and reinfection to everyone irrespective of ages and countries. Therefore, adults do require vaccination for protection against pertussis infection especially the HCW. However, the pertussis vaccine coverage is low among HCW due to low-risk perception. Protection Motivation Theory (PMT) is one of the most cited theories to explain risk perception and intention to change. Therefore, we developed a questionnaire based on the subconstructs of the PMT to assess the acceptance of the pertussis vaccine amongst the HCWs in Sabah and Sarawak. The motive of this study is to validate this questionnaire to see its validity and reliability. Method: Data was collected using a self-administered questionnaire via an online survey (Monkey Survey). The questionnaire was given to 250 HCW. Items that were identified as a problem were modified to increase reliability. Further validation was done among 853 HCWs working in various parts of Sabah and Sarawak. Results: The Cronbach alpha of the overall construct of PMT during the first pilot study was 0.66 and improved to 0.82. Principal components factor analysis using varimax rotations showed that the first four factors explained 28%, 2%, 9% and 5% of the variance respectively. Both the one level and two-level modelling indicated that it’s a good fit model. Conclusion: The study instrument that was developed for the study has been tested and proven to be relevant to assess the risk perception of an HCW towards 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.

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.

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.

Establishment of mouse neutralizing antibody detection method as potency assay for acellular pertussis vaccines / 中华微生物学和免疫学杂志

Objective@#To establish a functional antibody detection method for acellular pertussis vaccines in order to conveniently and effectively evaluate the production consistency and potency of acellular pertussis vaccine bulks and final products.@*Methods@#Chinese hamster ovary (CHO) cell clustering assay was optimized and used to measure titers of neutralizing antibodies against pertussis toxin in mouse immune serum samples.@*Results@#Vaccine samples were determined to be immunized intraperitoneally with 1/5 the human dose to ten female NIH mice (20-24 g, 5-week-old). Four weeks after immunization, blood samples were collected to isolate serum. Serially diluted serum samples were used to neutralize 0.1 IU/ml of pertussis toxin national reference product for 2 hours. Results of clustering were determined after 48 hours of incubation in pre-cultured CHO cell wells. The geometric mean of the serum dilution of the final unclustered wells was the neutralizing antibody titer of vaccine sample. There were significant differences in the titers of neutralizing antibodies elicited by acellular pertussis vaccines prepared with different manufacturing processes. Vaccine samples succeed or failed the modified intracerebral challenge assay (MICA) were easily distinguishable by neutralizing antibodies.@*Conclusion@#The method of detecting neutralizing antibodies to pertussis toxin greatly reduces the amount of animals used in research. CHO cell clustering assay that has better repeatability and precision can be used for monitoring and initial evaluation of the consistency and potency of the bulks and final products of pertussis vaccines prepared with different manufacturing processes.

Reemergência da coqueluche: perfil epidemiológico dos casos confirmados / Pertussis reemerging: epidemiological profile of confirmed cases

Resumo Introdução A coqueluche, doença infectocontagiosa, atualmente vem apresentando um perfil reemergente. Fatores como diminuição da imunidade, anos após a vacinação, mudanças no genótipo da bactéria e aumento da susceptibilidade entre jovens e adultos são considerados como contribuintes para o aumento da taxa da incidência da doença. Objetivo Assim, objetiva-se identificar e caracterizar o perfil epidemiológico dos casos confirmados de coqueluche no estado do Rio Grande do Norte. Método Analisou-se dados das bases do Sinan do estado do RN nos períodos de 2011 a 2014. Resultados Observou-se que os casos confirmados acometeram, predominantemente, os menores de 6 meses de idade. Os sintomas clássicos da doença foram identificados na maior parte dos acometidos. Verificou-se também que a confirmação de casos guarda estreita relação com a não vacinação ou vacinação incompleta. Conclusão Os achados sugerem a importância da vacinação para o controle da doença e a necessidade de melhoria das ações de vigilância para que haja uma representação epidemiológica fidedigna da doença.

Abstract Introduction Pertussis is an infectious disease that currently has a reemerging profile. Factors such as weaknesses in the immune system, 1-year follow-up vaccination, changes in genotype of the bacteria and increased susceptibility among young and adults have been raising rate of disease incidence. Objective Thus, it is aimed to identify and to characterize the epidemiological profile of confirmed cases in Rio Grande do Norte (RN) state. Method It was analyzed data from RN at Sinan databases from 2011 to 2014. Results It was observed that the confirmed cases were predominantly children under 6 months of age. The classic symptoms of the disease have been identified in most affected. It was also perceived that the confirmed cases were strongly linked to non-uptake of immunization or incomplete vaccination. Conclusion The findings suggest the importance of vaccination to control disease and the need to improve activities surveillance to provide an accurate epidemiological representation of the disease.

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.

Systematic review and meta-analysis of pertussis epidemiology in Latin America and the Caribbean: 1980-2015 / Examen sistemático y metanálisis de las características epidemiológicas de la tos ferina en América Latina y el Caribe: 1980-2015 / Revisão sistemática e metanálise da epidemiologia da coqueluche na América Latina e Caribe: 1980 a 2015

Objectives In Latin America and the Caribbean (LAC), pertussis disease incidence has reportedly increased since 2000 despite high vaccine coverage. A systematic review of pertussis literature and a meta-analysis was conducted to understand the burden of disease in LAC. Methods A systematic literature review was completed, using relevant search terms. Original articles describing pertussis epidemiology and vaccine coverage in LAC published between 1980 and 2015 were identified. Applying a Bayesian meta-analysis random-effects model, we calculated pooled estimates and corresponding 95% credible intervals (95% CrIs) for pertussis incidence, case fatality ratio (CFR), pertussis prevalence among contacts, and coverage with three doses of diphtheria, tetanus, and pertussis (DTP) vaccine (DTP3). Results A total of 59 studies meeting our selection criteria were identified, representing 15 countries. Of the 59, 15 of them provided incidence data, with 7 of the 15 reporting a pertussis case definition. The pertussis incidence estimate for the 1980-1999 period was 17.8 cases per 100 000 persons (95% CrI: 5.9-29.7); for the 2000-2015 period, it was 2.5 cases per 100 000 persons (95% CrI: 1.8-3.2). For the 1980-2015 period, the CFR, in 19 studies reviewed, was 3.9% (95% CrI: 2.9%-4.9%); for that same period, in 5 studies reviewed, pertussis prevalence among contacts was 24.9% (95% CrI: 13.7%-36.1%). Pooled DTP3 vaccine coverage estimates, in a total of 20 studies reviewed for the following three time periods, were: 1980-1990, 72.4% (95% CrI: 64.6%-80.2%); 1991-2000, 79.0% (95% CrI: 66.1%-91.9%); and 2001-2015, 90.0% (95% CrI: 87.7%-92.3%). Conclusion A decrease in pertussis incidence and an achievement of moderately high DTP3 vaccine coverage since the early 2000s was observed. The review highlights the need for increased publication of pertussis data at the country level and for LAC as a whole in order to better understand the true burden of the disease. Application of a standardized case definition and use of active case finding would aid in obtaining more accurate estimates of the disease burden in LAC.

RESUMEN Objetivos En América Latina y el Caribe, la incidencia de la tos ferina habría aparentemente aumentado desde el 2000, a pesar de la alta cobertura de vacunación. Se realizó una revisión sistemática de la bibliografía sobre tos ferina y un metanálisis para conocer la carga de esta enfermedad en América Latina y el Caribe. Métodos. La revisión bibliográfica sistemática se realizó utilizando términos de búsqueda pertinentes. Se encontraron artículos originales que describían las características epidemiológicas de la tos ferina y la cobertura de vacunación en América Latina y el Caribe publicados entre 1980 y el 2015. Aplicando un modelo bayesiano de efectos aleatorios para el metanálisis, se obtuvieron estimaciones combinadas y los correspondientes intervalos de credibilidad del 95% (ICr) para la incidencia, la tasa de letalidad y la prevalencia entre contactos de la tos ferina, y la cobertura con tres dosis de vacuna contra la difteria, el tétanos y la tos ferina (DTP3). Resultados Se encontraron en total 59 estudios de 15 países que cumplían con los criterios de selección. De ellos, 15 proporcionaban datos sobre incidencia. Siete de estos 15 contenían una definición de caso de tos ferina. La incidencia estimada de tos ferina para el período 1980-1999 fue de 17,8 casos por 100 000 (ICr 95%: 5,9-29,7) y para el período 2000-2015, de 2,5 casos por 100 000 (ICr 95%: 1,8-3,2). En cuanto a la tasa de letalidad, para el período 1980-2015 en 19 estudios examinados fue de 3,9% (ICr 95%: 2,9%-4,9%); en el mismo período, en 5 estudios examinados la prevalencia de tos ferina entre los contactos fue de 24,9% (ICr 95%: 13,7%-36,1%). Las estimaciones combinadas de cobertura con DTP3 en un total de 21 estudios examinados para los siguientes tres períodos fueron: en 1980-1990, 72,4% (ICr 95%: 64,6%-80,2%); en 1991-2000, 79,0% (ICr 95%: 66,1%-91,9%) y en el 2001-2015, 90,0% (ICr 95%: 87,7%-92,3%). Conclusiones Se observó una disminución de la incidencia de la tos ferina y el logro de una cobertura moderadamente alta con la vacuna DTP3 desde principios del siglo XXI. En el examen se subraya la necesidad de incrementar la publicación de datos sobre la tos ferina en los países y en América Latina y el Caribe en su conjunto, para conocer mejor la verdadera carga de enfermedad. La adopción de una definición de caso normalizada y la búsqueda activa de casos ayudarán a obtener estimaciones más precisas de la carga de enfermedad en América Latina y el Caribe.

RESUMO Objetivos Há relatos de que a incidência de coqueluche na América Latina e Caribe (ALC) tem aumentado desde o ano 2000, apesar da alta cobertura vacinal. Realizamos uma revisão sistemática e metanálise da literatura sobre a coqueluche para compreender a carga da doença na ALC. Métodos. Fizemos uma revisão sistemática da literatura usando termos de pesquisa relevantes. Identificamos artigos originais, publicados entre 1980 e 2015, que descrevessem a epidemiologia da coqueluche e a cobertura vacinal na ALC. Aplicando um modelo Bayesiano de efeitos aleatórios para a metanálise, calculamos estimativas agrupadas e seus correspondentes intervalos de credibilidade de 95% (CrIs 95%) para a incidência de coqueluche, a taxa de letalidade, a prevalência de coqueluche entre os contatos e a cobertura com três doses da vacina combinada para difteria, tétano e coqueluche (DTP3). Resultados Identificamos um total de 59 estudos que cumpriram os nossos critérios de seleção, representando 15 países. Destes 59, 15 apresentaram dados sobre a incidência, e 7 dos 15 apresentaram uma definição de "caso de coqueluche". A incidência estimada da coqueluche no período de 1980 a 1999 foi de 17,8 casos por 100.000 pessoas (CrI 95%: 5,9-29,7); no período de 2000 a 2015, foi de 2,5 casos por 100.000 pessoas (CrI 95%: 1,8-3,2). No período de 1980 a 2015, a taxa de letalidade, em 19 estudos revistos, foi de 3,9% (CrI 95%: 2,9%-4,9%); neste mesmo período, em 5 estudos revistos, a prevalência de coqueluche entre os contatos foi de 24,9% (CrI 95%: 13,7%-36,1%). A cobertura vacinal agrupada com DTP3, em um total de 21 estudos examinados nos seguintes três períodos, foi estimada em: 1980 a 1990, 72,4% (CrI 95%: 64,6%-80,2%); 1991 a 2000, 79,0% (CrI 95%: 66,1%-91,9%); 2001 a 2015, 90,0% (CrI 95%: 87,7%-92,3%). Conclusões Foi observada uma redução na incidência de coqueluche e uma cobertura vacinal com DTP3 relativamente alta desde o início da década de 2000. Esta revisão destaca a necessidade de melhorar a publicação de dados sobre a coqueluche ao nível nacional e na ALC como um todo, a fim de promover uma melhor compreensão sobre a verdadeira carga da doença. O uso de uma definição padronizada de "caso de coqueluche" e a busca ativa de casos ajudaria na obtenção de estimativas mais precisas da carga da doença na ALC.