Recomendaciones ALAT para el uso de vacunas respiratorias. Guía de práctica clínica basada en evidencias / ALAT Recommendations for the Use of Respiratory VaccinesEvidence-Based Clinical Practice Guideline

Introducción: Las infecciones respiratorias son las enfermedades respiratorias con mayor mortalidad en el mundo. Las causadas por Streptococcus pneumoniae, virus de influenza, Bordetella pertussis, SARS-CoV-2 y el Virus Sincitial Respiratorio, cuentan hoy día con vacunas seguras y efectivas. Este documento representa una guía de práctica clínica (GPC) de la Asociación Latinoamericana de Tórax (ALAT), elaborada por iniciativa de los departamentos de enfermedades infecciosas y pediatría, con el objetivo de establecer recomendaciones sobre vacunas respiratorias, utilizando la evidencia disponible. Método: Se estableció un grupo de desarrollo de las guías conformado por cinco médicos responsables globales del proyecto, se crearon cinco subgrupos de trabajo, uno por cada vacuna, con expertos neumólogos de adulto, pediatras e infectólogos invitados, que generaron preguntas clínicas. Se trabajó con un grupo de expertos metodólogos que transformaron preguntas clínicas en preguntas PICO, seleccionándose nueve preguntas por método DELPHI. Luego, se utilizó el sistema GRADE (Grading of Recommendations Assessment, Development and Evaluation) para evaluar la evidencia disponible. Resultados: Se obtuvieron recomendaciones para población adulta y pediátrica de las vacunas de neumococo, influenza, tos ferina, COVID-19 y Virus Respiratorio Sincitial basadas en preguntas PICO. También se agregaron recomendaciones basadas en preguntas narrativas relacionadas al uso de vacunas respiratorias en población con enfermedades respiratorias crónicas como asma, EPOC y fibrosis pulmonar.

Introduction: Respiratory infections are the leading cause of respiratory disease-related mortality worldwide. Infections caused by Streptococcus pneumoniae, influenza virus, Bordetella pertussis, SARS-CoV-2 and Respiratory Syncytial Virus (RSV) now have safe and effective vaccines available.This document represents a Clinical Practice Guideline (CPG) by the Latin American Thoracic Association (ALAT), developed through the initiative of the departments of in-fectious diseases and pediatrics, with the goal of establishing recommendations on respiratory vaccines using the available evidence. Method: A guideline development group was established, composed of five lead physicians responsible for the overall project. Five working subgroups were created, one for each vaccine, involving invited experts in adult pulmonology, pediatrics, and infectious diseases, who formulated clinical questions. A group of expert methodologists then transformed these clinical questions into PICO questions, with nine questions selected using the DELPHI method. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was then used to assess the available evidence. Results: Recommendations were obtained for the adult and pediatric populations for pneumococcal, influenza, pertussis, COVID-19 and Respiratory Syncytial Virus vaccines based on PICO questions. Additionally, recommendations based on narrative questions related to the use of respiratory vaccines in populations with chronic respiratory diseases such as asthma, COPD, and pulmonary fibrosis were included.

Programming Bordetella pertussis lipid A to promote adjuvanticity.

BACKGROUND: Bordetella pertussis is the causative agent of whooping cough or pertussis. Although both acellular (aP) and whole-cell pertussis (wP) vaccines protect against disease, the wP vaccine, which is highly reactogenic, is better at preventing colonization and transmission. Reactogenicity is mainly attributed to the lipid A moiety of B. pertussis lipooligosaccharide (LOS). Within LOS, lipid A acts as a hydrophobic anchor, engaging with TLR4-MD2 on host immune cells to initiate both MyD88-dependent and TRIF-dependent pathways, thereby influencing adaptive immune responses. Lipid A variants, such as monophosphoryl lipid A (MPLA) can also act as adjuvants. Adjuvants may overcome the shortcomings of aP vaccines. RESULTS: This work used lipid A modifying enzymes from other bacteria to produce an MPLA-like adjuvant strain in B. pertussis. We created B. pertussis strains with distinct lipid A modifications, which were validated using MALDI-TOF. We engineered a hexa-acylated monophosphorylated lipid A that markedly decreased human TLR4 activation and activated the TRIF pathway. The modified lipooligosaccharide (LOS) promoted IRF3 phosphorylation and type I interferon production, similar to MPLA responses. We generated three other variants with increased adjuvanticity properties and reduced endotoxicity. Pyrogenicity studies using the Monocyte Activation Test (MAT) revealed that these four lipid A variants significantly decreased the IL-6, a marker for fever, response in peripheral blood mononuclear cells (PBMCs). CONCLUSION: These findings pave the way for developing wP vaccines that are possibly less reactogenic and designing adaptable adjuvants for current vaccine formulations, advancing more effective immunization strategies against pertussis.

Seroprevalence of Bordetella pertussis infection in children 1-14 years old: Indonesia basic health research (Riskesdas) 2013 and 2018 data.

Bordetella pertussis infection is a highly contagious respiratory disease that can cause complications such as pneumonia and death. A total of 62,646 cases of pertussis worldwide were reported by WHO in 2022. This study aimed to obtain the pertussis seroprevalence and sociodemographic data in children aged 1-14 years and its association factors in the community based on Riskesdas 2013 and 2018. Bivariate and multivariate analysis was carried out on data from 12,753 children aged 1-14 years collected from Riskesdas 2013 and 2018 in Indonesia. Pertussis serology data was obtained based on the results of the ELISA examination which was categorized as seropositive if anti-pertussis toxin IgG ≥ 100 IU/mL or anti-pertussis IgG > 11 NTU. Pertussis seropositive indicated recent pertussis infection if no pertussis vaccine was received within the last twelve months. Pertussis seroprevalence was found at 9.8% and 33.4% in Riskesdas 2013 and 2018 respectively. While 10.1% of children aged 5-14 years were found pertussis seropositive by excluding the possible effect of vaccination in the last twelve months in Riskesdas 2013. The most important associated factor in seropositive pertussis at ages 1-4 years and 5-14 years was a history of pneumonia in the last month (OR = 2.709, 95%CI: 2.592-2.831 in Riskesdas 2013 and OR = 2.421, 95%CI: 2.299-2.550 in Riskesdas 2018). In the adjusted analysis for respondents' characteristics, low maternal education was the predictive factor that most influenced pertussis seropositivity, especially in the 2013 Riskesdas (APOR = 2.983, 95%CI: 2.670-3.333). In conclusion, the results of this study showed that the seroprevalence of pertussis was high, especially in children aged 5-14 years, so that pertussis vaccine booster administration could be considered. Because the most influencing factor towards pertussis seropositive was low maternal education, the groups of children with low-educated mothers should be targets for strengthening complete vaccination coverage and disease control.

[Factors associated with timely vaccination of pertussis-containing vaccines in children born from 2019 to 2023, Shanghai].

Objective: To analyze factors associated with timely vaccination of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023. Methods: Children born in Shanghai between 2019 and 2023 were selected using a stratified random sampling method, and their vaccination data were obtained from the Shanghai Vaccine Management and Vaccination Service Information System. The vaccination rates, timely vaccination rates, and the proportions of diphtheria-tetanus-acellular pertussis-haemophilus influenzae type b combination vaccine (DTaP-Hib) and diphtheria-tetanus-acellular pertussis-inactivated poliovirus-haemophilus influenzae type b combination vaccine (DTaP-IPV-Hib) for the substitution of diphtheria- tetanus-acellular pertussis vaccine (DTaP) were calculated. Also, the factors associated with timely vaccination rate was analyzed with multivariate logistic regression analysis. Results: The average vaccination coverage rate of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023 ranged from 94.71% to 99.53%. There were significant differences in the vaccination coverage of the 1st-4th doses of pertussis-containing vaccines among children born in different years (all P<0.05), but no gender and area specific significant differences were observed (all P>0.05). Non-national immunization program (non-NIP) vaccines were used to substitute DTaP vaccines in some children, with the proportion of DTaP-IPV-Hib vaccine accounting for 50.11%-52.69% and the proportion of DTaP-Hib vaccine accounting for 27.22%-28.43%. The proportions of DTaP-Hib and DTaP-IPV-Hib for the substitution of DTaP had increasing trends over the years. The overall timely vaccination rate of pertussis-containing vaccine vaccination was 84.09%. Analysis on the factors affecting the timely vaccination rate showed that the rate gradually decreased with the increase of the doses. Children who received the self-paid quadrivalent or pentavalent vaccines were less likely to have vaccination delays. Birth year had a significant impact on the timely vaccination rate, while the area had less impact. Additionally, the timely vaccination rate was also influenced by the degree of non-pharmaceutical intervention measures. Conclusions: The substitution of pertussis- containing vaccines with non-NIP vaccines was common in Shanghai. The coverage and timeliness of pertussis-containing vaccine vaccination were relatively high. The timely vaccination rate was significantly associated with gender, dose, vaccine type, and the degree of non-pharmaceutical interventions. There was a certain proportions of delayed and missed vaccinations, and it is necessary to pay attention to children who are not vaccinated timely and conduct high-quality catch-up vaccination to ensure timely and complete vaccination of pertussis-containing vaccines.

Insights into maternal pertussis vaccination counselling: a qualitative study on perspectives and experiences among midwives and gynaecologists in the Netherlands.

BACKGROUND: Healthcare professionals (HCPs) play a significant role in the decision-making process of pregnant women on maternal vaccinations. Whereas a high proportion of HCPs discuss maternal vaccinations with pregnant women, confidence in discussing maternal vaccinations is lacking and HCPs experience inadequate training to discuss maternal vaccinations with pregnant women. Furthermore, different practical barriers might influence the consultation process, such as lack of time. More studies on the barriers, as well as facilitators, to discussing maternal vaccinations is needed and will help us to better understand and support HCPs in discussing maternal vaccinations. METHODS: This qualitative study involved semi-structured interviews with fourteen HCPs working as midwives or gynaecologists in the Netherlands. An integrated theoretical approach was used to inform data collection and analysis. Thematic analysis was conducted using inductive and deductive approaches. This study followed the COnsolidated criteria for REporting Qualitative research (COREQ) guidelines. RESULTS: The thematic analysis of the data pointed to the following five themes of HCP counselling: the consultation process, attitude, perceived norm, perceived control and improvement ideas. Most HCPs follow a similar approach in maternal pertussis vaccination consultations, beginning by assessing clients' understanding, providing basic information, and addressing questions. However, consultation timing and prioritization vary among HCPs. Challenges in consultations include client requests for clear advice, with HCPs trained to remain neutral, emphasizing client autonomy in decision-making. Most HCPs acknowledge the importance of their consultations in informing pregnant women about maternal pertussis vaccination. CONCLUSIONS: This study offers a confirmation of the awareness of the pivotal role of HCPs in informing pregnant women about the maternal pertussis vaccination. HCPs stress the importance of neutral counselling, enabling pregnant women to make well-informed decisions independently. Because of upcoming vaccine hesitancy nowadays, HCPs must be equipped with the knowledge and confidence to navigate difficult conversations. Continuous education and training might help to increase HCPs' confidence in handling difficult consultations. Additionally, making the information materials for pregnant women available in multiple languages and incorporating more visuals to enhance comprehension could support HCPs in reaching a broader group of pregnant women.

Pertussis outbreak investigation in Likimsa-Bokore kebele, Meda Walebu district, Bale zone, Oromia region, Ethiopia, 2019: a descriptive cross-sectional study.

Introduction: pertussis is a major cause of childhood morbidity and mortality. Globally, an estimated 45 millions cases and 400,000 deaths occur every year. Meda Walebu surveillance office reported a pertussis outbreak among the residents of the Liqimsa-Bokore kebele communities. We investigated to describe the magnitude of the pertussis outbreak in Likimsa-Bokore kebele of Meda-Walebu district, Bale Zone, Southeast Ethiopia. Methods: we conducted a descriptive cross-sectional study in April 2019. We identified pertussis cases recorded on the line list. Suspected cases of pertussis were defined as any resident of Likimsa-Bokore kebele with cough illness and any of the following: paroxysms of coughing, inspiratory whooping, post-tussive vomiting, or apnea. The pentavalent vaccine coverage data were extracted from the Bale zone health management information system department database. Microsoft Excel pivot table and SPSS version 23 software cleaned and analyzed the data. Results: in three months period, a total of 439 suspected cases of pertussis were reported from Likimsa-Bokore kebele of the Meda-Walebu district. Half of the cases 220(50.1%) have occurred in females and the majority of cases 256 (58.3%) occurred in under five years children. The median age of cases was 4 years ranging from 2 months to 30 years (interquartile range= 4 years). The overall Attack Rate (AR) was 55 per 1000 population with a case fatality rate of 0.7% (3 deaths/439). Children less than five years were the most affected age group with an AR of 198 per 1000 population. The administrative pentavalent vaccine coverage of the district was above 100% during the year 2015-2018. Conclusion: the overall attack rate of pertussis outbreak was high. Children under five years were the most affected age group irrespective of high administrative coverage of the pentavalent vaccine. Strengthening routine immunization management and intensified surveillance system is required for early detection, investigation, and response activities.

Global tendency and frontiers of research on pertussis from 2000 to 2023: A bibliometric and visual analysis.

Pertussis has reemerged globally, with rising incidence in China. Controlling this disease remains a significant public health challenge worldwide. This study applies bibliometric methods to analyze global and Chinese research on pertussis, assessing current trends, identifying hot topics, predicting future research directions, and providing guidance for scientific research and clinical practice. Pertussis-related articles from 2000 to 2023 were retrieved from four major Chinese databases and three English databases. COOC and CiteSpace software were used to analyze publication trends, geographic distribution, institutions, disciplines, and keywords, to visualize through network maps. The study analyzed 2,580 Chinese and 5,311 foreign articles and reviews. Pertussis research publications have increased globally, with foreign research peaking earlier than in China. The United States leads in publication volume, while China showed the highest burst of activity from 2019 to 2023. Research mainly focuses on animal experiments, vaccine development and safety, clinical characteristics and treatment, and pertussis toxin. Pertussis research is thriving globally and in China. Future research should emphasize interdisciplinary collaboration across molecular biology, immunology, and epidemiology to innovate vaccines and control strategies. Additionally, continued development of treatment drugs remains crucial as current vaccines do not fully control pertussis.

What Is Pertussis?

This JAMA Patient Page describes pertussis illness, its signs and symptoms, and its diagnosis, treatment, and prevention measures.

Protective Activity and Safety of Experimental Acellular Pertussis Vaccines Based on Antigenic Complexes Isolated from Biofilm and Planktonic Cultures of Bordetella pertussis.

Continued circulation of the whooping cough pathogen, even in countries with high vaccine coverage, can be related to persistence of Bordetella pertussis biofilms in the respiratory tract. The films differ from planktonic cells by increased resistance to the host immune system and antibacterial drugs. The available acellular pertussis vaccines (aPV) containing antigens isolated from planktonic cultures of B. pertussis protect from severe forms of whooping cough, but do not effectively influence circulation of virulent strains in the subclinical forms of the disease and asymptomatic carriage. It is promising to create new generation aPV based on antigens isolated from biofilm cultures of B. pertussis capable of more effectively controlling the entire infectious cycle of whooping cough, including colonization, persistence, and transmission of the pathogen. From antigenic complexes isolated from the culture medium of biofilm and planktonic cultures of the strain B. pertussis No. 317 (serotype 1.2.3), experimental aPV were made: aPV-B and aPV-P, respectively. In intracerebral infection of mice with a virulent strain of B. pertussis, aPV-B demonstrated 2.5-fold higher protective activity than aPV-P and also more effectively reduced colonization of the lungs by B. pertussis cells in mice after intranasal infection with a virulent strain. Both vaccine preparations were safe and did not cause death in mice after administration of histamine.

Pertussis vaccination in adults in France: Overview and suggestions for improvement.

In France, the goal of the pertussis vaccination program is to protect newborns. All infants are vaccinated under the program and then given booster shots up to the age of 25 years. Pregnant women are likewise vaccinated, with the cocooning strategy reserved for infants born to unvaccinated mothers. Real-world data shows (i) inadequate coverage among adolescents and adults under 25; (ii) improper use of the tetanus, diphtheria, and polio (Td/IPV) vaccine in children under six years, adolescents, and young adults; and (iii) underdiagnosis of pertussis in adults. Older patients or those with specific chronic medical conditions are at risk of developing severe disease. Improving the diagnosis and surveillance of pertussis in adults and seniors would be one of the first steps in the right direction. Aligning pertussis vaccination in adults with the Td/IPV program (boosters at 45, 65 years of age, and then every 10 years) would make the vaccination schedule simpler, easier to understand, and easier to implement. Large-scale awareness campaigns targeting this population would increase coverage, thereby boosting the effectiveness of the other measures.

Timing of pertussis vaccination during pregnancy: Evidence and implementation - A systematic review.

BACKGROUND: Pertussis vaccination in pregnancy has been introduced in an increasing number of countries to better protect infants against the disease in their first weeks of life. The optimal timing of pertussis vaccination in pregnancy is however still under debate. METHODS: We systematically reviewed published literature on safety, immunogenicity and effectiveness of pertussis vaccination in pregnancy related to timing of vaccination. The search was conducted using PubMed, MEDLINE and Web of Science and yielded 1623 articles, thereof 777 duplicates. Screening resulted in the inclusion of 45 publications reporting on safety (n = 11), immunogenicity (n = 26) and/or effectiveness (n = 9). We also mapped pertussis recommendations in pregnancy by government institutions globally according to the recommended timing of vaccination. RESULTS: Overall, the selected publications did not indicate increased safety concerns associated with timing of pertussis vaccination in pregnancy. Immunogenicity studies often suggested optimal protection at birth after early third trimester vaccination. Few studies investigated qualitative antibody characteristics, and none investigated antibody titers in breastmilk or cellular-mediated immunity related to timing of vaccination. Effectiveness studies showed decreased vaccine effectiveness of late third trimester pertussis vaccination compared to vaccination earlier in pregnancy. Worldwide, a general recommendation for pertussis vaccination in pregnancy was found for 58 countries, with as many as 22 different recommended timings registered. CONCLUSION: The timing of pertussis vaccination in pregnancy seems to impact immunogenicity and vaccine effectiveness, with optimal immune responses at birth suggested following early third trimester vaccination and reduced vaccine effectiveness of late third trimester pertussis vaccination suggested compared to vaccination earlier in pregnancy. However, inconsistent and lacking data are reflected in the divergent national recommendations for pertussis vaccination in pregnancy worldwide. SUMMARY: Pertussis vaccination in pregnancy aims to protect infants in their first weeks of life. Our review suggests that immunogenicity and vaccine effectiveness are impacted by the timing of vaccination in pregnancy. National recommendations for pertussis vaccination in pregnancy vary widely worldwide.

Rising pertussis cases and deaths in China: current trends and clinical solutions.

Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently experienced a dramatic increase in incidence and associated deaths in China, drawing significant clinical attention. This article retrospectively analyzes national data on pertussis incidence and mortality from 2010 to 2024, exploring potential factors contributing to this trend. It also discusses strategies for enhancing vaccination programs, improving early diagnosis and treatment, and optimizing the clinical management of high-risk infants, with the aim of addressing the challenges posed by the current pertussis epidemic.

Pertussis vaccine effectiveness following country-wide implementation of a hexavalent acellular pertussis immunization schedule in infants and children in Panama.

Despite high pediatric vaccination coverage rates (VCRs), pertussis incidence has increased worldwide, including in several countries in Latin America in the last two decades. Given the few vaccine effectiveness (VE) studies in Latin American countries, this retrospective, observational, cohort study estimated the effectiveness of hexavalent acellular (aP) primary and booster vaccination (wP) against pertussis in infants (6.5-18.5 months) and children (18.5-48.5 and 48.5-72.5 months) in Panama. Age-specific incidence rates (IRs) were calculated for the vaccine's pre-initiation (2001-2013), initiation (2014), and post-initiation (2015-2019) periods. VCRs and trends were determined, and VE was analyzed using a case coverage or screening method to compare proportions of vaccinated cases and vaccinated individuals in the population. Between 2001-2019, 868 confirmed pertussis cases were reported in Panama; 712 (82.0%; 54.8 cases/year) during the pre-initiation period, 19 (2.2%; 19 cases/year) during the initiation period, and 137 (15.8%; 27.4 cases/year) during the post-initiation period. Panama underwent cyclical increases in IRs, which varied between age groups. VCRs increased for primary and booster doses. Between 2015 and 2019, third-dose yearly vaccine coverage increased, on average, 3.3%. Specifically, during the post-initiation period, 109/137 (79.6%) of cases were unvaccinated. Relative VE was estimated at 96.2% [95% CI: 86.5%, 98.9%] with three doses; 100% with 4 and 5 booster doses. Absolute VE was estimated at 99.3% with three doses only. These results show that vaccination played an important role in maintaining a low number of pertussis cases in Panama, affirming the need for sustained investment and commitment to vaccination programs.

Promotion and COVID-19 lockdown increase uptake of funded maternal pertussis vaccination in pharmacy: A mixed methods study.

Pertussis vaccination is recommended during pregnancy to protect the baby. Pertussis vaccination was initially free to pregnant people through general practice and hospitals in New Zealand, but uptake was suboptimal. In one district funding of maternal pertussis vaccination was widened to community pharmacies in 2016. Eighteen months later promotion to pharmacies, midwives and pregnant people took place. In 2020 and 2021, COVID-19 lockdowns occurred. AIM: To explore the effects of promotion and COVID-19 lockdowns on uptake of funded maternal pertussis vaccination in pharmacy, and awareness, use and opinions of promotional elements. METHODS: Five years of pharmacy claims data were analysed and 12 pharmacists, 18 people eligible/recently eligible for maternal pertussis vaccination and 11 midwives were interviewed. RESULTS: Provision of maternal pertussis vaccination increased during and after promotion. Qualitative data showed that pharmacists valued phone calls with information about maternal pertussis vaccination and recommendations for increasing uptake. Prompted by these calls, some pharmacists contacted midwives to inform them of funded maternal pertussis vaccination in the pharmacy (which midwives appreciated) and recommended pertussis vaccination to pregnant clients. Pharmacy staff reportedly were motivated to recommend this vaccination by being informed about it and having posters displayed in the pharmacy. Pregnant people valued healthcare professionals' conversations about maternal pertussis vaccination, but appeared to be uninfluenced by posters and promotional social media posts about this vaccination. During COVID-19, maternal pertussis uptake in pharmacies increased 31% March to May 2020 (before and during the first COVID-19 lockdown) versus the same time the previous year, then declined. CONCLUSION: Promotion appeared to have a sustained effect on uptake of maternal pertussis vaccination in pharmacies. Pregnant people were most influenced by discussions with healthcare professionals. Pharmacists and pharmacy staff increased proactivity with maternal vaccinations after promotion to them. Promotion may need to be repeated over time.