[Clinical characteristics of pertussis in hospitalized children under 3 months].

Demographic data and clinical data were collected retrospectively from patients with pertussis at the Children's Hospital Affiliated to the Capital Institute of Pediatrics between March 2011 and February 2023. Among the 270 hospitalized patients, 151 cases were male and 119 were female. The youngest age of admission was 10 days and the eldest age of admission was 11 years. The 270 hospitalized patients were divided into two groups according to onset age: <3 months (n=143) and≥3 months (n=127). For those in the <3-month-old group, the incidence of severe pneumonia and severe pertussis were 21.0% and 38.5%, respectively, both were significantly higher than those in≥3-month-old group (7.9% and 11.0%, both P<0.05). For those in the <3-month-old group, paroxysmal spasmodic cough, post-tussive vomiting, paroxysmal cyanosis, apnea, and decreased heart rate after coughing were 86.7%, 25.2%, 38.5%, 7.0% and 16.8%, respectively, all were significantly higher than those in ≥3-month-old group (76.4%, 10.2%, 15.7%, 1.6% and 1.6%, all P<0.05). For those in the<3-month-old group, the incidence of hypoxemia, respiratory failure, were 36.4%, 16.8%, respectively, and both were significantly higher than those in≥3-month-old group (10.2%, 7.1%, P<0.05). It indicated that among the infants under 3 months, the incidence of vomiting after coughing, paroxysmal cyanosis, apnea, hypoxemia, respiratory failure, decreased heart rate after coughing and severe pneumonia were significantly higher than those above 3 months. Infants under 3 months were prone to severe pertussis.

Facilitators and barriers to vaccination uptake in pregnancy: A qualitative systematic review.

INTRODUCTION: Vaccination during pregnancy protects both the mother and the foetus from vaccine-preventable diseases. However, uptake of the recommended vaccines (influenza, pertussis, COVID-19) by pregnant women remains low in Europe and the USA. Understanding the reasons for this is crucial to inform strategies to increase vaccination rates in pregnant women. This qualitative systematic review aimed to identify the barriers and facilitators to vaccination against influenza, pertussis/whooping cough and COVID-19 during pregnancy and identify possible strategies to increase vaccination rates. METHODS: We conducted a comprehensive search of electronic databases, including Medline, PsycINFO, CINAHL, Web of Science, WHO database, Embase and grey literature to identify qualitative studies that explored barriers and facilitators to vaccine uptake among pregnant women (PROSPERO CRD42023399488). The search was limited to studies published between 2012 and 2022 conducted in high-income countries with established vaccination programmes during pregnancy. Studies were thematically analysed and underwent quality assessment using the Joanna Briggs Institute validated critical appraisal tool for qualitative research. RESULTS: Out of 2681 articles screened, 28 studies (n = 1573 participants) were eligible for inclusion. Five overarching themes emerged relating to personal, provider and systemic factors. Barriers to vaccine uptake included concerns about vaccine safety and efficacy, lack of knowledge about vaccines' benefits and necessity, fear of adverse effects on the foetus or mother and low perception of disease severity. Facilitators included recommendations from trusted healthcare providers, easy access to vaccination, clear communication on the benefits and safety of vaccination, and positive social influences from family and friends. Strategies for increasing vaccination uptake included strong and proactive vaccine recommendations by trusted healthcare professionals, provision of vaccines during routine antenatal care, and clear and consistent communication about vaccines addressing pregnant women's concerns. CONCLUSION: This review highlights the need for interventions that address the identified barriers to vaccine uptake among pregnant women. Recommendation from a healthcare provider can play a significant role in promoting vaccine uptake, as can clear risk/benefit communication and convenient access to vaccination. Addressing concerns about vaccine safety and providing accurate information about vaccines is also important.

Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response.

For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMVBp) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMVBp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMVBp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMVBp and the immunogens at varying levels. These assays demonstrated that OMVBp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMVBp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMVBp, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMVBp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMVE.coli) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it's crucial to highlight that OMVBp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMVBp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.

Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded, randomized, parallel-group study.

OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).

[Guidelines for diagnosis and management and prevention of pertussis of China (2024 edition)].

Pertussis re-emergence is a global public health concern. The reported incidence of pertussis in China from 2018 to 2022 was comparable to that in the late 1980s. In fact, the incidence of pertussis is still significantly underestimated in China, owing to a lack of comprehensive active pertussis surveillance, missed diagnosis of atypical pertussis cases, and the fact that many medical institutions do not perform pertussis laboratory diagnosis. Meanwhile, China is also faced with the clinical issue that Bordetella pertussis is highly resistant to first-line macrolide treatment. To better guide and standardize the clinical diagnosis, treatment, monitoring, prevention and control of pertussis cases in China, a multidisciplinary guideline development group comprised of experts in infectious diseases, epidemiology, immunization planning and guideline methodology proposed 12 clinical issues related to the diagnosis, treatment and prevention, especially vaccine immunization strategies from a practical perspective. Through research question construction, evidence retrieval and synthesis, evidence appraisal and evidence-to-decision discussion, recommendations and implementation suggestions were formulated to provide references for clinical physicians engaged in the diagnosis and management of pertussis, microbiological laboratory professionals, hospital infection control professionals, and public health professionals involved in infectious disease prevention, control and immunization planning.

Global vaccine coverage and childhood survival estimates: 1990-2019.

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019. Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines. Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction). Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.

Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations.

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

Factors associated with pregnant women's willingness to receive maternal pertussis vaccination in Guizhou Province, China: An exploratory cross-sectional study.

The rise in pertussis incidence among infants in Guizhou, China underscores the need for maternal acellular pertussis vaccine (aP) immunization, a key strategy in protecting infants from severe health consequences. However, the willingness of pregnant women in Guizhou to receive this vaccine is not well-understood. This study aimed to explore pregnant women's intentions toward maternal pertussis vaccination in Guizhou and identify the associated factors. A questionnaire based on the health belief model, was administered in an exploratory cross-sectional study from January to February 2022. Data from 564 participants were collected and analyzed. The chi-square test, Mann-Whitney U test, and Poisson regression were used to identify potential factors associated with vaccination intentions. Participants' median age was 27 y (interquartile range (IQR): 24-31), and the median number of children per participant was one. The study found that only 36.0% of the participants intended to receive the aP vaccine while 64.0% were uncertain or negative in this regard. Significant factors associated with intentions to vaccinate included perceived barriers and cues for action and perceived benefits. The major barriers for low vaccination intentions were safety concerns for both the fetus and the mother, and family members' negative attitudes. Free vaccines, perceiving preventive benefits, observing other pregnant women getting vaccinated, and healthcare provider recommendations may facilitate vaccination intentions. Multiple immune strategies should be developed or optimized to cope with the resurgence of pertussis.

Pertussis epidemic in Denmark, August 2023 to February 2024.

We report a record high pertussis epidemic in Denmark since August 2023. Highest incidence was in adolescents, while peak incidence in infants was lower vs previous epidemics in 2019 and 2016. Among infants aged 0-2 months, over half (29/48) were hospitalised and one infant died, underlining the disease severity in the youngest. To protect infants, pertussis vaccination in pregnant women was introduced in January 2024 in the national vaccination programme. Improved vaccination surveillance in pregnant women is being implemented.

Reemergence of Bordetella parapertussis, United States, 2019-2023.

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.

Vacunación en el embarazo. Documento de consenso del CAV-AEP y la SEGO / Vaccination in pregnancy. Consensus document of the CAV-AEP and the SEGO

Durante el embarazo, los cambios fisiológicos en la respuesta inmunitaria favorecen que las gestantes sean más susceptibles a infecciones graves, tanto para ellas como para el feto, el recién nacido y el lactante. Todas las mujeres deberían entrar en el período reproductivo con su calendario vacunal correctamente cumplimentado, sobre todo en lo que respecta a enfermedades como tétanos, hepatitisB, sarampión, rubeola y varicela. Además de las vacunas recomendadas, en situaciones de riesgo las vacunas inactivadas podrían ser administradas en aquellas mujeres que no estuvieran correctamente inmunizadas con anterioridad, mientras que las atenuadas están contraindicadas.A pesar de que la vacunación durante el embarazo es una medida preventiva muy importante, y de las recomendaciones de autoridades sanitarias, sociedades científicas y profesionales sanitarios, las coberturas vacunales son claramente mejorables, especialmente en lo que respecta a gripe y COVID-19, por lo que todo profesional sanitario que atienda a la embarazada debe ser proactivo en aconsejarlas.La Asociación Española de Pediatría (AEP), a través de su Comité Asesor de Vacunas (CAV), y la Sociedad Española de Ginecología y Obstetricia (SEGO) recomiendan las siguientes vacunaciones durante la gestación: frente a gripe y COVID-19, en cualquier trimestre del embarazo, y durante el puerperio (hasta los 6meses) en aquellas que no hubieran sido vacunadas durante la gestación; frente a tosferina con Tdpa, entre las 27 y 36 semanas de gestación (el CAV-AEP da preferencia entre las 27 y 28 semanas); y frente al VRS con RSVPreF, entre las 24 y 36 semanas de gestación, de preferencia entre las 32 y 36 semanas. (AU)

During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitisB, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated.Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines.The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines (CAV), and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36. (AU)

Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis.

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.

Seroprevalence of tetanus and pertussis antibodies among health care workers in Wuhu, China.

This study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People's Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20-29 age group, followed by the 30-39 age group (10.57%), 40-49 age group (5.80%), and 50-59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20-39 age group and 40-59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

Immunogenicity at delivery after Tdap vaccination in successive pregnancies.

Background: Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination. Methods: Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay. Results: In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy. Conclusion: This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.

Promoting informed decision making about maternal pertussis vaccination: the systematic development of an online tailored decision aid and a centering-based group antenatal care intervention.

Introduction: Maintaining and enhancing vaccine confidence continues to be a challenge. Making an informed decision not only helps to avoid potential future regret but also reduces susceptibility to misinformation. There is an urgent need for interventions that facilitate informed decision-making about vaccines. This paper describes the systematic development of two interventions designed to promote informed decision making and indirectly, acceptance of maternal pertussis vaccination (MPV) in the Netherlands. Materials and methods: The 6-step Intervention Mapping (IM) protocol was used for the development of an online tailored decision aid and Centering Pregnancy-based Group Antenatal Care (CP) intervention. A needs assessment was done using empirical literature and conducting a survey and focus groups (1), intervention objectives were formulated at the behavior and determinants levels (2), theoretical methods of behavior change were selected and translated into practical applications (3), which were further developed into the two interventions using user-centered design (4). Finally, plans were developed for implementation (5), and evaluation (6) of the interventions. Results: The needs assessment showed that pregnant women often based their decision about MPV on information sourced online and conversations with their partners, obstetric care providers, and peers. Responding to these findings, we systematically developed two interactive, theory-based interventions. We created an online tailored decision aid, subjecting it to four iterations of testing among pregnant women, including those with low literacy levels. Participants evaluated prototypes of the intervention positively on relevance and usability. In addition, a CP intervention was developed with midwives. Conclusion: Using IM resulted in the creation of an online decision aid and CP intervention to promote informed decision making regarding MPV. This description of the systematic development of the interventions not only serves to illustrate design rationales, it will also aid the interpretation of the evaluation of the interventions, the development of future interventions promoting informed decision and acceptance of vaccines, and comparisons with other interventions.

Strengthening Bordetella pertussis genomic surveillance by direct sequencing of residual positive specimens.

Whole-genome sequencing (WGS) of microbial pathogens recovered from patients with infectious disease facilitates high-resolution strain characterization and molecular epidemiology. However, increasing reliance on culture-independent methods to diagnose infectious diseases has resulted in few isolates available for WGS. Here, we report a novel culture-independent approach to genome characterization of Bordetella pertussis, the causative agent of pertussis and a paradigm for insufficient genomic surveillance due to limited culture of clinical isolates. Sequencing libraries constructed directly from residual pertussis-positive diagnostic nasopharyngeal specimens were hybridized with biotinylated RNA "baits" targeting B. pertussis fragments within complex mixtures that contained high concentrations of host and microbial background DNA. Recovery of B. pertussis genome sequence data was evaluated with mock and pooled negative clinical specimens spiked with reducing concentrations of either purified DNA or inactivated cells. Targeted enrichment increased the yield of B. pertussis sequencing reads up to 90% while simultaneously decreasing host reads to less than 10%. Filtered sequencing reads provided sufficient genome coverage to perform characterization via whole-genome single nucleotide polymorphisms and whole-genome multilocus sequencing typing. Moreover, these data were concordant with sequenced isolates recovered from the same specimens such that phylogenetic reconstructions from either consistently clustered the same putatively linked cases. The optimized protocol is suitable for nasopharyngeal specimens with diagnostic IS481 Ct < 35 and >10 ng DNA. Routine implementation of these methods could strengthen surveillance and study of pertussis resurgence by capturing additional cases with genomic characterization.