Seroprevalence of IgG antibodies against pertussis toxin in the Chinese population: A systematic review and meta-analysis.

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.

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.

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.

Economic burden of pertussis in children: A single-center analysis in Hangzhou, China.

The "reemergence of pertussis" has elicited international concerns, occurring paradoxically amidst the expansion of immunization programs. This study was aimed to evaluate quantitatively the economic burden and identify the determinants that influence the cost associated with treating pertussis in Chinese children. We evaluated the economic burden by Chinese children diagnosed with pertussis at the Children's Hospital, Zhejiang University School of Medicine in 2022. Direct medical expenses and the utilization of medical resources attributed to pertussis were calculated. A generalized linear regression model was applied to analyze the determinants that were associated with the direct medical expenses among patients. Among the 1110 pertussis patients included in the study, 1060 were outpatients and 50 were inpatients. The average direct medical cost was ¥1878.70(i.e. $279.33). Living in urban areas (OR:1.27, p = .04), complications (OR:1.40, p < .001), hospitalization (OR:10.04, p < .001), and ≥ 3 medical visits (OR:3.71, p < .001) were associated with increased direct medical expenses. Having received four doses of the pertussis vaccine was associated with reduced direct medical expenses (OR:0.81, p = .04). This study underscores a substantial economic burden of pertussis in Hangzhou, with pronounced implications for patients residing in urban areas, experiencing complications, requiring hospitalization, having multiple medical consultations, or lacking comprehensive pertussis vaccination.

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.

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.

Quantitative analysis of pertussis, tetanus, and diphtheria antibodies in sera and breast milk from Tdap vaccinated women using a qualified multiplex assay.

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

The seroepidemiology of immunoglobulin G antibodies against pertussis toxin and filamentous hemagglutinin in the east of China during the COVID-19 pandemic.

This study employed sero-epidemiological methods to estimate the incidence of pertussis within a healthy population located in eastern China. The aim was to gain deeper insights into the epidemiological characteristics and burden of pertussis within the country. Blood samples were collected from healthy individuals in Jiangsu Province between June 2019 and December 2022. The levels of IgG antibodies against pertussis toxin (anti-PT) and filamentous hemagglutinin (anti-FHA) in the serum were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). Additionally, pertussis case data reported in Jiangsu Province were collected from the China Information System for Disease Control and Prevention and compared with the results of this study. In 2022, the reported incidence of pertussis stood at 1.0 per 100,000 individuals, marking the highest rate observed in the past two decades. Among 1,909 patients examined, the geometric mean concentration (GMC) of anti-PT IgG antibody was 20.2 (18.5-21.9) IU/ml, while that of anti-FHA IgG antibody was 27.0 (25.4-28.7) IU/ml. The IgG-PT and IgG-FHA seropositivity rate (>20.0 IU/ml) was highest in the 1 ~ 2 y old group and decreased rapidly to the lowest in the 3 ~ 4 y old group and then increased gradually with age. The estimated rate of pertussis infection based on seroprevalence was approximately 25,625-fold higher than the reported notification rate in the ≥15 year age group. Our findings highlight decreased immunity post-vaccination, stressing the importance of additional booster shots for adolescents and adults to maintain immunity and reduce severe illness. Additionally, they offer vital guidance for policymakers to enhance immunization strategies.

Maternal Vaccination in Pregnancy: An Assessment of Influenza, Pertussis, and COVID-19 Vaccination Rates in Cracow, Poland.

BACKGROUND Maternal vaccination during pregnancy reduces the risk of severe course and complications from infections both for the mother and her child. As information regarding immunization status of pregnant women with recommended vaccines in Poland is scarce, this questionnaire-based study aimed to identify influenza, pertussis (whooping cough), and COVID-19 vaccination in 205 pregnant women in Cracow, Poland, between February and April 2023. Another objective was to assess whether any of the maternal factors might influence women's decision to inoculate during pregnancy. MATERIAL AND METHODS An anonymous and self-reported questionnaire developed specifically for this study was disseminated among postpartum women, who gave birth and were hospitalized at the Department of Obstetrics and Perinatology of the University Hospital in Cracow, Poland, between February and April 2023. Study participants were asked about their basic sociodemographic and obstetric data, as well as their immunization status regarding influenza, pertussis, and COVID-19 during their most recent pregnancy. RESULTS Only 12.2% and 23.4% of study participants received influenza and pertussis vaccinations, respectively, during pregnancy, while 61.5% of pregnant women reported vaccination with at least 2 doses of the mRNA COVID-19 vaccine. Features including type of occupation, place of residence, gravidity, and parity were statistically significant (P.

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.

Vaccination during pregnancy and modulation of IgG response to pertussis vaccines in infants: The impact of different vaccine formulations.

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.

Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: Results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 - December 2019.

BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.

Reduced pertussis disease severity in infants following the introduction of pertussis vaccination of pregnant women in Spain, 2015-2019.

BACKGROUND: Maternal pertussis vaccination during the third trimester of pregnancy was implemented in 2015 in Spain, reaching a national coverage of 84% in 2019. In this ecological study, we investigated whether there was a change in the disease severity for pertussis in infants upon introduction of prenatal pertussis vaccination. METHODS: We performed a time-trend analysis of infant pertussis hospitalizations during 2005-2019 in Spain using national register data. Annual hospitalization rates per 100,000 population and the mean length of hospitalization were calculated for infants < 3 months of age (target group benefiting from the prenatal vaccination) and a reference group aged 3-11 months. We compared overall rates and annual percent changes of the above variables in both groups for the time period before (2005-2014) and after vaccination introduction (2015-2019), using segmented Poisson regression. RESULTS: During the pre-vaccination period, infants aged 0-2 months had a 5-times higher rate of pertussis hospitalization and spent on average 50 % longer in hospital than the reference group. After the maternal vaccination introduction, the hospitalization rate decreased more rapidly in infants aged 0-2 months than in infants aged 3-11 months: annual reduction of 34 % (95 % CI: 31-38) versus 26 % (95 % CI: 21-31) in the hospitalization rate and 13 % (95 % CI: 11-15) versus 6 % (95 % CI: 2-9) in the mean hospital stay, respectively. In 2019, the mean hospital stay for pertussis was about 4.5 days in both groups. CONCLUSIONS: Maternal pertussis vaccination in Spain led to a reduction in disease severity in the target group as compared to older infants, highlighting the need for increased efforts on educating healthcare professionals on the importance of maternal vaccinations.