Pertussis outbreak in neonates and young infants across Italy, January to May 2024: implications for vaccination strategies.

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.

Predictors of maternal pertussis vaccination acceptance among pregnant women in Norway.

Maternal vaccination against pertussis is safe and provides effective protection against pertussis for the newborn, but the vaccine coverage rate remains generally low. Norway is currently planning for introduction of routine maternal pertussis vaccination. To assess maternal pertussis vaccination acceptance among pregnant Norwegian women, we surveyed women at 20-40 weeks gestation in 2019. Among the 1,148 pregnant women participating in this cross-sectional study, 73.8% reported they would accept pertussis vaccination during pregnancy if it was recommended, 6.9% would not accept and 19.2% were undecided. Predictors for low likelihood of accepting pertussis vaccination during pregnancy included low confidence in health authorities and in maternal pertussis vaccination safety and effectiveness, low awareness and adherence to influenza vaccination during pregnancy, and low awareness of pertussis vaccination. The major reasons reported for not accepting or being undecided about maternal pertussis vaccination were lack of information on vaccine safety for both mother and child. Most women reported that they would consult their general practitioner or a midwife for information if they were offered maternal pertussis vaccination. General practitioners and midwives were also regarded as the most trustworthy sources of information if the women were in doubt about accepting vaccination. We conclude that information addressing safety concerns and raising awareness about maternal pertussis vaccination could increase acceptance of maternal pertussis vaccination. Our findings highlight the pivotal role of the antenatal and primary health care services in providing such information to pregnant women.

Increase of pertussis cases in the Vallès region, Catalonia, Spain, September 2023 to April 2024.

We describe a pertussis outbreak in the Vallès region of Catalonia, from September 2023 to April 2024. Incidence was high in children aged 10-14 years compared with previous outbreaks. Limited impact in newborns could be explained by the high vaccination coverage during pregnancy and at 11 months of age in 2022, at 85% and 94.1 %, respectively. A third booster vaccine dose during preadolescence should be considered and vaccination coverage in pregnant women be improved to control future outbreaks.

High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response.

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Seroepidemiology of pertussis in Huzhou: A population-based, cross-sectional study.

PURPOSE: The resurgence of pertussis has occurred around the world. However, the epidemiological profiles of pertussis cannot be well understood by current diseases surveillance. This study was designed to understand the seroepidemiological characteristics of pertussis infection in the general population of Huzhou City, evaluate the prevalence infection of pertussis in the population, and offer insights to inform adjustments in pertussis prevention and control strategies. METHODS: From September to October 2023, a cross-sectional serosurvey was conducted in Huzhou City, involving 1015 permanent residents. Serum samples were collected from the study subjects, and pertussis toxin IgG antibodies (Anti-PT-IgG) were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The analysis included the geometric mean concentration (GMC) of Anti-PT-IgG, rates of GMC≥40IU/mL, ≥100IU/mL, and <5IU/mL. Stratified comparisons were made based on age, vaccination history, and human categories. RESULTS: Among the 1015 surveyed individuals, the geometric mean concentration (GMC) of Anti-PT-IgG was 10.52 (95% CI: 9.96-11.11) IU/mL, with a recent infection rate of 1.58%, a serum positivity rate of 11.43%, and a proportion with <5IU/mL of 40.49%. Among 357 children with clear vaccination history, susceptibility decreased with an increasing number of vaccine doses (Z = -6.793, P < 0.001). The concentration of Anti-PT-IgG exhibited a significant post-vaccination decline over time (Z = -5.143, P < 0.001). In women of childbearing age, the GMC of Anti-PT-IgG was 7.71 (95% CI: 6.90-8.62) IU/mL, with no significant difference in susceptibility among different age groups (χ2 = 0.545, P = 0.909). The annual pertussis infection rate in individuals aged ≥3 years was 9321 (95%CI: 3336-16039) per 100,000, with peak infection rates in the 20-29, 40-49, and 5-9 age groups at 34363 (95%CI: 6327-66918) per 100,000, 22307.72 (95%CI: 1380-47442) per 100,000, and 18020(95%CI: 1093-37266) per 100,000, respectively. CONCLUSIONS: In 2023, the actual pertussis infection rate in the population of Huzhou City was relatively high. Vaccine-induced antibodies exhibit a rapid decay, and the estimated serum infection rate increases rapidly from post-school age, peaking in the 20-29 age group. It is recommended to enhance pertussis monitoring in adolescents and adults and refine vaccine immunization strategies.

Severe pertussis in infants: a scoping review.

BACKGROUND: Pertussis (Whooping Cough) is a respiratory infection caused by Bordetella pertussis. Pertussis usually occurs in childhood; severe infections are most common in infants. It can be fatal with severe complications such as pulmonary hypertension, heart failure, and encephalitis. OBJECTIVES: We sought to synthesize the existing literature on severe pertussis in infants and inform further study. METHODS: A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in Pubmed and Embase databases, with no restrictions on the language and date of publication. RESULTS: Of the 1299 articles retrieved, 64 were finally included. The selected articles were published between 1979 and 2022, with 90.6% (58/64) of the studies in the last two decades. The studies covered epidemiology, pathology, clinical characteristics, risk factors, treatments, and burden of disease. CONCLUSION: The literature reviewed suggests that studies on severe pertussis in infants covered a variety of clinical concerns. However, these studies were observational, and experimental studies are needed to provide high-quality evidence.

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.

fim3-24/ptxP-3 genotype is associated to whooping cough outbreak in Brazilian Midwest: The selection of Bordetella pertussis strains driven by vaccine immunization.

Whopping cough (or Pertussis) is an acute infectious respiratory disease caused by Bordetella pertussis bacteria. The disease is highly transmissible and can be fatal in children under two years old. Since the introduction of vaccine immunization in 1940, Pertussis incidence decreased worldwide. In Brazil, the immunization was introduced in 1977 using the whole cell (wP) vaccine. Despite the high vaccination coverage, an unexpected increase in the number of observed Pertussis cases was observed in 2012. In this year, 2257 cases were reported exceeding the average incidence rate of <1000 cases per year until 2010. This outbreak reached a peak level in 2014 and ended in 2018 according to the Brazilian National Surveillance System (SINAN). To understand the relationship between the outbreak and the vaccination, bacterial isolates (n = 136) from the Brazilian Midwest region obtained during the outbreak were submitted to genotyping of two vaccine loci: ptxP and fim3. Most of isolates (102) were obtained from nursing children (29 days to 2 years old). Genotyping of 94 isolates revealed that fim3-24/ptxP-3 was the most prevalent genotype (68%) associated with the outbreak peak. Two additional genotypes were also observed: fim3-1/ptxP-3 (15%) and fim3-3/ptxP-3 (17%). Conversely, the fim3-1/ptxP-2 genotype, which is harbored by the strain used in the wP vaccine (Bp137), was not observed. These results showed that B. pertussis circulating strains in the outbreak analyzed were different from the strain used for Pertussis immunization in Brazil. These observations provide insights that could be used to target vaccination programs to prevent future whooping cough outbreaks in Brazil.

[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.

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.

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.

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.