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Background: Vaccination during pregnancy with tetanus, diphtheria, acellular pertussis (aP) (Tdap) anti-gens is important for early protection of newborn infants against pertussis, particularly for preterm infants. This study evaluated the effect of Tdap vaccination during pregnancy on the immunogenicity of a diphtheria (D), tetanus (T), aP, inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influen-zae type b (PRP ti T) vaccine in term and preterm populations.Methods: A prospective, observational study (NCT02511327) recruited women and their infants based on delivery (term or preterm) and vaccination status (vaccinated with a Tdap vaccine [BoostrixTM, GlaxoSmithKline] during pregnancy or not vaccinated in the last 5 years). All infants received licensed DTaP-IPV-HB-PRP ti T (HexyonTM, Sanofi) (8, 12, 16 week primary series and booster at 13 months of age [preterm infants] or 15 months of age [term infants]). Immunogenicity was evaluated using validated assays. Data were pooled into term (N = 127) and preterm infants (N = 105), and infants of women who received a Tdap vaccine during pregnancy (N = 199) or not (N = 33).Results: Before primary vaccination, antibody levels were higher for term than preterm infants for anti-D, anti-polio 1, 2, 3, anti-PT, anti-FHA, and anti-PRP, and similar for anti-HBs and anti-T. At this time, infants of Tdap-vaccinated women had higher anti-D, anti-T, anti-PT, anti-FHA, and anti-PRP antibody levels than infants of Tdap-unvaccinated women; anti-HBs and anti-polio antibody levels were similar in both groups. Post-primary, pre-booster, and post-booster, there were only small differences in seroprotection rates (anti-D, anti-T, anti-polio 1, 2, 3, anti-HBs, anti-PRP) and seroconversion rates (anti-PT, anti-FHA), except for anti-HBs >= 10 mIU/mL and anti-PRP >= 0.15 lg/mL post-primary vaccination (higher for term [98.31 % and 90.91 %, respectively] versus preterm infants [89.80 % and 79.41 %, respectively]).Conclusions: These data support the use of DTaP-IPV-HB-PRP ti T vaccine for primary and booster vacci-nation in term and preterm born infants and in infants born to Tdap-vaccinated or Tdap-unvaccinated women.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Vaccine recommendations for healthcare workers (HCW) aim to protect them and reduce transmission to susceptible patients. We conducted a national randomised survey in 2019 whose main objectives were to estimate national vaccination coverage (VC) for measles, pertussis, varicella, and influenza in HCW working in healthcare facilities (HCF) in France, and to identify determinants associated with higher VC.We performed a cross-sectional survey of physicians, nurses, midwives and nursing assistants in HCF using a random stratified three-stage sampling design. Data were collected during face-to-face interviews using a tablet computer and complemented with information from the individual HCW vaccination records. We investigated possible determinants of higher VC using univariate and multivariate Poisson regressions and estimated the prevalence ratio (PR).We included 8594 HCW working in 167 HCF. Self-declared VC was 73.3% (CI95%: 71.0-75.5) for measles in HCW with no history of measles (at least one dose), 53.5% (49.9-57.0) for pertussis (booster dose during adulthood), 26.4% (23.0-30.2) for varicella in HCW with no history of varicella (at least one dose) and 34.8% (32.8-37.4) for influenza. Taking into account the history of each disease and related VC, 14.6% and 10.1 % of HCW were susceptible to measles and varicella. VC varied by profession, age group, ward and sex. Higher influenza VC was observed in HCW working in wards where i) there was a staff vaccination contact person (PRa: 1.2, CI95% 1.1-1.4), ii) staff vaccination was organized in the ward (1.4: 1.2-1.6), iii) information on influenza vaccines was provided (1.2: 1.1-1.4), and iv) the ward manager supported the HCW vaccination campaign (1.3: 1.1-1.6).Over a 10-year period, VC for HCW working in HCF improved in France. However, vaccination objectives were not achieved for measles (95%) or influenza (80%). Vaccination efforts should be continued, especially in wards with at-risk patients.

Whole cell and acellular pertussis vaccines have been very effective in decreasing the deaths of neonates and infants fromThis review discusses the different possibilities for improving current pertussis vaccines and the present state of knowledge on the pertussis vaccine candidates under development.Until there is a safe, effective, and affordable alternative to the two types of existing vaccines, we should maintain sufficient childhood coverage and increase the vaccination of pregnant women, adolescents, and young adults.

Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. From July 2019 to June 2020, we performed a case-control study among children aged 3–24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44–36.58, P = 0.0165). Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.

In recent years, the resurgence of pertussis has posed a public health challenge in many countries. This study aimed to evaluate the immunity levels against pertussis among populations of different ages in China.We conducted a cross-sectional serological survey in Zhejiang Province, China in 2020. Serum IgG antibodies against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA), and pertactin (anti-PRN) were quantitatively measured. The geometric mean concentration (GMC) of three antibodies was calculated. An anti-PT level 5 IU/mL was considered undetectable, ≥20 IU/mL as seropositive and ≥80 IU/mL as an indicator of recent infection. Mathematical models were fitted for anti-PT concentrations over time in children after four doses of the pertussis vaccination.A total of 4459 participants aged 0-59 years were included in the analyses. The overall positivity rate of anti-PT was 29.80% with the highest (81.44%) rate in the 1-2 years old and the lowest (4.72%) in 10-14 years old. The GMCs of anti-PT, anti-FHA and anti-PRN for the whole participants were 9.67 (95%CI: 9.25-10.10),18.93 (18.24-19.67), and 8.99 (8.61-9.38) IU/mL, respectively. Over 50% of subjects aged ≥ 7 years had undetectable anti-PT IgG antibodies (5IU/mL). The proportions of the populations with anti-PT IgG ≥ 80 IU/mL were approximately 0.9%, 0.3% and 1.1% among the 10-14, 15-29, and 40-59 years old groups, respectively. The power regression equation of the attenuation model after last dose of pertussis vaccine was y = 41.088xThe prevalence of pertussis decreased during the study period in the COVID-19 pandemic; however, there was still a certain proportion of adolescents and adults with evidence of recent infection. The decline in antibody levels after pertussis vaccination was observed, and booster doses are in urgent need in China.

This study examined healthcare resource use (HCRU) for selected vaccine-preventable diseases (VPD) in secondary care in England.The hospital episode statistics (HES) dataset covering all secondary care interactions within the English National Health Service (NHS) from 2015 to 2021 was used to identify and track HCRU for patients with a primary or secondary diagnosis for pertussis and Haemophilus influenzae type b (Hib), or a primary diagnosis only for hepatitis B, diphtheria, poliomyelitis, or tetanus. The first documented diagnosis during the study period (01/04/2015-31/03/2021) was the index event.7,274 patients with a total of 5,554,343 patient-days (mean follow up 1,491 days) were included. The total number of hospital admissions was 27,092 and total inpatient cost was £4,987,770, with hepatitis B making up ∼80 % of this. Mean outpatient hospital appointments per patient were highest for tetanus (4.00), but total outpatient AE cost burden was highest for Hib (£643,343 [mean per attendance £144.57]). For patients 0-9 years of age (n = 1,917), pertussis (n = 1,547) and Hib (n = 313) were by far the most commonly coded diseases. Hepatitis B was the most common disease in adults of working age and Hib was most prevalent in adults of retirement age. Surprisingly, poliomyelitis was observed in the database potentially due to historic diagnoses and/or coding inaccuracy. Other discrepancies with surveillance data were noted.VPDs impose a large burden on the NHS, but there is potential to reduce this and improve public health by optimising vaccination schedules, improving access and ensuring high coverage rates.

The recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalisation rate for pertussis in children under one year of age before and after the implementation of the vaccination programme.Observational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalisation rate of patients under one year of age of the period prior to the vaccination programme (2008-2013) was compared with the period with vaccination programme (2014-2019) in the total of children under one year of age and in 2 subgroups: children under 3 months and between 3-11 months.Hospitalization rate was significantly lower in the period with vaccination programme in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1000 person-years and 6.47 vs. 13.11 per 1000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods.The introduction of the pertussis vaccination programme in pregnancy was associated with a global lower hospitalisation rate for pertussis in children under one year of age and specifically in those under 3 months of age.

RESUMEN Objetivo. Desarrollar y evaluar un método de bajo costo basado en celulosa para la purificación rápida y amplificación directa de ADN de Bordetella pertussis de hisopados nasofaríngeos. Materiales y métodos. Se prepararon discos de celulosa y se evaluaron diferentes parámetros (buffers de lisis/lavado, número de discos y elución de ADN). El método se acopló a una amplificación directa por PCR en tiempo real (qPCR) y se estimó el rendimiento utilizando hisopados nasofaríngeos que fueron positivos (n=100) y negativos (n=50) para ADN B. pertussis por qPCR, comparado con el método basado en columnas de sílice. Se calculó el grado de concordancia, sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN). Se evaluó la factibilidad del método rápido para ser acoplado a un ensayo colorimétrico de amplificación isotérmica mediada por lazo (LAMP). Resultados. El método rápido con un disco de celulosa y buffer de lisis y lavado conteniendo PVP-40 y Tween 20, respectivamente, mostró una mayor capacidad para purificar ADN amplificable de B. pertussis. El método tuvo una sensibilidad de 89,0% (IC95%, 80,2%-94,9%) y una especificidad de 98,5% (IC95%, 92,1%-100,0%), con un buen grado de concordancia (Kappa=0,867; IC95% 0,788 - 0,946), respecto al método referencial. Los VPP y VPN fueron 98,6% (IC95%, 92,7,2%-100,0%) y 88,2% (IC95%, 78,7%-94,4%), respectivamente. Se evidenció una amplificación exitosa por LAMP, y se obtuvieron resultados comparables con el método por columnas de sílice. Conclusión. El método desarrollado es simple, de bajo costo y libre de equipos para la obtención rápida (60 segundos) de ADN en el punto de atención, y puede ser implementado en diversas técnicas moleculares orientados al diagnóstico oportuno y al estudio epidemiológico de tos ferina. ABSTRACT Objective. To develop and evaluate a low-cost cellulose-based method for rapid purification and direct amplification of Bordetella pertussis DNA from nasopharyngeal swabs. Materials and methods. We prepared cellulose discs and evaluated different parameters (lysis/wash buffers, number of discs and DNA elution). The method was coupled to a direct real-time PCR (qPCR) amplification and the performance was estimated using nasopharyngeal swabs that were positive (n=100) and negative (n=50) for B. pertussis DNA by qPCR, compared to the silica column-based method. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and the degree of agreement. The feasibility of the rapid method to be coupled to a loop-mediated isothermal amplification colorimetric assay (LAMP) was evaluated. Results. The rapid method, with a cellulose disk and lysis and wash buffer containing PVP-40 and Tween 20, respectively, showed a greater capacity to purify amplifiable DNA from B. pertussis. The method had a sensitivity of 89.0% (95%CI: 80.2%-94.9%) and a specificity of 98.5% (95%CI: 92.1%-100.0%), with a good degree of agreement (Kappa=0.867; 95%CI: 0.788 - 0.946), compared to the reference method. The PPV and NPV were 98.6% (95%CI: 92.7.2%-100.0%) and 88.2% (95%CI: 78.7%-94.4%), respectively. Successful amplification by LAMP was evident, and comparable results were obtained with the silica column method. Conclusion. The developed method is simple, low-cost and equipment-free for rapid (60 seconds) DNA collection at the point of care, and can be implemented in various molecular techniques aimed at the timely diagnosis and epidemiological study of pertussis.

Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine to identify critical quality attributes that inform the use of a comprehensive set of non-animal tests to release the vaccine, together with the principle that the quality of subsequent batches follows from their consistent production. Many vaccine antigens are by themselves not able to induce a protective immune response. The antigens are therefore administered together with adjuvant, most often by adsorption to aluminium salts. Adjuvant function is an important component of vaccine potency, and an important quality attribute of the final product. Aluminium adjuvants are capable of inducing NLRP3 inflammasome activation. The aim of this study was to develop and evaluate an in vitro assay for NLRP3 inflammasome activation by aluminium-adjuvanted vaccines. We evaluated the effects of Diphtheria-Tetanus-acellular Pertussis combination vaccines from two manufacturers and their respective adjuvants, aluminium phosphate (AP) and aluminium hydroxide (AH), in an in vitro assay for NLRP3 inflammasome activation. All vaccines and adjuvants tested showed a dose-dependent increase in IL-1β production and a concomitant decrease in cell viability, suggesting NLRP3 inflammasome activation. The results were analysed by benchmark dose modelling, showing a similar 50% effective dose (ED50) for the two vaccine batches and corresponding adjuvant of manufacturer A (AP), and a similar ED50 for the two vaccine batches and corresponding adjuvant of manufacturer B (AH). This suggests that NLRP3 inflammasome activation is determined by the adjuvant only. Repeated freeze-thaw cycles reduced the adjuvant biological activity of AH, but not AP. Inflammasome activation may be used to measure adjuvant biological activity as an important quality attribute for control or characterization of the adjuvant.

We reviewed cases of Bordatella pertussis (B. pertussis) cases in ambulatory clinics at a large academic health care institution in Los Angeles from 2019-2021. Public health prevention measures during the Coronavirus disease 19 (COVID-19) pandemic impacted the number of pertussis cases identified.

Routine infant primary series and toddler booster vaccination are associated with waning of antibody levels over time, which can lead to an increased incidence of vaccine-preventable diseases. A diphtheria-tetanus-pertussis (DTP) booster vaccination at school-entry (aged 4-7 years) allows continued protection against these diseases and is included in many national immunization programs.The available immunogenicity and safety data from 6 clinical studies of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (DTaP-IPV [Tetraxim®]) used as a school-entry booster vaccination were identified using a PubMed search or on file at Sanofi. The studies spanned a 15-year period (1995-2010) and were performed in different populations using different study designs, so all data were reviewed descriptively (no meta-analyses were conducted). Additionally, post-marketing experience was reviewed.Each vaccine antigen is highly immunogenic, and the safety profile of the vaccine is satisfactory. Post-marketing evaluations have shown the effectiveness of a school-age booster, particularly against increased pertussis disease incidence around the time of school entry and the associated risk of spreading the disease through contact with younger vulnerable infants. School-entry provides an ideal opportunity to implement DTaP-IPV vaccination to close the gap between waning immunity from the previous infant/toddler vaccination and future adolescent vaccination.

Background The emergence of macrolide resistance in Bordetella pertussis, the causative agent of pertussis, due to mutations in the 23S rRNA gene has been recently recognized. However, resistance mechanisms to macrolides in Bordetella parapertussis and Bordetella holmesii remain unknown. Objectives This study investigated genomic changes induced by in vitro exposure to erythromycin in these three main pathogens responsible for pertussis-like disease. Methods A set of 10 clinical and reference strains of B. pertussis, B. parapertussis and B. holmesii was exposed to erythromycin for 15 weeks or 30 subculture passages. Antibiotic pressure was achieved by growth on the selective media with erythromycin Etest strips or impregnated discs. Genome polymorphisms and transcriptomic profiles were examined by short- and long-read sequencing of passaged isolates. Results B. parapertussis and B. holmesii isolates developed significant in vitro resistance to erythromycin (MIC >256 mg/L) within 2 to 7 weeks and at 5 to 12 weeks, respectively. B. pertussis remained phenotypically susceptible to the antibiotic following 15 weeks of exposure, with the MIC between 0.032 to 0.38 mg/L. Genomic analysis revealed that B. holmesii developed resistance due to mutations in the 23S rRNA gene. The resistance mechanism in B. parapertussis was hypothesized as being due to upregulation of an efflux pump mechanism. Conclusions These findings indicate that both B. holmesii and B. parapertussis can be more prone to induced resistance following exposure to treatment with erythromycin than B. pertussis. The surveillance of macrolide resistance in Bordetella isolates recovered from patients with pertussis, especially persistent disease, is warranted.

Micropipette tips are currently among the most used disposable devices in bioresearch and development laboratories. Their main application is the fractionation of solutions. New functionalities have recently been added to this device, widening their applications. This paper analyzed disposable micropipette tips as reagent holders of PCR reagents. PCR has become a prevalent and often indispensable technique in biological laboratories for various applications, such as the detection of coronavirus and other infectious diseases. A functional micropipette tip was implemented to simplify PCR analysis and reduce the contamination chances of deoxynucleotides and specific primers. This disposable device is prepared by tip coating processes of reagents, using polyvinyl alcohol polymer and additives. The coated layer is optimized to load and release PCR reagents efficiently. As a proof of concept, we show that the detection of Bordetella pertussis, the etiological agent of whooping cough whose diagnostic relies on PCR, can be quickly done using practical-functional tips. This device is an excellent example of testing the functionality and contribution of molecular diagnostic PCR tips. KEY POINTS: • Functional micropipette tips are prepared by coating with dNTPs and primers. • Functional tips are used to replace dNTPs and primers in the PCR master mix. • PCR diagnostic of Bordetella pertussis is performed using functional tips.

The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia.The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test.441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents.A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden.

To evaluate the impact of a multi-component intervention package of maternal immunization uptake in obstetric care clinics.In a multi-level, cluster- and individually-randomized controlled trial we implemented an evidence-based intervention that targeted practice-, provider- and patient-level barriers to vaccine uptake. Obstetric practices were randomized to receive the practice and provider-level interventions or continue their normal standard of care. We enrolled pregnant women at practices in Georgia and Colorado and randomized women into patient-level intervention and control groups, resulting in four study arms. The primary outcomes were receipt of the influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccines during pregnancy. A sample size of 550 women per arm (2200 total) was planned and enrolled to compare the intervention between the four study arms.Between June 2017 and July 2018, 4907 women were screened and 2200 women were randomized, 550 to each of the four study arms. We were unable to follow-up with 108 women, for a final sample size of 2092. Sample characteristics and sample size were similar among study arms. There was no significant increase in Tdap or influenza vaccine uptake overall. Among women who had no intention of or were unsure about receiving the influenza vaccine during pregnancy, those who received just the patient-level intervention were 61% more likely to receive the influenza vaccine than those in the control arm (Relative risk: 1.61; 95% Confidence Interval: 1.18-2.21). There was no significant difference in vaccine uptake for either influenza or tetanus, diphtheria and acellular pertussis between the four arms of the study.This trial highlights the need for more targeted interventions to improve vaccine uptake. Future work should focus on clinics with low baseline vaccine uptake and the patient-level intervention should be expanded and targeted towards women with low vaccine confidence.

Objectives: to analyze a decade of spatio-temporal behavior of pertussis in Brazil and its epidemiological characteristics. Methods: ecological time series study of pertussis cases and deaths from the Notifable Diseases Information System in Brazil (2010-2019). The method of generalized linear analysis of Prais-Winsten and the Kernel analysis were used. Results: 32,849 cases were reported, of which 466 (1.42%) evolved to death, with a prevalence of 1.63/100,000 inhabitants and a mortality rate of 0.023/100,000 inhabitants. In the temporal analysis, the cyclical behavior of pertussis was evidenced, with trend variations in the period in 2014. Most cases occurred in children under 1 year of age (60.16%, p

To estimate hospitalisation rate and investigate the role of age, prematurity and vaccination status in severe pertussis cases.We retrospectively evaluated 200 children aged 0-14 years, admitted to the emergency rooms of Meyer Hospital of Florence and Pisa Hospital with a diagnosis of pertussis from 1 October 2010 to 31 January 2020.Children younger than 12 months were 63.0%. Preterm infants were 6.5%. The rate of hospitalisation was 49.0%. Among hospitalised cases, 80.6% were younger than 5 months. Overall, 62.0% were unvaccinated; this percentage increased among hospitalised (73.5%) and preterm subsamples (76.9%). Delays in pertussis vaccination were found in 57.7% of term infants and in 80.0% of preterms. Multivariable analysis confirmed the age under 2 months as the variable at higher risk for hospitalisation (OR 4.49, 95% CI 1.85-10.96, p 0.001). Being fully vaccinated represented a significant protective factor (OR 0.12, 95% CI 0.04-0.35, p 0.001).Older classes of age and a complete vaccination, in time with the recommended schedule, are both protective factors for hospitalisation in severe pertussis disease. The widespread vaccination delay frequently observed in preterm children may be the cause for their higher rate of hospitalisation.

Immunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic.Paired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p 0.016 using Bonferroni correction.Annual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2-10.9) vs. 8.4 IU/ml (5.1-13.9; p = 0.004); 18.8 IU/ml (10.9-32.2) vs. 23.6 IU/ml (13.2-42.1; p 0.001); and 37.1 IU/ml (18.1-75.9) vs. 47.2 IU/ml (24.8-89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018-2019, 8.4 IU/ml (95% CI, 5.1-13.9) vs. 5.4 IU/ml (95% CI, 3.8-7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2-42.1) vs. 20.1 IU/ml (95% CI, 13.4-30.2; p = 0.656), and 47.2 IU/ml (24.8-89.9) vs. 17.3 IU/ml (95% CI, 10.5-28.7; p = 0.021), respectively.B. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19.

Vaccinations are reported at the state level, but services are delivered at the county level through health departments (HD). This research contributes statistical models to predict county level HPV vaccination.Using a cross sectional study design, secondary data were analyzed for the years 2016-2018 for all counties of GA. Study population was male and female adolescents aged 13-17 who received the tetanus, diphtheria and pertussis (Tdap) vaccine. The number of administered HPV vaccine doses and HPV vaccination coverage rate were modeled using indicators of HD clinic access, age, sex, race/ethnicity, socioeconomic status, education, median household income, health insurance, and urban/rural residence.By county the number of administered HPV vaccine doses showed a statistically significant positive association with indicators of HD clinic access: public transit and the number of HD private clinics. HPV vaccination coverage showed a statistically significant negative association with White race and rural residency.Examining Tdap vaccinated adolescents conservatively predicted HPV vaccination and controlled for multiple confounders such as vaccination ineligibility, vaccine exemption, and vaccine opposition. Within this population, public health professionals and clinicians could use these statistical models to target HPV vaccination efforts among non-Hispanic whites and rural communities at the county level.

Background This study aims to assess the uptake of maternal pertussis and COVID-19 vaccination and the intention towards accepting the maternal influenza vaccination. Insights into different socio-demographic factors related to maternal vaccination coverage might help to address vaccine acceptance and improve maternal vaccine uptake in the future. Methods We conducted a cross-sectional survey among pregnant women and recent mothers, up to 6 months post-partum. The primary outcome measures of this study were behaviour for maternal pertussis and COVID-19 vaccination, and maternal influenza vaccination intention. Associations between socio-demographic factors and maternal pertussis vaccination and maternal COVID-19 vaccination behaviour; and socio-demographic factors and maternal influenza vaccination intention were assessed using binary logistic regression analyses. Results In total 1361 respondents filled out the questionnaire. Almost all women (95%) were vaccinated against pertussis during pregnancy, while almost two-third were vaccinated against COVID-19 during pregnancy (58%) and almost one-third (28%) had a positive intention towards receiving the maternal influenza vaccination. Results show that young maternal age and low education level were associated with lower maternal vaccination acceptance. Conclusion Vaccination campaigns focusing on the severity of diseases that are prevented, are needed to increase maternal vaccine acceptance in younger and low-educated pregnant women. We expect that differences in vaccination coverage between the three maternal vaccinations might partly be explained by existing recommendations, campaigns and whether the vaccination is part of the national immunisation program.

Background Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control. Methods Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the baboon airway were identified by transposon-directed insertion-site sequencing (TraDIS) analysis. Results In total, 314 B. pertussis antigens were identified by convalescent baboon serum and 748 by nasopharyngeal wash. Thirteen antigens were identified as immunogenic in baboons, essential for persistence in the airway by TraDIS, and membrane-localized: BP0840 (OmpP), Pal, OmpA2, BP1485, BamA, Pcp, MlaA, YfgL, BP2197, BP1569, MlaD, ComL, and BP0183. Conclusions The B. pertussis antigens identified as immunogenic, essential for persistence in the airway, and membrane-localized warrant further investigation for inclusion in vaccines designed to reduce or prevent carriage of bacteria in the airway of vaccinated individuals.

We described the population structure of Bordetella pertussis (B. pertussis) in Norway from 1996 to 2019 and determined if there were evolutionary shifts and whether these correlated with changes in the childhood immunization program. We selected 180 B. pertussis isolates, 22 from the whole cell vaccine (WCV) era (1996–1997) and 158 from the acellular vaccine (ACV) era (1998–2019). We conducted whole genome sequencing and determined the distribution and frequency of allelic variants and temporal changes of ACV genes. Norwegian B. pertussis isolates were evenly distributed across a phylogenetic tree that included global strains. We identified seven different allelic profiles of ACV genes (A–F), in which profiles A1, A2, and B dominated (89%), all having pertussis toxin (ptxA) allele 1, pertussis toxin promoter (ptxP) allele 3, and pertactin (prn) allele 2 present. Isolates with ptxP1 and prn1 were not detected after 2007, whereas the prn2 allele likely emerged prior to 1972, and ptxP3 before the early 1980s. Allele conversions of ACV genes all occurred prior to the introduction of ACV. Sixteen percent of our isolates showed mutations within the prn gene. ACV and its booster doses (implemented for children in 2007 and adolescents in 2013) might have contributed to evolvement of a more uniform B. pertussis population, with recent circulating strains having ptxA1, ptxP3, and prn2 present, and an increasing number of prn mutations. These strains clearly deviate from ACV strains (ptxA1, ptxP1, prn1), and this could have implications for vaccine efficiency and, therefore, prevention and control of pertussis.

To determine pertussis and influenza vaccination coverage during pregnancy among women delivering in all the maternities of Geneva (Switzerland), during the COVID-19 pandemic.All women delivering in all the maternity centres of the canton of Geneva from 1st November 2020 to 30th November 2020 (beginning of the flu vaccination season) and from 8th March 2021 to 7th April 2021 (end of the flu vaccination season) had their records checked upon admission to the labour ward regarding pertussis and influenza vaccination during pregnancy. Reasons for non-vaccination were recorded. Univariate and multivariate analyses were done to identify predictors of vaccine uptake.951 women delivered in Geneva during the two study periods, of which 950 were included in the study. 86.2% were vaccinated against pertussis, with no significant difference between the study periods (87.5% vs 85% at the beginning and end of the flu vaccination season respectively). 49.8% were vaccinated against influenza, with no significant difference between the study periods (48.8% vs 50.7% beginning and end of the flu vaccination season respectively). The influenza vaccine was 5 times more likely not to be proposed (8.9% vs. 1.7%) and 3 times more likely to be refused (26.6% vs. 8%) than the pertussis vaccine. Main reason for refusal was a lack of maternal desire for both vaccines, but not vaccine fear. Maternal parity ≥ 1 was significantly associated with pertussis vaccine uptake at univariate analysis. Women were significantly more likely to accept the influenza vaccine if they had a university degree or if they did not deliver in a midwife-only run delivery unit in both univariate and multivariate analysis.In Geneva, most gynaecologists offer pertussis immunization during antenatal care and uptake is high, but more efforts must be done to increase influenza vaccination coverage. Education level impacts maternal flu vaccination uptake, but other social disparities did not.

Adults with lung diseases, comorbidities, smokers, and elderly are at risk of lung infections and their consequences. Community-acquired pneumonia happen in more than 1% of people each year. Possible pathogens of community-acquired pneumonia include viruses, pneumococcus and atypicals. The CDC recommend vaccination throughout life to provide immunity, but vaccination rates in adults are poor. Tetravalent and trivalent influenza vaccine is designed annually during the previous summer for the next season. The available vaccines include inactivated, adjuvant, double dose, and attenuated vaccines. Their efficacy depends on the variant of viruses effectively responsible for the outbreak each year, and other reasons. Regarding the pneumococcal vaccine, there coexist the old polysaccharide 23-valent vaccine with the new conjugate 10-valent and 13-valent conjugate vaccines. Conjugate vaccines demonstrate their usefulness to reduce the incidence of pneumococcal pneumonia due to the serotypes present in the vaccine. Whooping cough is still present, with high morbidity and mortality rates in young infants. Adult’s pertussis vaccine is available, it could contribute to the control of whooping cough in the most susceptible, but it is not present yet in the calendar of adults around the world. About 10 vaccines against SARS-CoV-2 have been developed in a short time, requiring emergency use authorization. A high rate of vaccination was observed in most of the countries. Booster doses became frequent after the loss of effectiveness against new variants. The future of this vaccine is yet to be written.

Our aim was to estimate vaccination and susceptibility rates against vaccine-preventable diseases among healthcare personnel (HCP) in eight hospitals.Cross-sectional survey.A total of 1284 HCP participated (physicians: 31.3%, nursing personnel: 36.6%, paramedical personnel: 11.1%, administrative personnel: 13.2%, supportive personnel: 7.3%). Vaccination rates were 32.9% against measles and mumps, 38.1% against rubella, 5.7% against varicella, 9.2% against hepatitis A, 65.8% against hepatitis B, 31.8% against tetanus-diphtheria, 7.1% against pertussis, 60.2% against influenza, and 80.1% against COVID-19. Susceptibility rates were as follows: 27.8% for measles, 39.6% for mumps, 33.4% for rubella, 22.2% for varicella, 86.3% for hepatitis A, 34.2% for hepatitis B, 68.2% for tetanus-diphtheria, and 92.9% for pertussis. Older HCP had higher susceptibility rates against mumps, rubella, varicella, hepatitis A, hepatitis B, tetanus-diphtheria, and pertussis (p-values0.001 for all). Mandatory vaccinations were supported by 81.85% of HCP.Although most HCPs supported mandatory vaccinations, significant vaccination gaps, and susceptibility rates were recorded. The proportion of susceptible HCP to measles, mumps, rubella, and varicella has increased in the past decade, mostly because of reduction in acquired cases of natural illness. Vaccination programs for HCP should be developed. A national registry to follow HCP's vaccination rates is urgently needed.

Background A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. Methods A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PTgen and 1 μg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 μg PTgen and 5 μg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PTgen and 5 μg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PTchem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. Results Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81–98) for ap1gen, 88% (95% CI 76–95) for Tdap1gen, 80% (95% CI 66–90) for Tdap2gen, 94% (95% CI 83–99) for TdaP5gen, and 78% (95% CI 64–88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. Conclusions All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. Clinical Trial Registration: Thai Clinical Trial Registry, TCTR20180321004.

To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD.The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions.The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD.Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

Pertussis is a highly contagious, vaccine-preventable respiratory tract infection, with high morbidity and mortality and a particularly severe effect on newborns and infants under 2 months. The first pertussis vaccines were introduced in the 1940s. Since 1980, however, the incidence of cases has risen despite the extensive vaccination programmes and antibiotic adjuvant treatments available. Transition from the use of whole-cell vaccines to acellular vaccines and the antigenic modifications of Bordetella pertussis have contributed, among other factors, to a reduction in vaccine-acquired immunity and reemergence of the disease. Today, there are still unmet needs not covered by conventional prevention measures and existing antibiotic treatments. This review aims to update the available data, and to discuss which vaccine strategies might contribute to better disease control and prevention.

Background There are worrying indications that diphtheria-tetanus-pertussis (DTP) vaccine has negative non-specific effects for females. We previously found, in a trial of early-Bacillus Calmette-Guerin (BCG) to low weight (LW) neonates, that receiving early-DTP (before 2 months of age), was associated with increased female mortality compared with no-DTP/delayed-DTP. Within a subsequent LW trial, we aimed to retest this observation. Methods Between 2010 and 2014, in Guinea-Bissau, 2,398 infants were randomised 1:1 to early-BCG (intervention) or delayed-BCG (standard practice for LW neonates) and visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. DTP is recommended at 6 weeks of age. We examined the effect of having “early-DTP” versus “no-DTP” at the time of the 2-month visit on all-cause mortality between the 2- and 6-month visits in Cox models stratified by sex and adjusted for BCG-group and 2-month-weight-for-age (z-scores) providing adjusted mortality rate ratios (aMRRs). We analysed to which extent conditions varied between the present and the previous LW trials and how that might have affected the overall result of comparing the early-DTP and the no-DTP groups. Results At the time of the 2-month visit, 75% (1,795/2,398) had received DTP. Those vaccinated had better anthropometric indices than no-DTP infants at birth and by 2 months of age. Between the 2- and 6-month visits, 29 deaths occurred. The early-DTP/no-DTP aMRR was 1.09 (95% CI: 0.44–2.69); 1.19 (0.45–3.15) for females and 0.77 (0.14–4.19) for males. Compared to the previous study, the present study cohort had 56% (30–72%) lower overall mortality, fewer no-DTP infants, higher BCG vaccination coverage and several more oral polio vaccine campaigns. Conclusion We did not find that early-DTP was associated with increased female mortality as found in a previous study; differences in results may partly be due to a decline in overall mortality and changes in vaccination practices.

To assess the frequency and associated characteristics of COVID-19 vaccine hesitancy among pregnant and postpartum individuals.Cross-sectional study.Prenatal care at a single academic tertiary care centre.Pregnant and postpartum individuals enrolled in prenatal care at a single academic tertiary care centre from 22 March 2021 to 2 April 2021, concurrent with state guidelines recommending COVID-19 vaccination in pregnancy.We used logistic regression to identify characteristics associated with COVID-19 vaccine hesitancy, and adjusted for: age, parity, race, trimester of pregnancy, and chronic comorbidities.COVID-19 vaccine hesitancy, defined as uncertainty or refusal of the vaccine, despite the availability of vaccine services, in accordance with the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on vaccine hesitancy.Of the 485 individuals screened and approached, 456 (94%) enrolled and completed the survey (435/456, 95% pregnant). The frequency of COVID-19 vaccine hesitancy was 46% (95% CI 41%-51%). Sociodemographic characteristics, including non-Hispanic Black race, younger age, lower education, public health insurance receipt, parity1, and reported substance use, were associated with a higher odds of COVID-19 vaccine hesitancy, but not clinical risk conditions. Individuals who had a family or friend vaccinated for COVID-19, prior or planned vaccination for tetanus, diphtheria and acellular pertussis (Tdap) and/or influenza, and who perceived that vaccination benefited the baby were less likely to express COVID-19 vaccine hesitancy.COVID-19 vaccine hesitancy was frequent among pregnant and postpartum individuals. Those who may face barriers to accessing healthcare services were more likely to report vaccine hesitancy. These results can inform interventions to increase COVID-19 vaccine uptake in pregnancy.COVID-19 vaccination hesitancy is frequent among pregnant and postpartum individuals, and those who face barriers to accessing healthcare services are more likely to report COVID-19 vaccine hesitancy.

BACKGROUND It is well established that young infants have the highest risk of severe pertussis, which often results in hospitalization. Since the 2012 recommendation of administering tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine for every pregnancy, evaluation of pertussis hospitalizations among young infants in the United States has been limited. METHODS In this ecological study, we used the Kids’ Inpatient Database, the largest all-payer pediatric inpatient database in the United States, to study pertussis hospitalizations among infants RESULTS The overall rate of pertussis hospitalizations before the Tdap vaccination recommendation was 5.06 per 100 000 infants (95% confidence interval, 4.36–5.76) and 2.15 per 100 000 infants (95% confidence interval, 1.49–2.81) afterward. CONCLUSIONS This study supports maternal vaccination against pertussis as an important strategy in protecting young infants, and continued evaluation is needed to assess the long-term trends in hospitalization.

Pertussis hospitalisation is more common among infants born prematurely, who have significant comorbidities, or are Indigenous, but acellular pertussis (aP) vaccine effectiveness (VE) estimates in these sub-groups are lacking. We measured aP VE by Indigenous status, and policy-relevant categories of prematurity and comorbidity, in a population-based Australian cohort.Perinatal, disease notification, hospitalisation, mortality, and vaccination data were linked to birth records in two Australian states (Western Australia and New South Wales) 2001-2012, with follow-up to the end of 2013. Children followed to 18 months of age were stratified by Aboriginality, prematurity (32 vs 32-37 weeks gestation) and comorbidities identified from hospital discharge coding. Rates, rate ratios and VE were calculated for first episode of hospitalised and non-hospitalised pertussis notifications using adjusted Cox proportional hazards models.Among1,300,000 children, 63,867 (4·9%) were Aboriginal, 47,721 (3·6%) had at least one comorbidity and 3,771 first episodes of notified pertussis occurred18 months of age; of these, 1,207 (32.0%) had an associated pertussis-coded hospitalisation. For hospitalised pertussis in Aboriginal and non-Aboriginal children, there was significant protection post dose 1 (VE 51% v 25%), 2 (VE 69% v 74%) and 3 (VE 76% v 80%). For children with co-morbidities, VE for hospitalised pertussis was low and non-significant post dose 1 (0%) and 2 (30%). Post dose 3, VE was significant for hospitalised pertussis (70%; 95% CI 29-87) but not for non-hospitalised pertussis (24%; 95% CI -49 to 61).For most Aboriginal and non-Aboriginal children, improved timeliness of current infant doses and higher antenatal coverage should further improve protection against pertussis of any severity. For children at highest risk of severe pertussis (born32 weeks gestation or with significant medical comorbidities), our data suggest that additional measures-such as extra doses of pertussis-containing vaccines and/or vaccines with improved immunogenicity-are needed for protection.

GSK initiated a Pregnancy Registry in the United States (US) for the reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap; Boostrix, GSK) vaccine with the aim to detect and describe pregnancy outcomes in women vaccinated with Boostrix 28 days before estimated conception or during pregnancy.Voluntary reports of pregnancy exposure to Boostrix received from spontaneous and post-marketing surveillance sources in the US were assessed. Reports were classified as prospective or retrospective based on the knowledge of pregnancy outcomes at the time of reporting. For completeness, reports of exposure to Boostrix or to the Tdap-inactivated poliovirus vaccine (Boostrix-IPV, GSK) reported to the global safety database from countries outside the US were also evaluated.From May 2005 to August 2019, 1517 (1455 prospective and 62 retrospective) pregnancy reports were received in the Boostrix US Pregnancy Registry. Of the prospective reports, 250 had known outcomes: 244 live infants with no apparent birth defects (BDs), three live infants with BDs, and three spontaneous abortions with no apparent BDs. Of the retrospective reports, 55 had known outcomes: 33 live infants with no apparent BDs, 16 live infants with BDs, one spontaneous abortion with no apparent BDs, four stillbirths with no apparent BDs, and one stillbirth with BDs. Cumulatively, 1321 pregnancy reports (1006 for Boostrix; 315 for Boostrix-IPV) were received from countries outside the US. Of these, 163 prospective reports and 551 retrospective reports had known outcomes. Results were in line with those from the Boostrix US Pregnancy Registry.Data currently available from the Boostrix US Pregnancy Registry and from countries outside the US suggested that exposure to Boostrix or Boostrix-IPV during pregnancy does not raise safety concerns related to adverse pregnancy outcomes or BDs.

Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an evolution of concerns with acellular component vaccination have both sparked a renewed interest. Although simian models of infection best correlate with the observed attributes of human infection, several animal models have been used for decades and have positively contributed in many ways to the related science. Nevertheless, there is yet the lack of a reliable small animal model system that mimics the combination of infection genesis, variable upper and lower respiratory infection, systemic effects, infection resolution, and vaccine responses. This narrative review examines the history and attributes of non-primate animal models for pertussis and places context with the current use and needs. Emerging from the latter is the necessity for further such study to better create the optimal model of infection and vaccination with use of current molecular tools and a broader range of animal systems. Key points • Currently used and past non-primate animal models of B. pertussis infection often have unique and focused applications. • A non-primate animal model that consistently mimics human pertussis for the majority of key infection characteristics is lacking. • There remains ample opportunity for an improved non-primate animal model of pertussis with the use of current molecular biology tools and with further exploration of species not previously considered. Graphical abstract

Pertussis is a vaccine preventable cough illness. It can be controlled by universal pertussis vaccination.Pertussis cases and deaths in children are at a record low number. More complete use of adolescent/adult vaccine can further reduce morbidity and mortality.Considerable progress in the control of pertussis has occurred over the last 75 years. The universal use of Tdap vaccines in all pregnant women will prevent virtually all pertussis deaths.

Background Changes to pertussis vaccination programmes can have impacts on disease burden that should be estimated independently from factors such as age- and period-related trends. We used age-period-cohort (APC) models to explore pertussis incidence in Manitoba over a 25-year period (1992–2017). Methods We identified all laboratory-confirmed cases of pertussis from Manitoba’s Communicable Diseases Database and calculated age-standardized incidence rates. We used APC models to investigate trends in pertussis incidence. Results During the study period, 2479 cases were reported. Age-standardized rates were highest during a large outbreak in 1994 (55 cases/100 000 person-years), with much lower peaks in 1998, 2012 and 2016. We saw strong age and cohort effects in the APC models, with a steady decrease in incidence with increasing age and increased risk in the cohort born between 1980 and 1995. Conclusions The highest risk for pertussis was consistently in young children, regardless of birth cohort or time period. The 1981 programme change to an adsorbed whole-cell pertussis vaccine with low effectiveness resulted in reduced protection in the 1981–95 birth cohort and contributed to the largest outbreak of disease during the 25-year study period.

Background To identify risk factors associated with the prognosis of pertussis in infants ( Methods A retrospective study on infants hospitalized with pertussis January 2017 to June 2019. The infants were divided into two groups according to the severity of disease: severe pertussis and non-severe pertussis groups. We collected all case data from medical records including socio-demographics, clinical manifestations, and auxiliary examinations. Univariate analysis and Logistic regression were used. Results Finally, a total of 84 infants with severe pertussis and 586 infants with non-severe pertussis were admitted. The data of 75% of the cases (severe pertussis group, n = 63; non-severe pertussis group, n = 189) were randomly selected for univariate and multivariate logistic regression analysis. The results showed rural area [P = 0.002, OR = 6.831, 95% CI (2.013–23.175)], hospital stay (days) [P = 0.002, OR = 1.304, 95% CI (1.107–1.536)], fever [P = 0.040, OR = 2.965, 95% CI (1.050–8.375)], cyanosis [P = 0.008, OR = 3.799, 95% CI (1.419–10.174)], pulmonary rales [P = 0.021, OR = 4.022, 95% CI (1.228–13.168)], breathing heavily [P = 0.001, OR = 58.811, 95% CI (5.503–628.507)] and abnormal liver function [P Conclusions The findings indicated risk factor prediction models may be useful for the early identification of severe pertussis in infants.

Background: Vaccination of pregnant people with a vaccine containing acellular pertussis (tetanus–diphtheria–acellular pertussis [Tdap]) has been recommended in Canada since 2018, and the evaluation of delivery models for efficient maternal Tdap administration is a priority for the Quebec Ministry of Health. We implemented 3 vaccine delivery models, in addition to the existing standard of practice model, and compared the vaccine coverage achieved by the 4 models in Quebec. Methods: In this quasiexperimental, multicentre observational study, we recruited pregnant people at less than 21 weeks’ gestation in 4 Quebec regions from April to October 2019. We compared 4 vaccine delivery models: local community service centres (centre local de services communautaires [CLSCs], baseline), family medicine groups (FMGs), obstetrics clinic and the oral glucose challenge test (OGCT). In addition to the CLSCs, 3 FMGs, 1 obstetric clinic and a hospital-based OGCT screening program participated. We determined vaccination status from a self-reported questionnaire, the Quebec Immunization Registry or medical charts. We compared model-specific (for participants recruited to a model and subsequently vaccinated within that model) and overall vaccine coverage (considering all vaccine delivery pathways) and used logistic regression to adjust for sociodemographic variables. Results: Overall, 946 of 1000 recruited pregnant people were eligible for analyses. Vaccination via the FMGs achieved the highest model-specific vaccine coverage (67.8%, 95% confidence interval [CI] 60.5%–74.4%), but coverage was not significantly different from the CLSCs (63.8%, 95% CI 57.6%–69.6%). For overall vaccine coverage, the FMG (86.5%, 95% CI 80.6%–90.9%) and obstetrics models (85.9%, 95% CI 80.9%–89.7%) achieved significantly higher vaccine coverage than the CLSCs (66.3%, 95% CI 60.1%–71.9%). The OGCT model did not improve overall vaccine coverage (61.8%, 95% CI 56.1%–67.2%). Interpretation: Compared with CLSCs, overall vaccine coverage was higher when Tdap was offered in FMGs or an obstetrics clinic providing prenatal care. Health professionals involved in pregnancy follow-up recommending and offering the vaccine may be a key factor in optimizing vaccine coverage.

Despite the implementation of effective paediatric vaccination programmes, pertussis remains a global health problem. Disease epidemiology has changed over time, shifting towards the adolescent and adult populations. In adults, the true burden of pertussis is greatly underestimated and pertussis vaccine coverage rates are suboptimal, including individuals with chronic conditions. Here, we report the outcomes of a virtual international scientific workshop to assess the evidence on the burden of pertussis in older adults and identify potential solutions to improve uptake of pertussis vaccines. In adults, pertussis is underdiagnosed in part due to atypical or milder clinical presentation and the lack of testing and case confirmation. However, contemporary epidemiological data denoted an increase in the burden of pertussis among adolescents and adults. This might be related to a variety of reasons including the waning of immunity over time, the lack of booster vaccination, and the improved diagnostic methods that led to increased recognition of the disease in adults. Pertussis sequelae can be severe in older adults, particularly those with existing chronic medical conditions, and the vulnerability of these groups is further enhanced by low pertussis vaccine coverage. Possible measures to increase vaccine uptake include strengthening and harmonisation of immunisation guidelines, healthcare professionals taking a more active role in recommending pertussis vaccination, involvement of vaccination centres and pharmacies in the vaccination process, and improving knowledge of pertussis burden and vaccine efficacy among the general population.

OBJECTIVE: To assess whether cognitive reappraisal and acceptance are effective emotion regulation strategies to decrease the influence of negative affect on intention to accept maternal pertussis vaccination (MPV) among pregnant women in the Netherlands.METHODS: An experimental study with baseline and two follow-up measurements was conducted. Participants selected after baseline (N = 382) were randomized into two experimental groups (cognitive reappraisal, acceptance) and a control group. The effect of the experimental manipulations on negative affect was examined with multilevel analyses. A moderation analysis was performed to examine whether the manipulations moderated the association between negative affect and intention.RESULTS: All groups showed a decrease in negative affect (all p's < 0.001), with no differences between groups. A small decrease in the influence of negative affect on intention was found among those who used acceptance.CONCLUSION: No additional value of the emotion regulation strategies was found compared to the control group. However, exploratory analyses showed that acceptance seemed a promising strategy to decrease the influence of negative affect on intention to accept MPV.PRACTICE IMPLICATIONS: This study stressed the relevance for communication strategies to consider the emotions pregnant women experience during the decision-making process about the MPV.

This study investigated the implementation status, attitudes, and practices regarding maternal pertussis vaccination in delivery facilities in Kanagawa, Japan. We conducted a questionnaire survey of pertussis vaccination during pregnancy at 125 delivery service facilities, excluding midwifery clinics, in Kanagawa Prefecture from June 18 to July 20, 2020. The questionnaire comprised multiple-choice items, with single or multiple answers depending on the question. Of the 125 facilities surveyed, valid responses were obtained from 72 facilities (58%). There were 41 primary clinics with birthing facilities (57%), 16 general hospitals (not designated perinatal centers) (22%), 10 regional perinatal centers (14%), and five tertiary perinatal centers (7%). None of the facilities administered pertussis vaccination during pregnancy. Forty facilities (56%) reported knowledge of the severity of neonatal and infant pertussis infections. Twenty-three facilities (32%) reported knowledge of the prevention of pertussis infection by vaccination during pregnancy. All facilities reported willingness to consider vaccination if included in the Japanese guidelines. In Japan, the pertussis vaccination during pregnancy is not highly practiced by obstetricians; thus, it is not as popular as in other countries. Further studies are needed to promote strategies to prevent pertussis infection in the neonatal and infant periods.

O objetivo deste estudo foi investigar a reemergência da coqueluche, notificação e casos confirmados da doença na mesorregião do campo das vertentes, microrregião de São João del-Rei e o estado de Minas Gerais, além de correlacionar o número de casos nessas regiões. Materiais e Métodos: Investigou-se a incidência no estado de Minas Gerais e no município de São João del-Rei, através da coleta de dados no TABNET, DATASUS, SINAN e boletins da Secretaria Municipal de Saúde de São João del-Rei (SMS-SJDR), durante o período compreendido entre 2008 a 2018, considerando os casos suspeitos e os confirmados da doença. Resultados: Os dados permitiram informar a comunidade dos municípios pesquisados fornecendo informações que poderão alertar e prevenir a reemergência dessa doença. Conclusão: O diagnóstico precoce permite sucesso no tratamento e diminuição das complicações da doença. The objective of this study was to investigate the reemergence of pertussis, notification and confirmed cases of the disease in Campos das Vertentes mesoregion, São João del-Rei microregion, state of Minas Gerais, in addition to correlating the number of cases in these regions. Materials and Methods: The incidence in the state of Minas Gerais and in the São João del-Rei town was investigated, through data collection in TABNET, DATASUS, SINAN and bulletins from the Secretary of Municipal Health of São João del-Rei (SMS) -SJDR), from 2008 to 2018, considering the suspected and confirmed cases of the disease. Results: The data allowed informing the community of the surveyed municipalities by providing information that could alert and prevent the reemergence of this disease. Conclusion: Early diagnosis allows successful treatment and reduction of disease complications. El objetivo de este estudio fue investigar la reemergencia de la tos ferina, la notificación y los casos confirmados de la enfermedad en la mesorregión de Campos das Vertentes, microrregión de São João del-Rei, estado de Minas Gerais, además de correlacionar el número de casos en esas regiones. Materiales y Métodos: Se investigó la incidencia en el estado de Minas Gerais y en la ciudad de São João del-Rei, a través de la recolección de datos en TABNET, DATASUS, SINAN y boletines de la Secretaría de Salud Municipal de São João del-Rei (SMS) -SJDR), de 2008 a 2018, considerando los casos sospechosos y confirmados de la enfermedad. Resultados: Los datos permitieron informar a la comunidad de los municipios encuestados brindando información que pudiera alertar y prevenir el rebrote de esta enfermedad. Conclusión: El diagnóstico precoz permite el éxito del tratamiento y la reducción de las complicaciones de la enfermedad.

Vaccine-preventable infectious diseases are still prevalent today. Hence, accurate data and techniques such as mathematical modelling are required to better understand their impact on a population level. This is especially the case for measles, as it has been identified to cause immune amnesia (IA): the loss of pre-existing immunological memory for other diseases after a measles infection. First, spectral analysis was used to describe the recurrent patterns of measles and whooping cough (WC) using weekly London mortality data between 1750–1900. Then, stochastic simulations of a model incorporating IA were performed to understand the effect of IA on the recurrent patterns of WC. The periodograms of the simulated model revealed that increasing IA strength and duration caused the longer periodicities of WC to resemble those of measles. This shift was seen for different population sizes, seasonal forcing amplitudes, and mean transmission rates, suggesting this trend can be observed in different ecological or social contexts. When the birth and death rates of London were used in the model with IA duration of less than a year, the WC periodogram of the simulations resembled that of the London mortality data between 1842–1900. Overall, the simulations demonstrate that IA may have contributed to the longer period spectral structure of WC that was found in the real data. Additionally, the mortality, birth rate, and death rate data presented in this thesis provide new tools for future studies in mathematical epidemiology. Thesis Master of Science (MSc) This thesis presents the weekly mortality time series of measles and whooping cough between 1750 and 1900, and describes their epidemic patterns over time. We also model the phenomenon of measles-induced immune amnesia (reduced pre-existing immunity after a measles infection), and examine how it alters the recurrent patterns of whooping cough at a population level. Additionally, we construct a plausible time series of the birth and all-cause mortality rate over the same 150 years. Overall, our analysis suggests immune amnesia alters the longer periodicities of whooping cough to resemble that of measles. Furthermore, we show that this longer periodic structure is similar to that of whooping cough in the late 19th century. Finally, the given mortality, birth rate, and all-cause mortality rate time series can serve as tools for other epidemiological studies, such as predicting long-term epidemic patterns of other diseases.

Whooping cough (pertussis) is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, pertussis has re-emerged in many countries and caused two large epidemics in Australia since 2007. Here, we undertook a genomic and phylogeographic study of 385 Australian B. pertussis isolates collected from 2008 to 2017. The Australian B. pertussis population was found to be composed of mostly ptxP3 strains carrying different fim3 alleles, with ptxP3-fim3A genotype expanded far more than ptxP3-fim3B. Within the former, there were six co-circulating epidemic lineages (EL1 to EL6). The multiple ELs emerged, expanded, and then declined at different time points over the two epidemics, likely driven by immune selection from pertussis vaccination and natural infection in addition to local and global transmission events. Both hard and soft selective sweeps through vaccine selection pressures determined the current B. pertussis population dynamics. Relative risk analysis found that once a new B. pertussis lineage emerged, it was more likely to spread locally within the first 1.5 years. However, after 1.5 years, any new lineage was likely to expand to a wider region and became no longer spatially structured across the country. Phylogenetic analysis revealed the expansion of ptxP3 strains was also associated with replacement of the type III secretion system allele bscI1 with bscI3. This study advanced our understanding of the epidemic population structure and spatial and temporal dynamics of B. pertussis in a highly immunised population.

We previously demonstrated that Bordetella pertussis, the etiologic agent of whooping cough, is able to survive inside human macrophages. The aim of this study was to examine the influence of macrophage polarization in the development of B. pertussis intracellular infections. To this end, primary human monocytes were differentiated into M1, M2a, or M2c macrophages and further infected with B. pertussis. Infected M1 macrophages showed a proinflammatory response evidenced by the production of TNF-α, IL-12p70, and IL-6. Conversely, infection of M2a and M2c macrophages did not induce TNF-α, IL-12p70, nor IL-6 at any time postinfection but showed a significant increase of M2 markers, such as CD206, CD163, and CD209. Interestingly, anti-inflammatory cytokines, like IL-10 and TGF-β, were induced after infection in the 3 macrophage phenotypes. B. pertussis phagocytosis by M1 macrophages was lower than by M2 phenotypes, which may be ascribed to differences in the expression level of B. pertussis docking molecules on the surface of the different phenotypes. Intracellular bactericidal activity was found to be significantly higher in M1 than in M2a or M2c cells, but live bacteria were still detected within the 3 phenotypes at the late time points after infection. In summary, this study shows that intracellular B. pertussis is able to survive regardless of the macrophage activation program, but its intracellular survival proved higher in M2 compared with the M1 macrophages, being M2c the best candidate to develop into a niche of persistence for B. pertussis.

PLAIN LANGUAGE SUMMARYPertussis, also called whooping cough, is a common disease in adults. However, how it affects adults in some countries in the Asia-Pacific region is not well understood. In 2019, a panel of experts met to review the available information on adult cases of pertussis in Australia, Hong Kong, New Zealand, Singapore, South Korea, and Taiwan. Here, we present the outcomes of the meeting. Pertussis is increasingly reported in the Asia-Pacific region, including cases diagnosed in adults. The diagnosis may be missed in countries where awareness is still low and/or it is not tested routinely. The experts concluded that physicians should consider recommending pertussis vaccination to older adults (aged 65 or older) on an individual basis, as well as people with asthma or chronic obstructive pulmonary disease, who appear to be at higher risk of severe pertussis. Uptake of pertussis vaccination in adults could be improved by increasing awareness of the vaccines available and vaccination infrastructure for this age-group. Some of the measures proposed were as follows: improved access to vaccination; personalized reminders when vaccines are due; and more education about pertussis in adults for doctors, nursesnurses, and patients. The experts also proposed setting up adult vaccination registries for tracking and evaluation of vaccine uptake. This expert opinion might help the healthcare community build action plans to recognise the burden of the disease and increase rates of vaccination among adults. In addition, better data on the disease burden would help to generate awareness.

Neonatal pertussis can potentially cause severe complications and even death. Mothers have been most frequently identified as the source of neonatal pertussis. Approximately a dozen countries have implemented pertussis vaccination programs for pregnant women to protect neonates; however, in Japan, this has not been implemented. The aim of this questionnaire-based study was to ascertain the willingness of women to be vaccinated during pregnancy and the factors associated with willingness. The subjects were 977 pregnant women who visited either of the two selected hospitals for maternity health checks. Most of the women were in their first pregnancy (96%), and approximately half of them considered a physician to be the most reliable source of information about vaccination (481/977, 49%). "Willingness to receive pertussis vaccination" was significantly associated with the factors "no fear of receiving vaccination" (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 2.21-4.34), "necessary to prevent pertussis" (OR = 8.70, 95% CI: 6.17-12.28), "effective in pregnancy" (OR = 5.46, 95% CI: 3.94-7.56), and "no concern about the side effects after vaccination" (OR = 3.03, 95% CI: 1.66-5.55). Pregnant women are likely to consider vaccination if they have a good understanding of the disease and its outcomes. Physicians are well positioned to improve knowledge and attitudes toward pertussis vaccination during pregnancy.

Relevance. Currently, the national calendar of preventive vaccinations does not provide for revaccination against whooping cough in children over the age of 18 months. At the same time, the epidemiological and economic feasibility of revaccination against whooping cough in children aged 6–7 years, as well as adolescents, has been demonstrated in world practice. Aim. Based on a mathematical model, develop a forecast of pertussis morbidity dynamics and assess the potential socio-economic damage under the current and expanded vaccine prophylaxis algorithms.Methods. Mathematical modeling of the potential effect of revaccination against whooping cough in children aged 6–7 years (scenario 1) and at 6–7 years and 14 years (scenario 2) was carried out within the framework of the national calendar of preventive vaccinations. A simulation dynamic mathematical model is constructed that allows predicting the development of the epidemiological process of whooping cough on the basis of the dynamics of the main indicators of its prevalence in the population that developed in previous years. The model took into account dynamic changes in the preventive effectiveness of vaccinations and the potential level of underestimation of morbidity. The obtained arrays of indicators served as the basis for extrapolating trends in morbidity and mortality until 2034.The calculation of epidemiological benefits was carried out in the metrics of prevented loss of years of life under the two scenarios under consideration in comparison with the current vaccination algorithm. The calculation of the economic effect was carried out on the basis of the obtained indicators of epidemiological benefits in the metrics of the monetary equivalent of the average cost of a year of life, taking into account the projected inflation coefficients until 2034.Results. The projected decrease in the number of years of life lived in a state of illness, in comparison with the current situation, will total 44.5 thousand years for the period 2019–2034 under scenario 1 and 66.7 thousand years under scenario 2. The socio-economic damage from prevented cases of the disease, expressed in the monetary equivalent of the average cost of living, will decrease by 28.6% (scenario 1) or 42.0% (scenario 2).Conclusions. A comparison of the received public benefits with the costs of vaccination shows that the expansion of the NCPP with additional revaccinations against whooping cough (at 6–7 years or at 6–7 and at 14 years) is advisable both in epidemiological and economic aspects.

Relevance. Whooping cough remains a pressing public health problem worldwide, including in countries with high vaccination rates. One of the probable causes of the ongoing epidemic process of pertussis infection is B. pertussis biofilms, which differ from plankton cultures by an altered gene expression spectrum and are highly resistant to environmental conditions, antibiotics, and immune factors.Aims. Analysis of literature data on the genetic and molecular - cellular mechanisms of biofilm formation by bacteria of the genus Bordetella, as well as approaches to the search for means aimed at suppressing the growth of biofilms and the destruction of formed biofilms in the macroorganism.Conclusions. Biofilm formation by microbes of the genus Bordetella is a complex multistage process regulated by genetic signaling systems: the Bvg AS system and the 2-nucleotide (p) ppGrp system, as well as other regulatory proteins and the polysaccharide complex. The matrix of B. pertussis biofilms consists of extracellular DNA, proteins, and a polysaccharide polymer that play an important role in the formation of biofilms in the respiratory tract and on abiotic surfaces. The genetic and molecular-cellular processes of biofilm formation and maintenance, as well as the various components of the biofilm matrix, can serve as targets for new antimicrobial drugs and more effective pertussis vaccines that will better control the entire pertussis infection cycle, including colonization, persistence, and transmission of the causative agent. One of the approaches to the development of new-generation cell-free pertussis vaccines is the identification of new biofilm-associated antigens that can induce effective cellular and humoral responses. The search for drugs that can destroy biofilms, including substances that affect the matrix and facilitate the access of antibacterial drugs to microbial cells, is promising.