Pertussis Vaccine Effectiveness Research Articles

Pertussis Vaccines Scarcely Provide Protection against Bordetella parapertussis Infection in Children-A Systematic Review and Meta-Analysis.

Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against Bordetella pertussis infections, but their effectiveness against Bordetella parapertussis remains debated due to conflicting study outcomes. A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against B. parapertussis infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against B. parapertussis infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain. These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against B. parapertussis. Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against B. parapertussis.

The effectiveness of maternal pertussis vaccination for protecting Aboriginal and Torres Strait Islander infants against infection, 2012-2017: a retrospective cohort study.

To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. Retrospective cohort study; analysis of linked administrative health data. Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.

Evaluation of the effectiveness of maternal immunization against pertussis in Alberta using agent-based modeling: A Canadian immunization research network study

IntroductionThe re-emergence of pertussis has occurred in the past two decades in developed countries. The highest morbidity and mortality is seen among infants. Vaccination in pregnancy is recommended to reduce the pertussis burden in infants. MethodsWe developed and validated an agent-based model to characterize pertussis epidemiology in Alberta. We computed programmatic effectiveness of pertussis vaccination during pregnancy (PVE) in relation to maternal vaccine coverage and pertussis disease reporting thresholds. We estimated the population preventable fraction (PFP) of different levels of maternal vaccine coverage against counterfactual ”no-vaccination” scenario. We modeled the effect of immunological blunting and measured protection through interruption of exposure pathways. ResultsPVE was inversely related to duration of passive immunity from maternal immunization across most simulations. In the scenario of 50% maternal vaccine coverage, PVE was 87% (95% quantiles 82–91%), with PFP of 44% (95% quantiles 41–45%). For monthly age intervals of 0–2, 2–4, 4–6 and 6–12, PVE ranged between 82 and 99%, and PFP ranged between 41 and 49%. At 75% maternal vaccine coverage, PVE and PFP were 90% (95% quantiles 86–92%) and 68% (95% quantiles 65–69%), respectively. At 50% maternal vaccine coverage and 10% blunting, PVE and PFP were 86% (95% quantiles 77–87%) and 43% (95% quantiles 39–44%), respectively, while at 50% blunting, the corresponding values of PVE and PFP were 76% (95% quantiles 70–81%) and 38% (95% quantiles 35–40%). PVE attributable to interruption of exposure pathways was 54–57%. ConclusionsOur model predicts significant reduction in future pertussis cases in infants due to maternal vaccination, with immunological blunting slightly moderating its effectiveness. The model is most sensitive to maternal vaccination coverage. The interruption of exposure pathways plays a role in the reduction of pertussis burden in infants due to maternal immunization. The effect of maternal immunization on population other than infants remains to be elucidated.

An observational, cohort, multi-centre, open label phase IV extension study comparing preschool DTAP-IPV booster vaccine responses in children whose mothers were randomised to one of two pertussis-containing vaccines or received no pertussis-containing vaccine in pregnancy in England

An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study.Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP3-IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP5-IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP5-IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared.Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP3-IPV and dTaP5-IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP3-IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22–0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups.The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose.ClinicalTrials.gov registration number: NCT03578120

Effectiveness of maternal pertussis vaccination in Singapore: A test-negative case-control study

Pertussis vaccination (Tdap -Tetanus-diphtheria-acellular pertussis) for pregnant women has been recommended since November 2017 in Singapore. In this prospective test-negative case-control study from 2018 to 2019, we aimed to evaluate vaccine effectiveness (VE) against pertussis infection and pertussis-related intensive care unit (ICU) admission according to Tdap (Tetanus-diphtheria-acellular pertussis) during pregnancy and/or infant pertussis vaccination. A total of 58 children (26 cases, 32 controls) were recruited with 4 ICU admissions. The median age was 3 months (interquartile range [IQR] 1.50–4.56 months). Overall, 25.9 % of mothers had received antenatal Tdap vaccination and 43.1 % of infants received pertussis vaccination, majority only 1 dose. Tdap in pregnancy alone without infant vaccine or with 0–1 infant dose had a VE of 97.62 % (95 % confidence interval [CI] 53.25–99.88 %), 98.17 % (95 %CI 66.61–99.9 %) respectively, against pertussis infection and 71.9 % (95 %CI 0.0–98.64), 75.86 % (95 % CI 0.0–98.78) respectively, against ICU admissions. Conclusion: Maternal Tdap vaccination was highly protective against infant pertussis and should be routinely recommended for all pregnant women.

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged

BackgroundPERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2–11 months, VE of vaccination in pregnancy and of primary vaccination (PV). MethodsFrom December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants’ age group. ResultsOf 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35–91%] and 88% [95%CI: 57–96%].Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33–90] and 95% [95%CI: 69–99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27–86] and 94% [95%CI: 59–99]. ConclusionOur findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2–11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.

Effect of pertussis vaccine in pregnancy and COVID-19 pandemic in the cases of wooping cough

BackgroundWhooping cough has had an increased incidence and severity specially in infants and maternal immunization has been implemented as a prevention strategy. COVID-19 pandemic seems to decrease the incidence of other respiratory diseases. MethodsRetrospective study from 2012 to 2021 to assess the influence of pertussis maternal immunizations and the first year of COVID-19 pandemic in the cases of whooping cough. Results960 suspected cases from primary care and hospital, with 130 cases (104 children and 26 adults) being diagnosed of whooping cough. In the post-vaccination period, a reduction in the cases and severity in infants up to 6 months old was observed as well as in the pertussis diagnosis in adult women. There were no whooping cough cases during the COVID-19 period. ConclusionsBoth the pertussis vaccination in pregnancy and the first year of the COVID-19 pandemic have decreased the number of pertussis cases.

Pertussis burden and acellular pertussis vaccine effectiveness in high risk children

BackgroundPertussis 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. MethodsPerinatal, 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. ResultsAmong >1,300,000 children, 63,867 (4·9%) were Aboriginal, 47,721 (3·6%) had at least one comorbidity and 3,771 first episodes of notified pertussis occurred <18 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). ConclusionsFor 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 (born <32 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.

Maternal Vaccination Protects Infants Against Flu and Pertussis

Source: Rowe SL, Leder K, Perrett KP, et al. Maternal vaccination and infant influenza and pertussis. Pediatrics. 2021;148(3): e2021051076; doi.10.1542/peds.2021-051076Investigators from multiple institutions in Australia conducted a population-level inception cohort study to assess the effectiveness of maternal influenza and pertussis vaccination during pregnancy in preventing these diseases in their children during the first 6 months of life. For the study, they abstracted data from the Victorian Perinatal Data Collection (VPDC) on women whose pregnancies ended between September 2015 and December 2017. The VPDC includes information on all live births and stillbirths in Victoria, Australia, including demographic and clinical data related to pregnancy and birth. In addition, whether the mother received influenza and/or pertussis vaccine at any time during pregnancy is recorded. Data from multiple databases were reviewed to identify laboratory-confirmed cases of influenza and pertussis in infants <6 months old during the study period and record ED visits, hospital admissions, and deaths from influenza and pertussis. Information from these databases and VPDC were linked to identify mother-infant dyads.The primary study outcomes were laboratory-confirmed cases of influenza and pertussis in infants born to mothers included in the study, and secondary outcomes included cases of severe disease, defined as ED visit, hospitalization, or death from influenza or pertussis in study infants. Poisson regression was used to calculate the relative risk (RR) for influenza and pertussis in infants of mothers vaccinated during pregnancy vs not vaccinated, after adjusting for multiple confounders. Results were stratified in infants <2 months old, and those 2 to <6 months of age. Vaccine effectiveness (VE) of maternal immunization in preventing childhood illness was estimated as (1-RR) × 100.Data were analyzed on 186,962 mother-infant dyads. Overall, 45.9% of study women were vaccinated against influenza during pregnancy and 68.5% against pertussis. There were 185,404 and 184,194 infants, respectively, included in influenza and pertussis vaccination analyzes. The risk of influenza was significantly reduced in children whose mothers were vaccinated, both among children <2 months old (RR, 0.44; 95% CI, 0.25, 0.77), and in those 2 to <6 months of age (RR, 0.64; 95% CI, 0.42, 0.98), with VE estimated as 56.1% (95% CI, 23.3%, 74.9%) and 35.7% (95% CI, 2.2%, 57.7%), respectively. Maternal vaccination reduced the risk of pertussis in infants <2 months old (RR, 0.20; 95% CI, 0.06, 0.63), with an estimated VE of 80.1% (95% CI, 37.1%, 93.7%), but no significant effect was noted among infants 2 to <6 months old (RR, 0.68; 95% CI, 0.33, 1.39). Maternal pertussis immunization reduced the risk of severe pertussis in infants <2 months old (RR, 0.38; 95% CI, 0.16, 0.94). There were no significant effects from maternal vaccination on severe cases of pertussis in children 2 to <6 months old or on influenza among children <6 months old.The authors conclude that maternal vaccination during pregnancy reduces the risk of influenza and pertussis in infants <2 months old.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The goal of maternal immunization is to provide infants with passive antibodies prior to their first dose of vaccines. In a previous study, Baxter et al1 noted that maternal Tdap during pregnancy significantly reduced pertussis risk during the entire first year of life (See AAP Grand Rounds. 2017;38[2]:15.)1 In the current study, which included infants born at ≥30 weeks’ gestation, this benefit was most notable only in infants <2 months. In contrast, Baxter et al1 enrolled only infants born at ≥37 weeks’ gestation, allowing more time for antibody transfer after maternal Tdap receipt (usually between 27–36 weeks’ gestation).2As demonstrated by the results of the current study, maternal vaccination during pregnancy also reduces the infant’s risk for influenza during the first 6 months of life. Tdap and influenza vaccination rates during pregnancy, however, remain suboptimal.3 To assess influenza and Tdap vaccination coverage among women pregnant during the 2020–21 influenza season, the Centers for Disease Control and Prevention (CDC) conducted a survey during April 2021.4 Among 1,795 survey respondents who were pregnant anytime during October 2020–January 2021, 54.5% reported receiving an influenza vaccine before or during pregnancy. Among 729 respondents, 53.5% reported receiving Tdap during pregnancy. Unfortunately, receipt of both influenza and Tdap vaccines was reported by only 30.7% of women.COVID-19 vaccines also are recommended for all pregnant women.5 Providers need to take every opportunity to recommend these vaccines for their pregnant patients.Vaccination of pregnant women with Tdap, influenza, and COVID-19 vaccines is safe and protects the mother and her young infant.As influenza vaccines are approved only for infants ≥6 months of age, the 6-month duration of immunity conferred by maternal influenza vaccination provides further support for maternal immunization.

Maternal Vaccination and Infant Influenza and Pertussis.

Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants. This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged <2 months, 2 to <6 months, and <6 months combined. Secondary outcomes included infant hospitalization (emergency presentation or admission) and death. Risk ratios and 95% confidence intervals (CIs) were estimated by Poisson regression. Vaccine effectiveness (VE) was estimated as (1 minus the risk ratio) x 100%. Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged <2 months and 35.7% (2.2% to 57.7%) for infants aged 2 to <6 months. Pertussis VE was 80.1% (95% CI, 37.1% to 93.7%) for infants aged <2 months and 31.8% (95% CI, -39.1% to 66.6%) for infants aged 2 to <6 months. Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged <2 months. The findings strengthen the importance of maternal vaccination to prevent these diseases in infants.

Exploring the reasons for low pertussis vaccine effectiveness in Ontario, Canada, 2006-2008: a Canadian Immunization Research Network study.

Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008. We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies. We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years. VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.

Effectiveness of maternal pertussis vaccination in protecting newborn: A matched case-control study

IntroductionThe objective was to estimate the effectiveness of maternal pertussis vaccination in protecting infants aged < 2 months. MethodsWe performed a case-control study. Laboratory-confirmed cases aged <8 weeks at disease onset were identified and 2–4 matched-controls born within ± 15 days of the case were included. Information was obtained from healthcare providers and maternal interviews. Odds ratios (OR) were calculated using multivariable conditional logistic regression. Vaccine effectiveness (VE) was estimated as (1 – OR) × 100%. Results47 cases and 124 controls were studied. The mean age (in days) (39.8 ± 12.7 vs. 40.8 ± 13.2), weeks of gestation (38.8 vs. 39.1, p = 0.43) and mean birth weight (3.309 vs. 3.253 kg, p = 0.55) were comparable between cases and controls. Mothers of cases were less frequently vaccinated in the third trimester (59.6% vs. 83.9%, p <0.001). The VE of maternal vaccination in pregnancy was 88.0% (95%CI 53.8% -96.5%), and was slightly higher in those vaccinated before the 32nd week of gestation (88.5% vs 87.8%). ConclusionPertussis vaccination in pregnancy is very effective in reducing pertussis in children aged < 2 months. Vaccination before and after the 32nd week of pregnancy are equally effective in reducing the risk of pertussis.

Effectiveness of experimental and commercial pertussis vaccines in the elimination of Bordetella pertussis isolates with different genetic profiles in murine model

The aim of this study was to compare the elimination of Bordetella pertussis clinical isolates, representing different genotypes in relation to alleles encoding virulence factors (MLST—multi-locus antigen sequence typing), MLVA type (multi-locus variable-number tandem repeat analysis) and PFGE group (pulsed-field gel electrophoresis) from the lungs of naive mice or mice were immunised with the commercial whole-cell pertussis vaccine, the acellular pertussis vaccine and the experimental whole-cell pertussis vaccine. Molecular data indicate that the resurgence of pertussis in populations with high vaccine coverage is associated with genomic adaptation of B. pertussis, to vaccine selection pressure. Pertactin-negative B. pertussis isolates were suspected to contribute to the reduced vaccine effectiveness. It was shown that one of the isolates used is PRN deficient. The mice were intranasally challenged with bacterial suspension containing approximately 5 × 10 7 CFU/ml B. pertussis. The immunogenicity of the tested vaccines against PT (pertussis toxin), PRN (pertactin), FHA (filamentous haemagglutinin) and FIM (fimbriae types 2 and 3) was examined. The commercial whole-cell and acellular pertussis vaccines induced an immunity effective at eliminating the genetically different B. pertussis isolates from the lungs. However, the elimination of the PRN-deficient isolate from the lungs of mice vaccinated with commercial vaccines was delayed as compared to the PRN ( +) isolate, suggesting phenotypic differences with the circulating isolates and vaccine strains. The most effective vaccine was the experimental vaccine with the composition identical to that of the strains used for infection.

A multisite study of pertussis vaccine effectiveness by time since last vaccine dose from three Canadian provinces: A Canadian Immunization Research Network study

BackgroundPertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta-analytic approach to improve precision and explore regional variation in VE and durability of protection. MethodsStudies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age. ResultsData on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I2 = 81.5%) at < 1 year since last vaccination to 51% (11%-74%, I2 = 80.9%) by ≥ 8 years. Effect estimates were the most heterogeneous in the least and most elapsed time periods since last vaccine dose. This was attributable mostly to variation between provinces in the distribution of age groups and number of vaccine doses received within time periods, as well as study design and small numbers in the most elapsed time period.Interpretation: Consistent trends of decreasing pertussis VE with increasing time since last vaccination across three Canadian provinces indicate the need for immunization schedules and vaccine development to optimize protection for all individuals, especially for adolescents and young adults at greatest risk of infection.

Systematic review and meta-analysis of the effect of pertussis vaccine in pregnancy on the risk of chorioamnionitis, non-pertussis infectious diseases and other adverse pregnancy outcomes

BackgroundSeveral countries have introduced maternal immunisation with pertussis vaccine to provide protection against pertussis in early infancy. There is increasing interest in non-specific effects of vaccines including that non-live vaccines may enhance susceptibility to non-targeted infections in females. Some studies have shown increased risk of chorioamnionitis among women receiving pertussis vaccine during pregnancy. We aimed to conduct a systematic review and meta-analysis of the effect of maternal pertussis immunisation on the risk of chorioamnionitis, as well as the secondary outcomes of non-pertussis infections in women, non-pertussis infections in infants, spontaneous abortion or stillbirth, maternal death and infant death. MethodsWe searched PubMed and Embase for articles published until January 14, 2021. We screened articles for eligibility and extracted data using Covidence. Quality was assessed using Cochrane RoB tool and Newcastle-Ottawa Scale. Data were imported into RevMan for pooling and conduction of a meta-analysis stratified by study type. Outcomes are presented as risk ratios. ResultsWe identified 13 observational studies and six randomized controlled trials eligible for inclusion. We pooled data on chorioamnionitis from six observational studies and found maternal pertussis vaccine (mostly compared with other maternal immunizations with non-live vaccines) to be associated with an increased risk among the pertussis vaccinated women, RR = 1.27 [CI 95%: 1.14–1.42]. We found no difference in the analysis of our secondary outcomes of non-pertussis infections, spontaneous abortion or stillbirth and death. ConclusionWe found an increased risk of chorioamnionitis among women who received pertussis vaccine in pregnancy. The large number of women receiving pertussis vaccine during pregnancy, as well as the growing evidence of non-live vaccines causing increased susceptibility to infections, indicates a need for further randomised trials to assess potential adverse effects of maternal immunisation with pertussis-containing vaccines.

Assessment of Pertussis Vaccine Protective Effectiveness in Children in the Amhara Regional State, Ethiopia.

Background Bordetella pertussis is a human pathogen which causes pertussis, or whooping cough. The diphtheria-tetanus-pertussis immunization has significantly reduced the morbidity and mortality of pertussis globally. However, higher prevalence and resurgence of pertussis cases among both vaccinated and unvaccinated people has raised questions on the effectiveness of pertussis vaccine over time. Therefore, the objective of this study was to assess the protective effectiveness of pertussis vaccine in the Amhara Regional State, Ethiopia. Methods A nested matched case-control study design approach was used with vaccinated individuals as cases and unvaccinated individuals as controls. The study was conducted from July 2018 to February 2019. Real-time (RT-) PCR assay was done to ascertain the presence of pertussis among clinically suspected patients. Bivariable and multivariable logistic regression analyses were computed to estimate the crude and adjusted odds ratios (ORs), respectively. Vaccine effectiveness was calculated as (1 − OR) × 100. Adjusted OR with 95% CI and a P value <0.05 were used to assess statistical significance. Results A total of 112 vaccinated and 223 unvaccinated controls were enrolled for the study. Of the total participants, 173/335 (51.6%) were males. The prevalence of pertussis among vaccinated was 35/112 (31.3%), whereas it was 84/223 (37.7%) among the control group. The adjusted matched vaccine protective effectiveness against B. pertussis infection following three doses of whole-cell vaccine was 25% among children aged between 6 and 9 years. Adjusted estimates of vaccine protective effectiveness for participants who had complete vaccination, stratified by time since last vaccination, were 50% at 6 years, 34% at 7 years, and 2% at 8–9 years since last vaccination. Conclusion Despite the availability and good coverage of childhood vaccination, the effectiveness of pertussis vaccine was found to be low in the Amhara region, Ethiopia. Moreover, we observed declining trends in the protective effectiveness of the vaccine after 6 years of vaccination. Thus, by considering the waning nature of immune response which is induced by whole-cell vaccine during early life, booster dose is highly recommended to optimize pertussis prevention and control strategies.

Brand-specific rates of pertussis disease among Wisconsin children given 1–4 doses of pertussis Vaccine, 2010–2014

BackgroundAcellular pertussis vaccines were initially licensed based on placebo-controlled efficacy trials, but such trials are no longer ethical. The effectiveness of current pertussis vaccines among properly vaccinated children <5 years is so high that a randomized trial is infeasible. Fluctuations in pertussis incidence and characteristics of the US vaccine marketplace make selection of suitable controls for a case-control study problematic. To satisfy an FDA requirement to evaluate rates of pertussis following licensure of Pentacel® vaccine, we used a case-cohort study design with a novel method for characterizing the cohort population. MethodsThis prospective, observational study was conducted in Wisconsin from 2010 to 2014 among Wisconsin residents <60 months of age who received ≤four doses of pertussis vaccine (surveillance population). Cases were identified by the Wisconsin Division of Public Health. Characteristics and pertussis vaccinations of the surveillance population were estimated by ongoing random telephonic survey. The primary objective was to determine rates of pertussis disease among those who received only Pentacel vaccine (Group 1) vs those who received a single brand of vaccine other than Pentacel vaccine (Group 2). Results1195 pertussis cases were identified. It was estimated that the surveillance population accrued a total of 1,133,403 person-years (Group 1, 39%; Group 2, 41%; Group 3 [those not in Group 1 or Group 2], 20%). Pertussis rates were similar in Group 1 (98.9/100,000) and Group 2 (96.2/100,000); rate ratios were 1.03 (unadjusted; 90% CI, 0.92–1.15) and 0.99 (adjusted; 90% CI, 0.89–1.12). Persons with one or more delayed vaccinations had a 66% higher risk of pertussis (90% CI, 39–96%). DiscussionPertussis protection was not found to differ for recipients of the newly licensed vs other available pertussis vaccines. Delayed vaccination substantially increased risk of pertussis. Sample survey methodology was able to characterize the study cohort and enable an otherwise-infeasible study.Clinical Trial Registry number: ClinicalTrials.gov, NCT01129362.

Comparison of whole-cell versus acellular pertussis vaccine effectiveness in school clusters of pertussis, France, 2013

Objectives and methodWe conducted a prospective study in 2013 to compare the whole-cell versus acellular pertussis vaccines effectiveness and duration of protection, following the occurrence of pertussis clusters. ResultsDuring seven school outbreaks, we identified 102 clinical pertussis cases, including 10 cases biologically confirmed by Bordetella pertussis specific PCR, among a cohort of 305 children in 2nd to 6th grade. The risk of pertussis when vaccinated with an acellular vaccine alone was 1.6 (RR=1.6; 95% CI=1.1–2.5) times higher than when vaccinated with a whole-cell vaccine or using a combined schedule. ConclusionsThe limited duration of protection conferred by the acellular vaccine reinforces the 2013 introduction of the pertussis booster at six years old.

Pertussis epidemiology and effect of vaccination among diagnosed children at Vietnam, 2015-2018.

To evaluate effect and costs of pertussis vaccination at Vietnam National Children's Hospital. Pertussis cases were defined by positive laboratory tests of children under 5years January 2015-June 2018, and data on patient characteristics, clinical data and hospitalisation costs were collected through patient records. Of 909 inpatients, 400 (44%) were <2months, the age for first DPT vaccination, and mechanical ventilation was more common than in children >2months (9% vs 4%, OR=2.3, CI 1.3-3.9), as well as persistent cough (99%), violent cough (87%) and pneumonia (91%). Comparing non-vaccinated (172 cases, 19%) and DPT vaccinated patients >2months of age hospitalisation was 106-fold higher (149.6 vs 1.39 per 100000 population), and proportion of severe patients, length of hospital stay and hospitalisation costs were significantly greater (23.9% vs 12.8%; 13 vs 10days; 826 USD vs 582 USD, CI 23-423, P=.03). Incidence and proportion of complications among under 2-month infants were higher than in older patients. DPT vaccination protects children from pertussis infection, and in case of pertussis infection decreases severity. Results indicate that the Ministry of Health should consider adding a booster vaccine for pregnant women in an extended vaccination programme.

Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review

BackgroundInfants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy.MethodsWe searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach.ResultsWe identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome.ConclusionAlthough an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented.Trial registrationPROSPERO CRD42018087814, CRD42018090357.