Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: The NSW Public Health Network case-control study

BackgroundInfants are at the highest risk of severe complications – including death – as a result of pertussis infection. Controlling pertussis in this group has been challenging, particularly in those too young to be vaccinated. Following revised national recommendations in March 2015, the state of New South Wales, Australia, introduced a funded maternal vaccination campaign at 28 – 32 weeks of gestation using a 3-component tetanus-diphtheria-acellular pertussis vaccine (dTpa; Boostrix, GSK). This study aimed to assess the effectiveness of maternal vaccination and add to the growing body of evidence for this strategy.MethodsA 1:1 matched case-control study was conducted between 16 August 2015 and 17 August 2016. Cases were laboratory or doctor notified, laboratory confirmed (nucleic acid testing or culture) and aged <6 months at onset. Each control infant was randomly selected from public hospital births in the same geographical area in the period up to 3 days before and after the case’s birthdate. Odds ratios (OR) were calculated using conditional logistic regression. Vaccine effectiveness (VE) was calculated as 1 – OR.FindingsIn total, 117 cases and 117 controls were recruited. The overall VE estimate was non-significantly protective for infants <6 months old (VE 39%, 95% CI −12 to 66%). Higher VE was observed for infants <3 months old (VE 69%, 95% CI 13–89%) and against hospitalisation (VE 94%, 95% CI 59–99%).InterpretationMaternal pertussis vaccination with a 3-component acellular vaccine was found to be highly effective at preventing severe disease in infants, but was less effective at preventing disease which did not require hospitalisation. The overall VE reported in this study was lower than in prior studies and suggests that maternal vaccination, while an effective strategy at preventing severe pertussis, is less effective at protecting against infection or mild disease.     

Uptake of a government-funded pertussis-containing booster vaccination program for parents of new babies in Victoria,Australia

IntroductionAn epidemic of Bordetella pertussis in Victoria, Australia, led to the implementation of a Government-funded vaccination program for parents of new babies. The rationale was to protect unimmunised infants from infection by vaccinating parents with a pertussis-containing vaccine. This is known as cocooning.AimTo estimate uptake of the vaccine among parents of new babies, two-and-a-half years after the program was implemented.MethodsA state-wide cross-sectional survey of parents was conducted to ascertain vaccine uptake, and to identify where and when the vaccination took place. Surveys were administered between 15 February and 14 March 2012, inclusive.ResultsOf 6308 surveys distributed, 2510 completed surveys were returned (response rate 40%). Ninety-five surveys completed outside the study period were excluded, leaving 2415 available for analysis. Overall, 1937 (80%) mothers and 1385 (70%) fathers were vaccinated in relation to the birth of their most recent child. A majority of mothers were vaccinated in hospital (62%). Most fathers were vaccinated by a general practitioner (72%). The most common point at which mothers were vaccinated was before their child turned two weeks of age (65%). Fathers’ vaccination time-point varied more widely: during pregnancy (25%); before their child turned two weeks of age (29%); and when their child was between two and eight weeks of age (28%).ConclusionResults of this survey indicated excellent uptake of the vaccine among both mothers and fathers under the Government-funded cocooning program. The findings are suggestive of an effective communications program designed to raise awareness of the risks of pertussis, and to promote availability of the funded vaccination program. The results may contribute to policy implementation of adult immunisation programs such as cocooning.     

Prenatal tetanus-diphtheria-acellular pertussis vaccine effectiveness at preventing infant pertussis

ObjectiveTo evaluate the effectiveness of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine containing five pertussis components (Tdap5; Adacel®, Sanofi) when given during pregnancy at preventing pertussis in infants less than 2 months of age.MethodsThe US Centers for Disease Control and Prevention (CDC), in collaboration with the Emerging Infections Program (EIP) Network, undertook a case-control study evaluating the effectiveness of Tdap vaccination in pregnancy against pertussis in infants less than 2 months of age based on data collected by the EIP Network from 2011 through 2014. The dataset from the CDC/EIP Network study was used to conduct this product-specific vaccine effectiveness analysis of Tdap5 vaccination in pregnancy to prevent disease in young infants. The main outcome of interest was vaccine effectiveness in infants whose pregnant parents were vaccinated with Tdap5 between 27 and 36 weeks’ gestation, in accordance with the ideal timing for Tdap vaccination in pregnancy recommended by the US Advisory Committee on Immunization Practices. Odd ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression, and vaccine effectiveness was calculated as (1–OR) × 100 %.ResultsThere were 160 infant pertussis cases and 302 matched controls included in this Tdap5-specific study. Tdap5 effectiveness in preventing pertussis in infants whose pregnant parents were vaccinated between 27 and 36 weeks’ gestation was 92.5 % (95 % CI, 38.5 %–99.1 %). Effectiveness of Tdap5 against pertussis-related hospitalization in infants whose pregnant parents were vaccinated between 27 and 36 weeks’ gestation could not be calculated due to lack of discordance among matched cases and controls. Vaccination of the parents after pregnancy or less than 14 days before delivery did not protect infants from pertussis.ConclusionsTdap5 vaccination in pregnancy between 27 and 36 weeks’ gestation is highly effective at protecting young infants from pertussis.Study registration: ClinicalTrials.gov, NCT05040802.     

The effectiveness of maternal pertussis vaccination in protecting newborn infants in Brazil: A case-control study

IntroductionIn 2014, the Brazilian Ministry of Health (MoH) recommended Tdap to pregnant women in response to a significant increase in the incidence of pertussis among infants. The present study assessed the effectiveness of maternal immunization in preventing pertussis in infants.MethodsAn unmatched case-control study was undertaken in São Paulo State, Brazil from February 2015 to July 2016. Cases were infants aged <8 weeks at onset of pertussis reported to the Surveillance System and confirmed by real-time polymerase chain reaction or culture. Four to six healthy infants were selected as controls per case from birth certificates in the Information System on Live Births database. General characteristics and mother’s vaccination status were compared between cases and controls. The vaccine effectiveness (VE) was calculated as 1 – odds ratio (OR). For the adjusted VE, the OR was calculated using logistic regression analysis.ResultsForty-two cases and 248 controls were enrolled in the study. Mothers of 8 cases (19.1%) and 143 controls (57.4%) were vaccinated during pregnancy, resulting in an unadjusted VE of 82.6% (95% confidence interval [CI], 60.8–92.3%). The VE was unchanged after adjusting for maternal age and monthly household income.ConclusionMaternal pertussis vaccination during pregnancy was effective in protecting infants aged <8 weeks from pertussis.     

Cost–benefit of the introduction of new strategies for vaccination against pertussis in Spain: Cocooning and pregnant vaccination strategies

BackgroundPertussis remains a public health problem in countries with high vaccination coverage. Classic vaccination approaches have failed to effectively control the infection. The incidence of pertussis hospitalizations in infants is high, especially in those younger than 3 months who are in high risk of a severe disease and death. Additional strategies are recommended for short-term protection of this vulnerable population. In this study, we estimated the impact of 2 strategies for pertussis prevention in infants younger than 1 year of age—a cocoon vaccination strategy and the vaccination of pregnant women (VPW)—and the cost–benefit of these approaches relative to the current vaccination policy in Spain.MethodsA cost–benefit analysis was conducted from the perspective of the publically-funded Spanish healthcare system, based on the yearly number of hospitalizations during the period of 2009 to 2011. We calculated the absolute risk reduction, the number of parents that would need to be vaccinated to prevent 1 hospitalization or death in infants <1 year, and the net benefit-to-cost ratio of each strategy.ResultsFrom 2009 to 2011, the incidence of pertussis in Spain was 153.44 hospitalizations per 100,000 infants <1 year. The absolute risk reduction for hospitalization would be 42.1/100,000 with cocooning and 75.2/100,000 with VPW. The number of parents needed to vaccinate with the cocoon strategy to prevent 1 pertussis hospitalization would be 4752 and to prevent 1 death, more than 900,000. With VPW, 1331 pregnant women would have to be vaccinated to prevent 1 hospitalization and 200,000 to prevent 1 death. The benefit-to-cost ratio was 0.04 for cocooning and 0.15 for VPW.     

The impact of parental postpartum pertussis vaccination on infection in infants: A population-based study of cocooning in Western Australia

During a pertussis epidemic in 2011–2012 the Western Australian (WA) Department of Health implemented a ‘cocooning’ programme, offering free pertussis-containing vaccine (dTpa) to new parents. We assessed the impact of vaccinating parents with dTpa on the incidence of pertussis infection in newborns.Births in WA during 2011–2012 were linked to a register of parental pertussis vaccinations and to notified reports of laboratory-proven pertussis in children <6 months of age. Parents who received dTpa during the four weeks after their child's birth were defined as ‘vaccinated postpartum.’ Cox proportional-hazards methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of pertussis infection among infants born to parents vaccinated postpartum vs. unvaccinated parents, adjusted for maternal age, geographic region, timing of birth, and number of siblings.Of 64,364 live-births, 43,480 (68%) infants had at least one vaccinated parent (60% of mothers and 36% of fathers). After excluding records where parent(s) were either vaccinated prior to the birth, vaccinated >28 days after the birth, the vaccination date was uncertain, or the child died at birth (n = 42), the final cohort contained 53,149 children, 118 of whom developed pertussis. There was no difference in the incidence of pertussis among infants whose parents were both vaccinated postpartum compared to those with unvaccinated parents (1.9 vs 2.2 infections per 1000 infants; adjusted HR 0.91; 95%CI 0.55–1.53). Similarly, when assessed independently, maternal postpartum vaccination was not protective (adjusted HR 1.19; 95%CI 0.82–1.72). Supplemental sensitivity analyses which varied the time period for parental vaccination and accounted for under-reporting of vaccination status did not significantly alter these findings.In our setting, vaccinating parents with dTpa during the four weeks following delivery did not reduce pertussis diagnoses in infants. WA now provides dTpa vaccine to pregnant women during the third trimester.     

Estimates of pertussis vaccine effectiveness in United States air force pediatric dependents

BackgroundPertussis vaccination compliance is critical for reduction in the prevalence of disease; however, the current acellular pertussis vaccine may not provide sufficient protection from infection. This study examined acellular pertussis vaccine effectiveness (VE) for Air Force dependents less than 12 years of age.MethodsWe conducted a case-control study among Air Force pediatric dependents from 2011 to 2013, comparing cases with positive pertussis test results to controls who received the same lab tests with a negative result. Our study population was categorized by age group and vaccination status based on the Centers for Disease Control and Prevention recommended pertussis vaccination schedule. VE was calculated with respect to vaccination status and pertussis lab results.ResultsWe compared 27 pertussis laboratory positive cases with 974 pertussis laboratory negative controls, 2 months to <12 years old. Comparing completely vaccinated to non-vaccinated patients, the overall VE was 78.3% (95% confidence interval (CI): 48.6, 90.8; p < 0.001). VE was highest among those 15 months to <6 years old: 97.6% (95% CI: 78.5, 99.7; p < 0.001). Children 6 to <12 years old had the lowest VE: 48.5% (95% CI: −74.0, 84.7; p = 0.28). Comparing partially vaccinated patients to nonvaccinated patients yielded 64.2% (95% CI: −7.2, 88.1; p = 0.06) overall VE.ConclusionsAcellular pertussis vaccination was effective at preventing laboratory confirmed pertussis among our Air Force pediatric dependent population, with highest protection among completely vaccinated, young children. Older children received the lowest amount of protection. Partial vaccination had near significant protection. Our overall calculated pertussis VE corroborates other pertussis VE studies looking at similar age groups.     

Risk factors for measles in children aged 8 months–14 years in China after nationwide measles campaign: A multi-site case-control study, 2012–2013

IntroductionEndemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. In 2011, almost half of the 9943 measles cases in China occurred in children eligible for measles vaccination. We conducted a case-control study during 2012–2013 to identify risk factors for measles infection in children aged 8 months–14 years.MethodsChildren with laboratory-confirmed measles were age- and neighborhood-matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. We calculated adjusted matched odds ratios and 95% confidence intervals of risk factors. We calculated attributable fractions for risk factors that could be interpreted as causal and vaccine efficacy (VE) for the measles containing vaccine (MCV) used in the Chinese immunization program.ResultsIn all, 969 case-patients and 2845 controls were enrolled. In multivariable analysis, lack of measles vaccination both overall (mOR 22.7 [16.6, 31.1] and when stratified by region (east region, mOR 74.2 [27.3, 202]; central/western regions mOR 17.4 [12.5, 24.3]), hospital exposure (mOR 63.0, 95% CI [32.8, 121]), and migration among counties (overall mOR 3.0 [2.3, 3.9]) were significant risk factors. The calculated VE was 91.9–96.1% for a single dose of MCV and 96.6–99.5% for 2 doses.ConclusionsLack of vaccination was the leading risk factor for measles infection, especially in children born since the 2010 supplementary immunization activity. Reducing missed vaccination opportunities, improving immunization access for migrant children, and strengthening school/kindergarten vaccine checks are needed to strengthen the routine immunization program and maintain progress toward measles elimination in China.     

Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial

BackgroundPertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization.MethodsThis phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6–14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (27^0/7–36^6/7 weeks’ gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination.Results601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5–77.1%) versus placebo (90.0–99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related.ConclusionsPertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant’s ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience.Clinical Trial Registration: ClinicalTrials.gov: NCT02422264.     

Evaluating the impact of a continued maternal pertussis immunisation programme in England: A modelling study and cost-effectiveness analysis

IntroductionAn unexpected resurgence of pertussis cases and infant deaths was observed in some countries that had switched to acellular pertussis vaccines in the primary immunisation schedule. In response to the outbreaks, maternal pertussis vaccination programmes in pregnant women have been adopted worldwide, including the USA in 2011 and the UK in 2012. Following the success of the programme in England, we evaluated the health and economic impact of stopping versus continuing the maternal pertussis immunisation to inform public health policy making.MethodsWe used a mathematical model to estimate the number of infant hospitalisations and deaths related to pertussis in England over 2019–2038. Losses in quality-adjusted life years, QALYs, were considered for infants (aged 0–2 months) who survived or died from pertussis, bereaved parents (of infants who died from pertussis), and women with pertussis (aged 20–44 years). Direct medical costs to the National Health Service included infant hospitalisations, maternal vaccinations, and disease in women. Costs and QALYs were discounted at 3.5%. Changes in the incremental cost-effectiveness ratio, ICER, were explored in sensitivity analyses.ResultsThe model supports continuing the maternal pertussis immunisation programme as a cost-effective intervention at an ICER of £14,500/QALY (2.5% and 97.5%-quantile: £7,300/QALY to £32,400/QALY). Stopping versus continuing the maternal programme results in an estimated mean of 972 (range 582 to 1489) versus 308 (184 to 471) infant hospitalisations annually. Results were most sensitive to the number of hospitalisations and deaths when stopping the maternal programme. At a cost-effectiveness threshold of £30,000/QALY, the probability of the maternal programme being cost-effective was 96.2%.ConclusionOur findings support continuing the maternal pertussis vaccination programme as otherwise higher levels of disease activity and infant mortality are expected to return. These results have led policy makers to decide to continue the maternal programme in the UK routine immunisation schedule.     

A nested case-control study measuring pertussis vaccine effectiveness and duration of protection in Manitoba,Canada, 1992–2015: A Canadian Immunization Research Network Study

BackgroundPertussis persists in Manitoba despite the universal availability of pertussis vaccines. Recent cases have included previously vaccinated individuals, raising concerns about declining vaccine effectiveness (VE). We measured pertussis VE and duration of protection using Manitoba’s provincial immunization and communicable disease registries.MethodsUsing a nested case-control design, individuals with laboratory-confirmed pertussis in Manitoba diagnosed between April 1, 1992, and March 31, 2015, were matched to up to five population-based controls on age, gender, geography, and case physician or number of physician visits. Conditional logistic regression was used to estimate VE against pertussis for both the whole-cell (wP) and acellular (aP) pertussis vaccines. Duration of protection was assessed using time since last dose.ResultsData on 534 eligible cases and 2614 controls were available for analysis. The adjusted VE estimate for aP-containing vaccines was 85% (95%CI: 74–91%); VE was 89% (66–96%) one to three years after the last vaccination. The adjusted VE of wP-containing vaccines was –15% (–91–31%) during a large outbreak in 1994 and 1995 compared to 35% (–26–66%) during non-outbreak years.ConclusionsOur estimates suggest that the aP vaccine was effective in preventing pertussis since its introduction in Manitoba. VE was lower during a large outbreak, highlighting the importance of separately analyzing outbreak periods when estimating pertussis VE over time.     

Community awareness and predictors of uptake of pertussis booster vaccine in South Australian adults

ObjectivePertussis is a highly virulent vaccine preventable disease that remains a global challenge. This study aimed to assess community knowledge of pertussis infection as well as awareness and uptake of adult pertussis booster vaccine.MethodsA cross-sectional survey was conducted of randomly selected households in South Australia by Computer Assisted Telephone Interviews in 2011. Survey data were weighted to the age, gender and geographical area profile of the population.ResultsFrom 3124 randomly sampled contactable households, 1967 interviews were conducted (participation rate 63%) with individuals aged 18–93 years, including 608 parents of children aged <18 years. The majority of respondents (97%) had heard of pertussis (whooping cough) and 18% reported that a household member had previously contracted whooping cough infection. Most respondents considered whooping cough to be highly contagious (73%) and severe for infants (89%). Over half (51%) of those surveyed were aware that family members commonly transmit pertussis to infants. Despite high knowledge, pertussis vaccine uptake was low, with only 10% of respondents reporting pertussis vaccination in the previous five years. Whilst 61% of respondents were aware of the availability of an adult pertussis booster vaccine, only 8% (n = 154) reported their Family Physician had discussed it with them. If provided free, 77% agreed that they would be more likely to accept a booster pertussis vaccination. Independent predictors of recent pertussis vaccination included higher education, larger household size, perception of greater disease severity for infants and discussion with a Family Physician about pertussis vaccination.ConclusionsWhilst knowledge regarding transmission and severity of Bordetella pertussis was high, uptake of pertussis vaccination for adults is remarkably low amongst the South Australian community. Improved awareness regarding the availability of a booster pertussis vaccine through Family Physicians and/or provision of funded pertussis vaccination for adults has the potential to improve pertussis vaccine coverage.     

Adherence to pneumococcal conjugate vaccination schedule and uptake rate as compared to the established diphtheria-tetanus-acellular pertussis vaccination in Cyprus

BackgroundPneumococcus is a common cause of invasive and non-invasive infections in children. In areas with high vaccination coverage, universal infant vaccination with conjugated pneumococcal vaccine (PCV) has significantly decreased the incidence of vaccine type nasopharyngeal carriage and invasive pneumococcal disease. The aim of this study is to examine immunization coverage rate and timely administration of the recently introduced PCV and compare to the established diphtheria-tetanus-acellular pertussis vaccine (DTaP) with similar schedule.MethodsA stratified random sample of healthy infants and children 6–36 months of age were recruited. Demographic data were collected from parents. Among enrolled children, immunization status for DTaP and PCV was noted from the child's health booklet.ResultsOf 1105 children enrolled in the study, 586 (53%) were vaccinated in the private sector and the rest in the public sector. A significant higher proportion of children vaccinated at the private sector were fully vaccinated for PCV (71% versus 58%, p < 0.05) while no difference in the DTaP coverage was observed. Conversely, the compliance to the recommended vaccination schedule was much higher in the public sector for the first and second dose of PCV and second dose of DTaP.The overall, timely administration was higher for the DTaP vaccine when compared to PCV (p < 0.05).Moreover, adherence to the program was higher for the firstborn child of the family while significant differences were observed between different geographic regions. Interestingly, co-administration of DTaP and PCV was observed in only 2% of the children.ConclusionIn children residing in Cyprus, vaccination coverage and adherence to PCV vaccination schedule are significantly lower compared to the established DTaP vaccine. There is an urgent need for increasing the overall vaccination coverage as well as improving the adherence to vaccination schedule. Possible interventions are proposed.     

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.     

Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting

BackgroundMaternal vaccines against pertussis are not yet recommended in the developing world. Besides unclear burden estimates, another concern is that transplacental transfer of maternal pertussis antibodies could result in attenuation of the immune response to whole cell pertussis (DTwP) primary vaccination series in infants. This study was taken up to determine whether higher levels of maternal pertussis antibodies attenuate immune response of infants to DTwP vaccination series given at 6–10–14 weeks of age.MethodologyA total of 261 pregnant women and their infants from four low-income settlements in Karachi, Pakistan were enrolled in this study. The study endpoints were infant antibody titers for Pertussis toxin (PTx), Filamentous hemagglutinin antigen (FHA), Pertactin (PRN) and Fimbriae type 2/3 (FIM) – from birth through 18 weeks of age. Cord blood or pre-vaccine pertussis antibody titers indicate the concentration of maternal antibodies transferred to infants. Linear regression models were used to determine the association between higher maternal antibody titers and infant immune response to DTwP vaccine. Geometric Mean Ratio (GMR) was calculated as the ratio of infant antibody titers at specified time points against the maternal antibody titers at the time of delivery.ResultsAt eighteen weeks of age, the adjusted β regression coefficient for PTx was 0.06 (95% CI: -0.49-0.61), FHA 0.02 (95% CI: -0.26 -0.29), PRN 0.02 (95%CI -0.38- 0.43), and FIM 0.17 (95%CI: -0.21-0.54). Among infants who received at least two doses of DTwP vaccine, higher maternal antibody titers did not have any attenuating effect on infant post-immunization antibody titers against all four pertussis antigens.ConclusionMaternal pertussis antibodies did not attenuate infant’s immune response to pertussis antigens in DTwP primary vaccine given at 6–10–14 weeks of age.     

A cross-sectional study of Bordetella pertussis seroprevalence and estimated duration of vaccine protection against pertussis in St. Petersburg,Russia

BackgroundIn Russia as in other countries introduction of infant vaccination against pertussis in 1950s led to dramatic decrease of whooping cough. The current vaccination schedule includes a 3-dose infant series and toddler booster; the pre-school booster was cancelled in 1980s and never reintroduced. Whole-cell vaccines, and in a smaller proportion acellular vaccines are used for all doses. However, pertussis incidence in urban settings is high with highest burden in school children. We conducted a study of seroprevalence of recent pertussis infection to estimate the duration of protection from the 4-dose series.Materials and methodsSera sample from 395 St Petersburg children aged ≥3 years and <14 years were tested for pertussis toxin antibodies using a commercial PT ELISA test. Only children with completed 4-dose vaccination course were included in the study. Age-specific seroprevalence of recent pertussis infection was analyzed for trends.ResultsChildren fully vaccinated against pertussis at 3 years old had significant delays in infant vaccination schedule: only 83.5% received at least one dose of pertussis vaccine at 6 months of age and 25.6% received their toddler booster before 24 months-old. Overall, 10.6% of children demonstrated the serological signs of the infection in the last 12 months. A clear trend (r² = 0.692) of increasing proportion of infection in the last 12 months was observed in children who had received their last dose of vaccine 6 years and more prior to the study.ConclusionOur study demonstrates that Russian children become susceptible to infection at or soon after entering school. The results confirm the waning of vaccine-elicited immunity around school-age and support the need for a booster dose at that age.     

Dose-dependent effectiveness of acellular pertussis vaccine in infants: A population-based case-control study

BackgroundPertussis is a vaccine-preventable disease which is most severe in young infants. More than two decades after the introduction of acelluar pertussis vaccines (aPV) in national immunization programs in many countries worldwide, a resurgence of pertussis has been recognized. Suboptimal effectiveness of aPV has been blamed as one major reason but only few studies have evaluated dose-dependent vaccine effectiveness (VE) provided by aPV in current practice.MethodsWe performed a population-based retrospective case-control study by comparing pertussis immunization data of children 2.5 months to 2 years of age hospitalized for pertussis and residing in Switzerland with immunization data of a random control sample of children aged 2 years and residing in Switzerland. VE was defined as the percentage of hospitalizations avoided by number of aPV doses. It was calculated as 1-infection rate ratio (IRR)*100. IRR was calculated by dividing infection rates of vaccinated children and infection rates of unvaccinated children. To get dose specific VE, infection rates were stratified by number doses received.ResultsVE against hospitalization due to pertussis increased significantly with each consecutive aPV dose in a “3 + 1” primary course in infants: 42.1% (95% CI: 11.3–62.6), 83.9% (70.2–92.1), 98.2% (96.1–99.3), and 100% (97.9–100) after the 1st, 2nd, 3rd, and 4th dose, respectively.ConclusionAcellular pertussis vaccines continue to demonstrate protection against hospitalization due to pertussis in infants and young children. Therefore, together with advancing immunization of pregnant women and household contacts, better control of severe pertussis in young infants can be achieved by timely initiation of immunization.     

Reciprocal interference of maternal and infant immunization in protection against pertussis

BackgroundBecause of the current re-emergence of pertussis, vaccination during the 3rd trimester of pregnancy is recommended in several countries in order to protect neonates by placental transfer of maternal antibodies. Here, we examined the potential reciprocal interference of mother and infant vaccination in protection against pertussis in mice.MethodsFemale mice were vaccinated with acellular pertussis vaccines and protection against Bordetella pertussis challenge, as well as functional antibodies were measured in their offspring with or without re-vaccination.ResultsMaternal immunization protected the offspring against B. pertussis challenge, but protection waned quickly and was lost after vaccination of the infant mice with the same vaccine. Without affecting antibody titers, infant vaccination reduced the protective functions of maternally-derived antibodies, evidenced both in vitro and in vivo. Protection induced by infant vaccination was also affected by maternal antibodies. However, when mothers and infants were immunized with two different vaccines, no interference of infant vaccination on the protective effects of maternal antibodies was noted.ConclusionIt may be important to determine the functionality of antibodies to evaluate potential interference of maternal and infant vaccination in protection against pertussis.     

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months

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.