Modeling the cost-effectiveness of maternal acellular pertussis immunization (aP) in different socioeconomic settings: A dynamic transmission model of pertussis in three Brazilian states

ObjectivesUsing dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions.MethodsWe tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014–2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System.ResultsBased on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs.ConclusionsThe same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.     

Evaluating the cost-effectiveness of maternal pertussis immunization in low- and middle-income countries: A review of lessons learnt

This issue of Vaccine is devoted to papers from a research project that developed two types of simulation models, static and dynamic transmission, to evaluate the cost-effectiveness of maternal immunization to prevent pertussis in infants in low- and middle-income countries (LMICs). The research was conducted by a multinational team of investigators and funded by the Bill & Melinda Gates Foundation to gain an understanding of when and where maternal immunization might be a good public health investment for LMICs. Here we review the project’s central lessons for vaccine policy and research. Models require a lot of data. As most LMICs lack good data, the models were built using pertussis disease burden data from Brazil, a middle-income country with three long-established, independent information systems (disease surveillance, hospitalization, and mortality), on the hypothesis that the disease process is similar across countries. Values for key parameters, particularly infant mortality, infant vaccine coverage, and costs of vaccination and treatment, were then varied to represent other LMICs. The results show that coverage levels of infant whole cell pertussis (wP) vaccine are key to the cost-effectiveness of maternal pertussis immunization. In settings where infant wP coverage is below the threshold thought necessary to eliminate pertussis in the population, 90–95%, maternal immunization is cost-effective, even cost-saving. By contrast, it is very expensive in countries capable of maintaining infant vaccination in or above the threshold range. The research also suggests that, while static models may serve to explore an intervention’s cost-effectiveness initially, dynamic transmission models are essential for more accurate estimates. These findings can help guide policies toward maternal pertussis immunization, but also show that developing better data on neonatal pertussis mortality burden and infant vaccine coverage in LMICs, and on the duration of immunity of currently available pertussis vaccines, are key priorities to support better vaccine policy.     

Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil

BackgroundPertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants <4 months are most affected. This study aimed to evaluate the cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil.MethodsEconomic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed.ResultsMaternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness.ConclusionThe results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil.     

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.     

Impact of a maternal immunization program against pertussis in a developing country

BackgroundPertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20 weeks of gestation with the intent of reducing morbidity and mortality in young infants.MethodsMaternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program.FindingsWe observed a relative reduction of 51% (95% CI [−67%, −35%]; p = 0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [−66%, −24%]; p = 0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013.InterpretationWe show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.     

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries

ObjectiveThis study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model.MethodsWe developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY).ResultsThe dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90–95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model’s time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage.ConclusionA dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90–95%.     

Infant pertussis and maternal immunity: The curious case of Canada

BackgroundThe United Kingdom (UK) and Canada use the same acellular pertussis vaccine and both experienced large pertussis outbreaks in the past, occurring in the 1980s in the UK and 1990s in Canada, yet current epidemiology differs. A national outbreak with infant deaths occurred in the UK in 2012, yet outbreaks remain localized and death from pertussis rare in Canada.AimWe explored whether past outbreaks in children may influence future risk when those children become parents.MethodsWe conducted an ecological within-country birth cohort analysis in women of childbearing age of the relative risk of ever having pertussis infection by two points in time, 2002 and 2012, comparing with 1992 as the baseline. We used notified cases of pertussis in England and Wales and Canada to compare trends in relative risk. We projected forward to 2022 in Canada assuming incidence remained stable.ResultsIn Canada, the cumulative risk of previous pertussis was similar in 2002 and 2012 and, in both periods, was higher than in 1992. In England and Wales, the cumulative risk of pertussis fell stepwise from 1992 to 2012. Projecting forwards, the pattern of risk in Canada becomes similar to England and Wales in 2022.ConclusionsWidespread pertussis outbreaks in children may reduce the risk of pertussis in infants when those children become parents. Further research is needed to determine the mechanism. As birth cohorts that experienced outbreaks grow past childbearing age, pertussis burden in infants in Canada may increase, following trends observed in England and Wales.     

Influence of maternal antibodies on active pertussis toxoid immunization of neonatal mice and piglets

Whooping cough caused by infection with Bordetella pertussis, is a serious illness in infants and young children. Mortality due to whooping cough is being reported in infants too young to be immunized as well as those who have not completed their series of vaccinations. One of the major factors that interferes with successful active immunization in early life is the presence of maternal antibodies (MatAbs). Using the mouse and pig models, we evaluated the effect of maternal antibodies on active immunization with pertussis toxoid (PTd) and explored strategies to overcome this interference. Our results indicate that passively transferred maternal antibodies interfered with active immunization using pertussis toxoid. The level of passively transferred antibodies directly correlated with the level of interference observed. However, this interference could be overcome by using a second booster immunization or by co-formulating the toxoid with novel adjuvants. These results support the need for novel vaccine formulations that are optimized for the neonate and that can be used not only to modulate the inherently biased neonatal immune system but also to prime the response in the presence of passively transferred maternal antibodies.     

Multi-tiered intervention to increase maternal immunization coverage: A randomized,controlled trial

ObjectiveTo evaluate the impact of a multi-component intervention package of maternal immunization uptake in obstetric care clinics.MethodsIn 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.ResultsBetween 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.ConclusionsThis 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.     

Practical aspects in the use of passive immunization as an alternative to attenuated viral vaccines

Passive immunization as a method to protect birds has been tested for many years and shown to be effective. Its advantages over active vaccination include no use of partially virulent viruses, overcoming the gap in the level of protection at young age due to interference of maternal antibodies to raise self-immune response following active vaccination and the possible immunosuppressive effect of attenuated vaccine viruses. However, a major obstacle to its implementation is its relatively high cost which is dependent, among other things, mainly on two factors: the efficacy of antibody production, and the use of specific pathogen-free (SPF) birds for antibody production to avoid the possible transfer of pathogens from commercial layers. In this study we show efficient production of immunoglobulin Y (IgY) against four different pathogens simultaneously in the same egg, and treatment of the extracted IgY with formalin to negate the need for SPF birds. Formalin, a common registered sterilization compound in vaccine production, was shown not to interfere with the Fab specific antigen binding or Fc-complement activation of the antibody. Following injection of 1-day-old broilers with antibodies against infectious bursal disease virus, protective antibody levels were acquired for the entire period of sensitivity to this pathogen (35 days). Passive vaccination with formalin-sterilized IgY against multiple antigens extracted from one commercial egg may be a cost-effective and advantageous complementary or alternative to attenuated vaccines in poultry.     

Impact and cost-effectiveness of a second tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccine dose to prevent pertussis in the United States

IntroductionThe United States experienced a substantial increase in reported pertussis cases over the last decade. Since 2005, persons 11 years and older have been routinely recommended to receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine. The objective of this analysis was to evaluate the potential impact and cost-effectiveness of recommending a second dose of Tdap.MethodsA static cohort model was used to calculate the epidemiologic and economic impact of adding a second dose of Tdap at age 16 or 21 years. Projected costs and outcomes were examined from a societal perspective over a 20-year period. Quality-adjusted Life Years (QALY) saved were calculated.ResultsUsing baseline pertussis incidence from the National Notifiable Diseases Surveillance System, Tdap revaccination at either age 16 or 21 years would reduce outpatient visits by 433 (5%) and 285 (4%), and hospitalization cases by 7 (7%) and 5 (5%), respectively. The costs per QALY saved with a second dose of Tdap were approximately US $19.7 million (16 years) and $26.2 million (21 years). In sensitivity analyses, incidence most influenced the model; as incidence increased, the costs per QALY decreased. To a lesser degree, initial vaccine effectiveness and waning of effectiveness also affected cost outcomes. Multivariate sensitivity analyses showed that under a set of optimistic assumptions, the cost per QALY saved would be approximately $163,361 (16 years) and $204,556 (21 years).ConclusionA second dose of Tdap resulted in a slight decrease in the number of cases and other outcomes, and that trend is more apparent when revaccinating at age 16 years than at age 21 years. Both revaccination strategies had high dollar per QALY saved even under optimistic assumptions in a multivariate sensitivity analysis.     

Determinants of maternal immunization in developing countries

BackgroundMaternal immunization is an effective intervention to protect newborns and young infants from infections when their immune response is immature. Tetanus toxoid vaccination of pregnant women is the most widely implemented maternal vaccine in developing countries where neonatal mortality is the highest. We identified barriers to maternal tetanus vaccination in developing African and Asian countries to identify means of improving maternal immunization platforms in these countries.MethodWe categorized barriers into health system, health care provider and patient barriers to maternal tetanus immunization and conducted a literature review on each category. Due to limited literature from Africa, we conducted a pilot survey of health care providers in Malawi on barriers they experience in immunizing pregnant women.ResultsThe major barriers of the health system are due to inadequate financial and human resources which translate to inadequate vaccination services delivery and logistics management. Health care providers are limited by poor attendance of Antenatal Care and inadequate knowledge on vaccinating pregnant women. Patient barriers are due to lack of education and knowledge on pregnancy immunization and socioeconomic factors such as low income and high parity.ConclusionThere are several factors that affect maternal tetanus immunization. Increasing knowledge in health care providers and patients, increasing antenatal care attendance and outreach activities will aid the uptake of maternal immunization. Health system barriers are more difficult to address requiring an improvement of overall immunization services. Further analyses of maternal immunization specific barriers and the means of addressing them are required to strengthen the existing program and provide a more efficient delivery system for additional maternal vaccines.     

Psychosocial determinants of pertussis and influenza vaccine uptake in pregnant women: A prospective study

ObjectiveTo identify the psychosocial factors influencing women’s uptake and willingness to receive pertussis and influenza vaccine during pregnancy.MethodsThe study population comprised 1364 healthy nulliparous pregnant women who participated in a prospective cohort study at two obstetric hospitals in South Australia between 2015 and 2017. Information on women's vaccination status, sociodemographic, lifestyle and psychological state were collected at 9–16 weeks’ gestation and medical case notes were checked post-delivery to verify the reported vaccination status. Poisson regression models were used to estimate the crude and adjusted prevalence ratios (aPRs) to identify psychosocial factors influencing uptake of vaccination during pregnancy.ResultsWillingness to receive the recommended maternal vaccines was high (90%). Overall, 79% and 48% received maternal pertussis and influenza vaccines respectively. There was no evidence to support the influence of psychosocial factors on women’s willingness to receive immunization during pregnancy. High levels of anxiety (aPR 0.98, 95% CI: 0.87–1.09) was not associated with uptake of maternal pertussis vaccine. However, elevated depressive symptoms (aPR 1.14, 95% CI: 1.00–1.30) and very high-perceived stress during pregnancy were significantly associated with receipt of pertussis vaccination (aPR 0.87; 95% CI 0.76–0.99). Women with mild depressive symptoms (aPR 1.21, 95% CI 1.00–1.44) and mild anxiety symptoms (aPR 1.21, 95% CI: 0.99–1.48) were more likely to receive influenza vaccine during pregnancy (aPR 1.27, 95% CI: 1.08–1.49). A history of major depressive disorder was independently associated with receipt of pertussis (aPR 1.16, 95% CI 1.06–1.26) and influenza vaccination during pregnancy (aPR 1.32; 95% CI 1.14–1.58).ConclusionRegardless of psychosocial factors, most women reported a positive willingness to receive the recommended vaccinations during pregnancy. However, psychosocial factors influenced the uptake of pertussis and influenza vaccines during pregnancy. Psychosocial factors should be taken into consideration in designing interventions and implementation of maternal pertussis and influenza immunization programs.     

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.     

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.     

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women

IntroductionDespite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PT_gen) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdap_chem) shown effective for maternal immunization.MethodsThis phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PT_gen and 1 µg FHA (ap1_gen), or tetanus, reduced-dose diphtheria combined with ap1_gen (Tdap1_gen), or combined with 2 µg PT_gen and 5 µg FHA (Tdap2_gen), or with 5 µg PT_gen and 5 µg FHA (TdaP5_gen, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.5 µg pertactin (Boostrix™, Tdap8_chem). Blood was collected at Day 0 and Day 28 post-vaccination. The non-inferiority of the study vaccines was assessed based on anti-PT IgG antibody levels on Day 28 pooled with results from a similarly structured previous trial in non-pregnant women.Results400 healthy pregnant women received one dose of vaccine. Combined with data from 250 non-pregnant women, all study vaccines containing PT_gen were non-inferior to comparator vaccine (Tdap8_chem). Both ap1_gen and TdaP5_gen vaccines could be considered to have superior immunogenicity to Tdap8_chem. Local and systemic solicited reactions were similar among all vaccine groups.ConclusionsVaccine formulations containing PT_gen were safe and immunogenic in pregnant women. The ap1_gen vaccine, with the lowest cost and reactogenicity, may be suitable for use in pregnant women when diphtheria and tetanus toxoids are not needed.This study is registered in the Thai Clinical Trial Registry (www.clinicaltrials.in.th), number TCTR20180725004.     

Reactogenicity and safety of second trimester maternal tetanus,diphtheria and acellular pertussis vaccination in the Netherlands

BackgroundMaternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction.MethodsPregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age.ResultsAmong 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0?C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes.ConclusionsSecond trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns.     

Intention to accept pertussis vaccine among pregnant women in Karachi,Pakistan

BackgroundMaternal immunization against pertussis is a potential strategy to protect young infants from severe disease. We assessed factors associated with intention to accept pertussis vaccination among pregnant women in Karachi, Pakistan.MethodsWe conducted a cross-sectional survey between May and August 2013 in pregnant women who visited healthcare centers in urban slums of Karachi city. Women completed a survey examining socio-demographic factors, vaccination history, knowledge on pertussis disease, perception of vaccine recommendation sources, and potential influences on vaccine decision-making.ResultsOf the 283 participants, 259 (92%) provided their intention to either accept or decline pertussis vaccination. Eighty-three percent women were willing to accept the pertussis vaccine if offered during pregnancy. About half (53%) of the participants had ever heard of pertussis disease. Perceptions of pertussis vaccine efficacy, safety, and disease susceptibility were strongly associated with intention to accept pertussis vaccine (p < 0.01). Healthcare providers, Ministry of Health, and mass media were considered as highly reliable sources of vaccine recommendation and associated with intention to accept antenatal pertussis vaccination (p < 0.001). Healthcare provider recommendation was a common reason cited by respondents for pregnant women to accept antenatal pertussis vaccination (p = 0.0005). However, opinion of primary decision-makers in the family (husbands and in-laws) was a crucial reason cited by respondents for pregnant women to reject pertussis vaccination in pregnancy (p = 0.003).ConclusionAntenatal pertussis vaccination initiatives in South Asia should strongly consider inclusion of family members, healthcare providers, national health ministries, and mass media to help implement new vaccination programs.     

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.