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.     

Patient attitudes toward influenza and tetanus,diphtheria and acellular pertussis vaccination in pregnancy

BackgroundRoutine influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccination of pregnant women to prevent poor maternal, fetal and neonatal outcomes is recommended practice; however, actual rates of influenza vaccine acceptance are typically well below the (Healthy People 2020, 2015) goal of 80%.ObjectiveWe sought to identify barriers to accepting either vaccination.Materials and MethodsFrom December 2014 to April 2015 women were given a questionnaire eliciting their experiences, attitudes and history of influenza and Tdap vaccination in pregnancy during their routine prenatal care appointments at a tertiary care center. Patient demographics were included in the questionnaire. A similar questionnaire was administered to prenatal care providers. Patient influenza and Tdap vaccination acceptance rates were compared and predictors of vaccine acceptance were analyzed with bivariate logistic regression.ResultsOut of the 400 patient questionnaires distributed, 338 (84.5%) were completed and returned; 24 of 45 (53.3%) provider questionnaires were returned. Vaccination acceptance rates were 70.7% for the influenza vaccine and 76.3% for the Tdap vaccine. The logistic regression model indicated that predictors of acceptance for either vaccine in pregnancy are patient attitude and previous vaccination history. Patient attitudes were more favorable towards Tdap than influenza vaccination. The combination of healthcare provider recommendation and educational materials was significantly predictive of both Tdap and influenza vaccine acceptance. The most common reasons given for declining the influenza vaccine were safety concerns; the most common reasons given for declining the Tdap vaccine were that patients did not think it was required again when they received the vaccine before pregnancy.ConclusionsOur study suggests that providers can improve Tdap and influenza vaccination acceptance in pregnancy by recommending the vaccination in combination with provision of educational materials on the vaccines.     

Enhanced surveillance of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011–2015

BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.     

Maternal immunization in Malawi: A mixed methods study of community perceptions,programmatic considerations,and recommendations for future planning

BackgroundSafe, effective vaccines are given to pregnant women to protect their infants and/or themselves against certain infectious agents; however, apart from tetanus vaccination, maternal immunization in low- and middle-income countries (LMICs) remains low. Tetanus toxoid vaccine is integrated into antenatal care services in Malawi with high coverage and provides an opportunity to identify factors that facilitate successful immunization delivery to pregnant women in LMICs.MethodsPATH and the University of Malawi’s Centre for Social Research conducted a mixed-methods study in 2015 to document community perceptions of maternal immunization, using tetanus vaccine as an example, and to identify factors perceived to be important to successfully introducing other maternal vaccines, such as influenza vaccine, in Malawi. We conducted 18 focus group discussions with pregnant and recently pregnant women and their family members and 76 semi-structured interviews with pregnant and recently pregnant women, community leaders, health workers, public health program managers, non-governmental partners, and policy makers.ResultsWe identified factors perceived to support the introduction of new maternal vaccines, including strong maternal vaccine acceptance in the community, an existing strategy for maternal tetanus vaccine delivery, and positive health workers’ views about the introduction of additional maternal vaccines. Potential challenges to adoption and acceptance included identifying and tracking the target population and monitoring adverse events, and the need to ensure operational capacity of the health system to support the introduction and wide-scale use of an additional vaccine. For influenza vaccine specifically, additional challenges included limited awareness of influenza disease and its low prioritization among health needs.ConclusionsLessons from the successful delivery of maternal tetanus immunization in Malawi may be informative for similar countries considering new vaccines for pregnant women or striving to optimize the delivery of those currently provided.     

Reactogenicity and immunogenicity of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women

ObjectiveTetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt.Study designPregnant women (gestational age 20–34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt.Results374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or “any” fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01).ConclusionTdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust.Clinical Trial Registration@ClinicalTrials.gov. NCT02209623.https://clinicaltrials.gov/ct2/show/NCT02209623.     

Evaluation of two vaccine education interventions to improve pertussis vaccination among pregnant African American women: A randomized controlled trial

BackgroundVaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in pregnancy or immediately postpartum has been low. Limited data exist on rigorously evaluated interventions to increase maternal vaccination, including Tdap. Tailored messaging based on the Elaboration Likelihood Model (ELM) framework has been successful in improving uptake of some public health interventions. We evaluated the effect of two ELM-based vaccine educational interventions on Tdap vaccination among pregnant African American women, a group of women who tend to have lower vaccine uptake compared with other groups.MethodsWe conducted a prospective randomized controlled trial to pilot test two interventions – an affective messaging video and a cognitive messaging iBook – among pregnant African American women recruited during routine prenatal care visits. We measured Tdap vaccination during the perinatal period (during pregnancy and immediately postpartum), reasons for non-vaccination, and intention to receive Tdap in the next pregnancy.ResultsAmong the enrolled women (n = 106), 90% completed follow-up. Tdap vaccination in the perinatal period was 18% in the control group; 50% in the iBook group (Risk Ratio [vs. control group]: 2.83; 95% CI, 1.26–6.37), and 29% in the video group (RR: 1.65; 95% CI, 0.66–4.09). From baseline to follow-up, women’s reported intention to receive Tdap during the next pregnancy improved in all three groups. Among unvaccinated women, the most common reason reported for non-vaccination was lack of a recommendation for Tdap by the woman’s physician.ConclusionsEducation interventions that provide targeted information for pregnant women in an interactive manner may be useful to improve Tdap vaccination during the perinatal period. However, larger studies including multiple racial and ethnic groups are needed to evaluate robustness of our findings.Trial Registration: clinicaltrials.gov Identifier: NCT01740310.     

Effectiveness of a multimodal intervention to increase vaccination in obstetrics/gynecology settings

ObjectiveTo test the effectiveness of a multimodal intervention in obstetrics/gynecology (ob-gyn) clinics to increase uptake of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines in pregnant women and these vaccines plus human papillomavirus (HPV) vaccine in non-pregnant women.MethodsA cluster randomized controlled trial among 9 private ob-gyn practices in Colorado from 9/2011 to 5/2014. The intervention consisted of: designation of immunization champions, staff/provider trainings, assistance with vaccine purchasing/management, identification of eligible patients, standing order implementation, chart review/feedback, and patient education materials. Control practices continued usual care. Primary outcomes were receipt of influenza and Tdap vaccines among pregnant women and these vaccines plus HPV vaccine among non-pregnant women, comparing a Baseline period (Year 0/Year 1) to Year 2, intervention versus control. With an estimated sample size of 32,590 per arm, there would be >80% power to detect a 10% difference between groups.ResultsIn the Baseline period, 27% of pregnant women in both intervention and control practices received influenza vaccine. In Year 2, 29% of pregnant women in intervention practices received influenza vaccine versus 41% in control practices. In the Baseline period, 18% of pregnant women in intervention practices received Tdap vaccine versus 22% in control practices. Both intervention and control practices increased to 51% in Year 2, representing an increase of 33% for intervention practices and 29% for control practices, consistent with a change in Tdap recommendations. Relatively few HPV, influenza or Tdap vaccines (≤6% of eligible patients) were given to non-pregnant patients in either intervention or control practices at any time during the study.ConclusionIn this cluster randomized trial designed to increase vaccination uptake, both intervention and control practices showed improved vaccination of pregnant but not non-pregnant patients. Future work should focus on tailoring evidence-based immunization practices or developing new approaches to specifically fit busy ob-gyn offices.     

Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women

IntroductionPregnant Thai women have low antibody titers against B. pertussis antigens, which coincide with an increasing incidence of pertussis among Thai infants. Thus, there exists a potential benefit of a booster dose of tetanus- diphtheria-acellular pertussis (Tdap) vaccine administered during pregnancy. Here, we report the vaccine reactogenicity profile and birth outcomes in Tdap-vaccinated pregnant women who have or have not had prior immunization with tetanus vaccine, and the IgG levels to B. pertussis antigens in maternal and cord sera at delivery.Materials and methodsPregnant women (N = 370) aged 18–40 years were administered the Tdap vaccine (Boostrix®, GlaxoSmithKline, Rixensart, Belgium) at 26–36 weeks gestation. Adverse events following vaccination were identified by follow-up telephone call and medical record review. IgG against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) in both maternal and umbilical cord blood obtained at delivery were quantitatively evaluated using enzyme-linked immunosorbent assay (EUROIMMUN®, Lübeck, Germany).ResultsThere was no reported increase in the severity or duration of adverse events associated with the administration of an extra tetanus-containing vaccine within the previous five years (N = 181) or multiple doses of tetanus-containing vaccines during the current pregnancy (N = 98). Vaccination at least eight weeks prior to delivery resulted in high antibody titers to all B. pertussis antigens studied.ConclusionsThe reactogenicity of Tdap vaccine administered during pregnancy was not affected by prior tetanus toxoid immunization. High transplacental antibody against B. pertussis antigens in the cord blood provides evidence of antibody transfer and should thus help to protect newborns from pertussis during early life.     

Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007–2013

IntroductionSince October 2012, the combined tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine (Tdap) has been recommended in the United States during every pregnancy.MethodsIn this observational study from the Vaccine Safety Datalink, we describe receipt of Tdap during pregnancy among insured women with live births across seven health systems. Using a retrospective matched cohort, we evaluated risks for selected medically attended adverse events in pregnant women, occurring within 42 days of vaccination. Using a generalized estimating equation, we calculated adjusted incident rate ratios (AIRR).ResultsOur vaccine coverage cohort included 438,487 live births between January 1, 2007 and November 15, 2013. Across the coverage cohort, 14% received Tdap during pregnancy. By 2013, Tdap was administered during pregnancy in 41.7% of live births, primarily in the 3rd trimester. Our vaccine safety cohort included 53,885 vaccinated and 109,253 matched unvaccinated pregnant women. There was no increased risk for a composite outcome of medically attended acute adverse events within 3 days of vaccination. Similarly, across the safety cohort, over a 42 day window, incident neurologic events, thrombotic events, and new onset proteinuria did not differ by maternal receipt of Tdap. Among women receiving Tdap at 20 weeks gestation or later, as compared to their matched controls, there was no increased risk for gestational diabetes or cardiac events while venous thromboembolic events and thrombocytopenia were diagnosed within 42 days of vaccination at slightly decreased rates.ConclusionTdap coverage during pregnancy increased from 2007 through 2013, but was still below 50%. No acute maternal safety signals were detected in this large cohort.     

Socio-psychological determinants of second trimester maternal pertussis vaccination acceptance in the Netherlands

BackgroundA maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is offered to all pregnant women in the Netherlands in their second trimester since December 2019. However, former studies solely investigated the socio-psychological factors that influence vaccine acceptance among pregnant women in the third trimester. We identified predicting factors for attitude, intention and acceptance of maternal Tdap vaccination during the second trimester of pregnancy.MethodsAs part of a large prospective cohort study, women early in pregnancy completed a questionnaire on determinants regarding acceptance of maternal Tdap vaccination between 20 and 24w of gestation. The vaccine was offered after completion of the questionnaire. A random forest model and Receiver Operating Characteristics (ROC) analyses were carried out to identify the factors most predictive for vaccine acceptance on the whole data set, and also in sensitivity analysis on a subset reflecting the annual nationwide 70% vaccination uptake.ResultsAmong 1158 participants who were offered a Tdap vaccination between 20 and 24w of gestation, 1098 (94.8%) accepted and 60 (5.2%) rejected the vaccine. Random forest analyses identified intention as most predictive for acceptance, followed by attitude towards vaccination, beliefs regarding safety, risk perception of severity of side effects, moral responsibility, beliefs regarding effectiveness and risk perception of susceptibility of side effects, with a sensitivity of 100% and a specificity of 40%, for which this combination could be improved by the ROC analysis to 82% and 67%, respectively. The sensitivity analysis yielded an order of predictors that generally corresponded with the initial model.ConclusionsIntention, attitude, beliefs on safety and effectiveness, risk perception of side effects and moral responsibility were most predictive for maternal Tdap vaccine acceptance during the second trimester of pregnancy, in accordance with studies regarding third trimester vaccination. These should be discussed by healthcare professionals early in pregnancy to provide an informed choice towards vaccine acceptance.     

Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria,tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women

BackgroundMaternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy.ObjectivesThe primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td).MethodsThis randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27–36 weeks’ gestation. The antibody levels from both sera were compared between groups.ResultsThe seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. −7.4 IU/ml; p < 0.001).ConclusionMost pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.     

Increasing antepartum Tdap vaccine administration: A quality improvement initiative

The Centers for Disease Control and Prevention (CDC) recommends antepartum Tdap vaccination for women with each pregnancy to protect themselves and their vulnerable infants through transplacental transfer of maternal antibodies. Our aim was to increase the rate of antepartum Tdap vaccine administration by 20%. Obstetricians were surveyed to identify their present approaches and barriers to antepartum Tdap vaccine administration to help guide the development of our intervention. Limited staff training, lack of vaccine on site, and cost were the most commonly identified barriers. Using these survey responses, existing literature, and brainstorming conversations with colleagues, an interdisciplinary workgroup then created a fishbone analysis and developed a 5-step intervention to address these barriers: (1) educate providers and patients on Tdap and pertussis; (2) increase Tdap availability to all pregnant women; (3) remind staff of the established Tdap standing order to facilitate administration; (4) encourage obstetricians to offer Tdap; (5) transfer documentation of Tdap administration from office to hospital. To monitor changes in the process over 15 months of pre- and post-intervention, data were collected from monthly chart audits and a two-phase control chart was created. The main outcome measure was proportion of eligible women who received Tdap during current pregnancy. In the pre-intervention period, 362 of 636 eligible women (56.9%) received Tdap during their current pregnancy; in the post-intervention period, 457 of 708 eligible women (64.5%) received Tdap during their current pregnancy. This absolute difference of 7.6% (64.5% vs. 56.9%, p < 0.01) represents a 13.4% relative increase (64.5%/56.9%) in the proportion of clinically eligible pregnant women who received Tdap. This represents a clinically and statistically significant increase in the rate of antepartum Tdap immunization. More research is needed to further understand obstetric barriers and maternal refusal of antepartum Tdap administration.     

Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System

BackgroundIn October 2012, the Advisory Committee on Immunization Practices (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's prior history of receiving Tdap. A retrospective cohort study to assess the safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD) sites during 2010–2012 found a small but statistically significant increased risk of chorioamnionitis.ObjectiveWe conducted a review of the VAERS database to describe reports of chorioamnionitis following receipt of any vaccines.MethodsWe searched the VAERS database for reports of chorioamnionitis after any vaccine in the United States during the period from July 1, 1990 through February 2, 2014.ResultsVAERS received 31 reports of chorioamnionitis out of 3389 pregnancy reports in 24 years. The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported.ConclusionChorioamnionitis was found to be uncommonly reported, representing 1% of pregnancy reports to VAERS. A majority of reports had at least one risk factor for chorioamnionitis.     

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.     

Pertussis vaccine for adults: Knowledge,attitudes, and vaccine receipt among adults with children in the household

BackgroundPertussis is a highly contagious vaccine preventable disease resulting in significant infant morbidity and mortality. Despite the recommendations for pertussis vaccine (Tdap) in adults, coverage rates in this age group remain suboptimal. We sought to determine factors associated with Tdap receipt among adults with children in the household who live in central New York.MethodsThe study team surveyed Tdap immunization status of adults who accessed medical services for their children provided by Golisano Children's Hospital, Syracuse, New York. Adults who did not know their Tdap vaccine status were excluded. Each participant was asked a standard set of questions to determine factors associated with Tdap receipt. Logistic regression was used to calculate simple and adjusted odds ratios for Tdap receipt in relation to adults’ demographic characteristics, knowledge of Tdap and physician recommendations.ResultsEight hundred twenty four participants were included in this study; 34% had received Tdap in the past 5 years; 58% reported that their provider or child's pediatrician recommended adult Tdap vaccination. Tdap receipt was associated with knowing the symptoms of pertussis infection, female gender, younger age, and provider recommendation (p < 0.05). Participants whose provider recommended Tdap vaccine were 24.6 times more likely to receive vaccine when compared to those whose providers did not recommend vaccine (95% CI: 16.3, 37.2, p < 0.05).ConclusionTdap coverage rates are low among this study population, with provider recommendation most strongly associated with Tdap receipt. Future steps to improve vaccine coverage should include both increasing community awareness and determining barriers to provider recommendation.     

Levels of antibodies specific to diphtheria toxoid,tetanus toxoid,and Haemophilus influenzae type b in healthy children born to Tdap-vaccinated mothers

IntroductionVaccination of pregnant women protects both women and their newborns against some infectious diseases. Thailand implemented tetanus toxoid (TT) vaccination of pregnant women in 1977, which was replaced by tetanus–diphtheria toxoid (dT) vaccination in 2005. The tetanus–diphtheria–acellular pertussis (Tdap) vaccine has been recommended for pregnant women at 27–36 weeks of gestation since 2012 in several countries. Data on antibody responses to diphtheria toxoid (DT), TT, and Hemophilus influenzae type b (Hib) induced by combined vaccines in children born to TT-vaccinated and/or Tdap-vaccinated mothers are limited.Material and methodsWe investigated anti-DT, anti-TT, and anti-Hib IgG responses in a cohort of Thai children (ClinicalTrial.gov NCT02408926) born to mothers who received a TT-containing and/or the Tdap vaccine during pregnancy. Children born to Tdap-vaccinated mothers were randomized to receive either a hexavalent (Infanrix-hexa) or pentavalent (Quinvaxem) vaccine, whereas children born to TT-vaccinated mothers received only Quinvaxem vaccine at 2, 4, 6, and 18 months of age. IgG levels were evaluated at birth (cord blood), 2 (pre-primary), 7 (post-primary), 18 (pre-booster), and 19 months of age (post-booster) using a commercially available enzyme-linked immunoassay.ResultsSeroprotective concentrations of anti-DT, anti-TT, and anti-Hib IgG were achieved in >90% and >99% of children following primary and booster vaccination, respectively. Among children born to Tdap-vaccinated mothers, the pentavalent vaccine induced higher levels of anti-Hib IgG than the hexavalent vaccine after primary and booster vaccination. Significantly higher anti-Hib IgG levels were observed among children receiving the pentavalent vaccine and who were born to TT-vaccinated mothers than among children receiving the pentavalent vaccine and born to Tdap-vaccinated mothers after primary and booster vaccination.ConclusionsVaccination with a TT-containing and/or the Tdap vaccine during pregnancy did not compromise the seroprotection rate achieved following primary and booster immunization in individuals receiving either the pentavalent or hexavalent vaccine.     

Implementation of maternal influenza immunization in El Salvador: Experiences and lessons learned from a mixed-methods study

IntroductionThe World Health Organization (WHO) recommends that countries prioritize pregnant women for influenza vaccination, yet few low- or middle-income countries (LMICs) have implemented maternal influenza immunization programs. To inform vaccine decision-making and operational planning in LMICs, there is a need to document and share experiences from countries that provide seasonal influenza vaccine to pregnant women, particularly those with high coverage, like El Salvador.MethodsIn 2015 and 2016, PATH and country researchers conducted a mixed-methods study to document the experience and lessons learned from maternal influenza immunization delivery and acceptance in El Salvador as part of a collaborative effort between WHO and PATH. Researchers conducted focus group discussions, semi-structured interviews, antenatal clinic exit interviews, and key informant interviews with 326 participants from two municipalities in each of the country’s three regions. Respondents included pregnant and recently pregnant women, family members, community leaders, health personnel, public health managers and partners, and policymakers.ResultsFactors perceived as positively influencing maternal influenza immunization delivery and acceptance in El Salvador include the use of multiple vaccine delivery strategies, targeted education and community engagement efforts, and a high degree of trust between the community and health care providers. Influenza vaccine acceptance by pregnant women is high and has improved over time, largely attributed to education targeting health care advisors. Perceived challenges to pregnant women receiving health care and vaccination include the need for permission to attend services and limited access to health services in insecure areas related to the presence of criminal gang activity.ConclusionsWe identified approaches and barriers perceived to affect maternal influenza vaccine delivery in El Salvador. This information will be useful to public health decision-makers and implementers in El Salvador and other countries considering introduction of new maternal vaccines or striving to increase coverage of vaccines currently provided.     

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.     

Impact of pregnancy on polyfunctional IgG and memory B cell responses to Tdap immunization

BackgroundMaternal pertussis immunization using Tdap vaccine is recommended in many countries to protect newborns from severe post-natal infection. Immunological changes during pregnancy may influence the response to vaccines. The quality of IgG and memory B cell responses to Tdap immunization in pregnant women has not yet been described.MethodsThe impact of pregnancy on the response to Tdap vaccination was assessed by comparing humoral immune responses in 42 pregnant and 39 non-pregnant women. The levels of serum pertussis antigens and tetanus toxoid-specific IgG, IgG subclasses, IgG Fc-mediated effector functions, as well as memory B cell frequencies were assessed before and at several time points after vaccination.ResultsTdap immunization induced similar levels of pertussis and tetanus-specific IgG and IgG subclasses in pregnant and non-pregnant women. Pregnant women produced IgG promoting complement deposition, and neutrophils and macrophages phagocytosis at levels comparable to non-pregnant women. They were also able to expand pertussis and tetanus-specific memory B cells at similar frequencies as non-pregnant women, suggesting equivalent “boostability”. Higher levels of vaccine-specific IgG, IgG subclasses, and IgG Fc-mediated effector functions were detected in cord blood as compared to maternal blood, indicating efficient transport across the placenta.ConclusionsThis study demonstrates that pregnancy does not affect the quality of effector IgG and memory B cell responses to Tdap immunization and that polyfunctional IgG are efficiently transferred across the placenta.Registry's URL and the trial's registration numberClinicalTrials.Gov (NCT03519373).     

Predictors of maternal vaccination in the United States: An integrative review of the literature

ObjectivesThe purpose of this literature review was to identify, analyze, and synthesize existing research related to patient, provider, and health system predictors of maternal vaccination in the United States, strategies used to increase maternal vaccination rates, and major theoretical frameworks used to guide maternal vaccination research.MethodsA search for evidence was conducted in CINAHL, PubMed, PsychINFO, Cochrane Systematic Reviews, and Google Scholar. Twenty-two articles were identified as best evidence for inclusion in this review: five randomized control trials, one cluster randomized trial, one mixed methods study, 12 observational studies, and three qualitative studies.ResultsPatient-focused predictors of maternal vaccination included provider recommendation; knowledge, attitudes, and beliefs; cues to action; and race and ethnicity. Provider-focused predictors included knowledge, attitudes, and beliefs; and multi-component intervention packages. Health system predictors included standing order protocols and practice site logistics. The major theoretical frameworks that emerged were the Health Belief Model, Theory of Reasoned Action/Theory of Planned Behavior, and Message Framing/Prospect Theory. Provider recommendation was the single most important predictor of vaccine acceptance among pregnant women.ConclusionsAn abundance of theoretically-supported, patient-focused research was found in the literature. A minimal number of U.S.-based, provider-focused research was found and none of these used a theoretical framework. Minimal research examining health system barriers to maternal vaccination was found. Additional research into the logistical barriers to maternal vaccination programs within obstetrical practice locations in other geographical locations within the U.S. is warranted. Future provider- and health system-focused research needs to be grounded in theory. The field of implementation science may offer the theoretical guidance necessary to better understand problems in obstetrical practice work flow and streamlining of vaccinations.