Vaccine effectiveness of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis vaccine during a pertussis outbreak in Maine

BackgroundMultiple school-associated pertussis outbreaks were reported in Maine from 2010 to 2011. These outbreaks were associated with an overall increase in pertussis cases statewide. Waning of protection in students recently vaccinated with tetanus, diphtheria, and acellular pertussis (Tdap) has been implicated in the increase in reported rates of pertussis nationally.MethodsWe conducted a retrospective cohort study to evaluate Tdap vaccine effectiveness (VE) among students aged 11–19 years in two schools reporting outbreaks in 2011. All pertussis cases reported from August through November, 2011 at the two schools were included. Vaccination history was verified using provider information, state vaccine registry data, and parental verification. Attack rates (AR) were calculated. VE and duration of protection was calculated as VE = 1 − (AR_vaccinated/AR_unvaccinated) × 100% using a log binomial regression model.ResultsOf 416 students enrolled, 314 were included in the analyses. Twenty-nine cases collectively in Schools A and B. Tdap coverage was 65% at School A and 42% at School B before the start of the outbreak. Among students enrolled in the study, attack rates were 11.9% and 7.7% at Schools A and B, respectively. Overall VE was 68.5% (95% confidence interval (CI) 37.7–86.2). VE was 70.4% (95% CI 17.5–89.4) for School A and 65.2% (95% CI −19.2 to 89.9) for School B. VE <2 years versus ≥2 years from outbreak onset was not significantly different.ConclusionsTdap was moderately effective in preventing disease among vaccinated students. Vaccine coverage of 65% or less was suboptimal and might contribute to outbreaks. Waning VE was not demonstrated. Increased vaccination coverage rates as well as further evaluation of the role of acellular vaccine on VE is needed.     

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.     

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

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

Effectiveness of different vaccine schedules for heptavalent and 13-valent conjugate vaccines against pneumococcal disease in the Community of Madrid

IntroductionThe heptavalent pneumococcal conjugate vaccine (PCV-7) was added to the childhood routine vaccination program in the Community of Madrid in November of 2006 with 3 + 1 recommended doses and a catch-up for those under 2 years old. In June 2010, PCV-7 was replaced by 13-valent vaccine (PCV-13) with 2 + 1 recommended doses. In July of 2012, the PCV-13 was removed from the funded program and reintroduced again (2 + 1 recommended doses) in December 2014. In between, children were vaccinated privately with 3 + 1 recommended doses of PCV-13. The aim of this study was to evaluate the effectiveness of each vaccination schedule used in the Community of Madrid.MethodsWe included all cases of invasive pneumococcal disease (IPD) reported between 2007 and 2015 to the Notifiable Diseases Surveillance System. Vaccination information was obtained from the Immunization Registry. Vaccine effectiveness (VE) was estimated using the indirect cohort design for cases with serotype information.ResultsA total 779 cases were included in the study. Among them 47.6% of the cases were primo-vaccinated with booster, 20% primo-vaccinated, 15.9% incompletely primo-vaccinated and 16.5% not vaccinated. The VE for ≥1 doses of any PCV was 82% (CI 95%: 67.8–89.9%): 91.9% (CI 95%: 76.5–97.2%) for PCV-7 and 77.2% (48.6–89.9%) for PCV-13. VE in those receiving the full 2 + 1 or 3 + 1 schedules was 100% for both vaccines.ConclusionsA high number of vaccine failures were reported in children before they had the opportunity to receive the booster dose, especially due to PCV-13-non-PCV-7 serotypes. VE was higher for PCV-7 compared to PCV-13, except for those that received the complete schedule with booster that achieved 100% of VE, which shows the relevance of the vaccines and complying with all doses scheduled.     

Effectiveness of quadrivalent influenza vaccination in the first year of a funded childhood program in Queensland,Australia, 2018

BackgroundFollowing high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program.MethodsA matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VE_adj) for sex and First Nations status.ResultsThere were 1,125 cases and 10,645 matched controls analysed. Overall VE_adj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41–60). VE_adj was 60% (95% CI 46–70) for children who received two doses in 2018, and 60% (95% CI 48–69) for children vaccinated appropriately according to schedule completeness. VE increased with age.ConclusionsModerate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.     

Pertussis burden and acellular pertussis vaccine effectiveness in high risk children

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

Vaccine effectiveness of PCV13 in a 3 + 1 vaccination schedule

ObjectiveTo assess the vaccine effectiveness (VE) of PCV13 for invasive pneumococcal disease (IPD) regarding the extra six serotypes with a 3 + 1 schedule in Germany.MethodsActive surveillance for IPD in children <16 years eligible for PCV13 vaccination. We used the Broome method and logistic regression to estimate VE.ResultsData on 164/304 reported IPD cases were informative and met the inclusion criteria. VE for the extra six serotypes was 88% [95% confidence interval (CI): 73; 95] and 83% [56; 94] for at least one and for at least two doses respectively. VE for the complete 3 + 1 vaccination schedule was not conclusive because of a wide 95% CI. For serotype 3 VE appeared to be zero with an even wider 95% CI.ConclusionPCV13 VE against the extra six serotypes with the 3 + 1 schedule in Germany was only marginally higher compared to previously published data for the 2 + 1 schedule.     

Seroprevalence of anti-HBs antibodies at young adulthood,before and after a booster vaccine dose,among medical personnel vaccinated in infancy

BackgroundQuestions remain regarding the long-term protection provided by childhood HBV vaccination. The goals of this study were to assess HBV seroprevalence among medical personnel purportedly vaccinated in infancy; to investigate the immune response after a booster dose given in young adulthood; and to identify predictors of non-responders.MethodsBetween 2011 and 2013 we studied Israeli male military recruits purportedly vaccinated in infancy. All subjects were born after January 1st 1992 and were undergoing medic training. We collected personal data and blood samples at baseline, and administered a dose of HBV vaccine. Subjects were retested one month later and received a second dose. A third blood draw was conducted one month after the second dose. Data collected at baseline were used as predictor variables of seropositivity (anti-HBs ≥ 10 mIU/ml).Results617 subjects were available for baseline analysis and 539 for paired observations at one month. Baseline seropositivity was 33.7%. Subjects who received post-infancy vaccine doses had a seropositivity rate double that of those denying additional doses (RR 2.22, 95% CI 1.55–3.18). One month after the first booster dose, the overall cumulative population seropositivity reached 87.7%. One month after the second vaccine dose, population seropositivity was 97.9%. Heavy smokers were 5 times less likely to demonstrate detectable antibodies after a single booster dose (OR 0.196, 95% CI 0.060–0.641, P = 0.007).ConclusionsThis population-based study is important for informing public health vaccination policy. Our results strongly indicate that among cohorts vaccinated in infancy, two doses in adulthood will provide maximal protective antibody levels, while one dose will provide sufficient population protection.     

Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24 months and immunogenicity of a fifth dose administered at 4 years of age-a phase 3 extension to a randomised controlled trial

Background4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age.MethodsA phase 3, open label, multi-centre extension to a randomised controlled trial (ClinicalTrials.gov identifier NCT01717638) conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule.ResultsAt baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192).ConclusionWaning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.     

Evaluating the effectiveness of the universal immunization program against varicella in Japanese children

ObjectiveMatched case control study was conducted to elucidate the effectiveness of the Oka/Biken vaccine immediately after implementation of the universal immunization program in Japan.MethodsCases were laboratory confirmed varicella patient under 15 years of age diagnosed at 14 designated pediatric clinics between September 2015 and September 2016. Controls were selected from patients who visited the same practice for different reasons as the varicella case within 2 weeks. Swab samples were collected from varicella suspected patients and molecular diagnostic assays were used to confirm varicella cases. Matched odds ratio were used to calculate vaccine effectiveness (VE).ResultsVaricella zoster virus DNA was detected in 183 (81.3%) of 225 suspected cases. One sample was excluded because it was positive for the Oka vaccine strain (182/225, 80.9%). Three hundred twenty-three control subjects were enrolled. The effectiveness of 1 dose of the Oka/Biken vaccine compared with no vaccine was 76.7% (95% confidence interval [CI]: 58.6–86.9%; P < 0.001). The effectiveness of 2 doses of the Oka/Biken vaccine was 94.2% (95% CI: 85.7–97.6%; P < 0.001). After adjusting for potential confounding effects, the adjusted VE of 1 and 2 doses of varicella vaccine were 76.9% (95% CI: 58.1–87.3%; P < 0.001) and 94.7% (95% CI: 86.0–98.0%; P < 0.001), respectively.ConclusionsVE of one dose of Oka/Biken varicella vaccine was insufficient to control varicella. Therefore, two doses of Oka/Biken varicella vaccine is significant for controlling varicella in Japan.     

The predicted persistence and kinetics of antibody decline 9 years after pre-school booster vaccination in UK children

BackgroundLong term follow-up of vaccine trials is essential to establish the duration of protection. In the context of worldwide concern about rising pertussis incidence, estimates of antibody persistence after vaccination, which do not account for the rise in antibody due to natural boosting or infection, may overestimate the degree of protection afforded by pertussis vaccines.MethodsThis was a 5 year follow up study of a randomised controlled trial of diphtheria, tetanus, pertussis and polio booster vaccines in UK children aged 3.5–5 years. Antibody persistence was measured at 1 month, 1, 3, and 5 years after vaccination and the kinetics of antibody decline were modelled longitudinally. Estimates of predicted antibody persistence 9 years after the pre-school booster were derived from model parameters.ResultsAntibody levels 9 years after vaccination were predicted to be above accepted thresholds for protection for diphtheria, tetanus and polio. Antibody responses to pertussis toxoid were undetectable in 49% of children at the 5 year follow up visit, and responses were predicted to be undetectable in 69% (95% CI 45–88%) of children by the time of their teenage booster at 13–14 years of age.ConclusionsThere is no defined correlate of protection for pertussis. However, the large proportion of participants in this study with undetectable pertussis antibody levels at both measured and predicted timepoints suggests sub-optimal immunity in adolescence. Adding pertussis to the teenage booster for UK children as is done in other countries, would enhance immunity in adolescence.     

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis

BackgroundThe clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines.MethodsWe searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR) 1 100. Narrative synthesis was undertaken where meta-analysis was not possible.ResultsWe identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE = 80%; 95% confidence interval [CI] 59–90%; unadjuvanted: VE = 66%; 95% CI 47–78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14–82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18–64 years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes.ConclusionsAdjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.     

What predicts postpartum pertussis booster vaccination? A controlled intervention trial

Background‘Cocooning’ aims to protect susceptible infants from pertussis via caregiver vaccination. Control trials evaluating educational interventions to promote cocooning are lacking. We evaluated the role of message-framing vs. standard health information in promoting pertussis vaccination.MethodsWe recruited postpartum women from a maternity hospital in Sydney, Australia (November 2010–July 2012). Participants self-completed a pertussis knowledge and attitudes questionnaire. We then assigned pertussis-susceptible (no pertussis vaccine ≤10 years) participants to receive a gain-framed, loss-framed pamphlet or control (Government Pertussis factsheet) using weekly sequential block allocation. Next, participants were offered a pertussis vaccine (dTpa) and completed a post-questionnaire on discharge.ResultsA baseline questionnaire was completed for 96.4% (1433/1486) of postpartum women approached. Missing data was excluded (n = 29). Next, participants (1404) were screened for vaccine status: 324 (23%) reported prior pertussis booster vaccine receipt, leaving 1080 participants requiring vaccination. Among susceptible mothers, 70% (754/1080) were vaccinated post-intervention. Rates were similar between ‘gain’, ‘loss’ or ‘control’ pamphlets (69.1% vs. 71.8% vs. 68.8%; p = 0.62). Intention to be vaccinated (OR 2.46, p < 0.001; 95% CI: 1.69–3.58), perceived vaccine benefits (OR: 1.61, p < 0.001; 95% CI: 1.25–2.15) and having received a vaccine recommendation (OR 1.68; p = 0.025; 95% CI: 1.07–2.65) were independent predictors of vaccine uptake. At discharge, overall pertussis vaccine coverage had increased from 23% to 77% among women screened (1078/1404).ConclusionA cocooning strategy for pertussis vaccination can be highly effective when partially implemented within maternity hospitals, with information accompanied by a funded vaccine. Mothers were highly receptive to vaccination in the postnatal ward: facts about pertussis were as effective as message-framing in promoting a high uptake of 70%. Perceived vaccine benefits, intentions and vaccine recommendation were important predictors of uptake. Our intervention trial increased the existing pertussis vaccine coverage of 23–77%.     

Waning protection following 5 doses of a 3-component diphtheria,tetanus, and acellular pertussis vaccine

BackgroundThe effectiveness of diphtheria, tetanus, and acellular pertussis (DTaP) vaccines wanes substantially after the 5^th dose given at ages 4–6 years, but has not been described following 5 doses of the same type of DTaP vaccine. We investigated waning effectiveness against pertussis in California over nearly 10 years, which included large pertussis outbreaks, following 5 doses of GSK DTaP vaccines (DTaP₃).MethodsWe conducted a case-control study (NCT02447978) of children who received 5 doses of DTaP at Kaiser Permanente Northern California from 01/2006 through 03/2015. We compared time since the 5^th dose in confirmed pertussis polymerase chain reaction (PCR)-positive cases with pertussis PCR-negative controls. We used logistic regression adjusted for calendar time, age, sex, race, and service area to estimate the effect of time since the 5^th DTaP dose on the odds of pertussis. Our primary analysis evaluated waning after 5 doses of DTaP₃. We also examined waning after 5 doses of any type of DTaP vaccines.ResultsOur primary analysis compared 340 pertussis cases diagnosed at ages 4–12 years with 3841 controls. The any DTaP analysis compared 462 pertussis cases with 5649 controls. The majority of all DTaP doses in the study population were DTaP₃ (86.8%). Children who were more remote from their 5^th dose were less protected than were children whose 5^th dose was more recent; the adjusted odds of pertussis increased by 1.27 per year (95% CI 1.10, 1.46) after 5 doses of DTaP₃ and by 1.30 per year (95% CI 1.15, 1.46) after any 5 DTaP vaccines doses.ConclusionsWaning protection after DTaP₃ was similar to that following 5 doses of any type of DTaP vaccines. This finding is not unexpected as most of the DTaP vaccines administered were DTaP_3. Following 5 doses of DTaP₃ vaccines, protection from pertussis waned 27% per year on average.NCT number: NCT02447978.     

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.     

Effectiveness of acellular pertussis vaccine in a routine immunization program: A multicenter,case-control study in Japan

In 2008, the number of pertussis cases increased substantially among Japanese adolescents, despite high coverage with acellular pertussis vaccine (DTaP). This study examined the effectiveness of DTaP vaccine in the routine immunization program in Japan. Between April 2009 and October 2012, we conducted a multicenter, case-control study, and compared the history of DTaP vaccination between 55 newly diagnosed pertussis cases and 90 age- and sex-matched controls. DTaP vaccine history was obtained by a self-administered questionnaire completed by their parents or guardians. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis.DTaP vaccination of ≥1 dose revealed a significantly lower OR for pertussis (OR = 0.20, 95%CI, 0.04–0.97), and the OR of complete vaccination (4 doses) was 0.22 (0.04–1.05). Even after limiting subjects to those whose vaccination status could be confirmed by the immunization records, the negative associations were observed. The decreasing ORs of 4-dose vaccinees remained, even among subjects who had received the fourth dose ≥9.2 years earlier (OR = 0.11, 95%CI, 0.01–1.02).In conclusion, DTaP vaccination had a preventive effect for pertussis. Effectiveness was observed even 9 or more years after the final dose.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

Decennial administration in young adults of a reduced-antigen content diphtheria,tetanus, acellular pertussis vaccine containing two different concentrations of aluminium

BackgroundRegular booster vaccination might be necessary throughout life to protect against pertussis infection. Nevertheless the duration of protection after booster vaccination remains unclear. In this study, antibody persistence up to 10 years after previous vaccination of adolescents (N = 478) with combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (dTpa, Boostrix™, GlaxoSmithKline Belgium) containing 0.5 mg, 0.3 mg or 0.133 mg of aluminium was assessed. The immunogenicity, reactogenicity and safety of a decennial booster dTpa dose were also investigated.MethodsYoung adults vaccinated as adolescents in the initial booster study were invited to participate in an assessment of antibody persistence at years 8.5 and 10, and to receive a dTpa booster dose at year 10 with immunogenicity assessment one month later. Those who originally received the 0.5 mg or 0.3 mg formulations received the same vaccine at year 10. Those in the 0.133 mg group received the 0.5 mg formulation. Reactogenicity and safety endpoints were captured until 30 days after booster vaccination.ResultsPrior to the decennial booster at year 8.5 and year 10, all participants had seroprotective antibodies for diphtheria (ELISA or neutralisation assay) and tetanus. At least 77.8% were seropositive for anti-pertussis toxin (PT) antibodies at year 8.5 and 82.8% at year 10. All participants were seropositive for antibodies for filamentous haemagglutinin and pertactin at both time points. The decennial booster dose induced robust increases in antibody GMCs to all antigens. The post-booster anti-PT geometric mean concentration was 82.5 EL.U/ml (95%CI 67.0–101.6) and 124.0 (103.5–148.5) in the 0.3 mg and 0.5 mg groups, respectively. The reactogenicity and safety profile of the decennial booster dose was consistent with the known safety profile of dTpa. No serious adverse events were reported.ConclusionsDecennial booster vaccination with either of the two licensed formulations of dTpa was highly immunogenic and well tolerated in young adults. Either formulation could be confidently used as a decennial booster.This study is registered at www.clinicaltrials.gov NCT01147900