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.     

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis.After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR = 0.11, 95% CI, 0.01–0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR = 0.07, 95%CI, 0.01–0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR = 5.67) and those with a recent contact with a lasting cough (OR = 4.12).When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique.     

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

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

Impact of routine vaccination with a pertussis toxoid vaccine in Denmark

In many countries, acellular pertussis vaccines have replaced whole-cell vaccines. We evaluated the impact of a pertussis toxoid vaccine on pertussis in Denmark. We calculated incidence rates for pertussis before and after pertussis toxoid vaccine was introduced, and estimated vaccination effectiveness (VE). We found that routine vaccination with pertussis toxoid vaccine was effective against both hospitalisation with pertussis (VE, 93% for three doses) and non-hospitalised pertussis (VE, 78% for three doses). However, after the introduction we found an increase in pertussis among the youngest infants, a direct result of the new schedule (ages 3, 5 and 12 months) where the youngest infants are unvaccinated for a longer time-period compared with the prior schedule (ages 5, 9 weeks and 10 months).     

Effectiveness of pertussis vaccination in New South Wales,Australia, 1996-1998

Pertussis notifications have increased over the past decade in Australia and other industrialised countries. This study estimates the effectiveness of pertussis vaccination in one Australian State (New South Wales, NSW) among children aged less than 14 years, during a period when an Australian whole-cell pertussis vaccine was in routine use. Cases notified with pertussis between 1996 and 1998 and pertussis vaccine coverage estimates from the Australian Childhood Immunisation Register were used. Vaccine effectiveness (VE) was calculated using the screening method, with adjustment for age group, year of disease onset and area of residence. VE was highest (91%) in the youngest age group (8–23 months) and lowest (78%) in the oldest age group (9–13 years). Pertussis vaccination is highly effective at preventing pertussis in NSW children, as measured by notified cases. Ongoing monitoring will be important to evaluate VE following Australia's change to an acellular vaccine based program.     

Cost-effectiveness of pertussis booster vaccination for preschool children in Japan

Introduction: Japan currently recommends four doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in its routine vaccination program, but the introduction of a fifth dose is currently under consideration. An objective of the booster vaccination is to prevent severe cases of pertussis in infants through herd immunity. Thus, the aim of this analysis was to demonstrate the cost-effectiveness of a fifth-dose of the DTaP vaccine for 6-year-old children, taking herd immunity for unvaccinated infants into account.MethodAn economic model analysis was conducted comparing the cost and effectiveness of the two strategies based on quality-adjusted life years (QALYs). We evaluated the incremental cost-effectiveness ratio (ICER) of the booster strategy to the no booster strategy. This model contained two sub-models: one for children aged 6 years or older and one for infants under 3 months old. Herd immunity for infants is modeled as when siblings in the same family are infected.ResultsThe ICER was JPY 71,605,491 (USD 656,931) per QALY gained from the societal perspective, and 7.10% of incremental QALYs (0.0000934) were from a reduction in infant infection. In the sensitivity analysis, no variables moved the ICER under the threshold (JPY 5,000,000 per QALY gained), and the duration of pertussis disease and the incidence rate of pertussis had a significant impact on the ICER. When the disease burden of pertussis decreased, the booster strategy resulted in fewer QALYs gained and greater costs compared with the no booster strategy.ConclusionThe introduction of a DTaP booster vaccination to the routine immunization schedule can be expected to reduce the number of pertussis cases in the target population. However, our study showed that adding a booster vaccination for 6-year-old children to the schedule in Japan would not be cost-effective in terms of achieving herd immunity among unvaccinated infants.     

Cost-effectiveness analysis of a pertussis vaccination programme for Japan considering intergenerational infection

Objective

The incidence of pertussis in adolescence and adulthood has been increasing, and pertussis outbreaks have occurred sporadically in Japan. The risk of intergenerational infection of pertussis is of concern. The aim of this study is to assess the cost-effectiveness of alternative vaccination programmes for replacing the conventional diphtheria–tetanus (DT) vaccine programme administered in adolescence, considering the risk of intergenerational infection.

Methods

We examined the cost-effectiveness of 4 pertussis vaccination programmes: (1) one-time adolescent DT vaccination (DT); (2) one-time adolescent DT-acellular pertussis (DTaP) vaccination; (3) one-time adolescent DTaP with decennial booster (DTaP + booster); and (4) one-time adolescent DTaP with additional vaccination targeted at parents with infants (additional DTaP for parents). We adapted a state-transition Markov model to estimate the costs and effectiveness of vaccination in the adolescent and adult cohorts and then considered intergenerational infection from adolescents/adults to infants. We assumed a societal perspective to estimate results and expressed these in terms of cost, life expectancy, quality-adjusted life expectancy, benefit-cost ratio (BCR), and incremental cost-effectiveness ratio (ICER).

Results

At an incidence of 25 per 100,000, the ICERs of the DTaP and additional DTaP for parents strategies were 3,576,072 JPY and 240,055,273 JPY, respectively, when intergenerational transmission of infection was considered. The ICER for the DTaP + booster strategy was dominated.

Major conclusion

Alternative vaccination programmes are not currently cost-effective. If intergenerational infection considered, one-time adolescent DTaP vaccination is cost-effective. More accurate reports of pertussis incidence are required as the results of cost-effectiveness analyses of vaccination vary greatly depending on incidence.     

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

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

Effectiveness of parental cocooning as a vaccination strategy to prevent pertussis infection in infants: A case-control study

BackgroundDuring a pertussis epidemic in 2009, the Department of Health, Victoria, Australia, implemented a cocoon program offering parents of new babies a funded-dose of pertussis-containing vaccine. We assessed vaccine effectiveness (VE) of the program in reducing pertussis infection in infants.MethodsUsing a matched case-control design, infants aged <12 months that were notified with pertussis between 1 January 2010 and 31 December 2011, and born during the time that the cocoon program was in place, were identified. Controls were matched by area of residence and date of birth. Telephone interviews we conducted to ascertain parents’ vaccination status, and if vaccinated, timing of vaccination receipt relative to the birth of their baby. Odds ratios (ORs) were calculated for the association between vaccination and pertussis infection, with VE calculated as (1 – OR) × 100%.ResultsThe study recruited 215 cases and 240 controls (response rates 67% and 25% of eligible participants, respectively). Vaccination of both parents after delivery of the infant and ≥28 days prior to illness onset reduced pertussis infection by 77% (Vaccine Effectiveness [VE] = 77% (confidence interval [95% CI], 18–93%). After adjusting for maternal education, presence of a sibling within the household, and the infants’ primary course vaccination status, the adjusted VE was 64% (95% CI, −58–92%).ConclusionsAlthough not reaching statistical significance, our results demonstrated that cocoon immunisation – where both parents are vaccinated in the post-partum period – may offer some protection again infant pertussis infection. Cocoon immunisation could be considered in circumstances where antenatal vaccination of the mother has not occurred.     

Effectiveness of the 2003-2004 influenza vaccine among U.S. military basic trainees: a year of suboptimal match between vaccine and circulating strain

Effectiveness of the 2003-2004 influenza vaccine was evaluated at five military basic training centers throughout the United States. Data from surveillance conducted in December and January 2003-2004 in this highly vaccinated population were evaluated. During this period, 10.6% (37/350) of specimens were positive for influenza A. A 14-day period after vaccination was considered the period prior to immune protection; vaccine effectiveness (VE) was calculated based on febrile respiratory illness presentation and laboratory confirmation of influenza before or after this 14-day period. Thirty-two cases presented within 14 days of vaccination, and five cases presented beyond 14 days from vaccination. VE in this population was estimated to be 94.4% for laboratory-confirmed influenza. In contrast, VE was only 13.9% for influenza-like illness (ILI) without a laboratory confirmation.     

IgE sensitization to gelatin: the probable role of gelatin-containing diphtheria-tetanus-acellular pertussis (DTaP) vaccines

We recently found that most events of anaphylaxis to live attenuated viral vaccines containing gelatin as a stabilizer might be caused by the gelatin. However, the mechanism that the children were sensitized to gelatin was unclear. In Japan, both diphtheria-tetanus-acellular pertussis (DTaP) vaccines with and without gelatin are available. We explored the possibility that gelatin-containing DTaP vaccines before live viral vaccines sensitize children to gelatin. We received the serum samples of 87 children who had systemic immediate-type reactions including anaphylaxis to the vaccines from both physicians and vaccine manufacturers throughout Japan. We then surveyed the DTaP vaccination histories of the children who demonstrated anti-gelatin IgE. Of the above 87 children, 79 (91%) had anti-gelatin IgE. We successfully collected DTaP vaccination histories including the manufacturers' names and numbers of doses on 55 children. Only one child had not received any DTaP vaccine, the other 54 had received gelatin-containing DTaP vaccines and none received gelatin-free DTaP vaccines. We concluded that there was a strong causal relationship between gelatin-containing DTaP vaccination, anti-gelatin IgE production, and risk of anaphylaxis following subsequent immunization with live viral vaccines which contain a larger amount of gelatin.     

Pertussis--United States, 1997-2000

Pertussis was a major cause of morbidity and mortality among infants and children in the United States during the prevaccine era (i.e., before the mid-1940s). Following the introduction and widespread use of whole-cell pertussis vaccine combined with diphtheria and tetanus toxoids (DTP) among infants and children in the late 1940s, the incidence of reported pertussis declined to a historic low of 1,010 cases in 1976 (Figure 1). However, since the early 1980s, reported pertussis incidence has increased cyclically with peaks occurring every 3-4 years. In 1996, less reactogenic acellular pertussis vaccines (DTaP) were licensed and recommended for routine use among infants. This report summarizes national surveillance data for pertussis during 1997-2000 and assesses the effectiveness of pertussis vaccination in the United States during this period. The findings indicate that pertussis incidence continues to increase in infants too young to receive 3 doses of pertussis-containing vaccine and in adolescents and adults. Prevention efforts should be directed at maintaining high vaccination rates and managing pertussis cases and outbreaks.     

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

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

Rapid assessment of influenza vaccine effectiveness: analysis of an internet-based cohort

The effectiveness of influenza vaccination programmes is seldom known during an epidemic. We developed an internet-based system to record influenza-like symptoms and response to infection in a participating cohort. Using self-reports of influenza-like symptoms and of influenza vaccine history and uptake, we estimated vaccine effectiveness (VE) without the need for individuals to seek healthcare. We found that vaccination with the 2010 seasonal influenza vaccine was significantly protective against influenza-like illness (ILI) during the 2010-2011 influenza season (VE 52%, 95% CI 27-68). VE for individuals who received both the 2010 seasonal and 2009 pandemic influenza vaccines was 59% (95% CI 27-77), slightly higher than VE for those vaccinated in 2010 alone (VE 46%, 95% CI 9-68). Vaccinated individuals with ILI reported taking less time off work than unvaccinated individuals with ILI (3.4 days vs. 5.3 days, P<0.001).     

Cost-effectiveness analysis of pertussis vaccination during pregnancy in Japan

BackgroundBoth re-emergence of pertussis outbreak among adolescents/adults and recent approval of the extended use of DTaP vaccine for boosting adolescents/adults against pertussis in Japan, have raised the possibility of using aP-containing vaccine in pregnant women to protect neonates and unvaccinated infants. There is a need, therefore, to evaluate the value for money of such possibility.MethodsWe evaluated the cost-effectiveness of conducting antepartum maternal vaccination (AMV) strategy in Japan. Considering the duration of vaccine effectiveness for infant (single year) and for mother (multiple years), the decision tree model and Markov model was adapted for infant and mother, respectively. Incremental cost-effectiveness ratio (ICER) compared with current no AMV strategy from societal perspective were calculated. The transition probabilities, utility weights to estimate quality-adjusted life year (QALY), and disease treatment costs were either calculated or extracted from literature. Costs per vaccination was assumed at ¥6000/US$54.5. Markov model for mothers with one-year cycle runs up to year four after vaccination, based on the waning of vaccine effectiveness. Infant who survived from pertussis was assumed to live until to his/her life expectancy.ResultsAMV strategy reduces disease treatment costs, while the reduction cannot offset the vaccination cost. Incremental QALYs were at 0.0002802, among them 79.5% were from infants, and others from mothers. ICER was ¥9,149,317/US$83,176 per QALY gained. One-way sensitivity analyses identified that the incidence rate and costs per shot were the two main key variables to impact the ICER.ConclusionWe found that vaccinating pregnant women with aP-containing vaccine to prevent neonatal and unvaccinated infants from pertussis-associated disease in Japan can be cost-effective from societal perspective, under the WHO-suggested “cost-effective” criteria (1 to 3 times of GDP). Pertussis is expected be designated as a notifiable disease in 2018, re-analysis should be conducted when straightforward incidence data is available.     

Effectiveness of Rubella vaccine in a rubella outbreak in Guangzhou city,China, 2014

BackgroundWHO recommends the use of rubella-containing vaccine (RCVs) to prevent rubella and congenital rubella syndrome (CRS). Most licensed rubella vaccines in use globally are based on RA27/3 strains and have estimated vaccine effectiveness (VE) rates of 95–100%. In contrast, China uses a BRD-II strain-based rubella vaccine. Few field studies have been conducted that estimate VE of China's RCV. On March 17, 2014, a rubella outbreak was reported in a middle school in Guangzhou city, China. We conducted an investigation to understand reasons for the outbreak, and we used that investigation to estimate vaccine effectiveness of China's rubella vaccine.MethodsTo identify cases, investigators reviewed records kept by the school doctor and absentee records kept by teachers. Self-administered questionnaires were sent to parents of all students to collect information about the students’ symptoms, the results of any physician consultation, and disease history. We obtained demographic information and illness information for all students in the school; vaccination status was determined by inspection of official, parent-held vaccination records. A retrospective cohort study was conducted in 13 classes that had secondary cases of rubella. Using the secondary attack rates, we evaluated VE by the number of RCV doses received and age at vaccination.ResultsDuring the period February 17–May 23, 2014, 162 students (50 suspected cases, 88 probable cases, 24 confirmed cases) were diagnosed with rubella, yielding an overall attack rate of 10% (162/1621). Cases occurred in 27 classes (73%) of 37 classrooms. Secondary cases occurred in 13 classes (35%) of 37 classrooms. A total of 1130 students (69.7%) have vaccination certificates; 419 (37%) students were record-confirmed to have received RCV. For those vaccinated using BRD-II strain vaccine, vaccine effectiveness (VE) was 94% (95%CI: 75–98). VE for measles, mumps, and rubella (MMR) vaccine which is based on either BRD-II or RA27/3 strain was 89% (95%CI: 56–97). VE of a single dose of domestic monovalent rubella vaccine that used BRD-II strain vaccine was 93% (95%CI: 73–98). VE for those who received the vaccine between 1 and 2 years of age was 95% (95% CI: 67–99) while the VE was 100% for those vaccinated after 2 years of age. VE among those who received RCV <12 years ago was 100% while VE among those who received RCV ≥12 years ago was 92% (95%CI: 70–98).ConclusionsThe rubella vaccines used in China that are based on the BRD-II rubella vaccine strain have VE of 94%, which is similar to the more commonly used RA27/3-based RCVs. Low vaccination coverage contributed to this outbreak; early reporting of an outbreak is necessary for effective outbreak response immunization.     

Th2-polarisation of cellular immune memory to neonatal pertussis vaccination

Current infant vaccination against pertussis in North America and Australia requires three doses of vaccines including diphtheria, tetanus and acellular pertussis antigens (DTaP) at 2, 4 and 6 months of age. Interest is growing in the possibility that vaccination at birth might provide earlier protection of infants, but early vaccination also gives rise to concerns over the potential for excessive Th2-polarisation of pertussis-specific T-cell memory profiles. We evaluated this issue as part of a small pilot study comparing infants receiving a monovalent acellular pertussis vaccine (aP) at birth or birth and at 1 month, followed by DTaP at 2, 4 and 6 months with infants receiving DTaP only from 2 months. We compared in vitro Th-memory responses at 8 months and pertussis-specific IgG in serum at 2, 4, 6 and 8 months. Neonatal vaccination elicited earlier IgG responses, but accompanying Th-memory profiles displayed a strong Th2 bias with high IL-5 and IL-13 production. The correlation between T-cell memory profiles and other clinical outcomes should be evaluated in larger trials of neonatal aP vaccine.     

Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™

BackgroundCo-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria–tetanus–acellular pertussis vaccine (DTaP) at age 15–18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers.MethodsInfants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12–15 months and DTaP at 15–18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15–18 months (Coad group); or HibMenCY-TT at 12–15 months and DTaP at 15–18 months (HibMenCY-TT group). Controls received DTaP at 15–18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination.ResultsPre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone.ConclusionRoutine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the administration of a fourth DTaP dose following a 4-dose HibMenCY-TT vaccination series, or co-administered with MenACWY-TT in HibMenCY-TT-primed children.     

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

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

Health and Economic Evaluation of Vaccination Against Pertussis in China: A 40-Year Analysis

ObjectivesThis study aimed to evaluate the health and economic impact of diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) and diphtheria-tetanus-acellular pertussis vaccine (DTaP) vaccination on pertussis prevention and control in China during the 40 years from 1978 to 2017.MethodsWe conducted cost-benefit analyses with a decision tree model populated with historical vaccination coverage levels and pertussis incidence and mortality data from before 1978 and during 1978 to 2017. We modeled 40 birth cohorts from birth until death. Costs and benefits were estimated from direct cost and societal perspectives (direct and indirect costs). Costs and benefits were adjusted to 2017 US dollars (USD), and future values were discounted at a 3% annual rate. We calculated net benefit values (net savings) and benefit-cost ratios of pertussis vaccination of children younger than 5 years. We conducted sensitivity analyses by varying key parameters within plausible ranges.ResultsWithout DTwP and DTaP vaccination, there would be an estimated 115.76 million pertussis cases and 426 650 pertussis deaths in the 40 cohorts. With DTwP/DTaP vaccination, pertussis cases and deaths were decreased by an estimated 92.57% and 97.43%, saving 46 987.81 million USD in direct costs and 82 013.37 million USD from societal perspective. Pertussis vaccination program costs were 2168.76 million USD and 3961.28 million USD from direct cost and societal perspectives. Benefit-cost ratios were 21.67:1 from the direct cost perspective and 20.70:1 from the societal perspective. Sensitivity analyses showed the results to be robust.ConclusionsOver the lifetime of 40 birth cohorts, China’s immunization program is preventing 93% of pertussis cases and 97% of pertussis deaths, resulting in substantial savings to the healthcare system and society.