Duration of Protection After First Dose of Acellular Pertussis Vaccine in Infants

ArticleinPEDIATRICS 133(3) · February 2014with11 Reads
DOI: 10.1542/peds.2013-3181 · Source: PubMed
Data on the effectiveness of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in the first 4 years of life are sparse. We evaluated the vaccine effectiveness (VE) of 1 and 2 doses of DTaP before 6 months of age and of 3 doses from 6 months of age in Australia, where, since 2003, a fourth dose is not given until 4 years. We matched reported pertussis cases aged 2 to 47 months between January 2005 and December 2009 to controls from a population-based immunization register by date of birth and region of residence. VE by number of doses and age group was calculated as (1 - odds ratio) × 100%. VE against hospitalization increased from 55.3% (95% confidence interval [CI], 42.7%-65.1%) for 1 dose before 4 months of age to 83.0% (95% CI, 70.2%-90.3%) for 2 doses before 6 months. The VE of 3 doses of DTaP against all reported pertussis was 83.5% (95% CI, 79.1%-87.8%) between 6 and 11 months, declining to 70.7% (95% CI, 64.5%-75.8%) between 2 and 3 years of age and 59.2% (95% CI, 51.0%-66.0%) between 3 and 4 years of age. DTaP provided good protection against pertussis in the first year of life from the first dose. Without a booster dose, the effectiveness of 3 doses waned more rapidly from 2 to 4 years of age than previously documented for children >6 years of age who had received 5 doses.
    • This study is also consistent with a recent meta-analysis of DTaP waning that estimated that the odds of pertussis increased by 33% each additional year since the last dose (either 3 rd or 5 th ) of DTaP[18]. Further, a recent Australian study evaluated children through age 3 years following 3 doses of DTaP 3 administered in infancy and found that VE against laboratory-confirmed pertussis was 83.5% (95% CI 79.1, 87.0) after the 3rd dose between ages 6–11 months, 79.2% (95% CI 75.0, 82.8) at age 1 year, and 59.2% (95% CI 51.0, 66.0) at 3 years of age[19]. The Australian study suggests that 3 doses of DTaP 3 vaccine provide reasonable protection during the first year of life, but that this protection waned substantially even before administration of their next recommended DTaP dose between ages 4 to 6 years.
    [Show abstract] [Hide abstract] ABSTRACT: Background: The effectiveness of diphtheria, tetanus, and acellular pertussis (DTaP) vaccines wanes substantially after the 5(th) dose given at ages 4-6years, 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 10years, which included large pertussis outbreaks, following 5 doses of GSK DTaP vaccines (DTaP3). Methods: We 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. Results: Our primary analysis compared 340 pertussis cases diagnosed at ages 4-12years 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. Conclusions: Waning 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 DTaP3. Following 5 doses of DTaP3 vaccines, protection from pertussis waned 27% per year on average. NCT number: NCT02447978.
    Full-text · Article · May 2017
    • Results from various sensitivity analyses did not change our primary finding that there was no evidence of reducing VE following the primary 3-dose series through to age 3 years, or following the first preschool-age booster dose through to age 7 years. Our findings align with two recently published studies [8,10] and two older studies [21,22], but conflict with a national-level Australian study [9] and a meta-analysis [4]. The meta-analysis suggested that the odds of pertussis increased by a multiple of 1.33 for every year since the last dose of acellular pertussiscontaining vaccine; however, the observed increase between intervals of the time since last dose was not linear.
    [Show abstract] [Hide abstract] ABSTRACT: Background: Though it is believed the switch from whole cell to acellular pertussis vaccine has contributed to the resurgence of pertussis disease, few studies have evaluated vaccine effectiveness (VE) and duration of protection provided by an acellular vaccine schedule including three primary doses but no toddler-age dose. We assessed this schedule in New Zealand (NZ), a setting with historically high rates of pertussis disease, and low but recently improved immunisation coverage. We further evaluated protection following the preschool-age booster dose. Methods: We performed a nested case-control study using national-level healthcare data. Hospitalised and non-hospitalised pertussis was detected among children 6weeks to 7years of age between January 2006 and December 2013. The NZ National Immunisation Register provided vaccination status for cases and controls. Conditional logistic regression was used to calculate dose-specific VE with duration of immunity examined by stratifying VE into ages aligned with the immunisation schedule. Results: VE against pertussis hospitalisation was 93% (95% confidence interval [CI]: 87, 96) following three doses among infants aged 5-11months who received three compared to zero doses. This protection was sustained through children's fourth birthdays (VE⩾91%). VE against non-hospitalised pertussis was also sustained after three doses, from 86% (95% CI: 80, 90) among 5-11month olds to 84% (95% CI: 80, 88) among 3-year-olds. Following the first booster dose at 4years of age, the protective VE of 93% (95% CI: 90, 95) among 4-year-olds continued through 7years of age (VE⩾91%). Conclusions: We found a high level of protection with no reduction in VE following both the primary course and the first booster dose. These findings support a 3-dose primary course of acellular vaccine with no booster dose until 4years of age.
    Full-text · Article · Nov 2016
    • Although 'cocoon' doses for parents were recommended nationally in 2003 to provide indirect protection to newborns, cocoon doses were not free of charge until 2009, by when most states and territories provided Tdap vaccine to parents in response to epidemics. However, subsequent evaluations found only modest benefit in reducing pertussis risk in early infancy[16][17][18]. Lack of impact of cocooning was in part related to recently vaccinated siblings (3–4 years of age) emerging as the most common source of transmission following discontinuation of the 18month booster dose in 2003[19,20].
    [Show abstract] [Hide abstract] ABSTRACT: Despite long-standing vaccination programs, substantial increases in reported cases of pertussis have been described in several countries during the last 5 years. Cases among very young infants who are at greatest risk of pertussis-related hospitalizations and mortality are the most alarming. Multiple hypotheses including but not limited to the availability of more sensitive diagnostic tests, greater awareness, and waning vaccine-induced immunity over time have been posited for the current challenges with pertussis. The conference “Pertussis: biology, epidemiology and prevention” held in Annecy-France (November 11–13, 2015) brought together experts and interested individuals to examine these issues and to formulate recommendations for optimal use of current vaccines, with a particular focus on strategies to minimize severe morbidity and mortality among infants during the first months of life. The expert panel concluded that improving vaccination strategies with current vaccines and development of new highly immunogenic and efficacious pertussis vaccines that have acceptable adverse event profiles are currently the two main areas of investigation for the control of pertussis. Some possible pathways forward to address these main challenges are discussed in this report.
    Full-text · Article · Oct 2016
    • These case-control studies characterize effectiveness rather than efficacy at the time of vaccination ; however, under the assumption that no waning occurs in the time between the administration of each of the three primary doses, vaccine effectiveness and efficacy are equivalent. Efficacy for the fourth and fifth dose was calculated previously [17] by simultaneously fitting both efficacy and duration to case-control data [12,13]. To model an improvement to efficacy, we simultaneously increased the efficacy of each dose by a factor p, such that
    [Show abstract] [Hide abstract] ABSTRACT: Despite steady vaccination coverage rates, pertussis incidence in the United States has continued to rise. This public health challenge has motivated calls for the development of a new vaccine with greater efficacy and duration of protection. Any next-generation vaccine would likely come at a higher cost, and must provide sufficient health benefits beyond those provided by the current vaccine in order to be deemed cost-effective. Using an age-structured transmission model of pertussis, we quantified the health and economic benefits of a next-generation vaccine that would enhance either the efficacy or duration of protection of the childhood series, the duration of the adult booster, or a combination. We developed a metric, the maximum cost-effective price increase (MCPI), to compare the potential value of such improvements. The MCPI estimates the per-dose price increase that would maintain the cost-effectiveness of pertussis vaccination. We evaluated the MCPI across a range of potential single and combined improvements to the pertussis vaccine. As an upper bound, we found that a next-generation vaccine which could achieve perfect efficacy for the childhood series would permit an MCPI of $18 per dose (95% CI: $12-$31). Pertussis vaccine improvements that extend the duration of protection to an average of 75 years would allow for an MCPI of $22 per dose for the childhood series (CI: $10-$33) or $12 for the adult booster (CI: $4-$18). Despite the short duration of the adult booster, improvements to the childhood series could be more valuable than improvements to the adult booster. Combining improvements in both efficacy and duration, a childhood series with perfect efficacy and average duration of 75 years would permit an MCPI of $39 per dose, the highest of any scenario evaluated. Our results highlight the utility of the MCPI metric in evaluating potential vaccines or other interventions when prices are unknown.
    Article · Apr 2016
    • The model's findings support the notion that replacement of the 18 mth booster with an adolescent booster from 2003 contributed to a substantial increase in disease in children aged 18 mth–<4 yr. Modelled age incidence patterns are consistent with the higher incidence observed in children aged 2 and 3 years from 2008 to 2010 compared to previous epidemics [6]
    [Show abstract] [Hide abstract] ABSTRACT: Pertussis resurgence has been reported from several developed countries with long-standing immunisation programs. Among these, Australia in 2003 discontinued an 18 months (fourth) booster dose in favour of an adolescent (fifth) dose. We developed a model to evaluate determinants of resurgence in Australia and alternative vaccine strategies for mitigation. Novel characteristics of our model included the use of seroepidemiologic data for calibration, and broad investigation of variables relevant to transmission of, and protection against, pertussis. We simulated multiple parameter combinations, retaining those consistent with observed data for subsequent use in predictive models comparing alternative vaccination schedules. Reproducing the early control of pertussis followed by late resurgence observed in Australia required natural immunity to last decades longer than vaccine-acquired immunity, with mean duration exceeding 50 years in almost 90% of simulations. Replacement of the dose at 18 months with an adolescent dose in 2003 resulted in a 40% increase in infections in the age group 18-47 months by 2013. A six dose strategy (2, 4, 6, 18 months, 4 and 15 years) yielded a reduction in infection incidence (pre-school 43%, infants 8%) greater than any alternative strategies considered for timing of five administered doses. Our finding that natural immunity drives long-term trends in pertussis cycles is relevant to a range of pertussis strategies and provides the necessary context in which to consider maternal vaccination. Comparatively short-lived vaccine-acquired immunity requires multiple boosters over the first two decades of life to maximise reduction in infections.
    Article · Sep 2015
  • Full-text · Article · Apr 2014
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