Dataset Information

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage.

ABSTRACT: BACKGROUND:There is great interest in the use of reduced dosing schedules for pneumococcal conjugate vaccines, a strategy premised on maintaining an acceptable level of protection against disease and carriage of the organism. We asked about the practicality of measuring differential effectiveness against carriage in a population with and without widespread use of the vaccine for infants. METHODS:We adapted an existing transmission-dynamic, individual-based stochastic model fitted to the prevaccine epidemiology of pneumococcal carriage in the United States, and compared the observed vaccine-type carriage prevalence in different arms of a simulated trial with one, two, or three infant doses plus a 12-month booster. Using these simulations, we calculated vaccine efficacy that would be estimated at different times post-enrollment in the trial and calculated required sample sizes to see a difference in carriage prevalence. RESULTS:In a pneumococcal conjugate vaccine (PCV)-naïve population, the difference in vaccine-type (VT) pneumococcal carriage prevalence between trial arms was less than 7% and varied with sampling time. In a population already receiving routine PCV administration, VT pneumococcal prevalence is nearly indistinguishable between trial arms. Relative efficacy of different dosing schedules was strongly dependent on the time between enrollment and sampling, with maximal prevalence differences reached 1-3?years post-enrollment. Moreover, vaccine efficacy estimates were typically slightly higher in trials in communities already receiving vaccination. Despite this, much larger sample sizes-by more than an order of magnitude-are required for a vaccine trial conducted in a population receiving routine PCV administration as compared to in a PCV-naïve population. CONCLUSIONS:These findings highlight some underappreciated aspects of clinical trials of pneumococcal conjugate vaccines with efficacy endpoints, such as the context- and time-dependence of efficacy estimates. They support the wisdom of conducting comparative dose schedule trials of conjugate vaccine effects on carriage in vaccine-naïve populations.

SUBMITTER: Yang A

PROVIDER: S-EPMC6402138 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage.

Yang Alan A Cai Francisco F Lipsitch Marc M

BMC infectious diseases 20190305 1

<h4>Background</h4>There is great interest in the use of reduced dosing schedules for pneumococcal conjugate vaccines, a strategy premised on maintaining an acceptable level of protection against disease and carriage of the organism. We asked about the practicality of measuring differential effectiveness against carriage in a population with and without widespread use of the vaccine for infants.<h4>Methods</h4>We adapted an existing transmission-dynamic, individual-based stochastic model fitted ...[more]

PMID: 30836941

Similar Datasets

Project description:BackgroundThe PCV13 immunization demonstration program began in October 2017 in Indonesia. The aim of this study is to assess the dynamic changes of pneumococcal serotype before and after PCV13 administration, with two primary and one booster doses.MethodsThe prospective cohort study was conducted as a follow up study measuring the impact of PCV13 demonstration program by the Indonesian Ministry of Health in Lombok Island, West Nusa Tenggara, Indonesia, from March 2018 to June 2019. The subjects were two-month-old healthy infants who were brought to the primary care facility for routine vaccination and followed until 18 months of age. We use convenience sampling method. There were 115 infants in the control group and 118 infants in the vaccine group, and the PCV immunization was given on a 2+1 schedule. Nasopharyngeal (NP) swabs were collected four times during the vaccination periods by trained medical staff. Specimens were analyzed by culture methods to detect S. pneumonia colonization and multiplex polymerase chain reaction (mPCR) to determine serotype. The most frequently detected serotypes will be named as dominant serotypes. Descriptive analysis of demographic characteristics, the prevalence of overall and serotype colonization, and the distribution of serotypes were performed. The prevalence of both cohort groups were compared using chi-square test. Statistical significance was set at p < 0.05.ResultsTwo hundred and thirty three infants age two months old were recruited, with 48.9% of the subjects were male and 51.1% of the subjects were female. Sociodemographic data in both cohort groups were relatively equal. Nasopharyngeal pneumococcal colonization before PCV13 administration occurred in 19.1% of the control and 22.9% of the vaccine group. The prevalence increased with increasing age in both groups. The prevalence of VT serotypes in control groups aged 2 months, 4 months, 12 months, and 18 months was 40.9%, 44.2%, 53.8%, and 54.3%, respectively, and in the vaccine group, 25.9%, 40.4%, 38.0%, and 22.6%, respectively. The most common VT serotypes in both groups were 6A/6B, 19F, 23F, and 14. The prevalence of VT serotypes decreased significantly compared to non-vaccine type serotypes after three doses of the PCV13 vaccine (p < 0.001). Another notable change was the decline in prevalence of serotype 6A/6B after PCV13 administration using the 2+1 schedule.ConclusionsThis study shows lower prevalence of VT and 6A/6B serotypes in the nasopharynx among children who were PCV13 vaccinated compared with those who were unvaccinated. The result from this study will be the beginning of future vaccine evaluation in larger population and longer period of study.

Project description:For encapsulated bacteria such as Streptococcus pneumoniae, asymptomatic carriage is more common and longer in duration than disease, and hence is often a more convenient endpoint for clinical trials of vaccines against these bacteria. However, using a carriage endpoint entails specific challenges. Carriage is almost always measured as prevalence, whereas the vaccine may act by reducing incidence or duration. Thus, to determine sample size requirements, its impact on prevalence must first be estimated. The relationship between incidence and prevalence (or duration and prevalence) is convex, saturating at 100% prevalence. For this reason, the proportional effect of a vaccine on prevalence is typically less than its proportional effect on incidence or duration. This relationship is further complicated in the presence of multiple pathogen strains. In addition, host immunity to carriage accumulates rapidly with frequent exposures in early years of life, creating potentially complex interactions with the vaccine's effect. We conducted a simulation study to predict the impact of an inactivated whole cell pneumococcal vaccine-believed to reduce carriage duration-on carriage prevalence in different age groups and trial settings. We used an individual-based model of pneumococcal carriage that incorporates relevant immunological processes, both vaccine-induced and naturally acquired. Our simulations showed that for a wide range of vaccine efficacies, sampling time and age at vaccination are important determinants of sample size. There is a window of favorable sampling times during which the required sample size is relatively low, and this window is prolonged with a younger age at vaccination, and in a trial setting with lower transmission intensity. These results illustrate the ability of simulation studies to inform the planning of vaccine trials with carriage endpoints, and the methods we present here can be applied to trials evaluating other pneumococcal vaccine candidates or comparing alternative dosing schedules for the existing conjugate vaccines.

Project description:BackgroundThe indirect effects of pneumococcal conjugate vaccines (PCVs) are mediated through reductions in carriage of vaccine serotypes. Data on PCVs in Asia and the Pacific are scarce. Fiji introduced the ten-valent PCV (PCV10) in 2012, with a schedule consisting of three priming doses at 6, 10, and 14 weeks of age and no booster dose (3 + 0 schedule) without catch-up. We investigated the effects of PCV10 introduction using cross-sectional nasopharyngeal carriage surveys.MethodsWe did four annual carriage surveys (one pre-PCV10 and three post-PCV10) in the greater Suva area in Fiji, during 2012-15, of 5-8-week-old infants, 12-23-month-old children, 2-6-year-old children, and their caregivers (total of 8109 participants). Eligible participants were of appropriate age, had axillary temperature lower than 37°C, and had lived in the community for at least 3 consecutive months. We used purposive quota sampling to ensure a proper representation of the Fiji population. Pneumococci were detected by real-time quantitative PCR, and molecular serotyping was done with microarray.Findings3 years after PCV10 introduction, vaccine-serotype carriage prevalence declined, with adjusted prevalences (2015 vs 2012) of 0·56 (95% CI 0·34-0·93) in 5-8-week-old infants, 0·34 (0·23-0·49) in 12-23-month-olds, 0·47 (0·34-0·66) in 2-6-year-olds, and 0·43 (0·13-1·42) in caregivers. Reductions in PCV10 serotype carriage were evident in both main ethnic groups in Fiji; however, carriage of non-PCV10 serotypes increased in Indigenous Fijian infants and children. Density of PCV10 serotypes and non-PCV10 serotypes was lower in PCV10-vaccinated children aged 12-23 months than in PCV10-unvaccinated children of the same age group (PCV10 serotypes -0·56 [95% CI -0·98 to -0·15], p=0·0077; non-PCV10 serotypes -0·29 [-0·57 to -0·02], p=0·0334).InterpretationDirect and indirect effects on pneumococcal carriage post-PCV10 are likely to result in reductions in pneumococcal disease, including in infants too young to be vaccinated. Serotype replacement in carriage in Fijian children, particularly Indigenous children, warrants further monitoring. Observed changes in pneumococcal density might be temporal rather than vaccine related.FundingDepartment of Foreign Affairs and Trade of the Australian Government through the Fiji Health Sector Support Program; Victorian Government's Operational Infrastructure Support Program; Bill & Melinda Gates Foundation.

Dataset Information

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage.

Publications

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets