Use of surveillance data to estimate the effectiveness of the 7-valent conjugate pneumococcal vaccine in children less than 5 years of age over a 9 year period
Highlights
► The indirect cohort method appears suitable for estimating pneumococcal conjugate vaccine effectiveness. ► An indirect cohort design confirms the findings of the case–control study. ► This method would be most useful shortly after vaccine introduction. ► The method is less useful in a setting of high vaccine coverage and few vaccine-type cases.
Introduction
In a large randomized clinical trial, four doses of seven-valent pneumococcal conjugate vaccine (PCV7) were shown to have an efficacy of 94% against invasive pneumococcal infection [1]. A case–control study conducted during the three years following the routine introduction of PCV7 into the U.S. childhood immunization schedule in 2001 not only confirmed the excellent protection given by a four-dose schedule but also found that three and even two doses were nearly as protective [2]. This three-year case–control study was expensive and labor intensive. Alternative methods of evaluating post-licensure effectiveness of new conjugate vaccines would be useful, especially in settings where classical case–control studies are not feasible due to infrastructure issues or cost constraints.
The indirect cohort study design was proposed in 1980 by Broome et al. to evaluate the protection given by the polysaccharide pneumococcal vaccine [3]. Despite its name, this study design is equivalent to a case–control study where patients with pneumococcal infections caused by non-vaccine serotypes (NVT) serve as a comparison group to cases infected by vaccine serotype pneumococci. Because pneumococcal vaccines do not protect against NVTs, the risk of NVT disease should be independent of the vaccination status with PCV7 in the comparison group. This approach is advantageous as it can be performed using only surveillance data, as long as the surveillance program collects information on all invasive pneumococcal infections and pneumococcal isolates are available for serotyping. Increases in the incidence of certain serotypes not included in the PCV7 have been observed since the beginning of the PCV7 program in the US [4], [5], [6], [7].
The objective of this study was to demonstrate that the indirect cohort design gives vaccine effectiveness results similar to those of the previously conducted classical case–control study. We applied the indirect cohort design to all invasive pneumococcal infections among children 2–59 months old identified between 2001 and 2009 by the Active Bacterial Core surveillance network and explored the impact of changes in the distribution of non vaccine type IPD on the VE results obtained by this design.
Section snippets
Case identification
Cases were identified through Active Bacterial Core surveillance (ABCs), an active population- and laboratory-based surveillance system operated by the Centers for Disease Control and Prevention's Emerging Infections Program Network [8]. Cases were identified in California (San Francisco, Alameda, and Contra Costa counties); Colorado (5 county Denver area); Connecticut; Georgia (20 county Atlanta area); Maryland (6 county Baltimore metropolitan area); Minnesota (Minneapolis and St. Paul
Results
Between 2001 and 2009, 4225 IPD cases were reported by ABCs. Among the 3642 cases with a known serotype, vaccine history was retrieved for 2680 (74%), including the 782 cases from 2001 to 2003 who were enrolled in the case–control study (Table 1). The characteristics of VT (cases) and NVT (comparison group) IPD during the 2001–2009 study period are shown in Table 2. VT cases were significantly different from NVT cases by age (p-value for t-test <0.001), presence of comorbid conditions (p <
Discussion
Our study demonstrated that the indirect cohort design using invasive pneumococcal disease surveillance data appears suitable for estimating the effectiveness of the pneumococcal conjugate vaccine in a setting with a routine national vaccination program. The US clinical trial assessing efficacy against IPD reported overall efficacy results for only one schedule (3 doses ≤7 months, 1 dose 12–16 months) for the conjugate vaccine; the sample size was insufficient to assess protection against the
Funding
Emerging Infections Program Network, Centers for Disease Control and Prevention.
Conflict of interest
Dr. De Serres has received unrelated research grants from GSK and Sanofi Pasteur. Dr. Harrison reports having received lecture honoraria from Wyeth and consulting fees from Merck. Dr. Schaffner reports having received a consulting fee from Wyeth and is a member of Safety Evaluation Committee for experimental vaccine trials for Merck. Dr. Bennett has served on Adult Vaccine Advisory Boards for Wyeth and Merck.
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