Effectiveness of abbreviated and delayed 7-valent pneumococcal conjugate vaccine dosing regimens

Department of Pediatrics, Boston University, Boston, Massachusetts, United States
Vaccine (Impact Factor: 3.62). 04/2006; 24(14):2514-20. DOI: 10.1016/j.vaccine.2005.12.025
Source: PubMed


We estimated the effectiveness of abbreviated regimens of 7-valent pneumococcal conjugate vaccine (PCV7) based on serotyped cases of invasive pneumococcal disease (IPD) in children under 5 reported from 2001 to 2004 to two US surveillance programs. Vaccination regimens included in the analysis were 1 dose < 3 months old, 2 doses < 5 months old, 3 doses < 7 months old, full schedule (3 doses and a booster), 1 dose at 12-23 months, and 2 doses at 12-23 months. Vaccine effectiveness (VE) was calculated as (1-Mantel-Haenszel summary odds ratio in vaccinated children, as compared to unvaccinated children)x100% for each regimen, stratifying by year. Among 400 eligible cases, for vaccine-type IPD, VE was 90.5% for the full schedule, 76.6% for 3 doses < 7 months old, and 70.5% for 2 doses < 5 months old; 1 dose < 3 months provided no significant protection. No regimen provided significant protection against vaccine-related serotypes. Data for regimens begun at 12-23 months were inconclusive. These data support the use of the 2-dose and 3-dose infant PCV7 regimens when the full series cannot be delivered and detail the limitations of abbreviated dosing regimens.

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    • "While this theory is supported by immunological and carriage data,48,49 our search identified only 1 study that directly compared schedules to evaluate the benefit of a booster dose on VT-IPD outcomes.17 This study found that a booster confers slightly higher protection against VT-IPD; however, other case-control and indirect cohort studies that compared various PCV dosing schedules against no vaccine all found similar point estimates of effectiveness for schedules with or without a booster.16,18–21 All of these studies were conducted among the general population of young children. "
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    ABSTRACT: Pneumococcal conjugate vaccines (PCV) are being implemented globally using a variety of different schedules. The optimal schedule to maximize protection of vaccinated children against vaccine-type invasive pneumococcal disease (VT-IPD) is not known. To assess the relative benefit of various PCV dosing schedules, we conducted a systematic review of studies published in English from 1994 to 2010 (supplemented post hoc with studies from 2011) on PCV effectiveness against VT-IPD among children targeted to receive vaccine. Data on 2-dose and 3-dose primary series, both with and without a booster ("2+0," "2+1," "3+0" and "3+1"), were included. For observational studies using surveillance data or case counts, we calculated percentage reduction in VT-IPD before and after PCV introduction. Of 4 randomized controlled trials and 31 observational studies reporting VT-IPD among young children, none evaluated a 2+0 complete series, 7 (19%) evaluated 2+1, 4 (11%) 3+0 and 27 (75%) 3+1. Most (86%) studies were from North America or Europe. Only 1 study (observational) directly compared 2 schedules (3+0 vs. 3+1); results supported the use of a booster dose. In clinical trials, vaccine efficacy ranged from 65% to 71% with 3+0 and 83% to 94% with 3+1. Surveillance data and case counts demonstrate reductions in VT-IPD of up to 100% with 2+1 (6 studies) or 3+1 (17 studies) schedules and up to 90% with 3+0 (2 studies). Reductions were observed as early as 1 year after PCV introduction. These data support the use of 2+1, 3+0 and 3+1 schedules, although most data of PCV impact on VT-IPD among young children are from high-income countries using 3+1. Differences between schedules for impact on VT-IPD are difficult to discern based on available data.
    Full-text · Article · Jan 2014 · The Pediatric Infectious Disease Journal
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    • "As another type of OR for the estimation of vaccine effectiveness, an indirect cohort method, or the so-called Broome method, has been applied to pneumococcus [14], [15], [16], in which the OR of “vaccination” among VT cases to NVT cases with IPD (invasive pneumococcal disease) has been used for the assessment of vaccine effectiveness. This method has been proposed because the exposure with pneumococcus tends to result in clinically very mild infection or carriage, and perhaps also because the method requires us to collect only the counts of IPD cases with strain information (i.e. "
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    ABSTRACT: Many novel vaccines can cover only a fraction of all antigenic types of a pathogen. Vaccine effectiveness (VE) in the presence of interactions between vaccine strains and others is complicated by the interacting transmission dynamics among all strains. The present study investigated how the VE estimates measured in the field, based on estimated odds ratio or relative risks, are scaled by vaccination coverage and the transmission dynamics in the presence of cross-protective immunity between two strains, i.e. vaccine and non-vaccine strains. Two different types of epidemiological models, i.e. with and without re-infection by the same antigenic type, were investigated. We computed the relative risk of infection and the odds ratio of vaccination, the latter of which has been measured by indirect cohort method as applied to vaccine effectiveness study of Streptococcus pneumoniae. The VE based on the relative risk was less sensitive to epidemiological dynamics such as cross-protective immunity and vaccination coverage than the VE calculated from the odds ratio, and this was especially the case for the model without re-infection. Vaccine-induced (cross-protective) immunity against a non-vaccine strain appeared to yield the highest impact on the VE estimate calculated from the odds ratio of vaccination. It is essential to understand the transmission dynamics of non-vaccine strains so that epidemiological methods can appropriately measure both the direct and indirect population impact of vaccination. For pathogens with interacting antigenic types, the most valid estimates of VE, that are unlikely to be biased by the transmission dynamics, may be obtained from longitudinal prospective studies that permit estimation of the VE based on the relative risk of infection among vaccinated compared to unvaccinated individuals.
    Full-text · Article · Nov 2012 · PLoS ONE
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