Systematic Review of the Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Prevention of Pneumonia

The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 01/2014; 33 Suppl 2(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence Supportin g Different Schedules):S140-51. DOI: 10.1097/INF.0000000000000082
Source: PubMed


Pneumonia is the leading cause of morbidity and mortality among children <5 years of age globally. Pneumococcal conjugate vaccines (PCVs) are known to provide protection against vaccine serotype pneumococcal pneumonia; uncertainty exists regarding the optimum PCV dosing schedule.
We conducted a systematic review of studies published from 1994 to 2010 (supplemented post hoc with studies from 2011) documenting the effect of PCV dosing schedules on clinical and radiologically confirmed pneumonia, pneumococcal pneumonia and empyema among children of ages targeted to receive vaccine. Data on 2- and 3-dose schedules were included. Percent change of pneumonia incidence rates from baseline to most recent year post-PCV introduction was calculated.
We identified 42 primary citations that evaluated PCV schedules and pneumonia. Thirty-seven (88%) were from North America, Europe or Australia; 37 (88%) evaluated PCV7 and 1 (2%) PCV10. Two studies (both observational) compared multiple schedules within the study. We found evidence of reduced clinical and radiologically confirmed pneumonia incidence for all schedules, including 2+1 (1 nonrandomized trial, 5 observational studies), 3+0 (5 randomized trials, 2 observational studies) and 3+1 (5 clinical trials, 24 observational studies) schedules. The magnitude of disease impact did not differ among schedules. Evidence for impact on pneumococcal pneumonia and empyema varied.
All schedules (2+1, 3+0 and 3+1) reduced clinical and radiologically confirmed pneumonia. Quantifying differences in pneumonia disease impact between schedules was difficult due to heterogeneity among studies in design, case definition and population. These findings support World Health Organization recommendations for 3-dose schedules administered as either 3+0 or 2+1 regimens. Pneumonia impact data are still needed on expanded serotype PCV products, developing country settings and the role for a booster dose.

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Available from: Katherine E Fleming-Dutra, Aug 18, 2014
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    • "Much of the evidence regarding PCV impact has focused on young children targeted to receive vaccine using 2 primary doses plus a booster (2+1) or 3 primary doses with or without a booster (3+0 or 3+1).3–6 Clinical trials and observational studies have demonstrated a significant direct impact of PCV on both vaccine-type invasive pneumococcal disease (VT-IPD) and pneumococcal and syndromic pneumonia among children <5 years of age.3,6 Reductions in nasopharyngeal (NP) carriage of vaccine-type pneumococci (VT-NP), a necessary precursor to clinical disease, have also been demonstrated among young children receiving the vaccine.4 "
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    ABSTRACT: To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical outcomes among nontargeted age groups. We systematically reviewed the English literature on infant PCV dosing schedules published from 1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5 years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP), vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia. Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9 pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5 (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated reductions in incidence among young adult groups. Among syndromic pneumonia observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed significant indirect effect. The 1 study to directly compare between schedules was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings and parents of vaccinated children with either schedule. Indirect benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT-NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by data paucity on indirect effects, especially a lack of head-to-head studies and studies of PCV10 and PCV13.
    The Pediatric Infectious Disease Journal 01/2014; 33 Suppl 2(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence Supportin g Different Schedules):S161-71. DOI:10.1097/INF.0000000000000084 · 2.72 Impact Factor
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    • "For controlled trials, case-control studies and indirect cohort studies, data on children ≤5 years of age were also included as long as they were eligible to receive vaccine. We excluded studies that reported pneumococcal bacteremia only in the setting of clinical pneumonia as well as those that reported IPD only among older age groups; these data are included in the articles on pneumonia and indirect effects, respectively, found in this supplement.9,10 We also excluded review articles, those that only provided data for single serotypes and those that only reported data from either before or after PCV introduction but not from both periods. "
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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.
    The Pediatric Infectious Disease Journal 01/2014; 33 Suppl 2(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence Supportin g Different Schedules):S109-18. DOI:10.1097/INF.0000000000000078 · 2.72 Impact Factor
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    • "While few data are available from developing countries, preliminary data from Kilifi, Kenya indicate promising reductions in invasive disease using 3 doses at 6, 10 and 14 weeks with catch-up provided for children up to age 5 years.46 To date, 33 surveillance-type studies have assessed a pneumonia or empyema endpoint after introduction into a routine immunization schedule.43 While results of surveillance studies of pneumonia endpoints are less consistent than those evaluating invasive disease, in general, the findings suggest 2+1, 3+0 and 3+1 schedules are all effective. "
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    ABSTRACT: Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses-the schedule-that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses.
    The Pediatric Infectious Disease Journal 01/2014; 33 Suppl 2(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence Supportin g Different Schedules):S172-81. DOI:10.1097/INF.0000000000000076 · 2.72 Impact Factor
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