Systematic Review of the Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Vaccine-type Invasive Pneumococcal Disease Among Young Children

Abstract

Background: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.Methods: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.Results: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.Conclusions: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.

Immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) according to different schedules in infants in South Africa: a phase III trial

“…This might however be redressed through the indirect effect of PCV immunization which results from reduced circulation of vaccine serotypes in the community [29]. Other systematic reviews assessing the effect of PCV dosing schedules concluded that available data on vaccine-type IPD supported the use of 3 + 1, 3 + 0, and 2 + 1 schedules [30], and that all three schedules reduced N: number of doses (primary/booster). Vomiting and diarrhea were solicited due to co-administration of human rotavirus vaccine and were thus only solicited after visit 2 and visit 3 (i.e.…”

Public health impact of pneumococcal conjugate vaccine infant immunization programs: assessment of invasive pneumococcal disease burden and serotype distribution

“…Accordingly, significant drops in nasopharyngeal carriage and IPD caused by vaccine serotypes (VTs) have been observed in the pediatric populations of countries that implemented PCVs in their infant immunization programs [10,22,23]. In addition, in countries with high vaccination coverage, VT IPD in older vaccine-ineligible children and adults declined (herd effect), likely due to reduced transmission of VTs [22,24,25].…”

Evaluating the impact of PCV-10 on invasive pneumococcal disease in Brazil: A time-series analysis

“…Universal vaccination programs have significantly impacted the burden of IPD in different population. 3,4 When evaluating PCV impact, the main challenge lies in the fact that we do not know what would disease incidence be in the absence of vaccination in the same study population. Therefore, one should estimate the IPD incidence in the post vaccination period (if the population had not been vaccinated), and measure the incidence in vaccinated and unvaccinated population in an unbiased way to avoid inaccurate conclusions, or uninterpretable data, refraining from the temptation of seeing what we expect to see.…”