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Impact of Pneumococcal Conjugate Vaccine Administration in Pediatric Older Age Groups in Low and Middle Income Countries: A Systematic Review

Friday, 22nd of April 2016

Impact of Pneumococcal Conjugate Vaccine Administration in Pediatric Older Age Groups in Low and Middle Income Countries: A Systematic Review

Kimberly Bonner,¹ Emily Welch,³ Kate Elder,² and Jennifer Cohn^1,4,*

 

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Abstract below; full text is at

http://www.be-md.ncbi.nlm.nih.gov/pmc/articles/PMC4557974/

Introduction

Pneumococcal conjugate vaccine (PCV) is included in the World Health Organization’s routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries.

Methods

An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes.

Results

Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2ug/ml and 0.35ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality.

Discussion

PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older children. For countries to effectively implement extended age vaccinations, access to affordably-priced PCV is critical.

Responsible for 1.3 million deaths annually in children under five years, pneumonia remains a major cause of mortality, particularly in low and middle income countries[1]. Most deaths from severe pneumonia cases (33%) are caused by S. pneumoniae[1]. Over 90 serotypes have been identified, with distribution varying by geography[2].

Three vaccines protect against S. pneumoniae serotypes. Pneumococcal conjugate vaccine (PCV) 10 (GlaxoSmithKline, Belgium) contains antigens for serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F[2]; PCV13 (Pfizer, USA) contains antigens for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and PCV7 (Pfizer, USA) against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Pooled vaccine efficacy to protect against invasive pneumococcal disease (IPD) caused by vaccine serotypes ranges from 71–93%, depending on schedule[2].

The World Health Organization (WHO) recommends vaccine schedules include two or three doses in the first year of life, with a booster at 9–15 months of age if using the two-dose schedule (3+0 or 2+1). If employing a three dose schedule in the first year of life, an optional booster after 12 months can be considered; however, it is noted that HIV+ infants can benefit from a booster dose in their second year of life. For children who did not receive PCV in the first year of life and as part of the national immunization schedule, the WHO recommends completing vaccination as part of a delayed or interrupted schedule for all children aged 12–24 months and children aged 2–5 years who are at high risk of pneumococcal infection [2].

PCV introduction across WHO Member States has begun in 70% of low-income, 64% of lower-middle income, and 45% of upper-middle income countries [3]. Coverage lags behind with Gavi, the Vaccine Alliance, estimating that PCV vaccine coverage of children was only 19% in countries it supports [4,5]. Consequently, many children eligible for PCV immunization in LMIC are not fully vaccinated before 12 months. Under-vaccination remains a problem even for traditional vaccines, leaving nearly 22 million children under 12 months of age unvaccinated each year. For example, a cross-sectional study in Ethiopia demonstrated that only 36.6% of children 12–23 months were fully vaccinated, and in an observational cohort study in rural Guinea-Bissau only half of infants were fully vaccinated by 12 months of age [6,7]. Low immunization coverage reduces potential indirect effects on adult morbidity and mortality from reduced nasopharyngeal carriage in paediatric populations [8]. One study in the US modeled a 54% reduction in nonbacteremic pneumococcal pneumonia in adults 65 years and older in states that had achieved over 80% vaccination coverage in children under two years [9]. In areas where vaccination coverage is low, more flexible immunization schedules are needed to enable the expanded coverage that can drive reductions in morbidity and mortality in both pediatric and adult populations.

Although the WHO recommends completing the immunization schedule for unvaccinated or not fully vaccinated children over 12 months, few countries are implementing this recommendation. Many of the LIC and LMIC have introduced PCV with funding from Gavi, which provides support for PCV administered in the first year of life, but not for older pediatric age groups. This is a risk to both children and their communities, as children under 5 years are at highest risk of contracting severe pneumonia as well as the most likely to transmit S. pnuemoniae [1, 10].

The effectiveness of extended age group vaccination with PCV in LMICs has not been explored. This systematic review examines the evidence base of the direct impact of extended age vaccination for children over 12 months with PCV in LMIC. Additional questions remain on the indirect effects of extended age group vaccination and would further complement this research.