Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project

Abstract

Background: Approximately 800,000 children die each year due to pneumococcal disease and >90% of these deaths occur in developing countries where few children have access to life-saving serotype-based vaccines. Understanding the serotype epidemiology of invasive pneumococcal disease (IPD) among children is necessary for vaccine development and introduction policies. The aim of this study was to systematically estimate the global and regional distributions of serotypes causing IPD in children <5 years of age.

Methods and findings: We systematically reviewed studies with IPD serotype data among children <5 years of age from the published literature and unpublished data provided by researchers. Studies conducted prior to pneumococcal conjugate vaccine (PCV) introduction, from 1980 to 2007, with ≥12 months of surveillance, and reporting ≥20 serotyped isolates were included. Serotype-specific proportions were pooled in a random effects meta-analysis and combined with PD incidence and mortality estimates to infer global and regional serotype-specific PD burden. Of 1,292, studies reviewed, 169 were included comprising 60,090 isolates from 70 countries. Globally and regionally, six to 11 serotypes accounted for ≥70% of IPD. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) were the most common globally; and based on year 2000 incidence and mortality estimates these seven serotypes accounted for >300,000 deaths in Africa and 200,000 deaths in Asia. Serotypes included in both the 10- and 13-valent PCVs accounted for 10 million cases and 600,000 deaths worldwide.

Conclusions: A limited number of serotypes cause most IPD worldwide. The serotypes included in existing PCV formulations account for 49%-88% of deaths in Africa and Asia where PD morbidity and mortality are the highest, but few children have access to these life-saving vaccines. Please see later in the article for the Editors' Summary.

Figure 1. Proportion of IPD in young children due to the most common serotypes globally.

Error bars indicate the 95% CI for the proportion of invasive PD due to each of the 21 serotypes. Cumulative line indicates the cumulative proportion of invasive PD due to the 21 serotypes. *Adjusted for regional incidence of cases.

Figure 2. Proportion of IPD in young children due to the 21 most common or important serotypes by GAVI Alliance eligibility.

(A) GAVI Alliance–eligible countries and (B) non-GAVI Alliance eligible countries. Error bars indicate the 95% CIs. Line indicates the cumulative proportion across serotypes.

Figure 3. Proportion of IPD in young children globally due to the most common serotypes by age.

(A) children age 0–23 mo (n = 18,829 isolates) and (B) children age 24–59 mo (n = 6,664 isolates). Error bars indicate the 95% CIs. Line indicates the cumulative proportion of IPD across serotypes. *Limited to studies (n = 49) with serotype data available for both age groups.

Figure 4. (A) Proportion of IPD, number of (B) PD cases, and (C) deaths in children <5 y of age due to serotypes in existing PCV formulations.

Assumes serotype 6A/6B cross-protection, globally and by region. Error bars indicate the 95% CIs (A) or uncertainty estimates (B, C). PCV7 serotypes include: 4, 6B, 9V, 14, 18C, 19F, 23F. PCV10 adds serotypes: 1, 5, and 7F. PCV13 adds serotypes: 3, 6A, and 19A.