Serotype Replacement in Childhood Invasive Pneumococcal Disease

Understanding pneumococcal population dynamics will drive an effective next-generation vaccine design, according to a study published in the Lancet Infectious Diseases.

Although pneumococcal conjugate vaccines (PCVs) have significantly reduced the global burden of invasive pneumococcal disease in children by targeting up to 13 pneumococcal serotypes that account for most of the disease in infants, invasive pneumococcal disease remains a health priority because of an increase in disease incidence caused by nonvaccine serotypes or serotype replacement.

After the introduction of the 13-valent PCV (PCV13), several countries (not including the United States) have reported serotype replacement, and there have been increases in nonvaccine serotypes. Previous studies have characterized serotype replacement in cases of invasive pneumococcal disease, but primarily focused on changes in serotypes. The mechanisms that the pneumococcal population used to evolve and adapt to selective pressures of PCVs, and how these mechanisms contribute to the increase in nonvaccine serotypes, remain unclear. Therefore, this study investigated the pneumococcal lineages behind the predominant stereotypes, the mechanism of serotype replacement in disease, and the major pneumococcal lineages contributing to invasive pneumococcal disease in the postvaccine era and their antibiotic-resistant traits.

In total, 3233 invasive pneumococcal disease isolates with whole-genome sequence data were included from laboratory-based surveillance programs in the United States (n=674), Hong Kong (n=78), Israel (n=701), South Africa (n=1351), The Gambia (n=203), and Malawi (n=226). The genomes represented pneumococci from before and after PCV introductions and were from children younger than age 3 years. Predominant serotypes were identified by prevalence, and their major contributing lineages by country. In addition, serotype replacement was assessed by comparing pre-PCV and PCV period incidence rates for the United States, Israel, and South Africa. On the basis of initial serotype composition detected in the earliest vaccine period to measure individual contribution toward serotype replacement in each country, the status of lineage was defined as either vaccine-type Global Pneumococcal Sequence Clusters (³50% 13-valent PCV serotypes) or nonvaccine-type Global Pneumococcal Sequence Clusters (>50% non-13-valent PCV serotypes). Using a random effects model, major pneumococcal lineages in the PCV period were identified by pooled incidence rate.

During the PCV13 period, the 5 most prevalent serotypes varied between countries, with serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D being common between 2 or more countries. Except for serotype 5 (Global Pneumococcal Sequence Cluster 8), all the common serotypes were associated with more than 1 lineage. In the PCV13 period, Global Pneumococcal Sequence Cluster 3 was the most common lineage causing nonvaccine serotype invasive pneumococcal disease, and it expressed invasive serotypes 33F in the United States and 8 in South Africa. Serotype replacement was mainly mediated by the expansion of nonvaccine serotypes within vaccine-type Global Pneumococcal Sequence Clusters, and by increases in nonvaccine type Global Pneumococcal Sequence Clusters. Further, in different countries, the same prevalent nonvaccine serotypes could be associated with distinctive lineages and exhibited different antibiotic resistance profiles. In the nonvaccine serotype isolates, significant increases in resistance were detected in the PCV13 period when compared with the pre-PCV period, including penicillin (P =.0016) and erythromycin (P =.0031).

Overall, the study authors concluded that, “Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design.”

Reference

Lo SW, Gladstone RA, van Tonder AJ, et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study [published online June 10, 2019]. Lancet Infect Dis. doi:10.1016/S1473-3099(19)302897-X