Lo SW, et al. - Researchers performed whole-genome sequencing of 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programs in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674) in order to determine the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. As per findings, countries showed variation in the five most prevalent serotypes in the 13-valent pneumococcal conjugate vaccine [PCV13] period, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. Expansion of non-vaccine serotypes within vaccine-type Global Pneumococcal Sequence Clusters (GPSCs), to a higher extent, and increases in non-vaccine-type GPSCs, to a lesser extent, mediated serotype replacement. Findings suggest an important role of globally spreading lineages expressing invasive serotypes in serotype replacement. They noted an association of emerging non-vaccine serotypes with different pneumococcal lineages in different countries that might be correlated to local antibiotic-selective pressures. They suggest performing continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period to produce additional knowledge for optimizing future vaccine design.