The utility of NP carriage as a surrogate marker for pneumococcal disease EPZ-6438 mw is not equal for all pneumococcal serotypes. Some serotypes are rarely found in carriage though they

are known to cause disease (serotypes 1, 5, 7 and 12F). This is presumably due to short duration of carriage or difficulty detecting such serotypes on NP sampling when other dominant serotypes are present. However, even for these serotypes, the progressive steps in disease pathogenesis from acquisition, to movement across the nasopharyngeal epithelium and extension to mucosal or invasive disease, are thought to be the same even if some steps in this chain are short in duration. As summarized by Professor Ron Dagan, the direct effect of PCV

can be measured only in clinical efficacy trials conducted in settings where most children are unvaccinated against the pneumococcal vaccine serotypes, thus minimizing any confounding by herd immunity [2]. Various vaccine efficacy trials have looked at impact on pneumococcal NP carriage using different PCV formulations and in different country settings (summarized in Table 1 and Ref. [19] Section III), and all studies have demonstrated a reduction in VT carriage among vaccinated children. The magnitude of VE-col across studies is around 50% which is lower than vaccine efficacy against KU57788 disease (VE-disease): either vaccine efficacy against invasive pneumococcal disease (IPD) is about 80%, against VT pneumococcal acute otitis media (AOM) about 60%, and approximately 35% against radiologically confirmed pneumonia. Assuming that about half of the latter episodes are caused by VT pneumococcus,

the inferred vaccine efficacy against VT pneumococcal pneumonia is 70% [2]. PCV may reduce pneumococcal disease in two ways: (1) by preventing pneumococcal NP acquisition, duration or density of carriage, or (2) by preventing progression of pneumococcal carriage to disease. A considerable proportion of the NP effect of vaccination may be in reducing VT acquisition. While some evidence suggests PCV decreases density of carriage, it is still unclear whether this is always the case [2]. There is also evidence demonstrating a dose effect on VT carriage reduction, with three primary doses having a greater effect on VT NP reduction than two doses and one dose being more effective than no PCV. Indirect effects of vaccination were discussed by Professor Anthony Scott and are defined as those effects observed in unvaccinated persons (See Ref. [19]: Section III). Post-PCV licensure surveillance has revealed reductions in both VT pneumococcal disease and carriage in unvaccinated populations, including the elderly and infants too young to be immunized.