Rethinking Replacement and Resistance

Abstract

Before 2000, the year in which the 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth) was introduced into the US infant immunization schedule, most antibiotic-resistant strains of Streptococcus pneumoniae belonged to serotypes included in PCV7. During just the first 3 years after vaccine introduction, we observed profound reductions in the incidence of invasive pneumococcal disease (e.g., bacteremia and meningitis) caused by vaccine serotypes and their associated antibiotic-resistant strains, not only among vaccinated children but also among persons too young [1] and too old [2] to receive the vaccine. The dramatic success of PCV7 in reducing pneumococcal disease in wealthy countries [3-6] and the potential benefits to poor countries [7, 8] have led to World Health Organization recommendations for the global introduction of conjugate vaccines [9] and to extraordinary efforts to finance vaccine purchase and delivery to the poorest countries of the world [10]. At the same time we were heralding the benefits of PCV7, we were alert to the unintended consequence of serotype replacement. This phenomenon, demonstrated convincingly in randomized, controlled trials [11], occurs when serotypes not included in a conjugate vaccine colonize the nasopharynx and replace the vaccine serotypes whose colonization is prevented by the vaccine. The net effect is that PCV7 does not reduce the overall prevalence of nasopharyngeal colonization. PCV7 serotypes are, on average, better suited to causing invasive disease than non-PCV7 serotypes [12, 13]; therefore, vaccine-induced elimination of PCV7 serotypes from the nasopharynx leads to a net reduction in invasive disease and antibiotic resistance. Of all the serotypes, 19A may come closest to having certain characteristics that make it a successful