Impact of long-term routine pneumococcal conjugate vaccine use in Navajo and White Mountain Apache communities: Carriage prevalence, mechanisms of replacement & genetic analysis of nontypeable pneumococci

Background. The 7-valent pneumococcal polysaccharide-conjugate vaccine, PCV7, contains capsule polysaccharide antigens of seven serotypes that caused the majority of disease in children and were associated with antibiotic resistance among all ages in the United States. PCV7 has made a significant impact on pneumococcal carriage and disease since its introduction in 2000. However in subsequent years, replacement with serotypes not included in the vaccine has been observed.;Objective. The objective of this research was to assess the impact of long-term routine PCV7 use on carriage prevalence, to identify molecular mechanisms behind replacement in carriage and disease, and to improve our understanding of pneumococcal adaptations to vaccine pressure among Navajo and White Mountain Apaches (N/WMA) who are at high risk for pneumococcal carriage and disease.;Methods. Pneumococcal nasopharyngeal carriage studies and invasive disease surveillance have been conducted on N/WMA reservations before and after introduction of PCV7. Pneumococcal isolates were serotyped by the Quellung reaction and multi-locus sequence typing was used to molecularly characterize the isolates. Microarray techniques were employed to assess the presence or absence of known serotype-specific capsule genes.;Results. Pneumococcal carriage prevalence decreased by 13.3% in children <2 years old (yo), 12.6% in children 2-<5yo, and 22.1% in adults in the PCV7 era. Vaccine-serotype prevalence decreased by 94% in children < 5yo; however, non-vaccine serotype prevalence increased by 39.2%. No increase in serotype invasive potential was observed in the PCV7 era. Sequence-type (ST) replacement was primarily an introduction of new STs into the population, with a secondary mechanism of expansion of pre-existing STs. No significant capsule gene adaptations to vaccine pressure were identified.;Conclusion. PCV7 has made a profound impact on pneumococcal carriage and disease in N/WMA communities; however, expansion and replacement with serotypes not included in the upcoming PCV 13 vaccine warrants continued surveillance in the PCV13 era. Improved serotype coverage of PCV 13 combined with sustainable funding for global PCV distribution will make a significant impact on pneumococcal disease and reduce health disparities worldwide.