title: Differences in serious clinical outcomes of infection caused by specific pneumococcal serotypes among adults.
abstract: BACKGROUND
  Infections due to Streptococcus pneumoniae serotypes differ in clinical manifestations among adults, varying in propensity for severity, invasiveness, and lethality. To characterize differences in serious outcomes between pneumococcal serotypes, we systematically reviewed the literature.
  
  
  METHODS
  After distilling 676 hits to 28 relevant articles, statistically significant differences in individual serotypes associated with serious clinical outcomes were assessed. Serotypes associated with elevated risk of serious clinical outcomes were evaluated in terms of serotypes included in licensed adult pneumococcal vaccines (i.e., 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13)). Repeated findings were considered a measure of robustness.
  
  
  RESULTS
  Among adult studies evaluating serious clinical outcomes, the following serotypes were associated with elevated risk: Empyema (serotypes 1, 3, 5, 7F, 8, 19A), necrotizing pneumonia (serotype 3), septic shock (serotypes 3, 19A), meningitis (repeatedly serotypes 10A, 15B, 19F, 23F), reduced quality-adjusted life years (QALYs, serotypes 15B, 3, 10A, 9N, 19F, 11A, 31), and increased case-fatality rates (repeatedly serotypes 3, 6B, 9N, 11A, 16F, 19F, 19A).
  
  
  CONCLUSIONS
  Both vaccine formulations include multiple pneumococcal serotypes associated with increased risk for serious clinical outcomes. Three studies found elevated risk from serotype 6A (unique to PCV13). Fourteen studies found elevated risk from nine serotypes unique to PPSV23 (repeatedly: case-fatality-11A & 9N, meningitis-10A & 15B). Seven studies found elevated risk from serotypes not represented in either vaccine formulation (notably 16F). The pneumococcal serotypes repeatedly associated with elevated risk of serious outcomes in adults are an important consideration for vaccine policy making.
authors.affiliation: Merck Vaccines, 770 Sumneytown Pike, WP97-B364, West Point, PA 19426, USA. Electronic address: john_grabenstein@merck.com.
authors.forename: John D
authors.initials: JD
authors.lastname: Grabenstein
authors.affiliation: Merck Research Laboratories, Upper Gwynedd, PA 19454, USA. Electronic address: luwy_musey@merck.com.
authors.forename: Luwy K
authors.initials: LK
authors.lastname: Musey
mesh_terms: D000328:Adult; D006801:Humans; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D019057:Quality-Adjusted Life Years; D012307:Risk Factors; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification*; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: C538862:13-valent pneumococcal vaccine; C414006:23-valent pneumococcal capsular polysaccharide vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Case-fatality rate; Meningitis; Mortality; Pneumococcal vaccine; Serotyping; Streptococcus pneumoniae