Background Acute otitis media (AOM) is a common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations, the increasing problem of bacterial resistance to antibiotics, and the large estimated direct and indirect annual costs associated with otitis media have prompted a search for effective vaccines to prevent AOM. Methods Search methods: A search was performed of CENTRAL (2013, Issue 11), MEDLINE (1995 to November week 3, 2013), EMBASE (1995 to December 2013), CINAHL (2007 to December 2013), LILACS (2007 to December 2013) and Web of Science (2007 to December 2013). Selection criteria: Randomized controlled trials (RCTs) investigating the use of pneumococcal conjugate vaccines (PCVs) in preventing AOM in children <= 12 years of age, with a follow-up of at least six months after vaccination. Data analysis: Two review authors independently assessed trial quality and extracted data. Results In total, 11 publications, including nine RCTs (n = 48,426 children, range 74 to 37,868 children per study), investigating 7- to 11-valent PCVs (with different carrier proteins) were included. Five trials (n = 47,108) included infants and four trials (n = 1318) included children one to seven years of age who were either healthy (one study, n = 264) or had a previous history of upper respiratory tract infection including AOM. The methodological quality of the included studies was evaluated to be moderate to high. There was considerable clinical diversity among studies with respect to study population, type of conjugate vaccine and outcome measures; therefore, results were not pooled. In three studies, a 7-valent PCV (PCV-7) with the carrier protein CRM197 (CRM197-PCV-7) administered during early infancy was associated with a relative risk reduction (RRR) ranging from -5% (95% CI -25% to 12%) in high-risk children to 7% (95% CI 4% to 9%) in low-risk children for all-cause AOM. Another PCV-7, administered in infancy, with an outer membrane protein complex of Neisseria meningitidis serogroup B as a carrier protein, did not reduce overall AOM episodes, while a precursor 11-valent PCV (PCV-11) with Haemophilus influenzae protein D as a carrier protein was associated with an RRR of 34% (95% CI 21% to 44%) for all-cause AOM episodes. A 9-valent PCV (PCV-9) (with CRM197 carrier protein) administered in healthy toddlers was associated with an RRR of 17% (parent-reported) (95% CI -2% to 33%) for otitis media episodes. CRM197-PCV-7 followed by a 23-valent pneumococcal polysaccharide vaccination administered after infancy in older children with a history of AOM showed no beneficial effect on first occurrence and later AOM episodes. In one RCT, children 18 to 72 months of age who received trivalent influenza vaccine/placebo and CRM197-PCV/trivalent influenza vaccine had fewer overall AOM episodes (RRR 71% [95% CI 30% to 88%] and (RRR 57% [95% CI 6% to 80%], respectively) during influenza season compared with those who received hepatitis B virus vaccine/placebo. This study suggests that influenza prevention may be important for AOM prevention, and CRM197-PCV-7 given after infancy may have had a negative effect on AOM occurrence in this setting. Conclusions Based on current evidence regarding the effects of PCVs for preventing AOM, the licensed CRM197-PCV-7 has modest beneficial effects in healthy infants with a low baseline risk for AOM. Administering PCV-7 in high-risk infants after early infancy and in older children with a history of AOM appears to have no benefit in preventing further episodes. Currently, several RCTs are investigating different (newly licensed, multivalent) PCVs administered during early infancy to establish their effects on AOM. Results of these studies may provide a better understanding of the role of newly licensed, multivalent PCVs in preventing AOM. Also, the impact of carrier protein D, used in certain pneumococcal vaccines, needs to be further established.
