Novel conjugate vaccine decreases incidence of otitis media
Article Outline
- Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein d for prevention of acute otitis media caused by both streptococcus pneumoniae and non-typable haemophilus influenzae: A randomised double-blind efficacy study. Lancet 2006;367:740-8
- Reference
- Copyright
Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein d for prevention of acute otitis media caused by both streptococcus pneumoniae and non-typable haemophilus influenzae: A randomised double-blind efficacy study. Lancet 2006;367:740-8
Question Can a novel vaccine, containing polysaccharides from 11 different Streptococcus pneumoniae serotypes each conjugated to Haemophilus influenzae–derived protein D, prevent acute otitis media?
Design Randomized, controlled trial.
Setting 27 pediatric centers in the Czech Republic and 23 in Slovakia.
Participants 4968 infants, ages 6 weeks to 5 months.
Intervention Infants were randomly assigned to receive either pneumococcal protein D conjugate or hepatitis A vaccine at the ages of 3, 4, 5, and 12-15 months and were followed up until the end of the second year of life. Middle ear fluid was obtained for bacteriologic culture and serotyping in children who presented with abnormal tympanic membrane or presence of middle-ear effusion, plus 2 predefined clinical symptoms.
Outcomes Protective efficacy against the first episode of acute otitis media caused by vaccine pneumococcal serotypes.
Main Results From 2 weeks after the third dose to 24-27 months of age, 333 clinical episodes of acute otitis media were recorded in the protein D conjugate group (n = 2455) and 499 in the control group (n = 2452), giving a significant relative risk reduction of 33.6% [95% CI 20.8-44.3]) in the overall incidence of acute otitis media (Absolute risk reduction 6.8%, Number needed to treat = 14). Vaccine efficacy was shown for episodes of acute otitis media caused by pneumococcal vaccine serotypes (52.6%, 95% CI [35.0-65.5] for the first episode and 57.6% [41.4-69.3] for any episode). Efficacy was also shown against episodes of acute otitis media caused by non-typable H influenzae (35.3% [1.8-57.4]). The vaccine reduced frequency of infection from vaccine-related cross-reactive pneumococcal serotypes by 65.5%, but did not significantly change the number of episodes caused by other non-vaccine serotypes.
Conclusions Use of the H influenzae–derived protein D as a carrier protein for pneumococcal polysaccharides not only allowed protection against pneumococcal otitis, but also against acute otitis media caused by non-typable H influenzae. Whether this approach would also allow improved protection against lower respiratory tract infections warrants further investigation.
Commentary In this valid efficacy study, the novel 11-valent pneumococcal conjugate vaccine showed an efficacy against acute otitis media caused by the vaccine serotypes that was almost identical to that demonstrated in a Finnish efficacy study1 for the currently available 7-valent conjugate vaccine. Interestingly, the vaccine used in this study also seemed to provide protection against acute otitis media caused by non-typable H influenzae. One important point is worth noting: The design of this study apparently resulted in considerable selection of cases, since the observed incidence of acute otitis media in the control group was only about one-tenth of the incidence seen in most U.S. and European studies. The impact of a protein D conjugate vaccine on the overall incidence of acute otitis media in the United States and most of Europe is therefore difficult to anticipate. The relative risk reduction could hardly be as high as 33% since serotype replacement, although not detected during the study, is bound to be associated with the use of this pneumococcal conjugate vaccine also. However, it is reasonable to assume that the impact of this vaccine on pneumococcal otitis would be equivalent to that induced by the currently available vaccine. The observed efficacy of the protein D conjugate vaccine against acute otitis media due to H influenzae indicates that this type of vaccine has even more potential to reduce acute otitis media.
Reference
PII: S0022-3476(06)00357-X
doi:10.1016/j.jpeds.2006.04.031
© 2006 Elsevier Inc. All rights reserved.
