A recently updated Cochrane Review nicely summarises the very complicated results of trials of pneumococcal vaccines with the outcome of preventing acute otitis media (rather than the original target of invasive pneumococcal disease). This is clearly an important question; acute otitis media is one of the most common causes of children's visits to the doctor. It is also a common reason for prescribing antibiotics, so anything that prevents it has the extra bonus of contributing to reducing the worry of antibiotic resistance.
The data are complicated. This is because the vaccine can have a different number of valencies (the different components directed at different strains of Pneumococcus, ranging from 3 to 23 in this review). The vaccine can be conjugated with different carrier proteins, developed after finding that the original unconjugated pneumococcal vaccines did not generate an immune response. These carrier proteins are typically made of an inactivated bacterial capsule protein (such as CRM197, derived from Corynebacterium diphtheriae, which is also used in vaccines against Haemophilus and Meningococcus, for example).
The choice of valency and carrier protein affects efficacy, so the trial results are, not surprisingly, very heterogeneous. This is compounded by variation in follow-up (6 to 42 months), frequency of vaccine administration, ages of recipient children, and propensity of recipients to acute otitis media (risk ranging from normal to high, in indigenous people). Moreover, the controls were different (all studies used an alternate vaccine). Accordingly, the results are difficult to summarise.
As expected, pneumococcal vaccine is more effective at reducing pneumococcal-caused (with point estimates of relative reduction of about 50%, derived from one trial) rather than any-cause acute otitis media (range of reduction: 0% to 25%). The vaccine was also more effective for young healthy children (before their first episode of acute otitis media) than in older children, for whom it might even be less effective than the control – a trivalent influenza vaccine.
Only about 50% of fluid samples from infected middle ears contain bacteria as the only pathogen (virus presumably implicated in the remainder), and only a proportion of those are pneumococcus, so preventive potential of a vaccine directed at some pneumococcal strains could only be very incomplete. Nonetheless, a small relative reduction would benefit a lot of children for this all-too-common condition. The review does not mention harms from the intervention, presumably because they were either not measured or not reported.
Looking forward, the review points to five new trials underway, three in indigenous people. So more information might be forthcoming to resolve what is currently confusing for clinicians.
Chris Del Mar1, Jane Smith2
1Chris Del Mar (firstname.lastname@example.org), Professor of Public Health, and Co-ordinating Editor, Cochrane Acute Respiratory Infections Group, Bond University, Gold Coast, Australia; 2Jane Smith, Associate Professor of General Practice, Bond University, Gold Coast, Australia.
How to cite: Del Mar C, Smith J. Pneumococcal conjugate vaccine for preventing otitis media [editorial]. Cochrane Database of Systematic Reviews 2014;(5):ED000082.
1. Fortanier AC, Venekamp RP, Boonacker CWB, Hak E, Schilder AGM, Sanders EAM, et al. Pneumococcal conjugate vaccines for preventing otitis media. Cochrane Database of Systematic Reviews 2014;(3):CD001480. dx.doi.org/10.1002/14651858.CD001480.pub4
2. Malito E, Bursulaya B, Chen C, Lo Surdo P, Picchianti M, Balducci E, et al. Structural basis for lack of toxicity of the diphtheria toxin mutant CRM197. Proceedings of the National Academy of Sciences USA 2012;109:5229-34. dx.doi.org/10.1073/pnas.1201964109
Competing interests: The authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available upon request). CDM is Co-ordinating Editor of the Cochrane Acute Respiratory Infections Review Group (ari.cochrane.org) and has received grants from the Australian National Health and Medical Research Council (NHMRC) and personal fees and expenses from GlaxoSmithKline and Key Pharmaceuticals that relate to the work referred to by the editorial. CDM has also received other grants from NHMRC and the UK National Institute for Health Research, royalties from Elsevier and BMJ Books, and travel expenses from conference organisers. JS reports NHMRC Centres of Research Excellence funding paid to her institution and personal fees from the Australian Therapeutics Goods Administration's Advisory Committee on the Safety of Medicines.
Image credit: Oscar Burriel/Science Photo Library
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