Sona Chowdhary; Jacob Puliyel1
Department of Pediatrics, St Stephens Hospital, Tis Hazari, Delhi 110054, India
Madhi et al.1 write that the pneumococcal conjugate vaccine (PCV) is an effective instrument for pneumonia prevention in children. This is not strictly true. WHO data2 suggest that there are 450 million cases of pneumonia each year and that it causes 3.9 million deaths. In the sub-Saharan region of Africa, 1 022 000 die and 702 000 die in south Asia.1 The pneumonia referred to is "clinical pneumonia" a diagnostic syndrome within the Integrated Management of Childhood Illness WHO and United Nations Children's Fund (UNICEF) system for triage and clinical management in developing countries.3 The Cochrane database4 states that PCV does not reduce the incidence of clinical pneumonia, although it has been shown to reduce vaccine-serotype bacteraemic pneumonia and radiological pneumonia. The benefit of reducing bacteraemic pneumonia and radiological pneumonia is so minimal that it has no effect on "clinical pneumonia". Poor nations will need to assess its cost utility carefully.
A study from the Gambia showed that mortality was 16% lower in a PCV immunized group compared to placebo recipients (25.2/1000 children years versus 30.1/1000 children years).5 Data are also provided on adverse effects and deaths within 1 week of receiving any dose of the vaccine or placebo. The mortality benefit was seen in the first week after injection, well before vaccine efficacy could have been established. There were 12 deaths in the vaccine group and 15 among controls (23.8/1000 children years versus 29.8/1000 children years). This suggests that factors other than vaccine efficacy are responsible for the difference in mortality between the groups compared.
There is also another issue that we hope to raise here. The paper states that the vaccine programme would exceed the WHO threshold in 69 eligible countries. The authors assert that these findings are conservative in the sense that they did not assume any herd protection and did not assume protection beyond the age of 2.5 years. Beutels6 has cautioned against this trend of noting the "positive" uncertainties (herd immunity, protection beyond 2.5 years) without reporting the "negative" ones (serotype replacement,7 increased incidence of asthma),8 which could dampen enthusiasm for the intervention.
1. Madhi SA, Levine OS, Hajjeh R, Mansoor OD, Cherian T. Vaccines to prevent pneumonia and improve child survival. Bull World Health Organ 2008;86:365-372. PMID:18545739 doi:10.2471/BLT.07.044503
2. Revised global burden of disease 2002 estimates. Geneva: WHO. Available from: http://www.who.int/ healthinfo/bodgbd2002revised/en/index.html [accessed 5 August 2008] .
3. Integrated Management of Childhood Illness. Geneva: WHO; 2000.
4. Lucero MG, Dulalia VE, Parreno RN, Lim-Quianzon DM, Nohynek H, Makela H, et al. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age. Cochrane Database Syst Rev 2004;CD004977. PMID:15495133
5. Cutts FT, Zaman SM, Enwere G, Jaffar S, Levine OS, Okoko JB, et al.; Gambian Pneumococcal Vaccine Trial Group. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet 2005; 365:1139-46. PMID:15794968 doi:10.1016/S0140-6736(05)71876-6
6. Beutels P. Potential conflicts of interest in vaccine economics research: a commentary with a case study of pneumococcal conjugate vaccination. Vaccine 2004;22:3312-22. PMID:15308354 doi:10.1016/j.vaccine.2004.03.001
7. Eskola J, Kilpi T, Palmu A, Jokinen J, Haapakoski J, Herva E, et al.; Finnish Otitis Media Study Group. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001;344:403-9. PMID:11172176 doi:10.1056/NEJM200102083440602
8. Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N; Vaccine Trialists Group. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003;349:1341-8. PMID:14523142 doi:10.1056/NEJMoa035060