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Home Eurosurveillance Weekly Release  2006: Volume 11/ Issue 46 Article 4
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Eurosurveillance, Volume 11, Issue 46, 16 November 2006

Citation style for this article: Nohynek H. Pneumococcal conjugate vaccine is efficacious against invasive disease with fewer doses than currently recommended. Euro Surveill. 2006;11(46):pii=3082. Available online:

Pneumococcal conjugate vaccine is efficacious against invasive disease with fewer doses than currently recommended

H Nohynek (, National Public Health Institute, Helsinki, Finland

A recent study in The Lancet reported on the effectiveness against invasive pneumococcal disease of the only pneumococcal conjugate vaccine (PCV) currently available in routine American healthcare settings [1]. Due to an unexpected manufacturing shortage, the 7-valent PCV was given not according to the recommended four dose schedule starting at 2 months of age, but with different schedules and at different ages. Effectiveness against vaccine serotypes for one or more doses was 96% (95% CI 93%-98%) in healthy children under 5 years of age, and 81% (95% CI 57%-92%) in children with co-existing diseases. Efficacy was also demonstrated against vaccine-related pneumococcal serotype 6A, but not for 19A.

These vaccine effectiveness results provide further evidence to support suggestions from immunogenicity studies that a three-dose schedule with two doses given in the first year of life, followed by a third dose in second year of life, yields antibody concentrations comparable to those offered by the official four-dose schedule [2].

A critical reader may challenge these findings because they arise from an observational rather than analytical study. The design of the matched case-control study, however, carefully addressed potential bias and confounding. Bias was minimised by rigorous methods in locating and enrolling control children. Many possible confounding variables were controlled for, such as known risk for disease and access to vaccines. Of the 1267 cases identified during the study period of January 2001 to May 2004, covering approximately 5 million child years, 62% were included in the analysis.

The accompanying Lancet commentary is provocative: in the light of these encouraging results on vaccine effectiveness against invasive disease, it asks how much more evidence is needed before the global community commits to an affordable and sustainable pneumococcal vaccine for the world’s poorest children [3]. However, in its interpretation of the global programmatic importance of the study, the commentary overlooks the fact that the study did not address 7PCV effectiveness against the less severe forms of pneumococcal disease, such as nonbacteraemic pneumonia, which is the leading killer of children worldwide [4]. The 3 dose schedule in the first year has vaccine effectiveness of between 21% and 37% against radiological pneumonia [5,6,7], and 4%-19 % against clinical pneumonia depending on case definition and PCV used [7,8,9], but reduced dose schedules might not be as effective against pulmonary forms of pneumococcal disease. In addition, the distribution of pneumococcal vaccine serotypes varies geographically, as do the causative agents of pneumonia, which may vary between regions, even within the poorest countries.

For the World Health Organization European region which includes rich, intermediate and ‘in transition’ countries, the Lancet study is welcome evidence, but not a substitute for careful cost-effectiveness calculations that use local data on the pneumococcal disease burden, cost of illness (including diseases caused by antimicrobial resistant pneumococci), and expected indirect vaccine effects [10], all of which are needed to support national decision making. The United Kingdom with its 2, 4, and 13 month schedule of 7PCV, and Norway with its 3, 5, and 12 month schedule, are among the forerunners using front line scientific evidence rather than regulatory guidance in their national decision making [11,12]. Many other European countries have established task forces to reconsider the universal introduction in the light of the recent scientific evidence.

For low-income countries which cannot afford their own vaccines, but are not eligible for external support from the Global Alliance for Vaccines and Immunization [13], it is even more important to critically consider which vaccines and other intervention programs to introduce on national level in order to reach the Millennium Development Goals on reduction of child mortality overall, and mortality and morbidity from infectious diseases in general [14]. Multidisciplinary approaches are needed to solve the problems of the most vulnerable in the most cost-effective ways worldwide.

In summary, mounting evidence suggests that that invasive pneumococcal disease is preventable with fewer doses than recommended by the regulatory agencies and currently by most countries, but we are still far from the final global victory against pneumonia.

  1. Whitney CG, Pilishvili T, Farley MM, Schaffner W, Craig AS, Lynfield R, et al. Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study. Lancet 2006;368:1495-502.
  2. Käyhty H, Åhman H, Eriksson K, Sorberg M, Nilsson L. Immunogenicity and tolerability of a heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 12 months of age. Pediatr Infect Dis J. 2005 Feb;24:108-14.
  3. O’Brien K, Levine OS. Effectiveness of pneumococcal conjugate vaccine. Lancet 2006;368:1469-70
  4. Wardlaw T, Salama P, Johnson EW, Mason E. Pneumonia: the leading killer of children. Lancet 2006; 368:1048-50.
  5. Hansen J, Black S, Shinefield H, Cherian T, Benson J, Fireman B, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs. Pediatr Infect Dis J. 2006 Sep;25(9):779-81.
  6. Klugman K, Madhi S, Huebner R, Kohberger R, Mbelle N, Pierce N for the Vaccine Trialists Group. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. New Engl J Med 2003;349:1341-8.
  7. Cutts FT, Zaman SM, Enwere G, Jaffar S, Levine OS, Okoko JB, et al. 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.
  8. Black SB, Shinefield HR, Ling S, Hansen J, Fireman B, Spring D, Noyes J, Lewis E, Ray P, Lee J, Hackell J. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J. 2002 Sep;21(9):810-5.
  9. Madhi SA, Kuwanda L, Cutland C, Klugman KP. The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children. Clin Infect Dis. 2005 May 15;40(10):1511-8. Epub 2005 Apr 7.
  10. Centre for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease-United States, 1998-2003. MMWR Morb Mortal Wkly Rep. 2005; 54:893-7. (
  11. Cameron C, Pebody R. Introduction of pneumococcal conjugate vaccine to the UK childhood immunisation programme, and changes to the meningitis C and Hib schedules. Euro Surveill 2006;11(3):E060302.4. (
  12. Bergsaker MAR, Feiring B. Introduction of pneumococcal conjugate vaccine into the Norwegian childhood vaccination programme. Eurosurveillance 2006; 11(2): 060202. (
  13. Summary of eligibility for support from the GAVI Fund. Global Alliance for Vaccines and Immunization website. Accessed 16 November 2006. (
  14. UN Millennium Development Goals. United Nations website. Accessed 16 November 2006. (

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