title: Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality: re-analysis of a randomised trial in the Gambia.
abstract: BACKGROUND
  Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children.
  
  
  METHODS
  We reanalysed data from a randomised placebo-controlled trial. Infants aged 6-51 weeks were allocated to three doses of nine-valent PCV (n=8718) or placebo (n=8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules.
  
  
  RESULTS
  Predicted efficacy in the groups aged 6 weeks (n=2467, 154 events) or 10 weeks (n=2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19-43%) and 33% (95% CI 21-44%), against hospitalisation 14% (95% CI 3-23%) and 17% (95% CI 7-26%), and against mortality 17% (95% CI -3 to 33%) and 16% (95% CI -3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n=2701, 133 events) or 2 months (n=1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20-44%) and 36% (95% CI 24-46%), against hospitalisation 15% (95% CI 5-24%) and 18% (95% CI 8-27%), and against mortality 17% (95% CI -2 to 33%) and 13% (95% CI -8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules.
  
  
  CONCLUSIONS
  We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.
authors.affiliation: Medical Research Council (UK), The Gambia Unit, Fajara, PO Box 273, Banjul, The Gambia. Electronic address: gmackenzie@mrc.gm.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mackenzie
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Electronic address: Christian.bottomley@lshtm.ac.uk.
authors.forename: Christian
authors.initials: C
authors.lastname: Bottomley
authors.affiliation: Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK. Electronic address: albertjan.vanhoek@hpa.org.uk.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van Hoek
authors.affiliation: Medical Research Council (UK), The Gambia Unit, Fajara, PO Box 273, Banjul, The Gambia. Electronic address: djeffries@mrc.gm.
authors.forename: David
authors.initials: D
authors.lastname: Jeffries
authors.affiliation: Medical Research Council (UK), The Gambia Unit, Fajara, PO Box 273, Banjul, The Gambia. Electronic address: otama@afro.who.int.
authors.forename: Martin
authors.initials: M
authors.lastname: Ota
authors.affiliation: Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK. Electronic address: azaman@mrc.gm.
authors.forename: Syed M A
authors.initials: SM
authors.lastname: Zaman
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Electronic address: Brian.Greenwood@lshtm.ac.uk.
authors.forename: Brian
authors.initials: B
authors.lastname: Greenwood
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Electronic address: Felicity.Cutts@lshtm.ac.uk.
authors.forename: Felicity
authors.initials: F
authors.lastname: Cutts
mesh_terms: D002675:Child, Preschool; D005260:Female; D005714:Gambia; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000401:mortality / Q000517:prevention & control*; D018074:Vaccines, Conjugate
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Mortality; Pneumonia; Schedule; Streptococcus pneumoniae; Vaccine