title: Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants.
abstract: BACKGROUND
  In developing countries, pneumonia and meningitis due to Haemophilus influenzae type b (Hib) are common in children under age 12 months and the mortality from meningitis is high. Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries. We did a double-blind randomised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis, pneumonia, and other invasive diseases due to Hib.
  
  
  METHODS
  Between March, 1993, and October, 1995, 42,848 infants were randomly allocated the conjugate vaccine Hib polysaccharide tetanus protein (PRP-T) mixed with diphtheria-tetanus-pertussis vaccine (DTP), or DTP alone at age 2 months, 3 months, and 4 months. Children who presented with signs of invasive Hib were investigated by blood culture and, where appropriate, by lumbar puncture, chest radiograph, or percutaneous lung aspirate. Children were followed up for between 5 and 36 months.
  
  
  RESULTS
  The median ages at which children received the study vaccine were 11 weeks, 18 weeks, and 24 weeks. 83% of children enrolled received all three doses of vaccine. 17 cases of culture-positive Hib pneumonia, 28 of Hib meningitis, and five of other forms of invasive Hib disease were detected amongst the study children. The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95% (PRP-T vaccinees 1, controls 19 [95% CI 67-100]), for the prevention of Hib pneumonia after two or three doses, 100% (vaccinees 0, controls 10 [55-100]), and for the prevention of radiologically defined pneumonia at any time after enrollment, 21.1% (PRP-T vaccinees 198, controls 251 [4.6-34.9]).
  
  
  CONCLUSIONS
  PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis.
authors.affiliation: Medical Research Council Laboratories, Fajara, The Gambia.
authors.forename: K
authors.initials: K
authors.lastname: Mulholland
authors.forename: S
authors.initials: S
authors.lastname: Hilton
authors.forename: R
authors.initials: R
authors.lastname: Adegbola
authors.forename: S
authors.initials: S
authors.lastname: Usen
authors.forename: A
authors.initials: A
authors.lastname: Oparaugo
authors.forename: C
authors.initials: C
authors.lastname: Omosigho
authors.forename: M
authors.initials: M
authors.lastname: Weber
authors.forename: A
authors.initials: A
authors.lastname: Palmer
authors.forename: G
authors.initials: G
authors.lastname: Schneider
authors.forename: K
authors.initials: K
authors.lastname: Jobe
authors.forename: G
authors.initials: G
authors.lastname: Lahai
authors.forename: S
authors.initials: S
authors.lastname: Jaffar
authors.forename: O
authors.initials: O
authors.lastname: Secka
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Ethevenaux
authors.forename: B
authors.initials: B
authors.lastname: Greenwood
mesh_terms: D000367:Age Factors; D003906:Developing Countries; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005714:Gambia; D006192:Haemophilus Infections / Q000175:diagnosis / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage; D006193:Haemophilus influenzae / Q000145:classification; D006801:Humans; D007115:Immunization Schedule; D015994:Incidence; D007223:Infant; D008583:Meningitis, Haemophilus / Q000175:diagnosis / Q000517:prevention & control*; D019152:Paracentesis; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000517:prevention & control*; D013902:Radiography, Thoracic; D013129:Spinal Puncture; D013745:Tetanus Toxoid / Q000008:administration & dosage; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate