A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection.
BACKGROUND
Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa.


METHODS
At 6, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo. All children received Haemophilus influenzae type b conjugate vaccine. Efficacy and safety were analyzed according to the intention-to-treat principle.


RESULTS
Among children without human immunodeficiency virus (HIV) infection, the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent (95 percent confidence interval, 39 to 97; 17 cases among controls and 3 among vaccine recipients). Among HIV-infected children, the efficacy was 65 percent (95 percent confidence interval, 24 to 86; 26 and 9 cases, respectively). Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children). The incidence of invasive pneumococcal disease caused by penicillin-resistant strains was reduced by 67 percent (95 percent confidence interval, 19 to 88; 21 cases in the control group and 7 in the vaccinated group), and that caused by strains resistant to trimethoprim-sulfamethoxazole was reduced by 56 percent (95 percent confidence interval, 16 to 78; 32 and 14 cases, respectively).


CONCLUSIONS
Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia. The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection.
Klugman
Keith P
KP
Medical Research Council, University of the Witwatersrand, National Institute for Communicable Diseases, Respiratory and Meningeal Pathogens Research Unit, Johannesburg, South Africa. kklugma@sph.emory.edu
Madhi
Shabir A
SA
Huebner
Robin E
RE
Kohberger
Robert
R
Mbelle
Nontombi
N
Pierce
Nathaniel
N
D016667:Bacterial Capsules; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D005260:Female; D015658:HIV Infections / Q000150:complications*; D018073:Haemophilus Vaccines; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000401:mortality / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000009:adverse effects; D011018:Pneumonia, Pneumococcal / Q000517:prevention & control; D011135:Polysaccharides, Bacterial; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000302:isolation & purification; D018074:Vaccines, Conjugate / Q000009:adverse effects
D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate