A pneumococcal vaccine has been shown to protect children with HIV in a large study conducted in South Africa, reported today in the New England Journal of Medicine. Streptococcus pneumoniae is a leading cause of death in under-fives worldwide.
The study, sponsored by manufacturer Wyeth Pharmaceuticals and led by Prof. Keith Klugman of Emory University, Atlanta, randomised 40,000 infants in Soweto to receive a vaccine targeted at nine variants of streptococcus pneumoniae or a placebo (three doses).
Over an average follow-up of 2.3 years, the vaccine reduced the incidence of pneumonia in fully vaccinated children by 25 percent. In addition, the vaccine reduced the incidence of invasive pneumococcal disease (pneumococcal bacteria in the bloodstream) by more than 83 percent in non-HIV-infected children and by more than 65 percent in HIV-infected children. The vaccine also significantly reduced the incidence of invasive pneumococcal disease caused by antibiotic-resistant strains by between 56 and 67 percent, depending on the type of resistance.
Antibiotic-resistant strains of pneumococci are common in Soweto, and HIV infection is the leading risk factor for invasive pneumococcal disease. The overall mortality rate in the clinical trial was reduced by five percent among all children and by six percent among HIV-infected children.
No significant adverse events were associated with the vaccine during the month following vaccination, but children who received the pneumococcal vaccine were significantly more likely to experience generalised seizures than the placebo group (35 vs 19 cases, p=0.04). Asthma was also more common in vaccine recipients, although the incidence was low.
A vaccine is now recommended for all U.S. children to prevent invasive pneumococcal disease and bacterial meningitis, and is administered in infancy. The vaccine targets seven strains of pneumococcal disease, while the vaccine used in the South African clinical trial targets two additional strains of pneumococcus that are prevalent in developing countries. The 9-valent conjugate vaccine is currently under development for both developed and developing countries, but has not yet been licensed for use.
"With this reduction in the incidence of pneumonia in the developing world, we could potentially save over 500,000 lives each year," said Dr. Klugman. "In addition, no vaccine has previously been documented to prevent pneumococcal disease in HIV-infected children, and our study showed a 50 percent reduction in that group. In an era in which there is little to offer to children with HIV, we can clearly reduce invasive disease by providing this vaccine to all children. Our study provides evidence to support the use of this vaccine to prevent invasive pneumococcal disease, reduce antibiotic resistance and diminish the incidence of pneumonia in children".
The authors recommend that the vaccine should now be tested in HIV-positive adults. A previous Ugandan study of a pneumococcal vaccine that should have provided protection against 23 strains of S. pneumoniae found that the risk of streptococcal pneumonia was increased in vaccine recipients, possibly because it was not protective against all local strains of pneumococcus.
Reference
Klugman KP et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. New England Journal of Medicine 349: 1341-48, 2003.