A Vaccine Prevents Invasive Pneumococcal Infections in Infants

Abstract & Commentary

Synopsis: A new, as yet unlicensed, heptavalent conjugate pneumococcal disease was administered to 37,000 infants at 2, 4, and 6 months of age with a booster dose at 12-15 months in a double-blind study of efficacy in preventing invasive pneumococcal disease. The vaccine was at least 90% effective in preventing invasive pneumococcal infections.

Source: Black S, et al. Efficacy of heptavalent conjugate pneumococcal vaccine (Wyeth Lederle) in 37,000 infants and children: Results of the Northern California Kaiser Permanente efficacy trial. Program and Abstracts, 38th ICAAC, San Diego, CA, September 24-27, 1998. Abstract LB-9.

Black and associates studied 37,000 infant enrollees in the Kaiser Permanente health plan in northern California in a double-blind trial. Half of the infants received a heptavalent, conjugate pneumococcal vaccine and the other half was a control group that received an experimental meningococcal vaccine. The vaccine was given at 2, 4, and 6 months and boosted at 12-15 months.

As of July 1998, there were 17 invasive pneumococcal infections (bacteremia, meningitis) due to vaccine serotypes in fully vaccinated children. All were in the group that received the control vaccine and none in the group that received the pneumococcal vaccine, demonstrating 100% protection. In later data presented at the meeting and reported in the press ("Vaccine aids some babies in fending off earache germ," New York Times, Sept. 26, 1998), it was stated that there were now a total of three cases of invasive diseases in pneumococcal vaccines compared with 27 cases in the controls, for 90% protection. There was no increase in infections due to nonvaccine pneumococcal serotypes. Data for other pneumococcal infections, including otitis media and pneumonia, were not reported. (Editor’s Note: Pediatrics and Adolescent Medicine Reports has not previously included commentaries on articles presented at scientific meetings. However, the previous report on a paper delivered at a meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy [ICAAC], held in San Diego in late September, is important and exciting. It should be of great interest to physicians caring for children.)

Comment by Robert Baltimore, MD, FAAP

With the virtual eradication of invasive Haemophilus influenzae accomplished by the use of conjugate HIB vaccine, pneumococcal disease has become the most common cause of bacterial sepsis and meningitis after the neonatal period in the United States. The increasing prevalence of penicillin-resistant pnemococci is of great concern, and prevention of these infections with a vaccine would be of enormous importance.

The pneumococcal polysaccharide vaccine currently approved for prevention of pneumococcal pneumonia and other invasive infections due to Streptococcus pneumoniae is not effective in children under 2-4 years of age because the immature immune system does not respond optimally to capsular polysaccharide vaccines. Using the conjugate H. influenzae vaccine (which has virtually eliminated severe invasive H. influenzae infections in the United States) as a model, investigators and pharmaceutical companies have been developing conjugate pneumococcal vaccines. At the 38th annual ICAAC meeting, there were several abstracts presented that suggest that an effective vaccine may not be far off.

The large study from the Permanente Vaccine Study Group shows conclusively that the Wyeth-Lederle heptavalent conjugate pneumococcal vaccine was effective. The seven pneumococcal serotypes included in this vaccine cause about 90% of invasive pediatric pneumococcal infections. The study was terminated early because of the high level of efficacy that was demonstrated at early analysis of the data.

Obviously, these are preliminary data that have not yet gone through the peer review process required for formal publication. Also, the full effect of the vaccine can only be assessed when the data on otitis and pneumonia are analyzed. When the final data are published, they will be discussed here again.

Because pneumococci are the most common cause of community-acquired bacteremia and meningitis in children, a safe and effective vaccine would be great news. A vaccine effective in infancy would be of great value for infants and young children with asplenia and sickle cell disease, who are very susceptible to severe and often fatal pneumococcal sepsis and meningitis. An effective pneumococcal vaccine could make chronic penicillin prophylaxis unnecessary in these high-risk children.

This study did not report the effectiveness of the conjugate pneumoccocal vaccine in preventing the much more common pneumococcal infections of infancy, pneumonia and otitis media, but Black et al have and are undoubtedly analyzing these data from their study. If conjugate pneumococcal vaccine substantially reduces the incidence of these common diseases of infancy and childhood, it will be a monumental advance. (Dr. Baltimore is Professor of Pediatrics and Epidemiology and Public Health, Yale University School of Medicine.)