November 1999
A clinical trial of the new seven-valent conjugate pneumococcal vaccine (Prevenar, Wyeth Lederle Vaccines) showed that the vaccine was effective in reducing cases of otitis media (OM) caused by Streptococcus pneumoniae. The vaccine reduced the frequency of episodes and the number of office visits needed for the disease. In addition, fewer patients required tympanostomy tube placement.
But what does this mean for the overall incidence of OM in children?
"For children who have had problems with severe and recurrent infections of the middle ear, this will be an important part of the strategy of managing such children," said Jerome O. Klein, MD, professor of pediatrics at Boston Medical Center, Boston. "But I think the overall benefit to children will be as a prevention of pneumococcal disease in all its facets, including invasive disease, meningitis, pneumonia, as well as OM."
S. pneumoniae is a major cause of OM in children, making up approximately 30% of all cases, according to Gregory A. Poland, MD, professor of medicine and clinical pharmacology at the Mayo Clinic Foundation, Rochester, Minn. "As we use conjugate pneumococcal vaccine, we will decrease, if not eliminate, the number of ear infections due to S. pneumoniae, " he said. "The total number of otitis media cases should fall, and the composition of the remaining cases will be different, and it will be with different organisms."
Poland compared the pneumococcal vaccine's effect on S. pneumoniae associated OM to the Haemophilus influenzaevaccine's effect on meningitis. "When we started giving conjugate Haemophilusvaccine," he said, "we virtually eliminated that as a cause of meningitis in infants and children. It's not that we've eliminated meningitis, it's just that now other organisms cause it."
H. influenzae non-typable and Moraxella catarrhalis are other major causes of OM, in addition to a small proportion caused by various other causes. One may question whether these other organisms will "pick up the slack" for S. pneumoniae. Will an increase in OM cases due to M. caterrhalis, for instance, occur as a result of the reduction or elimination of cases caused by S. pneumoniae.
This did not appear to be the case during the trial, said Steven B. Black, MD, one of the lead investigators of the trial and codirector of the Kaiser Permanente Vaccine Study Center, Oakland, Calif. "I don't think the slack will be picked up, as we did not observe any evidence of this in our trial," he said. Black is also a member of the editorial advisory board of Infectious Diseases in Children.
Regardless of the efficacy of the vaccine against pneumococcal disease, however, the risk factors for OM in children remain the same. These include being cared for in a group setting, such as day care, bottle-feeding while lying down, and having parents who smoke cigarettes, according to the National Institutes of Health.
S. Michael Marcy, MD, of the University of Southern California School of Medicine, Kaiser Foundation Hospital, Panorama City, Calif., said that since the sampling of 37,000 children in the Kaiser study was random, the results will be indicative of what the general population will see, since risk factors are the same for both the children in the trial and children in the general population.
"The population that Black and Shinefield studied had the same risk factors as the general population. They had no selection of the kids they immunized. So there is no reason to believe that they had a select population that was either more or less prone to ear infections on the basis of day care attendance or age, or anything like that. I think they had a representative cross-sectional sample of the population," Marcy said.
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Another element to consider is how this decrease in OM cases will affect the individual pediatrician.
"It will be perceptible, probably, only on a population basis," said Klein, who is also a member of the Infectious Diseases in Children editorial advisory board. "As it appears now, you reduce the total burden of otitis by about 10%. The child or parent or even the pediatrician may not perceive the difference," he said.
For example, suppose one pediatrician sees 10 patients in one week for OM. A 10% decrease in the number of patients he sees in that one week would mean only one less patient.
"But it will be apparent in national figures," Klein said. "So, if we have 30 million office visits for OM, and you decrease by 10%, that's a substantial decrease in the overall burden of otitis media, including the decreasing morbidity and cost."
"It [the pneumococcal vaccine] is an important thing to consider," said Poland, "because there are 7 million cases a year due to otitis media. Take away 30% of that, you're talking about a lot of money and a lot of sickness."
Marcy believes that the observable decrease in the overall number of patient visits due to OM will be more subtle, while the rates involving recurrent cases and tympanostomy tube placements will be more substantial.
"I think it [the pneumococcal vaccine] will have a modest effect on the incidence of otitis media episodes and visits," said Marcy, who is also a member of the Infectious Diseases in Children editorial advisory board. "I think it will have a more substantial effect on the incidence of recurrent otitis - or five to six episodes in a year - about a 20% decrease. And it certainly will have a substantial effect on the incidence of tube placement, which is also around a 20% decrease."
Marcy concluded that monitoring will be key in determining the success of the pneumococcal vaccine, especially regarding disease prevalence due to S. pneumoniae serotypes which are not included in the vaccine. "Time will tell whether or not other serotypes will replace those that are in the vaccine. That certainly is something that will have to be monitored by both public health agencies and Wyeth over the course of years," he said.
The three-year trial included 37,000 children at 23 Kaiser Permanente sites in California. Infants were given the vaccine at 2, 4, 6 and 12-15 months of age in a double-blinded trial. The children were randomly assigned 1:1 to receive either the Wyeth Lederle heptavalent CRM197 vaccine or meningococcus type C CRM197 conjugate. Trial results were presented by Black and Henry Shinefield, MD, codirectors of the Kaiser Permanente Vaccine Study Center, at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.
For more information:
- Black S, Shinefield H, Ray P, et al. Efficacy of heptavalent conjugate pneumococcal vaccine (Wyeth Lederle) in 37,000 infants and children: impact on pneumonia, otitis media and an update on invasive disease - results of the Northern California Kaiser Permanente efficacy trial. Abstract 1398. Presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Sept. 26-28. San Francisco.
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