March 2000
ROCKVILLE, MD - The Food and Drug Administration (FDA) recently approved the first pneumococcal conjugate vaccine (Prevnar, Wyeth Lederle Vaccines) for use in infants to prevent invasive pneumococcal disease.
The pneumococcal seven-valent conjugate vaccine was proven effective in the prevention of invasive disease, bacteremia and meningitis caused by serotypes of Streptococcus pneumoniae contained in the vaccine
Infants should receive the vaccine at 2, 4, 6 and 12-15 months of age. For children who cannot receive the vaccine starting at 2 months of age, it is recommended that parents see their health care provider for alternative schedules, according to the manufacturer. The Advisory Committee on Immunization Practices recently recommended that all children up to age 23 months receive the vaccine, and highlighted certain high-risk populations who should also receive the vaccine (See related story "Infectious Diseases in Children: ACIP recommends routine use of pneumococcal vaccine for infants".).
For previously unvaccinated older infants and children, who are beyond the age of the routine infant schedule, the dosing schedule will vary.
The vaccine is expected to be available this month.
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The pneumococcal conjugate vaccine targets the seven most common strains of pneumococcus that account for approximately 80% of invasive disease in infants. The vaccine is manufactured by attaching the polysaccharides to a genetically modified nontoxic form of the diphtheria toxin protein called CRM197.
Clinical trials included a large multicenter safety and efficacy study conducted at Northern California Kaiser Permanente in Oakland, Calif. The controlled, double-blind trial enrolled approximately 38,000 children, about half of whom received pneumococcal conjugate vaccine. The vaccine was given at 2, 4, 6 and 12-15 months of age along with routinely recommended vaccines.
In this trial, the vaccine was 100% effective (95% confidence interval: 75.4% to 100%) in preventing invasive pneumococcal disease caused by the seven strains of pneumococcus in the vaccine. The vaccine was approximately 90% effective in preventing invasive disease caused by all pneumococcal subtypes.
This vaccine is not indicated for use in adults or as a substitute for other approved pneumococcal polysaccharide vaccines approved for high risk children older than 2 years.
Adverse events reported during the trials were generally mild and included local injection site reactions, irritability, drowsiness and decreased appetite. Approximately 21% of the children had fevers over 100.3° F compared with about 14% in the control group.
In clinical trials, use of the vaccine reduced by 7% the incidence of otitis media (OM) and decreased by 20% the need for insertion of ear tubes. In addition, children in the vaccine group were 23% less likely to have frequent bouts of ear infections, defined as five episodes in six months or six episodes within 12 months. However, these data have not been evaluated by FDA, but the manufacturer plans to seek an indication for OM.
As with many new vaccines, parent and physician acceptance of the product often takes time. Not only will it take many physicians time to accept a new product, but cost may also be an issue that will delay immediate success.
Larry K. Pickering, MD, editor of the American Academy of Pediatrics 2000 Red Book, said acceptance of any vaccine into the recommended immunization schedule occurs after consideration of many aspects.
"The most important is whether safety and efficacy data demonstrate a benefit to the health and welfare of children. If so then the ability to implement administration of the vaccine and the cost of the vaccine are considered," said Pickering, a member of the Infectious Diseases in Children editorial board and special consultant to the director at the National Immunization Program, Atlanta.
In the case of the pneumococcal conjugate vaccine, safety and efficacy data support the use of this vaccine in all children younger than 24 months of age and in high-risk children 24 to 59 months of age. "Because of the cost of this vaccine and the need for recall of children, full implementation of its use may be delayed," Pickering said.
The high price of the vaccine is an issue that reportedly concerns many physicians. The catalog price of Prevnar is $58 per dose, totaling $232 for the four-dose infant series which does not include administration costs.
According to Harold Marder, MD, senior vice president of global medical affairs at Wyeth-Ayerst Pharmaceuticals, because the vaccine has seven serotypes, it requires more testing. The pneumococcal conjugate vaccine is not simply one single vaccine, but the combination of seven separate vaccines. Each one of the seven serotypes requires separate processes for purification, conjugation and testing. Only after each of the seven components are complete can they be combined into a single vaccine, which then requires further testing and validation.
It is estimated that about 16,000 cases of pneumococcal bacteremia and 1,400 cases of pneumococcal meningitis occur among children younger than 5 years each year in the United States. Children younger than 2 are at highest risk for infection. In up to half the cases of meningitis, brain damage and hearing loss occurs and about 10% die.
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