A federal vaccine advisory panel is weighing options for a three-dose pneumococcal conjugate vaccination schedule for healthy infants and toddlers.
At least 34 developed countries, including most provinces in Canada, are already using a three-dose schedule for the 13-valent pneumococcal conjugate (PCV13) vaccine (Prevnar) as part of routine immunization programs. The three doses can be delivered either as a two-dose primary series followed by a booster (2+1) or a three-dose primary series without a booster (3+0).
Dr. Michael Brady
Current Centers for Disease Control and Prevention (CDC) recommendations call for routine immunization of generally healthy infants, aged 2-59 months, using a four-dose schedule at 2, 4, 6, and 12-15 months (3+1).
An exhaustive GRADE (Grading of Recommendations Assessment, Development & Evaluation) review of the evidence strongly supports all of the schedules (3+1, 3+0, and 2+1) compared with no vaccination. There was high-quality evidence that shows each schedule is effective against invasive pneumococcal disease and pneumonia in children, in addition to demonstrating large indirect herd effects among adults.
In the absence of randomized trials with clinical outcomes directly comparing three- and four-dose schedules, evidence supporting three-dose schedules was limited to immunogenicity studies, Sara Tomczyk, R.N., of the CDC National Center for Immunization and Respiratory Diseases (NCIRD), said at a meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).
The pneumococcal working group concluded that the GRADE review suggests that "three-dose schedules are likely equivalent to a four-dose schedule," strong evidence from countries using three-dose schedules is reassuring, and a three-dose schedule for infants is "likely appropriate to maintain already observed benefits from 13 years of PCV use in the U.S."
Dr. Michael T. Brady, chair of the American Academy of Pediatrics infectious diseases committee and an ACIP liaison representative, pointed out that vaccine efficacy against invasive pneumococcal disease with the 3+0 schedule was only about 74%, while it was in the mid-90s with the 2+1 and 3+1 schedules.
"I don’t think you can say they’re equivalent," he said. "If you’re looking at whether 3+0 prevents pneumococcal disease, yes, but is it equivalent to the other ones, no."
Dr. Brady also expressed concerns about the generalizability of the results to the U.S. population, as most of the 3+0 studies were conducted in African countries, and that use of a three-dose schedule could reintroduce disparities in pneumococcal disease rates among African American children observed prior to PCV introduction.
"I would hate to find that we actually do need higher levels of antibody to protect African American children," said Dr Brady, who is professor and chair of pediatrics at Ohio State University, Columbus. "If we went to a schedule that was either 2+1 or 3+0, and we now returned to having a disparity, I would be very uncomfortable. I think that’s one of the issues that needs to be addressed."
The working group is not prepared to make a specific policy recommendation at this time, but it is considering the following policy options:
• Option 1. 2+1 for routine use, 3+1 for high-risk groups, to be defined.
• Option 2. 3+0 for routine use, 3+1 for high-risk groups, to be defined
• Option 3. Three-dose schedules (2+1 or 3+0) for routine use, 3+1 recommended at provider discretion for healthy infants, 3+1 for high-risk groups, to be defined.
• Option 4. 3+1 for routine use, three-dose schedules (2+1 or 3+0) optional for healthy infants, 3+1 for high-risk groups.
• Option 5. Status quo.
Unpublished 2012 National Immunization Survey data, also presented at the meeting, show that only a small proportion (10.4%) of U.S. children receive a total of three PCV doses and that coverage decreases with increasing poverty for all schedules. In all, 89.5% of children living in families with an annual income of more than $75,000 received at least three PCV doses before 12 months versus 80.3% of children living below poverty. Within each poverty level, coverage was lowest for the 3+1 schedule, said Dr. Tamara Pilishvili, CDC/NCIRD liaison to the ACIP pneumococcal working group.
Although most parents follow the recommended vaccine schedules, evidence suggests that a large proportion of parents may be "at risk" of switching to an alternative schedule, she said.
A recent cross-sectional survey of 748 parents found that more than 1 in 10 parents of young children, aged 6 months to 6 years, already follow an alternative vaccination schedule, with nonblack race and not having a regular provider increasing the odds of doing so. Further, 28% of parents surveyed thought delaying vaccine doses was safer than the schedule they used (Pediatrics 2011;128:848-56).