VAIL, COLO. – Earlier this year, the Advisory Committee on Immunization Practices took the unusual step of updating recommendations for the use of the meningococcal conjugate vaccines and Tdap vaccine that are at odds with the Food and Drug Administration–approved licensed indications, Dr. Marc Fisher said.
"It’s sort of unusual for ACIP to make off-label indications," Dr. Fischer observed in presenting an update from the Centers for Disease Control and Prevention’s ACIP at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.
Dr. Marc Fischer
The extraordinary step wasn’t taken lightly. The ACIP issued its off-label recommendations after careful deliberation in an attempt to address several public health problems related to shortcomings in vaccination coverage. These concerns have come to the fore only since licensure of the meningococcal conjugate and Tdap (tetanus toxoid with reduced diphtheria toxoid and acellular pertussis) vaccines.
The committee weighed new data supporting the safety and efficacy of the vaccines in populations that were not included in the licensed indications, explained Dr. Fischer, surveillance and epidemiology chief at the CDC’s Division of Vector-Borne Infectious Diseases in Ft. Collins, Colo. He serves as an ACIP adviser.
For example, the package insert for the MCV4-D meningococcal conjugate vaccine (Menactra) lists a history of Guillain-Barré syndrome as a contraindication to giving the vaccine. However, given the reassuring findings of two population-based studies totaling more than 10 million teens – data which became available only after the product labeling was created – the ACIP has concluded there is no increased risk of Guillain-Barré syndrome after vaccination with MCV4-D. Also, the latest results from the Vaccine Adverse Event Reporting System (VAERS) show no signal of a relationship between the meningococcal conjugate vaccine and Guillain-Barré syndrome.
"So if you’re following the package insert you wouldn’t give the vaccine to an 18-year-old headed off to college who has a history of [Guillain-Barré syndrome], and if you’re following the ACIP recommendation you ignore the history of [Guillain-Barré syndrome] and give the vaccine," Dr. Fischer explained.
Off-label ACIP recommendations for the Tdap vaccine published this year (MMWR 2011;60:13-5) after deliberations at the fall 2010 ACIP meeting include the following:
• Children aged 7-10 years who aren’t fully vaccinated against pertussis should receive a single dose of Tdap.
• Adults aged 65 or older who anticipate having close contact with an infant should get a single dose of Tdap.
• Tdap can now be given regardless of how long it has been since the last dose of a tetanus- or diphtheria-containing vaccine. Tdap is actually licensed for use only 5 years or longer after the last dose.
ACIP took these actions in order to improve pertussis vaccine coverage rates and create a coordinated strategy for preventing disease in young infants. Such a strategy is sorely needed. The incidence of pertussis is highest in children 1 month of age or younger. So is the number of deaths. Moreover, both the absolute number of deaths and the proportion of pertussis-related deaths occurring before age 1 month have increased in each of the past 3 decades. During 2000-2009, fully 78% of all pertussis-related deaths in the United States occurred in infants aged 1 month or younger. "We’re not really solving this problem of deaths in young infants," Dr. Fischer commented.
The new off-label Tdap recommendations address two major gaps in pertussis vaccine coverage stemming from the fact that no pertussis vaccine is licensed for use in children aged 7-10 years or in adults aged 65 and older, even though grandparents and other older adults are now believed to be one of the main sources of infection in young infants.
Filling these two gaps in coverage is a strategy known in immunization circles as cocooning. Cocooning is half of a dual ACIP approach aimed at preventing pertussis in young infants. The other half is embodied in an ACIP recommendation that ob.gyns. should routinely administer Tdap to pregnant women who haven’t previously received the vaccine. This should be done after 20 weeks’ gestation, or – as a second-best alternative –immediately post partum.
"This is a pretty big step, recommending a vaccine during pregnancy," the medical epidemiologist commented.
The committee was swayed in part by a cost-effectiveness analysis which estimated that maternal Tdap vaccination would cost $400,000 per quality-adjusted life-year saved. That’s threefold less than for postpartum maternal vaccination, and 13-fold less costly per quality-adjusted life-year saved than for a cocooning strategy involving vaccination of the child’s parents and grandparents.
ACIP recommended maternal vaccination during pregnancy despite some cautionary evidence that transplacental antibodies may blunt levels of active antibody produced when infants later undergo primary pertussis vaccination. The committee nonetheless decided to act because it’s unclear whether this blunted infant immune response to Tdap is actually clinically significant – and even if it is, the net effect could be to shift cases from the youngest infants to older infants, a group with less-severe disease and a lower case fatality rate. Still, the committee is looking forward to the guidance anticipated to come from an ongoing study of infants born to mothers who received Tdap or tetanus/diphtheria vaccine during their third trimester.