Key Point

With the increasing frequency of pertussis among adolescents and adults, a booster vaccine should be given to reduce transmission of the illness to small children who have not yet been immunized.

ROCHESTER, NY—In 2003, 11,647 cases of pertussis in adults and adolescents were reported to the CDC. Preliminary numbers for pertussis cases in these age-groups for 2004 increased to 18,957. After completion of the primary immunization series in childhood, immunity remains high until early adolescence. However, with no booster vaccine available, adolescents and adults are increasingly vulnerable to pertussis. Although the disease is not life threatening in these populations, severe illness among adults can be a source of infection for unvaccinated infants or children who have not yet received the complete diphtheria, tetanus, and acellular pertussis (DTaP) series.

“The prevailing opinion among experts is that there are about a million cases of pertussis among adolescents and adults in the United States annually,” said Michael E. Pichichero, MD, Professor of Microbiology and Immunology at the University of Rochester in New York. “Although the reported incidence according to the CDC in 2004 was only about 20,000, this is thought to be an underestimate by about 100-fold. I’ve seen estimates of one to three million cases per year,” he emphasized. “Based on data from Massachusetts, it would appear that about two thirds of those cases are occurring in adolescents, and one third are occurring in adults.”

A recent phase III, randomized, controlled, double-blind trial—funded by sanofi pasteur—was conducted at 39 centers in the US to compare the immunogenicity provided by booster doses of the tetanus-diphtheria (Td) vaccine with that of a new tetanus, diphtheria, and acellular pertussis (Tdap) vaccine in adults and adolescents.¹

MEASURING REACTIONS AND TITERS

Over 4,000 participants were randomized either to receive Td or Tdap. Serum samples were obtained immediately before and 28 to 42 days after vaccination. Participants were observed for 30 minutes after vaccination for immediate reactions. Antibody titers were determined using enzyme-linked immunosorbent assay. For each antigen, booster response—defined as a twofold or fourfold increase in antibodies, depending on the prevaccination titers—was the primary outcome measure.

Between August 2001 and August 2002, 4,480 participants were enrolled. Of these, 2,053 were adolescents (1,232 received Tdap and 821 received Td) and 2,427 were adults (1,804 received Tdap and 599 received Td).

Booster response rates and one-month postimmunization geometric mean titers for tetanus and diphtheria were high and similar between both vaccine groups. In both adults and adolescents, pertussis antibody geometric mean titers following one dose of Tdap were higher than those seen in infants in whom a course of three doses of DTaP had been completed.

Proportions of immediate reactions to both vaccines were similar, with incidences of about 0.5% for adolescents and about 0.2% for adults. The most common reactions were syncope, dizziness, vasovagal reactions, and pain and swelling at injection site.

One obvious benefit of a pertussis booster is a decrease in the number of pertussis cases in persons 10 and older, which has increased from 15% in 1977–1979 to 49% in 1997–2000, and to 64% in 2003. The rising incidence is most likely caused by waning immunity in adolescents and adults.

IMMUNITY IS WANING, DIAGNOSIS IS DIFFICULT

“It is generally known in the medical community among pediatricians that pertussis immunity wanes over time because there have been many papers over the last five or six years in the pediatric journals and newspapers highlighting this fact,” Dr. Pichichero observed. “However, that information has not been transmitted to family physicians or general internists or other members of the medical community, such that the vast majority are unaware of this issue.”

Not only is much of the medical community unaware of the problem of waning pertussis immunity, the disease itself is difficult to diagnose. “Currently,” explained Dr. Pichichero, “to be completely sure of the diagnosis of pertussis, you have to take a culture, which is a catch-22 because the cultures are only positive at the very beginning of the illness in the first week or two. At this time, the cough is very mild and neither the patient nor the doctor is thinking about the diagnosis. By the time they do think of pertussis because the cough has become more severe or lasted for a couple of weeks, the culture—which is taken from the nose—is often negative.”

To get around this problem, said Dr. Pichichero, “pertussis should be considered as a diagnosis in any patient who has a cough that lasts more than a week, with no fever—especially if the cough tends to come in spells with intervals between when the patient feels totally fine. This is unlike the cough of a flu or a cold or an allergy, where the cough is more consistent throughout the day and evening.”

Booster vaccination with tetanus and diphtheria toxoids has become standard practice in the US. This study indicates that the Tdap vaccine can be used for the tetanus/diphtheria booster while providing additional protection against pertussis.

“Both booster vaccines—BOOSTRIX^® (GlaxoSmithKline) and ADACEL^™ (sanofi pasteur)—have been FDA approved in the US,” noted Dr. Pichichero. “The vaccines display a very favorable reaction profile quite similar to the standard diphtheria/tetanus booster that we’ve been using since the 1940s. We aren’t seeing very much of an increase in reaction with the addition of the pertussis component.”

On June 30, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended the use of the newly licensed vaccines for adolescents ages 11 and 12 in place of the Td booster that children this age would normally receive. The ACIP also recommended that the Tdap vaccine be given to anyone ages 13 to 18 who missed the Td booster. In addition, adolescents ages 11 to 18 who have already received the Td booster vaccine are encouraged to receive a dose of the Tdap vaccine. These are the first pertussis vaccines licensed for use in adolescents and adults.²

—Gale Jurasek

References
1. Pichichero ME, Rennels MB, Edwards KM, et al. Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults. JAMA. 2005;293:3003-3011.
2. CDC. ACIP recommends adolescent vaccination for tetanus, diphtheria and pertussis vaccine. Available at: www.cdc.gov/nip/pr/pr_tdap_jun2005.htm. Accessed June 30, 2005.

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