Pertussis vaccine for adolescents?

April 2005

There has been increased interest here in the United States in immunizing adolescents against pertussis. The impetus for this has been the rise in the number of cases of pertussis reported in the past decade in this age group. In addition to the morbidity pertussis produces in adolescents and is projected to cause even in older individuals (Clin Infect Dis. 2004;39:20), it also is a source of infection for younger children and infants (JAMA. 2003;290:2968). There also has been an increase in cases in the first year of life, when the risk of death or hospitalization is greatest (JAMA. 2003;290:2968). It is postulated that increasing immunity of potential mothers may confer protection on their newborns, which might prevent pertussis in those too young to be immunized.

During the 1990s, the rates of pertussis in those younger than 2 months of age increased from 72 to 107 per 100,000, and for those younger than 4 months, from 63 to 89 per 100,000 as compared with the rates in the ’80s. The number of deaths during the two decades increased from 61 to 93 per 100,000 (JAMA. 2003;290:2968).

The Hawthorne effect

However, there are some that question what would be gained by an adolescent immunization program (Clin Infect Dis. 2004;39:29). Even if it were found to have merit, there would be major hurdles to surmount in implementing it given the difficulty in accessing this group. Although the increase in pertussis in the newborn is credible, there is some concern about the reported rise in cases in the older groups.

Both figures may have increased by the “Hawthorne effect,” ie, when you measure something you influence the results. As we are told the problem is getting worse, we start looking for cases. The number of cultures for pertussis obtained within 10 days of onset rose from 40% to 78% between 1994 and 1996 in the state of Massachusetts (J Infect Dis. 1999;28:1230).

To what extent of these increases represent a Hawthorne effect is difficult to discern. One might simply compare the rates of infection by testing sera collected from adults at the present time and a similar group collected 10 or 20 years ago. That is, if one knows what to measure. Many would choose antibody against pertussis toxin, which apparently is less likely to result from cross-reacting antibody from related bacteria and has a shorter half-life than some of the other pertussis antibodies (Vaccine. 2003,21:3442 ; J Infect Dis. 2004; 190:535).

Neither the CDC nor WHO accepts any serologic test as acceptable criterion for confirming the diagnosis of pertussis.

It is likely that some of the apparent increase in cases, particularly in older individuals, from whom isolation of the organism is more difficult, may be due to the increased popularity of serologic tests. These have become more popular coincident with the rise in incidence during the past decade. The increase in reported cases in older individuals has been weighted by the reporting from a few states, at least one of which has relied heavily on serologic diagnosis (J Infect Dis. 1999;28:1230).

Despite the caveat about relying on antibody measurements, some have used these to promote particular pertussis vaccines over others. The FDA, in a letter to all vaccine manufacturers in 1998, has warned that there are “no clinical data on file that would support any claim or suggestion of clinical superiority or benefit regarding the numbers of combinations of pertussis antigens contained in the DTaP vaccines.” Serologic data have been used to support the use of booster doses in adolescents (J Infect Dis. 2004;190:535), although the licensure of the acellular pertussis vaccines had been based on clinical trials because of the lack of serologic correlates of protection. Several other countries have adolescent pertussis immunization programs, and perhaps, it would be prudent to just wait and see what is accomplished in these countries.

How much protection?

It is unclear if protection would be conferred on adolescent vaccinees or the duration of such protection and how much would be conferred on their babies. Based on serologic studies, it is estimated that immunoglobulin G (IgG) antibody will remain “above threshold” for four to 13 years. It appears, however, that this “threshold” is defined as “the lower limit of the precision of the assay” rather than the protective titer (J Infect Dis. 2004;190:535). IgG antibody is transmitted to infants, but how much protection this would confer in actual terms, given the uncertainty about the protective effects of various antibodies, the persistence of passively acquired antibody and the levels of maternal antibody at the time of gestation, are all unknown.

It is important that we address the problem of adolescent health care. There are vaccines that may be useful in this group, including those against meningococci, human papillomaviruses and pertussis. Immunization of babies has been credited by some as bringing them into the medical care system, and perhaps, this can be accomplished for adolescents. We certainly can do a better job of addressing the health problems of this group than we are doing at the present time. Finally, it may be a propitious time for vaccine producers to develop a better pertussis vaccine than we now have rather than trying to repackage the existing vaccine. Of the components of diphtheria-tetanus-pertussis vaccine, the latter has done the least to eliminate disease. Alternative approaches using existing vaccines, eg, immunization of adolescents, pregnant woman or newborns, have their proponents, but all have significant drawbacks.

For more information:

• Purdy KW, Hay JW, Botteman MF, Ward JI. Evaluation of strategies for use of acellular pertussis vaccine in adolescents and adults: a cost-benefit analysis. Clin Infect Dis. 2004;39:20-28.
• Tanaka M, Vitek CR, Pascual FB. Trends in pertussis among infants in the United States, 1980-1999. JAMA. 2003;290:2968-2975.
• Balcewicz-Sablinska MK, Gan H, Remold HG. Interleukin 10 produced by macrophages inoculated with Mycobacterium avium attenuates mycobacteria-induced apoptosis by reduction of TNF-alpha activity. J Infect Dis. 1999;180:1230-1237.
• Vandelaer J, Birmingham M, Gasse F, et al. Tetanus in developing countries: an update on the Maternal and Neonatal Tetanus Elimination Initiative. Vaccine. 2003;21:3442-3445.
• Le T, Cherry JD, Chang SJ, et al. Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study. J Infect Dis. 2004;190:535-544.

Editor’s Note: My colleague, Dr. Brunell, is a bit cautious about pertussis vaccine in adolescents. When it becomes available I will vigorously promote use of this vaccine in adolescents and young adults. — Theodore C. Eickhoff, MD