PEDIATRICS Vol. 116 No. 4 October 2005, pp. 1056 (doi:10.1542/peds.2005-1724)
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Cherry Picking
Philip Brunell, MS, MDChevy Chase, MD 20815
To the Editor.—
Dr Cherry1 has presented a case supporting the immunization of teenagers against pertussis based on his belief that the acellular pertussis (aP) vaccines now in use are less protective that the whole-cell vaccines that they replaced. He supports the use of aP to boost immunity in teenagers who, for a variety of reasons, have had an increase in pertussis in the recent past.
In 1982, Fine and Clarkson2 described the triennial cycling of pertussis and proposed that the perpetuation of this cycling was due to the relatively poor ability of the vaccine to prevent transmission while it was quite effective in reducing clinical disease. They postulated that the protective antibodies that prevented attachment and infection were short lived, whereas the ones preventing disease were longer lasting. Therefore, the disease diminished, but the organism continued to circulate even in a highly vaccinated population. Thus, Dr Fine is somewhat skeptical of our efforts to interrupt this cycle by teen immunization.3 If he were correct, it would require an intensive continuing program of immunization of teenagers and probably adults. Our record of reaching these groups in the past has been very poor.
Most of the increase in pertussis reported in recent years has been in teenagers and adults, although there has been a rise in young infants as well. Part of the increase in numbers can be attributed to the growth in population from 
190 million in 1970 to 295 million at the present time. The increase in the rate in infants, however, cannot be attributed directly to population growth. A large portion of population growth has been a result of immigration. The exact number is not known, but it is estimated that 11% of our present population was born abroad. Many of these adults and children are poorly immunized. From 1997 to 1999, 29% of cases in which the ethnicity of infant cases was identified were Hispanic. In the 4 states with the most Hispanic populations, the rate of pertussis was 68 per 100000 and 39 per 100000 for Hispanic and non-Hispanic populations, respectively.4
That there has been an increase in cases reported is clear. Many share Dr Cherry's view that some of the increase is the result of more intensive efforts to find cases. From 1981 to 1991, the number of culture specimens tested by the Massachusetts state laboratory increased from 160 to 1087 (P < .001). During this time the percent positive declined significantly (P < .007).5 The increase in cases in older groups has undoubtedly been stimulated by the use of serological diagnosis. Dr Cherry's own test1 is based on one developed by Charles Manclark at the US Food and Drug Administration; yet, the Food and Drug Administration has not seen fit to license this or any serological test for the diagnosis of pertussis. Nor is serological confirmation of pertussis acceptable by the Centers for Disease Control and Prevention, with 1 exception. Clinically compatible cases confirmed by serological testing in the Massachusetts state laboratory in those >11 years of age are acceptable. With this assay they reported that only 63% of culture-proven cases in this age group could be confirmed serologically.5 Thus, it is difficult to assess the significance of this increase in reported cases. It is of interest that many countries that give only 3 or 4 doses of pertussis vaccine have not reported increases in cases in pertussis. Are they not looking?
It is likely that much of the variation in reports of the frequency of adult pertussis cited by Dr Cherry1 is caused by differences in the laboratory tests used. The most carefully performed study done prospectively by Ward and his group6 in Los Angeles, California, reported a rate of "serologic evidence of infection" of 500 per 100000 person years, the vast majority of which were not accompanied by symptoms. It is of interest that the efforts to evaluate an aP vaccine in this population based on the number of cases projected from previous estimates of pertussis frequency in the adult population has been frustrated by the paucity of cases.
Dr Cherry selects 2 studies to support the contention that currently used aP vaccines are less effective than whole-cell pertussis (wP) vaccines. One compares a wP vaccine manufactured in Germany with an aP vaccine used in the United States. In this study, 52% and 72% of the aP and wP recipients, respectively (P = .006), received erythromycin prophylaxis at the time of exposure, which could account for the attenuation of disease in many of the wP recipients. Yet, the confidence limits in this unblinded study were overlapping.7 In the second study, in which parents chose whether their children would receive a Japanese aP vaccine similar to one used in the United States or a German wP vaccine, the efficacy was nearly identical using the World Health Organization case definition: 96% and 97%, respectively.8 A more relevant comparison would be between an American wP vaccine used in the United States when these adolescents were immunized as infants with the aP vaccine. One of the 2 wP vaccines used at this time was 30% effective as compared to placebo and far less effective than the aP vaccine.9 The poor efficacy of this wP vaccine and the reluctance of some parents and physicians to use these reactive wP vaccines might account for some of the increase in cases in this age group at the current time. Compared to the number of cases prevented by the other components of diphtheria-tetanus-aP, pertussis is a very poor vaccine. Cases of pertussis now are counted in the tens of thousands annually, whereas cases of diphtheria are almost nonexistent and cases of tetanus are counted in the dozens. Rather than relying on increased utilization of a relatively poor vaccine, we should insist that efforts be increased to develop reliable diagnostic tools, defining protective correlates, and increasing our understanding of this infection. Most important, we need to develop a better pertussis vaccine. It has been more than a quarter of a century since the Japanese gave us acellular vaccines; is it not time that we develop a better one? Fine caustically concluded his splendid article "Adult Pertussis: A Salesman's Dream—And an Epidemiologist's Nightmare" with "The decision to introduce a vaccine intervention should rest not on a salesman's need to market a product but on solid epidemiological evidence that such an introduction is justified as a cost-worthy investment."3
We have now embarked on a program of boosting teenagers. If this is to be successful, it will require a major effort to immunize as many as possible. It seems that this group will be targeted for additional vaccines still in development as well as the meningococcal vaccine. It is hoped that the increased contacts afforded by immunization will be seized as opportunities to address the many significant health problems of adolescents similar to that afforded by immunization of infants and children.
REFERENCES
- Cherry J. The epidemiology of pertussis: a comparison of the epidemiology of the disease pertussis with the epidemiology of Bordetella pertussis infection.
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[Abstract/Free Full Text] - Fine PE, Clarkson JA. The recurrence of whooping cough: possible implications for assessment of vaccine efficacy. Lancet. 1982;1 (8273):666–669
- Fine PE. Adult pertussis: a salesman's dream—and an epidemiologist's nightmare. Biologicals. 1997;25 :195 –198[Medline]
- Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, Murphy TV. Trends in pertussis among infants in the United States, 1980–1999.
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[Abstract/Free Full Text] - Marchant CD, Loughlin AM, Dett SM, et al. Pertussis in Massachusetts, 1981–1991: incidence, serologic diagnosis, and vaccine effectiveness. J Infect Dis. 1994;169 :1297 –1305[Web of Science][Medline]
- Purdy KW, Hay JW, Botteman MF, Ward JI. Evaluation for strategies for use of acellular pertussis vaccine in adolescents and adults: a cost-benefit analysis. Clin Infect Dis. 2004;39 :20 –28[CrossRef][Web of Science][Medline]
- Schmitt HJ, Wirsing von Konig CG, Neiss A, et al. Efficacy of acellular pertussis vaccine in early childhood after household exposure.
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[Abstract/Free Full Text] - Liese JG, Meschievits CK, Harzer E, et al. Efficacy of a two-component acellular pertussis vaccine in infants. Pediatr Infect Dis J. 1997;16 :1038 –1044[CrossRef][Web of Science][Medline]
- Greco D, Salmaso S, Mastrantonio P, et al. A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group.
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[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics
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