Correspondence

The 1993 Pertussis Epidemic in Cincinnati

N Engl J Med 1994; 331:1455-1456November 24, 1994

Article

To the Editor:

Christie and colleagues (July 7 issue)1 document the effect of the 1993 pertussis outbreak in Cincinnati and suggest that the proportion of cases in fully vaccinated children provides evidence of “the failure of the whole-cell pertussis vaccine.” However, their data prove only that pertussis vaccine is not 100 percent effective and that outbreaks of disease can occur in highly vaccinated populations. In outbreaks of any disease that can be prevented by vaccination, the proportion of cases in people who have been vaccinated will depend on both the efficacy of the vaccine and the vaccination coverage of the exposed population. For example, if 1000 children receive a vaccine that is 90 percent effective, 100 children will be fully vaccinated yet still susceptible. Should an outbreak of disease occur in such a population, 100 percent of the children will have a history of vaccination, yet 90 percent of the vaccinated children will be protected from disease.

The efficacy of the pertussis vaccine in Cincinnati may in fact have been quite high, if the data on vaccination coverage from a 1993 survey of 576 nursery-school children who had not previously attended day-care programs (predominantly middle-class children, like the majority of those affected by the outbreak) are representative of the population in which the outbreak occurred. The survey, conducted by the Cincinnati Health Department, showed that by 24 months of age, 4 children (0.7 percent) had received no doses of the diphtheria-pertussis-tetanus (DPT) vaccine, 10 (1.7 percent) had received one or two doses, and 562 (97.6 percent) had received three or more doses.

Christie et al. report that 86.4 percent of the children with pertussis who were 19 to 71 months old had received three doses or more of DPT vaccine. With the use of the screening equation VE = [(PPV - PCV) / PPV(1 - PCV)] × 100,2,3 where VE is the efficacy of the vaccine, PPV is the proportion of the population vaccinated, and PCV is the proportion of people with cases of infection who have been vaccinated, and with partially vaccinated people excluded from both PPV and PCV, the efficacy of three doses of DPT vaccine is 90.9 percent. Published estimates of the efficacy of the pertussis vaccine range from approximately 60 percent, for protection against mild disease, to more than 90 percent, for protection against severe disease.4,5

Data from all cases of pertussis in the United States reported to the Centers for Disease Control and Prevention (CDC) in 1993 indicate that 59.3 percent of children one to four years of age had received at least three doses of DPT vaccine, and 19.6 percent had received no doses. According to data from the National Health Interview Survey, an estimated 88.6 percent of children one to four years of age received three or more doses of DPT or diphtheria-tetanus (DT) vaccine, and 4.1 percent received no doses. On the basis of vaccine-distribution data, up to 6.7 percent of children received DT instead of DPT vaccine. The corresponding range of efficacy for the pertussis vaccine by the screening method is 60 to 86 percent. National data for 1993 continue to demonstrate that pertussis is milder in vaccinated children than in unvaccinated children (Table 1Table 1. 19931993 Data on Vaccination Status and Severity of Pertussis among Children Seven Months to Four Years of Age.).

Despite the resurgence of pertussis in 1993, the provisionally reported incidence of 2.5 cases per 100,000 population represents a 98 percent reduction in the incidence before the vaccine was available. Experience in countries such as the United Kingdom, Japan, and Sweden in the late 1970s shows that failure to vaccinate children against pertussis results in a significant increase in morbidity and mortality from this disease.6 The best strategy continues to be timely vaccination of infants and young children with available pertussis vaccines.

Iain R.B. Hardy, M.B., Ch.B., M.P.H.
Peter M. Strebel, M.B., Ch.B., M.P.H.
Melinda Wharton, M.D., M.P.H.
Walter A. Orenstein, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333

6 References

1. 1

   Christie CDC, Marx ML, Marchant CD, Reising SF. The 1993 epidemic of pertussis in Cincinnati -- resurgence of disease in a highly immunized population of children. N Engl J Med 1994;331:16-21
   Full Text | Web of Science | Medline

2. 2

   Orenstein WA, Bernier RH, Dondero TJ, et al. Field evaluation of vaccine efficacy. Bull World Health Organ 1985;63:1055-1068
   Web of Science | Medline

3. 3

   Orenstein WA, Bernier RH, Hinman AR. Assessing vaccine efficacy in the field: further observations. Epidemiol Rev 1988;10:212-241
   Web of Science | Medline

4. 4

   Fine PE, Clarkson JA. Reflections on the efficacy of pertussis vaccines. Rev Infect Dis 1987;9:866-883
   CrossRef | Medline

5. 5

   Onorato IM, Wassilak SG, Meade B. Efficacy of whole-cell pertussis vaccine in preschool children in the United States. JAMA 1992;267:2745-2749
   CrossRef | Web of Science | Medline

6. 6

   Cherry JD, et al. Report of the task force on pertussis and pertussis immunization -- 1988. Pediatrics 1988;81:939-984
   

Author/Editor Response

The authors reply:

To the Editor: In the 1993 epidemic of pertussis in Cincinnati, there was an increase in cases of pertussis and a shift in the distribution of cases toward older, fully immunized children, as compared with the pattern of the previous 14 years.1 This change in the epidemiology of pertussis should alert public health authorities, regulatory officials, and vaccine manufacturers to the possibility that the efficacy of the vaccine may have declined. In the strict sense, pertussis vaccine failed to protect these immunized children, as we discuss in our report in the Journal and elsewhere.1 This failure may have resulted from a decline in the efficacy of whole-cell pertussis vaccine, or it may merely represent expected failures with intense exposure to pertussis without a decline in the efficacy of the vaccine. Our report in the Journal addressed these issues, which are raised again by Hardy and his colleagues from the CDC.

Although we agree that the efficacy of whole-cell pertussis vaccine may not have declined, we cannot agree with the analysis of vaccine efficacy proposed by Hardy and his colleagues for several reasons. First, the vaccination rate for children at Cincinnati day-care centers (97 percent of the children received three or more doses of DPT) are extremely high, perhaps because immunization was required or strongly encouraged in these settings. These data are not representative of the Cincinnati population as a whole.

Second, the “screening” equation, VE = [(PPV-PCV)/PPV(1-PCV)] × 100, will exaggerate the efficacy of the vaccine if there is even a small overestimate of the proportion of the population that has been vaccinated, which is above 80 percent. The screening method should probably not be used when the proportion of the population vaccinated is high and the estimate is not obtained by representative-sampling methods.

More important, calculated estimates of the efficacy of pertussis vaccine vary widely according to the intensity of exposure, case ascertainment, study design, diagnostic methods, definition of disease, time since immunization, and so forth.2 These factors vary so widely that comparisons of protective-efficacy rates in different populations and at different times are of questionable validity. These factors need to be controlled for in a single comparative study. The estimate of 90.9 percent efficacy calculated by Hardy et al. may not be accurate and cannot be reliably compared with published estimates.

Finally, a pertussis epidemic in one or a few communities and a modest increase in reported cases in the nation as a whole are insufficient evidence that a change in the policy on vaccination is warranted. We agree with Hardy and colleagues that the best strategy continues to be timely vaccination of infants with whole-cell pertussis vaccine.

(The views expressed in this letter are those of the authors and do not reflect the policies of the Department of Public Health of the Commonwealth of Massachusetts.)

Celia D.C. Christie, M.D.
Shirley F. Reising, Ph.D.
Children's Hospital Medical Center, Cincinnati, OH 45229

Colin D. Marchant, M.D.
Tufts University School of Medicine, Boston, MA 02130

2 References

1. 1

   Hardy IR, Hoekstra E, Wells V, et al. Large pertussis outbreak, Cincinnati, 1993: high attack rate among vaccinated preschool children. In: Abstracts of the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, Fla., October 4-7, 1994. Washington, D.C.: American Society for Microbiology, 1994. abstract.
   

2. 2

   Fine PE, Clarkson JA. Reflections on the efficacy of pertussis vaccines. Rev Infect Dis 1987;9:866-883
   CrossRef | Medline

Citing Articles (4)

Citing Articles

1. 1

   Andrew L. Baughman, Kristine M. Bisgard, Freyja Lynn, Bruce D. Meade. (2006) Mixture model analysis for establishing a diagnostic cut-off point for pertussis antibody levels. Statistics in Medicine 25:17, 2994-3010
   CrossRef

2. 2

   Edward Mills, Alejandro R. Jadad, Cory Ross, Kumanan Wilson. (2005) Systematic review of qualitative studies exploring parental beliefs and attitudes toward childhood vaccination identifies common barriers to vaccination. Journal of Clinical Epidemiology 58:11, 1081-1088
   CrossRef

3. 3

   Edward J. Mills, Victor M. Montori, Cory P. Ross, Beverly Shea, Kumanan Wilson, Gordon H. Guyatt. (2005) Systematically reviewing qualitative studies complements survey design: An exploratory study of barriers to paediatric immunisations. Journal of Clinical Epidemiology 58:11, 1101-1108
   CrossRef

4. 4

   THOMAS A. KENYON, HECTOR IZURIETA, STANFORD T. SHULMAN, ELAINE ROSENFELD, MELANIE MILLER, ROBERT DAUM, PETER M. STREBEL. (1996) Large outbreak of pertussis among young children in Chicago, 1993: investigation of potential contributing factors and estimation of vaccine effectiveness. The Pediatric Infectious Disease Journal 15:8, 655-661
   CrossRef