An increasing number of pertussis outbreaks have occurred in populations with a high rate of vaccination. The presentation of pertussis is less severe in vaccinated persons than it is in unvaccinated persons, leading to underestimation and misdiagnosis of cases. Tozzi and colleagues investigated the presentation of pertussis in vaccinated and unvaccinated children to identify additional determinants of the severity of the disease.
The trial was conducted in three phases. Stage 1 included children six to 24 months of age who were randomized in double-blind fashion to receive diphtheria-tetanus (DT) or diphtheria-tetanus-acellular pertussis (DtaP) vaccine. Two acellular pertussis vaccines were used: Smithkline Beecham (SB) and Chiron Biocine (CB). Stage 2 followed randomized patients from 25 to 33 months; in this stage, parents were unblinded. Stage 3 included newly recruited children 34 months to six years of age who had not received the pertussis vaccine. Laboratory-confirmed pertussis cases were identified in the study population and examined.
A total of 788 cases of pertussis were confirmed during the three trial stages. The proportion of children with spasmodic cough was consistently higher in the DT group than in the DTaP group except in stage 2, when children who received the DT vaccine had more spasmodic cough than children who received only the DTaP-CB vaccine. Apnea, cyanosis, and vomiting were higher in the DT group than in the DTaP group in stages 1 and 2. Duration of spasmodic cough decreased greatly in stage 3 within each vaccine group. DTaP reduced cough duration by eight to 10 days in stage 1. A positive culture was associated with longer duration of cough and spasmodic cough. Compared with untreated patients, patients who took antibiotics had an additional five to six days of cough. The number of hospitalizations and emergency department visits were similar by vaccine group.
This study provides the only available results comparing the clinical course of pertussis in vaccinated and unvaccinated children. The results confirm that vaccination status significantly changes the clinical presentation of disease and that pertussis is more severe in unvaccinated children. Because the DTaP-SB vaccine lacked a significant effect in reducing the duration of cough in stage 2 and the rate of spasmodic cough in stage 3, this vaccine may be less effective in reducing symptoms than other vaccines, notably the CB vaccine used in this study.
Culture-confirmed pertussis, which occurred more frequently in the DT group, was associated with more severe symptoms at presentation. Antibiotic treatment in this study was a marker for severe disease, but the study was not designed to evaluate antibiotic efficacy. Sex had no influence on severity of disease, and age influenced duration of spasmodic cough but not duration of cough per se. Because vaccination attenuates the clinical presentation of pertussis, a more sensitive case definition than spasmodic cough of two weeks should be adopted in vaccinated populations.
Overall, it is likely that the incidence of pertussis is underestimated, which may be important because early treatment with antibiotics could improve the course of the disease and reduce transmission.