Pertussis Vaccine Effectiveness Among Children 6 to 59 Months of Age in the United States, 1998–2001
Authors: Bisgard Kristine M. , Rhodes Philip , Connelly Beverly L. , Bi Daoling , Hahn Christine , Patrick Sarah , Glodé Mary P. , Ehresmann Kristen R. ,   and the Pertussis Investigation Team
Published: August 2005

Background. Despite the dramatic pertussis decrease since the licensure of whole-cell pertussis (diphtheria-tetanus toxoids-pertussis [DTP]) vaccines in the middle 1940s, pertussis remains endemic in the United States and can cause illness among persons at any age; &gt;11000 pertussis cases were reported in 2003. Since July 1996, in addition to 2 DTP vaccines already in use, 5 acellular pertussis (diphtheria-tetanus toxoids-acellular pertussis [DTaP]) vaccines were licensed for use among infants; 3 DTaP vaccines were distributed widely during the study period. Because of the availability of 3 DTaP and 2 DTP vaccines and the likelihood of the vaccines being used interchangeably to vaccinate children with the recommended 5-dose schedule, measuring the effectiveness of the pertussis vaccines was a high priority.
Objective. To measure the pertussis vaccine effectiveness (VE) among US children 6 to 59 months of age.
Design. We conducted a case-control study in the Cincinnati, Ohio, metropolitan area, Colorado, Idaho, and Minnesota.
Participants. Confirmed pertussis cases among children 6 to 59 months of age at the time of disease onset, with onset in 1998–2001, were included. For each case subject, 5 control children were matched from birth certificate records, according to the date of birth and residence.
Outcome Measures. A standardized questionnaire was used to obtain vaccination data from parents and providers. Parents/guardians were asked about demographic characteristics, child care attendance, the number of household members who stayed at the same home as the enrolled child for ≥2 nights per week, and cough illness of ≥2-week duration among these household members in the month before the case patient's cough onset. Pertussis vaccine doses among case children were counted as valid if they were received ≥14 days before the cough onset date (“valid period”). The age of the case patient (in days) at the end of the valid period was determined, and doses of vaccine for the matched control subjects were counted as valid if they were received by that age. Conditional logistic regression models were used to estimate the matched odds ratios (ORs) for pertussis according to the number of pertussis vaccine doses. The VE was calculated with the following formula: (1 − OR) × 100. Because the pertussis antigen components or amounts differed according to vaccine, the VE of 3 or 4 doses of DTP and/or DTaP was estimated according to the recorded vaccine manufacturer and vaccine type.
Results. All enrolled children (184 case subjects and 893 control subjects) had their vaccine history verified. The proportions of children who received 0, 1 or 2, 3, and ≥4 pertussis (DTP and/or DTaP) vaccine doses among case subjects were 26%, 14%, 26%, and 34% and among control subjects were 2%, 8%, 33%, and 57%, respectively. Compared with 0 doses, the unadjusted VE estimate for 1 or 2 pertussis doses was 83.6% (95% confidence interval [CI]: 61.1–93.1%), that for 3 doses was 95.6% (95% CI: 89.7–98.0%), and for ≥4 doses was 97.7% (95% CI: 94.7–99.0%). Among children who received 4 pertussis vaccinations, the risk of pertussis was slightly higher among those who received only 1 type of vaccine (either 4 DTP doses or 4 DTaP doses), compared with those who received a combination of DTP for doses 1 to 3 and DTaP for dose 4 (OR: 2.4; 95% CI: 1.1–5.2). Among children who received 3 or 4 DTaP vaccine doses, the risk of pertussis was slightly higher among those who received a DTaP vaccine with 4 pertussis antigen components (a vaccine no longer available), compared with those who received the DTaP vaccine with 2 pertussis antigen components (OR: 2.5; 95% CI: 1.1–5.8). Among children who received 4 doses, the risk of pertussis was 2.7 times higher for children who received dose 4 early (age of ≤13 months), compared with children who received dose 4 at an older age (age of ≥14 months) (95% CI: 1.1–6.8). For children 6 to 23 months of age, features of household structure were significant risk factors for pertussis. In a multivariate model, compared with living with an older parent (≥25 years of age), not living with an “other” household member (a relative other than a parent or sibling or a nonrelated person), and not living with a sibling 6 to 11 years of age, the risk of pertussis for children 6 to 23 months of age was 6.8 times higher if they lived with a young parent (≤24 years of age) (95% CI: 3.1–15.0), 2.5 times higher if they lived with an “other” household member (95% CI: 1.2–5.4), and 2.2 times higher if they lived with a sibling 6 to 11 years of age (95% CI: 1.2–4.3). Adjusting for these risk factors did not change the VE. Compared with control children, case children were significantly more likely to live with a household member (representing all age groups and relationships) who reported a recent cough illness with duration of ≥2 weeks (87 [52%] of 168 case subjects, compared with 79 [8%] of 860 control subjects).
Conclusions. Any combination of ≥3 DTP/DTaP vaccine doses for children 6 to 59 months of age was highly protective against pertussis. However, there were differences according to vaccine type (DTaP or DTP) and DTaP manufacturer. Among children who received 4 pertussis vaccine doses, a combination of 3 DTP doses followed by 1 DTaP dose had a slightly higher VE than other combinations; among children who received 3 or 4 DTaP vaccine doses, 1 DTaP vaccine performed less well. The finding that pertussis dose 4 was more effective when given to children at ≥14 months of age might be confounded if health care providers were more likely to vaccinate children at 12 months of age because of a perceived risk of undervaccination and if these same children were also at higher risk for pertussis. Household members of any age group and relationship could have been the source of pertussis, and household structure was associated with risk for pertussis for children 6 to 23 months of age. In contrast to control children in the study, 26% of case children had never been vaccinated against pertussis. Unvaccinated children are at risk for pertussis and, in a community with other unvaccinated children, can lead to community-wide pertussis outbreaks. Parents need to be educated about the morbidity and mortality risks associated with Bordetella pertussis infection, and they need to be encouraged to vaccinate their children against pertussis on time and with the recommended number of vaccine doses for optimal protection.