Kristine M. Bisgard

BACKGROUND: In the United States in the 1990s, the incidence of reported pertussis in adults, adolescents and infants increased; infants younger than 1 year of age had the highest reported incidence. METHODS: In 4 states with Enhanced Pertussis Surveillance, we examined the epidemiology of reported pertussis cases to determine the source of pertussis among infants. A source was defined as a person with an acute cough illness who had contact with the case-infant 7-20 days before the infant's onset of cough. RESULTS: The average annual pertussis incidence per 100,000 infants younger than 1 year of age varied by state: 22.9 in Georgia; 42.1 in Illinois; 93.0 in Minnesota; and 35.8 in Massachusetts. Family members of 616 (80%) of 774 reported case-infants were interviewed; a source was identified for 264 (43%) of the 616 case-infants. Among the 264 case-infants, mothers were the source for 84 (32%) and another family member was the source for 113 (43%). Of the 219 source-persons with known age, 38 (17%) were age 0-4 years, 16 (7%) were age 5-9 years, 43 (20%) were age 10-19 years, 45 (21%) were age 20-29 years and 77 (35%) were age > or =30 years. CONCLUSIONS: The variation in reported pertussis incidence in the 4 states might have resulted from differences in awareness of pertussis among health care providers, diagnostic capacity and case classification. Among case-infants with an identifiable source, family members (at any age) were the main source of pertussis. Understanding the source of pertussis transmission to infants may provide new approaches to prevent pertussis in the most vulnerable infants.

Most studies are unable to follow nonrespondents prospectively to determine whether their disease rates are comparable with those of the respondents. The authors followed respondents and nonrespondents to a mailed questionnaire, sent to a random sample of Iowa women aged 55-69 years in 1986 (total sample, 98,029; 43% response), to characterize 5-year mortality rates for myocardial infarction and all causes, and attack rates for breast, endometrial, colon, lung, and all-site cancers. Compared with respondents, nonrespondents had higher myocardial infarction (1.47 vs. 0.93 per 1,000 person-years) and all-cause (12.32 vs. 7.89 per 1,000 person-years) mortality. They also had substantially higher attack rates for lung cancer (1.45 vs. 1.10 per 1,000 person-years), and slightly higher attack rates for all-site cancer (11.86 vs. 10.89 per 1,000 person-years). The associations of reported body mass index (weight/height2) with the study endpoints were generally similar among respondents and the total eligible sample, except for a more pronounced U-shaped total mortality association for the nonrespondents. Thus, although the occurrence of several diseases, especially those related to smoking, differed among respondents and nonrespondents, the association of body mass index with cancer occurrence was not appreciably affected by nonresponse bias.

Numerous reports have documented that serologic methods are much more sensitive than culture for the diagnosis of pertussis in adolescents and adults. However, a standardized serologic test for pertussis is not routinely available to most clinicians, and the serologic test levels or cutoff points correlated with diseases have not been determined. The goal of the present study was to examine the distribution of immunoglobulin G (IgG) levels against three Bordetella pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin [FHA], and fimbria types 2 and 3 [FIM]) and to determine population-based antibody levels for the purpose of establishing such diagnostic cutoff points. Enzyme-linked immunosorbent assays (ELISAs) were performed with sera from >6,000 U.S. residents aged 6 to 49 years who participated in the Third National Health and Nutrition Examination Survey. Mixture models were developed to identify hypothesized exposure groups and establish diagnostic cutoffs. Quantifiable (>20 ELISA units/ml [EU]) anti-FHA and anti-FIM IgG antibodies were common (65 and 62% of individuals, respectively), but quantifiable anti-PT IgG antibodies were less frequent (16%). Given the distributions of antibody levels, an anti-PT IgG level of > or =94 EU was proposed as the diagnostic cutoff point. Application of this cutoff point to culture-confirmed illness in a prior study investigating cough illness yielded a high diagnostic sensitivity (80%) and specificity (93%). A standardized ELISA for anti-PT IgG with a single serum sample appears to be useful for the identification of recent B. pertussis infection in adolescents and adults with cough illness. The PT cutoff point will be further evaluated in prospective studies of confirmed B. pertussis infection.

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; >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 > or =2 nights per week, and cough illness of > or =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 > or =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) x 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 > or =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 > or =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 < or =13 months), compared with children who received dose 4 at an older age (age of > or =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 (> or =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 (< or =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 > or =2 weeks (87 [52%] of 168 case subjects, compared with 79 [8%] of 860 control subjects). CONCLUSIONS: Any combination of > or =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 > or =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.

To elucidate the potential role of the etiologic agent in recent increases of pertussis incidence in the United States, we studied the polymorphism in pertactin and pertussis toxin, which are Bordetella pertussis proteins important for pathogenesis and immunity. We sequenced regions of their genes (prn and ptx) in 152 B. pertussis strains isolated from 1935 through 1999 and identified 2 prn sequences: prn1 (old), observed continuously since 1935, and prn2 (new), not recognized until 1981 but seen in 97% of tested isolates in 1999. There were 3 ptx S1 subunit sequences: ptxS1D (old) was identified in 3 strains (1935 and 1939); ptxS1B (old) represented 87% of the strains recovered during 1935-1974; and ptxS1A (new) was the most prevalent during 1975-1987 and 1989-1999 (64% and 78%, respectively). Potential association between vaccination and the observed shift from old to new types requires further study. Our results provide the basis for prospectively monitoring for changes among circulating B. pertussis that might have epidemiologic relevance.