Andrew L. Baughman

TO THE EDITOR—Ward et al. [1] analyzed serologic data from a large group of subjects who were followed-up prospectively, had known vaccination status, and were tested for all major pertussis antigens. The authors concluded that the Bordetella pertussis infection rate among 1228 subjects aged 15–65 years who had not been recently vaccinated was ∼1% over an 11-month period on the basis of significant increases in serum antibody titers to pertussis toxin (PT). The reported range in estimates (0.4%–2.7%) was based on increases in titers of antibodies to other pertussis antigens. The PT-based rate of ∼1% is at the low end of the range of PT-based incidence estimates reported in the 4 other serologic studies referenced in the article by Ward et al. [1]. These studies reported PT-based annual incidence estimates of ∼1% [2, 3], 2.2% [4], 3.3% [5], and 8% [6]. However, the studies used different sample populations, sample sizes, and laboratory methodology, all of which could influence the magnitude of the annual estimates.

Previous studies of pertussis (whooping cough) that have derived diagnostic cut‐off points for pertussis antibody levels have assumed a single distribution for antibody levels and have used small sample sizes. In a recent study of 5409 serum samples from the Third National Health and Nutrition Examination Survey (NHANES III), a finite mixture model was developed to examine the distribution of immunoglobulin G (IgG) antibody levels against pertussis toxin (PT), an antigen specific to the Bordetella pertussis bacterium. The mixture model identified three component populations with antibody levels greater than the quantitative assay's lower limit of quantitation (LLQ) and included a point distribution located at or below the LLQ to account for the excess number of antibody values that fell below the LLQ. The mixture model analysis accounted for the NHANES III design. A cut‐off point for anti‐PT IgG levels was chosen to have a 99 per cent model specificity based on the two overlapping normal distributions assumed for the two component populations with the highest antibody levels. This cut‐off point may have a higher diagnostic sensitivity for acute B. pertussis infection than other cut‐off points derived by assuming a single distribution for antibody levels. Published in 2005 by John Wiley & Sons, Ltd.

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 ≥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.