Specificity and sensitivity of high levels of immunoglobulin G antibodies against pertussis toxin in a single serum sample for diagnosis of infection with Bordetella pertussis

Abstract

Laboratory confirmation of pertussis by culture, PCR, or detection of antibody increase in paired sera is hampered by low sensitivity in the later stages of the disease. Therefore, we investigated whether, and at which level, concentrations of immunoglobulin G (IgG) antibodies against pertussis toxin (PT), IgG-PT, in a single serum sample are indicative of active or recent pertussis. IgG-PT, measured by enzyme-linked immunosorbent assay in units per milliliter, was analyzed in 7,756 sera collected in a population-based study in The Netherlands, in the sera of 3,491 patients with at least a fourfold increase of IgG-PT, in paired sera of 89 patients with positive cultures and/or PCR results, and in the sera of 57 patients with clinically documented pertussis with a median follow-up of 1.4 years. We conclude that, independently of age, IgG-PT levels of at least 100 U/ml are diagnostic of recent or active infection with Bordetella pertussis. Such levels are present in less than 1% of the population and are reached in most pertussis patients within 4 weeks after disease onset and persist only temporarily.

FIG. 1

IgG-PT distribution in the population-based study and in pertussis patients (second sera) with at least a fourfold increase in IgG-PT level in paired sera. Results for the population-based study are given in shaded bars, and results for second sera of pertussis patients are given in open bars; the total numbers of individuals/patients are given beside the bars.

FIG. 2

IgG-PT levels (in ²log U/ml) versus time elapsed (in ²log days) since date of onset for 57 patients with clinical pertussis.

FIG. 3

IgG-PT distribution in the first and second serum samples of patients with a positive culture and/or PCR for B. pertussis. White circles indicate sera with at least a fourfold increase in IgG-PT to a level of at least 20 U/ml. Black circles indicate sera without a fourfold increase in IgG-PT; pairs of sera are connected with a dotted line. Half-black, half-white circles indicate sera in which the degree of increase of IgG-PT could not be determined due to the upper limit of differentiation of the IgG-PT assay of ≥500 U/ml; pairs of sera are connected with a dotted line.