Assessment of IgA anti-PT and IgG anti-ACT reflex testing to improve Bordetella pertussis serodiagnosis in recently vaccinated subjects

• Published in: Clinical microbiology and infection Vol. 26; no. 5; pp. 645.e1 - 645.e8
• Main Authors: Subissi, L., Rodeghiero, C., Martini, H., Litzroth, A., Huygen, K., Leroux-Roels, G., Piérard, D., Desombere, I.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2020
• Subjects: ACT; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial - blood; Antibody; Antigens, Bacterial - immunology; Bordetella pertussis; Bordetella pertussis - immunology; Child; Female; Humans; IgA; Immunoglobulin A - blood; Immunoglobulin G - blood; Male; Middle Aged; Pertussis toxin; Pertussis Toxin - immunology; Pertussis Vaccine - administration & dosage; Pertussis Vaccine - immunology; Sensitivity and Specificity; Serodiagnosis; Serologic Tests - methods; Serology; Vaccination; Whooping Cough - blood; Whooping Cough - diagnosis; Whooping Cough - pathology; Whooping Cough - prevention & control; Young Adult; ACT; IgA; Antibody; Vaccination; Serology; Bordetella pertussis; Serodiagnosis; Pertussis toxin
• ISSN: 1198-743X; 1469-0691; 1469-0691
• DOI: 10.1016/j.cmi.2019.10.001

Quantifying IgG antibodies to pertussis toxin (PT) is the most specific and sensitive method for the serodiagnosis of a Bordetella pertussis infection. Since PT is a component of acellular pertussis vaccines, anti-PT IgG is also induced by vaccination, precluding pertussis serodiagnosis based exclusively on anti-PT IgG in recently vaccinated subjects. Here, we aim to identify additional B. pertussis-specific serological markers that can discriminate between infection and recent vaccination. The clinical usefulness of measuring IgA directed to the vaccine antigen PT and IgG directed to non-vaccine antigens (Fim2/3, LPS, ACT, CatACT) was evaluated in nine well characterized subject groups, aged 10–89 years (n = 390). Serum anti-PT IgG levels (>125 IU/mL) served as an indicator for a recent B. pertussis infection. Comparing symptomatic pertussis-infected subjects (n = 140) with recently vaccinated, non-infected subjects (n = 100) revealed the optimal cut-off, accuracy, sensitivity and specificity for each single parameter. For pertussis diagnosis in recently vaccinated subjects, the measurement of anti-PT IgA (cut-off 15 IU/mL) and anti-ACT IgG (cut-off 15 U/mL) resulted in accuracies of 95% (91.5–97.1) and 87.5% (82.7–91.1), sensitivities of 92.9% (87.4–96.0) and 83.6% (76.5–88.8) and specificities of 98% (93.0–99.4) and 93% (86.3–96.6), respectively. Comparing anti-PT IgA levels between the youngest (10–19 years, n = 38) and oldest (70–89 years, n = 17) age groups revealed an age-dependent increase in antibody levels in pertussis-infected subjects (p < 0.0001). Reflex testing of anti-PT IgA and anti-ACT IgG improves pertussis serodiagnosis in recently vaccinated symptomatic subjects with elevated anti-PT IgG levels. Furthermore, both markers can discriminate between vaccination and recent infection in pertussis serosurveillance studies.