L Subissi1, C Rodeghiero2, H Martini3, A Litzroth4, K Huygen2, G Leroux-Roels5, D Piérard3, I Desombere6. 1. National Reference Centre (NRC) for Bordetella pertussis, Sciensano, Brussels, Belgium; European Programme for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden. 2. National Reference Centre (NRC) for Bordetella pertussis, Sciensano, Brussels, Belgium. 3. National Reference Centre (NRC) for Bordetella pertussis, Universitair Ziekenhuis, Brussel, Belgium. 4. Epidemiology of Infectious Diseases, Sciensano, Brussels, Belgium. 5. Centre for Vaccinology, Ghent University, Belgium. 6. National Reference Centre (NRC) for Bordetella pertussis, Sciensano, Brussels, Belgium. Electronic address: isabelle.desombere@sciensano.be.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Annieck M Diks; Pauline Versteegen; Cristina Teodosio; Rick J Groenland; Bas de Mooij; Anne-Marie Buisman; Alba Torres-Valle; Martín Pérez-Andrés; Alberto Orfao; Guy A M Berbers; Jacques J M van Dongen; Magdalena A Berkowska Journal: Vaccines (Basel) Date: 2022-01-18
Authors: Annieck M Diks; Indu Khatri; Liesbeth E M Oosten; Bas de Mooij; Rick J Groenland; Cristina Teodosio; Martin Perez-Andres; Alberto Orfao; Guy A M Berbers; Jaap Jan Zwaginga; Jacques J M van Dongen; Magdalena A Berkowska Journal: Front Immunol Date: 2021-06-10 Impact factor: 7.561