title: The Use of Innovative Two-Component Cluster Analysis and Serodiagnostic Cut-Off Methods to Estimate Prevalence of Pertussis Reinfections.
abstract: Bordetella pertussis circulates even in highly vaccinated countries affecting all age groups. Insight into the scale of concealed reinfections is important as they may contribute to transmission. We therefore investigated whether current single-point serodiagnostic methods are suitable to estimate the prevalence of pertussis reinfection. Two methods based on IgG-Ptx plasma levels alone were used to evaluate the proportion of renewed seroconversions in the past year in a cohort of retrospective pertussis cases ≥ 24 months after a proven earlier symptomatic infection. A Dutch population database was used as a baseline. Applying a classical 62.5 IU/ml IgG-Ptx cut-off, we calculated a seroprevalence of 15% in retrospective cases, higher than the 10% observed in the population baseline. However, this method could not discriminate between renewed seroconversion and waning of previously infection-enhanced IgG-Ptx levels. Two-component cluster analysis of the IgG-Ptx datasets of both pertussis cases and the general population revealed a continuum of intermediate IgG-Ptx levels, preventing the establishment of a positive population and the comparison of prevalence by this alternative method. Next, we investigated the complementary serodiagnostic value of IgA-Ptx levels. When modelling datasets including both convalescent and retrospective cases we obtained new cut-offs for both IgG-Ptx and IgA-Ptx that were optimized to evaluate renewed seroconversions in the ex-cases target population. Combining these cut-offs two-dimensionally, we calculated 8.0% reinfections in retrospective cases, being below the baseline seroprevalence. Our study for the first time revealed the shortcomings of using only IgG-Ptx data in conventional serodiagnostic methods to determine pertussis reinfections. Improved results can be obtained with two-dimensional serodiagnostic profiling. The proportion of reinfections thus established suggests a relatively increased period of protection to renewed infection after clinical pertussis.
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Inonge
authors: I
authors: van Twillert
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Axel A
authors: AA
authors: Bonačić Marinović
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Jacqueline A M
authors: JA
authors: van Gaans-van den Brink
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Betsy
authors: B
authors: Kuipers
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Guy A M
authors: GA
authors: Berbers
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Nicoline A T
authors: NA
authors: van der Maas
authors: Julius Center Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Theo J M
authors: TJ
authors: Verheij
authors: Department of Pediatrics, Groene Hart Ziekenhuis, Gouda, the Netherlands.|Ghent University Hospital, department of pediatrics, Ghent, Belgium.
authors: Florens G A
authors: FG
authors: Versteegh
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.|RSPH, Emory University, Atlanta, United States of America.
authors: Peter F M
authors: PF
authors: Teunis
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors: Cécile A C M
authors: CA
authors: van Els
mesh_terms: D001427:Bacterial Toxins / Q000276:immunology; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D012698:Serologic Tests / Q000379:methods*; D014917:Whooping Cough / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D007074:Immunoglobulin G