International Bordetella pertussis assay standardization and harmonization meeting report. Centers for Disease Control and Prevention, Atlanta, Georgia, United States, 19–20 July 2007

Abstract

An international meeting on Bordetella pertussis assay standardization and harmonization was held at the Centers for Disease Control and Prevention (CDC), Atlanta, GA, 19-20 July 2007. The goal of the meeting was to harmonize the immunoassays used for pertussis diagnostics and vaccine evaluation, as agreed upon by academic and government researchers, regulatory authorities, vaccine manufacturers, and the World Health Organization (WHO). The primary objectives were (1) to provide epidemiologic, laboratory, and statistical background for support of global harmonization; (2) to overview the current status of global epidemiology, pathogenesis and immunology of pertussis; (3) to develop a consensus opinion on existing gaps in understanding standardization of pertussis assays used for serodiagnosis and vaccine evaluation; and (4) to search for a multicenter process for addressing these priority gaps. Presentations and discussions by content experts addressed these objectives. A prioritized list of action items to improve standardization and harmonization of pertussis assays was identified during a group discussion at the end of the meeting. The major items included: (1) to identify a group that will organize, prepare, maintain, and distribute proficiency panels and key reagents such as reference and control sera; (2) to encourage the development and identification of one or more reference laboratories that can serve as an anchor and resource for other laboratories; (3) to define a performance-based assay method that can serve as a reference point for evaluating laboratory differences; (4) to develop guidance on quality of other reagents, e.g., pertussis toxin and other antigens, and methods to demonstrate their suitability; (5) to establish an international working group to harmonize the criteria to evaluate the results obtained on reference and proficiency panel sera; (6) to create an inventory to determine the amount of appropriate and well-characterized sera that are available globally to be used as bridging reagents for vaccine licensure; and (7) to seek specific guidance from regulatory authorities regarding the expectations and requirements for the licensure of new multicomponent pertussis vaccines.

Age-Related Differences in Patterns of Increased Bordetella pertussis Antibodies

“…Our findings demonstrate that the distribution of 4 mutually exclusive positive B. pertussis antibody result patterns differs markedly depending on patient age. The proportion of positive results due to increased PT IgG and PT IgA, the pattern most strongly associated with recent B. pertussis infection (7,8,10,14,17,22,23,25), was similar in all Յ60-year-old patient age categories. Increased PT IgG but not PT IgA was the predominant positive result pattern in patients Ͻ21 years old, whereas increased FHA antibodies only was the predominant pattern in patients Ն21 years old.…”

“…Because PT is produced only by B. pertussis, detection of antibodies to PT is considered specific for B. pertussis infection or vaccination. FHA, in contrast, is found in other Bordetella species, including B. parapertussis, and patients infected with these organisms exhibit increased levels of FHA antibodies (14,23,25). Similarly, proteins closely related to FHA are found in other microorganisms, and infection with these microbes can induce cross-reactive antibodies (14,26).…”

“…An increased level of IgG or IgA antibody to filamentous hemagglutinin (FHA) also occurs in B. pertussis infection but is a less specific marker of B. pertussis infection because other Bordetella species express FHA and cross-reacting antibodies are also induced by other bacteria (14,17,26). The interpretation of increased antibody positive result patterns can be a challenge due to a variety of factors, including differing assay sensitivities and specificities and the complex relationship between patient age and the B. pertussis antibody isotypes produced following vaccination (25).…”

Serodiagnosis as Adjunct Assay for Pertussis Infection in São Paulo, Brazil

“…In the United States, serology was useful for confirming the diagnosis during outbreaks (16,19,20). Validation and harmonization of serologic methods are still necessary before they can be widely applied as diagnostic tools (21)(22)(23). In the present study, we tested the performance of the CDC PT ELISA (8,15) for routine diagnosis of pertussis in São Paulo, Brazil.…”

Does Tetanus-Diphtheria-Acellular Pertussis Vaccination Interfere with Serodiagnosis of Pertussis Infection?

“…Numerous pertussis serodiagnostic assays are currently available worldwide, and recommendations for testing, interpretation of results, and harmonization of assays have been recently published (10,23,26). An anti-PT IgG enzyme-linked immunosorbent assay (ELISA) was developed in 2004 by the Center for Biologics Evaluation and Research (CBER) and the Centers for Disease Control and Prevention (CDC) as a ready-to-use kit for the diagnosis of pertussis infection in adolescents and adults (19).…”