In a population of Tdap-vaccinated HCP who demonstrated expected booster responses to vaccination within the first 3 months, only 8% had antibody levels high enough to interfere with the diagnostic interpretation of the anti-PT IgG ELISA. Based on the upper prediction limit estimated by our model, the use of serology for diagnostic purposes should be considered valid in patients who have not received Tdap vaccination in the prior 45 days. Using the upper tolerance limit (75 days), it appears that a slightly longer time frame would provide even more confidence regarding the use of serodiagnosis in a population that will now be getting routinely vaccinated.
An elevated anti-PT IgG titer is currently the most sensitive and specific indicator of recent pertussis infection (10
). Previous kinetic studies have shown that HCP vaccinated with acellular vaccines can have anti-PT IgG antibody concentrations as high as ~331 EU/ml (22
). In response, many countries have adopted specific waiting periods, up to a year, before suggesting the use of serodiagnosis in a vaccinated patient (10
). However, study objectives, criteria, vaccine formulations, and ELISA methodology can be highly variable among previously published work, resulting in a wide range of observed decay rates and kinetic patterns (5
). Our modeling results suggest a waiting period of 3 months postvaccination in order to use our serodiagnostic ELISA.
While the GMCs were far below the diagnostic cutoff for a recent infection, the antibody levels of eight individuals still surpassed the diagnostic cutoff. A possible explanation is that these asymptomatic individuals had a stronger response because of previous or recent exposure, which could be likely since the cohort is composed of HCP. High antibody titers have been observed in previous population studies and may simply be a reflection of the normal variation observed in the population (2
This study was an extension of a study which measured antibody levels 1, 2, and 4 weeks postvaccination using a different ELISA performed at another laboratory (15
). Anti-PT IgG GMCs were much higher in that study than those seen here (112 EU/ml rather than 19.0 EU/ml and 109.5 EU/ml rather than 21.3 EU/ml for the 2- and 4-week postvaccination sampling times, respectively). Further inspection led us to examine if the PT antigen source alone or in combination with possible differences in ELISA methodology could have been a potential source of the differences in concentrations. Reanalysis of these sera by SP using a more highly purified antigen preparation produced values lower than those originally reported (personal communication with SP). These results led to a recently completed study to compare the effects of four sources of PT antigen preparations on four different ELISA methods. Results demonstrated that if the preparations are highly purified and well qualified and the ELISAs are calibrated to a reference standard and well validated, these different PT sources could be interchangeably used (13
One important limitation of our study is that the data were derived from subjects who received only one Tdap formulation. Vaccine formulations can differ by antigen type, quantity, and purification or detoxification processes. This study used the Tdap formulation Adacel from SP (Lyon, France), which contains 2.5 μg of PT. Formulations that contain larger amounts of PT may elicit a stronger antibody response that could take longer to decay and thus delay the time frame for the applicability of serodiagnosis with the ELISA. Recent vaccine response studies with a formulation that contains a higher concentration of PT (8 μg) observed higher peak postvaccination GMCs (126.5, 90.3, and 62.7 EU/ml) (3
); one observed a decay sampling at 1 year postvaccination with a GMC of 22.7 EU/ml (28
). Based on the data of these studies and the well-recognized rapid decline in titers soon after the peak, we believe that a 6-month waiting period after vaccination is sufficient.
Another potential limitation is that the postvaccination titers of adolescents may be different from those of adults. The time between vaccinations for adolescents is much shorter than that for adults, and therefore there may be a stronger response to the booster. However, Rieber et al. observed post-Tdap booster GMCs of 16.4, 17.1, and 50.3 EU/ml 1 month after vaccination in adolescents with five-dose acellular, four-dose acellular, and four-dose whole-cell vaccine primary series, respectively (21
). In addition, Mertsola et al. observed comparable antibody decay profiles from booster vaccinations of adolescents and adults (20
). These findings suggest that our results with the diagnostic ELISA for adults may be similarly interpreted for adolescents.
The need for a serological diagnostic tool has been increasing substantially as the public health community seeks to understand the true burden of pertussis. The anti-PT IgG assay is an ideal complement to culture and PCR to determine infection in the later phases of disease and in adolescents and adults who do not display typical pertussis symptoms. The late nature of reporting is the primary reason that outbreak investigations are often retrospective and dependent on serological testing for confirmation. Given recent initiatives to improve Tdap vaccination in adolescents and adults, clarifying confounding interpretations of serological results is crucial.
In summary, our study predicts that the anti-PT IgG ELISA will remain useful for the measurement of PT antibody levels in Tdap-vaccinated patients beginning as early as 75 days postvaccination. Certainly by 6 months postvaccination, predicted antibody levels of vaccinated adult populations fell far below the diagnostic cutoff, making interference with serodiagnosis interpretation quite unlikely. For epidemiological studies and as part of a public health response, public health laboratories may use this ELISA for pertussis diagnostics regardless of vaccination history. Clinicians managing individual patients should maintain a more comprehensive approach to diagnosing pertussis in a recently vaccinated person, considering symptoms and the appropriateness of other diagnostic tools, but should feel confident using this serologic test if vaccination has occurred more than 6 months previously.