Reply to Baughman et al

Clinical Infectious Diseases, Jan 2007

Joel I. Ward, James D. Cherry, Martin Lee, Swei-Ju Chang

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://cid.oxfordjournals.org/content/44/1/150.full.pdf

Reply to Baughman et al

Joel I. Ward 0 1 2 3 James D. Cherry 0 1 2 3 Martin Lee 0 1 2 3 Swei-Ju Chang 0 1 2 3 0 University of California at Los Angeles (UCLA) Center for Vaccine Research, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, David Geffen School of Medicine UCLA , Torrance, California 1 Henry F. Chambers Department of Medicine, University of California-San Francisco 2 Peter Horby Oxford University Clinical Research Unit, National Institute of Infectious and Tropical Diseases, Bach Mai Hospital , Hanoi, Vietnam 3 for Vaccine Research, Los Angeles Biomedical Research In- stitute, Harbor-UCLA Medical Center, David Geffen School of Medicine UCLA , 1124 W. Carson St., Torrance, CA (joelward @ucla.edu). Clinical Infectious Diseases 2007 ; 44:150-1 2006 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2007/4401-0030$15.00 D o w n l o a d e d f r o m h t t p : / / c .i d o x f o r d j o u r n a .l s o r g / b y g u e s t o n N o v e m b e r 3 , 2 0 1 4 - To the EditorAs reviewed in our articles reporting on our acellular pertussis vaccine trial [15], it is difficult to assess the incidence of pertussis in older persons. Beyond variations in incidence attributable to outbreaks, age, and regional and seasonal factors, there is difficulty in recognizing or diagnosing pertussis. Cultures and PCR are rarely performed early in the course of illness, when they are most likely to have positive results, and serological tests for pertussis have limitations. Consequently, one can easily underestimate or overestimate the infection burden. Approximately one-half of the pertussis cases in our trial were diagnosed by culture and PCR. Additional cases and asymptomatic infections were identified by systematic prospective serologic evaluations. To maximize sensitivity (i.e., to detect true cases) and specificity (i.e., avoid false-positive results), we employed exacting serologic methods. First, we prospectively collected serial blood specimens from each subject, and we assayed 9 pertussis antibodies as titer changes in sequential serum samples from the same individual (i.e., the assays were self-controlled). A multitude of assay variables exist that result in chance inaccurate quantitations. Our assays were developed to exacting US Food and Drug Administration specifications and were based on standards they provided. The validation of the assays included standardization of reagents, plates, dilution accuracy, and use of quantitative positive controls. All titer increases were determined with paired serum samples from the same subjects (i.e., they were selfcontrolled). All paired serum samples from the same individual were run on the same day and on the same microtiter plates to minimize assay variation. In an efficacy trial, one wants to maximize case detection but also avoid falsepositive results. To accomplish this, besides using precise assays, we evaluated remaining assay variability to determine the cut-off points for positivity (i.e., 2- or 4-fold increase). With same-plate evaluations of each set of paired serum samples, the coefficient of variation for the various pertussis antibody assays (pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae) ranged from only 0% to 18% for IgG assays and from 0% to 22% for IgA assays. Therefore, the 2-fold and 4fold cut-off points selected far exceeded the variation inherent in these assays. With these low coefficients of variation and our serologic criteria, one would expect !1 false-positive result per 10,000 assays. Our estimate of a 1.1%2.7% infection rate per year derives from examining the 36 permutations of results shown in table 1 of our article [1]. Independent of the criteria employed, we found the observed incidence values to be remarkably consistent. Undoubtedly, there are variations in different populations at different times and over longer intervals, but we believe few studies have been as rigorous as ours. Lastly, among control subjects, there were no titer differences between the samples obtained before and at 1 month after hepatitis A immunization. Therefore, our incidence estimate does not differ whether we use the preimmunization (12-month interval) or the 1-month postimmunization sample (11-month interval). We used the 11-month interval so that our comparisons between samples from subjects who had received acellular pertussis vaccine and control samples from unvaccinated subjects were identical. In conclusion, we find little meaningful difference between an estimate of 1.1% 2.7% and an estimate of 2.9%. An advantage of our study is that we could compare the infection rate to the active, prospectively ascertained disease incidence. We found a 5:1 ratio of asymptomatic to symptomatic cases, and this is, to our knowledge, the first estimate of this type to be assessed prospectively in a national cohort. Acknowledgments Potential conflicts of interest. All authors: no conflicts. 1. Ward JI, Cherry JD, Chang S- (...truncated)


This is a preview of a remote PDF: https://cid.oxfordjournals.org/content/44/1/150.full.pdf

Joel I. Ward, James D. Cherry, Martin Lee, Swei-Ju Chang. Reply to Baughman et al, Clinical Infectious Diseases, 2007, pp. 150-151, 44/1, DOI: 10.1086/510087