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Xinyi Chen, Beatriz Munoz, Harran Mkocha, Charlotte Gaydos, Laura Dize, Thomas Quinn, Sheila K West; Impact of indeterminant ranges around the cut-off for antibody positivity on the use of serology for trachoma monitoring. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2632.
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Serologic testing for chlamydial antibodies is a potential tool for trachoma surveillance. However, the impact of indeterminate ranges around the cut-off for seropositivity remains unclear. To understand this, we followed a longitudinal cohort of children in a formerly trachoma endemic district.
A total of 1719 children aged 1-9 years in Kongwa, Tanzania were followed for three years. We assessed their Median Fluorescence Intensity value (MFI-BG) of the antibodies to Chlamydia trachomatis antigen pgp3 at the baseline and three follow-up surveys. The cutoff for seropositivity was determined by receiver operative characteristic (ROC) curve analyses, using sera from children who were positive for both infection and clinical trachoma and a sample of US children who had never been exposed to trachoma. The indeterminate range was defined as the interval between the highest MFI-BG from the negative panel and the lowest MFI-BG from the positive panel.
The overall seropositivity rate was 31.5% at baseline and 36.4% at the last follow-up. The different trajectories of change in serostatus are shown in Table 1. Of the seropositive children at baseline, 12.1% seroreverted; 25.4% of these seroreversions occurred with an MFI-BG in the indeterminate range. Of the seronegatives, 13.0% seroconverted, with 1.9 % of those seroconversions having an MFI-BG in the indeterminant range. Thirty-one children (2% of 1719) experienced a transient seroconversion or seroreversion (Group 3 or 6). Only one child (3% of the 31) had MFI-BG in the indeterminate range for the survey that placed them as a transient change. Eight out of the 1719 children (0.5%) had unstable serostatus. If the serostatus instances where the values fall in the indeterminate range are instead counted as the alternate, then these children would fall into a more regular pattern, and only 3 children were truly alternating between seropositivity and seronegativity at each survey.
The majority of seroconversion and seroreversion was not influenced by indeterminate ranges for antibody levels. Transient changes in serostatus are real and not due to indeterminate values. The indeterminate ranges had the greatest impact on apparent unstable serostatus changes.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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