Abstract
BACKGROUND: The challenge of dealing with isolated reactive treponemal chemiluminescence immunoassay (CIA) results in clinical practice has prompted the development of a more efficient algorithm for distinguishing true infection from false reactivity in isolated CIA sera. METHODS: A prospective cohort study was conducted at Wuhan Tongji Hospital, involving 119,002 individuals screened for syphilis using CIA from January 1, 2015, to January 6, 2017. Samples with reactive CIA results underwent simultaneous testing with the T. pallidum passive particle agglutination assay (TPPA) and the rapid plasma reagin test (RPR). Additionally, a subgroup of 189 individuals with differing TPPA statuses was selected for further analysis using Western blotting (WB) and a modified TPPA assay (titer, 1:20). To identify the optimal serological approach for distinguishing true from false reactivity in sera with isolated reactive CIAs (CIA(+)TPPA(-)RPR(-)), two distinct algorithms were developed and evaluated. The first algorithm involved reflexively testing CIA(+)TPPA(-)RPR(-) sera with the modified TPPA, followed by WB if nonreactive. The second algorithm began with WB, followed by the modified TPPA if nonreactive or indeterminate. RESULTS: WB demonstrated lower sensitivity compared to TPPA, but it identified six syphilis cases among the 89 CIA(+)TPPA(-) samples. Both WB and modified TPPA exhibited a specificity of 100%. The two supplementary confirmatory algorithms detected 12 additional syphilis cases, with the first algorithm being more cost-effective and labor-saving. CONCLUSION: A combination of a modified TPPA (titer, 1:20) and WB can serve as a reliable algorithm for distinguishing true syphilis infection from false reactive signals in isolated reactive CIA sera. CLINICAL TRIAL NUMBER: Not applicable.