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Background: Very few studies have been conducted on the seroprevalence of syphilis in Gabon. According to the World Health Organization, the average seroprevalence of syphilis has declined from 5.5 to 1.1% in Central Africa. The aim of this study was to test the hypothesis that syphilis decreased in Gabon between 2004 and 2016 and to identify factors involved in this pattern by testing a large sample of first-time blood donors in the capital Libreville.Methods: The detection of Treponema pallidum was done using a Rapid Plasma Reagin test (RPR) and confirmed by an ELISA test using the Biorad Syphilis Total Antibody EIA II kit or BioMerieux Trepanostika TP recombinant. Assays were performed by dedicated technicians according to manufacturers' recommendations and following the laboratory standard operating procedures. Test results were manually transferred into the laboratory Excel files and hand-written in the laboratory logbook for syphilis testing. Logistic regression was used to assess the impact of sociodemographic characteristics on syphilis marker seroprevalence in both univariate and multivariable analysis. Odds ratios (OR) and 95% confidence intervals were calculated.Results: The seroprevalence of syphilis markers was 8.4% (95% CI = 7.9-8.9) in 2004 and 2.4% (95% CI = 2.1-2.7) in 2016. The difference was significant [OR = 3.78; 95% CI (3.26-4.38); P < 0.001]. The decrease in syphilis seroprevalence was significant in both women and men and in each age group in univariate analysis. In multivariable analysis, controlling for all sociodemographic factors, the decrease in syphilis seroprevalence from 2004 to 2016 remained significant (OR = 3.29; 95% CI = 2.88-3.88, P < 0.001). The seroprevalence of syphilis decreased significantly in men compared to women and young donors compared to donors aged ≥36 years.Conclusions: This study shows a significant decline in syphilis seroprevalence in first-time blood donors in Libreville, Gabon. Government actions, including multiple HIV prevention activities, are a likely part of this decline. [ABSTRACT FROM AUTHOR]