Objective  To understand the syphilis infection status and related factors among drug users in Hubei Province, and to provide a reference basis for syphilis prevention and control measures in this population.

Methods  Sentinel sites were set up in 9 major cities and prefectures of Hubei Province from 2016 to 2024. Anonymous questionnaires and blood samples were collected through continuous cross-sectional surveys to gather sociodemographic, sexual behavior, and serological information of the respondents. The Synthetic Minority Over-sampling Technique (SMOTE) model was used to handle the imbalance in category distribution, and the new random forest model (rfPermute) and logistic regression model were employed to analyze the related factors of syphilis infection.

Results  A total of 36,970 drug users were surveyed from 2016 to 2024. The positive rate of syphilis antibodies ranged from 2.03% to 3.26%, with no linear trend over the years (P > 0.05). The positive rates of HIV and HCV antibodies were 0.02% to 0.38% and 20.27% to 26.48%, respectively, showing a linear downward trend over the years (all P < 0.05). In 2024, the awareness rate of AIDS knowledge among the respondents was 93.16%, the proportion who had received intervention services in the past year was 88.24%, and the proportion who had been tested for HIV in the past was 66.48%. These indicators showed a linear upward trend from 2016 to 2024 (all P < 0.05). The proportion of injecting drug users was 26.80%, and the proportion who had sexual behavior after drug use in the past year was 32.91%. These indicators showed a linear downward trend from 2016 to 2024 (all P < 0.05). The results of the two models showed that educational level, type of drug used, having received intervention services in the past year, HCV test results, and gender were common related factors for syphilis infection (the top ten feature variable importance in the new random forest and all P < 0.05 in logistic regression). Age and marital status were highly important in the random forest, but not significant in logistic regression.

Conclusion The positive rate of syphilis antibodies among drug users in Hubei Province from 2016 to 2024 was generally at a low prevalence level. Those with low educational attainment, females, and users of traditional or mixed drugs were more likely to be infected with syphilis. It is recommended to strengthen publicity and education and precise intervention for these characteristic groups, and to improve multi-dimensional prevention and control strategies.