The results suggest that a range of unique biological and social forces are driving the spread of syphilis in China. A national campaign for detection and treatment of syphilis, and a credible prevention strategy, are urgently needed.

Background. Syphilis has made a rapid resurgence in China, especially among high-risk groups including female sex workers (FSWs).Methods. Two cities in each of 3 provinces in South China were chosen and allocated to intervention or control arms. The intervention consisted of enhancing community-based syphilis screening outreach intervention with comprehensive sexually transmitted infection services at designated clinics while the control maintained routine intervention activities. Generalized linear modeling was used to examine effect of the intervention on incident syphilis infection.Results. A total of 8275 women were eligible, and 3597 women enrolled (n = 2011 in control arm, n = 1586 in intervention arm) in the study. The median follow-up duration was 375 days (interquartile range, 267-475). Syphilis incidence density in the intervention group was reduced by 70% (95% confidence interval, 53%-81%) compared with the incidence in the control arm. The syphilis prevention intervention benefits were robust among FSWs at low-tier venues, individuals with less than high school education, migrants, and women who did not report condom use during the last episode of sex.Conclusions. Integrated sexually transmitted infection and human immunodeficiency virus prevention strategies substantially reduce syphilis incidence among FSWs, especially among those at low-tier venues. This intervention suggests the need for scaling up comprehensive FSW programs in China.