Females at the intersection: Housing instability, drug use, and syphilis risk among street-involved populations in Ontario, Canada

BACKGROUND: Infectious syphilis has reemerged as a global public health threat, disproportionately affecting females in Canada, whose rates have tripled in the last decade. We examined how sex interacts with emerging risk factors associated with new syphilis cases. METHODS: We used data from the Syphilis Point of Care Rapid Testing and Immediate Treatment Evaluation (SPRITE) study, a public health-led community-based study across Ontario. Sociodemographic and risk factor data, including being un(der)housed, using drugs and/or injecting drugs, were collected from public health intake forms. New syphilis cases were determined by healthcare providers, and test positivity was calculated as the proportion of tests yielding a new syphilis diagnosis. Sex-stratified mixed-effects logistic regression estimated the odds ratio (OR) of new syphilis infection. Absolute excess risk due to interaction (AERI) was calculated between drug use risk factors and sex. RESULTS: From June 2023 to December 2025, 1281 participants (1550 tests) were included: median age 39 (IQR 32-50); 43% female; 61% un(der)housed; 63% used drugs. Overall test positivity was 3.8%; higher among females (4.6%) compared to males (3.2%). Injection and other drug use were associated with new infections by both females (OR 2.0[95% CI: 1.0, 4.2]) and males (OR 2.0[1.2, 3.5]). AERI was 5.0% (95% CI: 1.0, 9.0) between sex (females) and illicit drug use, and 5.2% (95% CI: 1.2, 9.3) among females between being un(der)housed and reporting illicit drug use. CONCLUSION: Drug use and housing instability amplified syphilis risk among females, identifying a syndemic that may be contributing to high syphilis rates among women.