A NEW decision-analytic modelling study evaluating rapid diagnostic tests (RDTs) for syphilis highlights that no single testing algorithm is universally optimal. The analysis assessed clinical performance and cost-effectiveness across antenatal populations and men who have sex with men (MSM), two groups with very different epidemiological profiles.
Researchers compared three testing approaches: a treponemal-only RDT (T-RDT); a standard dual treponemal/non-treponemal RDT (standard T/NT-RDT); and a modified dual test, in which individuals testing positive on either component receive treatment. The latter reflects real-world practice in many low-resource settings where a patient’s syphilis history is often unknown.
Maternal Syphilis: Balancing Missed Cases and Overtreatment
Among pregnant individuals, the modified T/NT-RDT was far more sensitive than the T-RDT. At a syphilis prevalence of 0.5%, it missed only 10 active infections per 100,000, an 80% reduction compared with the T-RDT, which missed 68 cases. However, the modified dual test resulted in substantially more overtreatment (approximately 18,948 cases vs 9,993 with the T-RDT).
Costs differed significantly: the T-RDT remained the lowest-cost option (USD 1.09–1.51 per test) compared with the modified dual test (USD 3.59–4.12), making cost a critical consideration for antenatal programmes.
High-Risk Populations: Different Priorities for MSM
In MSM populations, both sensitivity and specificity requirements differ. The modified T/NT-RDT again missed the fewest cases but increased overtreatment. The standard dual test, though less sensitive, led to the lowest overtreatment (approximately 999 cases per 100,000 in low-prevalence settings), potentially reducing unnecessary antibiotic exposure.
Cost Drivers and Alternative Approaches
Across all strategies, RDT unit price was the dominant cost driver. Sensitivity analyses identified a promising sequential algorithm, using a T-RDT followed by the modified dual test, which reduced both missed cases and overtreatment, offering a middle-ground solution for some settings.
Implications for Syphilis Control
The findings emphasise that no single syphilis testing algorithm fits all contexts. While treponemal-only tests remain suitable for antenatal screening, dual RDTs, standard or modified, may offer better performance in higher-prevalence groups such as MSM. Programmes will need to tailor strategies to local epidemiology, available resources, and clinical priorities.
Reference
Zhang Y et al. Comparison of the performance and costs of testing algorithms using rapid diagnostic tests for detection and treatment of syphilis among pregnant individuals and men who have sex with men: a modelling study. Lancet Infect Dis. 2025;DOI:10.1016/S1473-3099(25)00588-2.
