Predictive risk assessment and targeted testing could enhance STI diagnosis in a high HIV prevalence setting in Eswatini.

Sexually transmitted infections (STIs) present significant public health challenges in resource-limited settings where syndromic management, which often leads to misdiagnosis and over-treatment, remains standard care. We retrospectively evaluated hypothetical STI risk assessment-only (Triage-only) and sequential risk assessment plus STI diagnostic testing (Triage&Test) approaches as potential enhancements to syndromic management in a high-burden setting. A retrospective analysis was conducted using historic data from a cross-sectional study of adults (≥ 18 years) accessing six outpatient care sites in Eswatini between July 2022 and April 2023. Clinical records included STI risk factor assessments, outcomes of syndromic assessment for vaginal discharge syndrome (VDS) and male urethritis syndrome (MUS), leukocyte esterase (LE) and HIV testing, and molecular-based testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Sex-specific predictive risk scores (PRS) tools for CT/NG/TV infections were developed using LASSO penalized logistic regression. Subsequently, the diagnostic performance of various hypothetical Triage-only and Triage&Test approaches was compared to molecular-based testing for CT/NG/TV infections. The aim was to identify strategies meeting programmatic benchmarks of ≥ 90% sensitivity and < 60% testing efficiency. Of 1396 participant records analysed, 65.4% (n = 913) were women and the median age was 29 years (IQR 23-36). Triage-only approaches underperformed, resulting in high proportions of false-positive and false-negative cases. Specifically, VDS showed a sensitivity of only 32.9% (95% CI 27.5-38.6) and a specificity of 75.1% (95% CI 71.5-78.5), while MUS had a sensitivity of 65.0% (95% CI 57.0-72.4) and specificity of 88.0% (95% CI 84.0-91.4). All PRS tools configurations in simulated Triage&Test approaches outperformed Triage-only methods by reducing false-negative and eliminating false-positive cases, thus achieving 100% specificity and positive-predictive value. Despite these improvements, no Triage&Test approach fully met established benchmarks. The highest sensitivity, observed in men, was 91.1% (95% CI 85.5-95) with an efficiency of 86.0%. In women, the best sensitivity was 79.0% (95% CI 73.8-83.6) at an efficiency of 60.1%. While PRS tools integrated within Triage&Test approaches may improve STI diagnosis in high-burden settings, challenges in balancing accuracy and resource demands persist. Access to affordable and well-targeted point-of-care rapid diagnostic tests appears essential to improve STI care quality in resource-limited environments.