Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: systematic review and meta-regression

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Abstract
Introduction: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings lacking aetiologic diagnostics. However, heterogeneity in underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review characterised aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). Methods: We searched Embase, MEDLINE, Global Health, and Web of Science until July 25, 2022, and grey literature until August 31, 2022, for studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance and used generalised linear mixed-effects meta-regressions to estimate aetiologic distributions, trends, and determinants. Results: Of 4136 identified records, 198 reports were included from 183 studies in 32 countries between 1969 and 2022. In 2015, primary aetiologies for vaginal discharge were candidiasis (69.4% [95% CI:44.1-86.6%], n=50), bacterial vaginosis (50.0% [32.3-67.8%], n=39), chlamydia (16.5% [8.7-29.0%], n=49), and trichomoniasis (12.9% [7.7-20.7%], n=78); for urethral discharge were gonorrhoea (78.8% [70.9-85.1%], n=67) and chlamydia (22.2% [16.0-30.1%], n=48); and for genital ulcer were HSV-2 (56.1% [39.2-71.6%], n=46) and syphilis (7.8% [5.3-11.4%], n=115). Regional variation was marginal. Temporal variation was substantial, particularly for genital ulcer. For each symptom, HIV-status and age were significantly associated with infection diagnoses, although aetiologic hierarchies were largely the same by strata. Conclusion: Syndrome aetiologies in SSA align with WHO guidelines without strong evidence of contextual or demographic variation, supporting broad guideline applicability. Temporal changes underscore the need for aetiologic re-assessment. STI surveillance using syndrome-based assessments is noncomprehensive and requires studies among symptomatic and asymptomatic populations.
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