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

Abstract

Background: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA).

Methods and findings: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies.

Conclusions: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management.

Prospero number: CRD42022348045.

Fig 1. Study selection flowchart.

Records include titles and abstracts identified for initial screening. Reports include full-text published articles or databases assessed for inclusion.

Fig 2. Estimated diagnosed proportion per pathogen over time among symptomatic adults of mixed or unmeasured HIV status in sub-Saharan Africa.

Diagnosed proportion per pathogen among adults symptomatic with (A) vaginal discharge, (B) urethral discharge, and (C) genital ulcer. Proportions estimated using generalised linear mixed-effects model for each symptom with fixed effects for RTI and the interaction of RTI with year and sex (genital ulcer only), random intercepts and slopes per year for the interaction of RTI and region, and observation-level random intercepts. Lines and shaded areas represent sex-matched population-weighted mean proportions and 95% CIs. Solid lines and darker shading denote estimates and confidence intervals within the observed data range (interpolated), while dotted lines and lighter shading indicate estimates and confidence intervals beyond that time frame (extrapolated). Blue points and labels represent population-weighted mean proportions in 2015. Vertical dotted lines are through the year 2015. Grey points represent study observations adjusted for diagnostic test performance. BV: Bacterial vaginosis, CA: Candida albicans, CS: Candida species (any), CT: Chlamydia trachomatis, HD: Haemophilus ducreyi, HSV: Herpes simplex virus (unspecified), HSV-1: Herpes simplex virus type 1, HSV-2: Herpes simplex virus type 2, LGV: lymphogranuloma venereum, MG: Mycoplasma genitalium, NG: Neisseria gonorrhoeae, TP: Treponema pallidum, TV: Trichomonas vaginalis, None: unknown aetiology.

Fig 3. Comparison of diagnosed proportion per pathogen by HIV status in sub-Saharan Africa.

Estimated diagnosed proportion per pathogen among adults with and without HIV in 2015 (left) and adjusted odds of diagnosis per pathogen among adults with HIV compared to adults without HIV (right) symptomatic with (A) vaginal discharge, (B) urethral discharge, and (C) genital ulcer. Proportions and odds estimated using generalised linear mixed-effects model for each symptom with fixed effects for RTI and the interaction of RTI with year, HIV status, and sex (genital ulcer only), random intercepts for the interaction of RTI and region, and observation-level random intercepts. Bars represent sex-matched population-weighted mean proportions in 2015. Points represent the adjusted odds of diagnosis among adults with HIV. Solid lines represent 95% CIs. BV: Bacterial vaginosis, CS: Candida species (any), CT: Chlamydia trachomatis, HD: Haemophilus ducreyi, HSV: Herpes simplex virus (unspecified), HSV-1: Herpes simplex virus type 1, HSV-2: Herpes simplex virus type 2, LGV: lymphogranuloma venereum, MG: Mycoplasma genitalium, NG: Neisseria gonorrhoeae, TP: Treponema pallidum, TV: Trichomonas vaginalis, None: unknown aetiology.

Fig 4. Comparison of diagnosed proportion per pathogen by age group in sub-Saharan Africa.

Estimated diagnosed proportion per pathogen among youth <25 years and adults ≥25 years in 2015 (left) and adjusted odds of diagnosis per pathogen among youth compared to adults (right) symptomatic with (A) vaginal discharge, (B) urethral discharge, and (C) genital ulcer. Proportions and odds estimated using generalised linear mixed-effects model for each symptom with fixed effects for RTI and the interaction of RTI with year, age group, and sex (genital ulcer only), random intercepts for the interaction of RTI and region, and observation-level random intercepts. Bars represent sex-matched population-weighted mean proportions in 2015. Points represent the adjusted odds of diagnosis among youth. Solid lines represent 95% CIs. *Confidence intervals truncated by x-axis. BV: Bacterial vaginosis, CA: Candida albicans, CS: Candida species (any), CT: Chlamydia trachomatis, HD: Haemophilus ducreyi, HSV: Herpes simplex virus (unspecified), HSV-1: Herpes simplex virus type 1, HSV-2: Herpes simplex virus type 2, LGV: lymphogranuloma venereum, MG: Mycoplasma genitalium, NG: Neisseria gonorrhoeae, TP: Treponema pallidum, TV: Trichomonas vaginalis, None: unknown aetiology.