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

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.

Extragenital Sexually Transmitted Infections Among High-Risk Men Who Have Sex With Men in Johannesburg, South Africa.

BACKGROUND: In South Africa, extragenital etiological sexually transmitted infection (STI) screening among men who have sex with men (MSM) is not routinely available. We aimed to determine the prevalence of STI pathogens at rectal and pharyngeal sites, syphilis seroprevalence, and associated risk factors among a selection of high-risk MSM without symptomatic urethritis attending a men's health clinic in Johannesburg, South Africa. METHODS: A cross-sectional study was conducted in 2022. Enrolled clients self-reported demographic, sexual behavioral risks, and clinical information. Client or clinician-collected rectal and pharyngeal swabs were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. C. trachomatis-positive rectal samples were reflex tested for lymphogranuloma venereum. Blood specimens were screened for syphilis. Univariate and multivariate regression models were used to determine factors independently associated with the presence of an extragenital STI or syphilis. RESULTS: Among the 97 participants (median age, 29 years), 24.7% had an extragenital STI and 9.4% had high nontreponemal antibody titers (rapid plasma reagin ≥1:16). Rectal STIs were detected in 26.4% participants: N. gonorrhoeae (14.3%), C. trachomatis (9.9%), and M. genitalium (5.5%). Pharyngeal STIs were less prevalent (4.1%). Overall, the prevalence of any STI was 41%. Sex under the influence of drugs (adjusted odds ratio, 4.94; 95% confidence interval, 1.56-15.69) and engaging in condomless receptive anal intercourse with a casual partner (adjusted odds ratio, 8.36; 95% confidence interval, 1.73-40.28) were independent risk factors for having an extragenital STI. CONCLUSIONS: The high burden of extragenital STIs and active syphilis in asymptomatic MSM underscores the importance of routine etiological screening in this key population, as the syndromic approach would not enable detection or treatment of these infections.

Compliance to Viral Load Monitoring Schedules Among Women Attending Prevention of Vertical HIV Transmission Services Before and During the COVID-19 Pandemic in Ehlanzeni District, Mpumalanga, South Africa.

Human immunodeficiency virus (HIV) viral load (VL) monitoring was likely interrupted during the Coronavirus disease 2019 (COVID-19) pandemic. We used routine data on repeat VL testing among 667 prevention of vertical HIV transmission (PVT) clients in Ehlanzeni district, to determine compliance to VL testing recommendations and associated factors during different time periods: pre-COVID-19, transition, and COVID-19. Descriptive and multivariable Poisson regression analyses were conducted, with and without including revised PVT-guidelines rolled out in January-2020. Among 405 women with ≥ 2 VL tests, the overall median age was 30 years (interquartile range: 26-35 years). Compliance to recommended VL testing guidelines ranged between 81.5% (172/211) and 92.3% (191/207) at different time periods. Across all three periods and when revised PVT-guidelines were used, being compliant was significantly reduced among those with earliest VL = 50-999 copies/ml (incidence rate ratio (IRR) = 0.71 [95% confidence interval (CI) 0.61-0.82], p value < 0.001) and VL ≥ 1000 copies/ml (IRR = 0.18 [95% CI 0.09-0.36], p value < 0.001). When guideline revisions were excluded, compliance was only significantly reduced among those with VL ≥ 1000 copies/ml (IRR = 0.14 [95% CI 0.06-0.32], p value < 0.001) and increased during the COVID-19 period versus pre-COVID-19 (IRR = 1.10 [95% CI 1.05-1.15], p value < 0.001). Similar significant associations between compliance and VL level were observed when the COVID-19 period was analyzed separately. Significantly increased compliance to VL testing among the 25-34 years age-group versus younger women was also observed across all periods. These results highlight the importance of strengthening strategies such as short message service reminders and educational messaging, reaching all age-groups, to fast-track implementation targets for VL monitoring.

Factors associated with an unsuppressed viral load among HIV-positive individuals attending STI services in South Africa, 2019.

BACKGROUND: Sexually transmitted infections (STIs), particularly in the absence of viral suppression, increase the risk of HIV transmission to uninfected partners. We determined factors associated with having an unsuppressed VL among HIV-positive individuals attending STI services in South Africa (SA). METHODS: We analysed secondary cross-sectional data collected on HIV-positive individuals presenting with STI symptoms s at sentinel sites in Western Cape and Gauteng provinces between January-December 2019 in SA. We compared demographic characteristics of individuals on ART or not on ART, and a Poisson regression model to identify factors associated with having an unsuppressed VL (≥ 50 copies/ml) was used. RESULTS: Among 93 HIV-positive individuals attending STI services with VL data, the median age was 32 years (IQR 27-37). Thirty-two (34.41%) individuals were on ART compared to 61 (65.59%) not on ART. Most of those on ART (56.25%) had an unsuppressed VL, while 86.89% of those not on ART had an unsuppressed VL. ART use was associated with a 33% lower prevalence of having unsuppressed VL. In a model adjusting for age, age at first sex and oral sex, none of the factors were significant. Among those on ART, individuals < 25 years were more likely to have an unsuppressed VL (aPRR = 1.94: 95% CI = 1.27-2.97) compared to those ≥ 25 years. CONCLUSION: ART use among HIV-positive individuals was low and VL suppression among those on ART was sub-optimal. Intensified ART initiation and adherence support to HIV-positive individuals seeking STI services could improve VL suppression.

Gaps in the prevention of mother-to-child transmission of syphilis: a review of reported cases, South Africa, January 2020-June 2022.

INTRODUCTION: Congenital syphilis (CS) is preventable through timely antenatal care (ANC), syphilis screening and treatment among pregnant women. Robust CS surveillance can identify gaps in this prevention cascade. We reviewed CS cases reported to the South African notifiable medical conditions surveillance system (NMCSS) from January 2020 to June 2022. METHODS: CS cases are reported using a case notification form (CNF) containing limited infant demographic and clinical characteristics. During January 2020-June 2022, healthcare workers supplemented CNFs with a case investigation form (CIF) containing maternal and infant testing and treatment information. We describe CS cases with/without a matching CIF and gaps in the CS prevention cascade among those with clinical information. FINDINGS: During January 2020-June 2022, 938 CS cases were reported to the NMCSS with a median age of 1 day (interquartile range: 0-5). Nine percent were diagnosed based on clinical signs and symptoms only. During January 2020-June 2022, 667 CIFs were reported with 51% (343) successfully matched to a CNF. Only 57% of mothers of infants with a matching CIF had an ANC booking visit (entry into ANC). Overall, 87% of mothers were tested for syphilis increasing to 98% among mothers with an ANC booking visit. Median time between first syphilis test and delivery was 16 days overall increasing to 82 days among mothers with an ANC booking visit. DISCUSSION: Only 37% of CS cases had accompanying clinical information to support evaluation of the prevention cascade. Mothers with an ANC booking visit had increased syphilis screening and time before delivery to allow for adequate treatment.

Untreated maternal syphilis has devastating consequences for the foetus. Congenital syphilis (CS) is preventable through timely maternal screening and treatment with robust surveillance. We evaluated CS surveillance data to identify gaps in CS surveillance and in the prevention cascade in South Africa.

Resistance is common in paediatric patients failing ART in South Africa.

BACKGROUND: Minimal data exist on HIV drug resistance patterns and prevalence among paediatric patients failing ART in resource-limited settings. We assessed levels of HIV drug resistance in children with virological failure. METHODS: This cross-sectional study, performed from March 2017 to March 2019 in South Africa, enrolled HIV-positive children aged ≤19 years, receiving ART through public health facilities with recent evidence suggestive of virological failure (at least one viral load ≥1000 copies/mL), across 45 randomly selected high-volume clinics from all nine provinces. Resistance genotyping was performed using next-generation sequencing technologies. Descriptive analysis taking into account survey design was used to determine outcomes. RESULTS: Among 899 participants enrolled, the adjusted proportion of HIV drug resistance among children with virological failure was 87.5% (95% CI 83.0%-90.9%). Resistance to NNRTIs was detected in 77.4% (95% CI 72.5%-81.7%) of participants, and resistance to NRTIs in 69.5% (95% CI 62.9%-75.4%) of participants. Overall, resistance to PIs was detected in 7.7% (95% CI 4.4%-13.0%) of children. CONCLUSIONS: HIV drug resistance was highly prevalent in paediatric patients failing ART in South Africa, with 9 in 10 patients harbouring resistance to NNRTIs and/or NRTIs. PI-based regimens are predicted to be highly efficacious in achieving virological suppression amongst patients failing NNRTI-based regimens. Scaling up resistance testing amongst patients would facilitate access to second- and third-line regimens in South Africa.

Etiological Surveillance of Male Urethritis Syndrome in South Africa: 2019 to 2020.

BACKGROUND: In South Africa, male urethritis syndrome (MUS) is the most common sexually transmitted infection (STI) syndrome in men. We determined the distribution of STI etiologies and the susceptibility profiles of Neisseria gonorrhoeae isolates from men presenting with MUS to 3 sentinel surveillance health care facilities. Secondary objectives were to determine the seroprevalence of coinfections (HIV, syphilis, herpes simplex virus 2). METHODS: Consecutive, consenting men with symptomatic urethral discharge were enrolled between January 1, 2019, and December 31, 2020. Genital discharge swab and blood specimens were collected and transported to a central STI reference laboratory in Johannesburg, South Africa. RESULTS: Among 769 men enrolled, N. gonorrhoeae was the commonest cause of MUS (674 [87.8%]; 95% confidence interval [CI], 85.2%-89.9%), followed by Chlamydia trachomatis (161 [21.0%]; 95% CI, 18.2%-24.0%). Of 542 cultivable N. gonorrhoeae isolates, all were susceptible to ceftriaxone (modal minimum inhibitory concentration, 0.004 mg/L) and azithromycin (modal minimum inhibitory concentration, 0.128 mg/L). Seroprevalence rates of HIV, syphilis, and HSV-2 were 21.4% (95% CI, 18.5%-24.5%), 2.3%, and 50.1%, respectively. Condom use at last sexual encounter was reported by only 7%, less than 50% had been medically circumcised, and only 66.7% (58 of 87) who self-reported an HIV-positive status were adherent on antiretroviral drugs. CONCLUSIONS: Neisseria gonorrhoeae and C. trachomatis were the predominant causes of MUS. Currently recommended dual ceftriaxone and azithromycin therapy are appropriate for MUS syndromic management; however, surveillance must be maintained to timeously detect emerging and increasing gonococcal resistance. Clinic-based interventions must be intensified in men seeing sexual health care to reduce the community transmission and burden of STI and HIV.

Etiological Surveillance of Genital Ulcer Syndrome in South Africa: 2019 to 2020.

BACKGROUND: Herpes simplex virus (HSV) has been the leading cause of genital ulcer syndrome (GUS) in South Africa for more than a decade, and acyclovir therapy is incorporated into syndromic management guidelines. We conducted surveillance at 3 sentinel sites to define the common sexually transmitted etiologies of GUS and to determine whether current syndromic management is appropriate. Secondary objectives of surveillance were to determine the seroprevalence of coinfections (HIV, syphilis, HSV-2) in persons presenting with GUS. METHODS: Consecutive, consenting adult men and women presenting with visible genital ulceration were enrolled between January 1, 2019, and December 31, 2020. Genital ulcer swab and blood specimens were collected and transported to a central sexually transmitted infection reference laboratory in Johannesburg. RESULTS: Among 190 participants with GUS, HSV-2 was the most frequently detected ulcer pathogen (49.0%; 95% confidence interval [CI], 41.9%-56.1%). The relative prevalence of the second most common ulcer-derived pathogen, Treponema pallidum, was 26.3% (95% CI, 20.5%-33.1%), with 90% of primary syphilis cases having a positive rapid plasma reagin (RPR) titer. Male sex was independently associated with primary syphilis compared with herpetic ulcers, after adjusting for the effect of casual sex partners and other exposures (adjusted odds ratio, 3.53; 95% CI, 1.35-9.21; P = 0.010). The overall HIV prevalence among participants was 41.3% (78 of 189; 95% CI, 34.2%-48.6%). CONCLUSIONS: Herpes simplex virus 2 remains the predominant cause of GUS, justifying the continued use of acyclovir in syndromic guidelines. Adequate supplies of benzathine penicillin G for syphilis treatment are essential at primary health care level, in addition to the provision of syphilis and HIV risk reduction services.

Etiological Surveillance of Vaginal Discharge Syndrome in South Africa: 2019 to 2020.

BACKGROUND: The syndromic management of vaginal discharge syndrome (VDS) is challenging because of the prevalence of mixed infection with sexually transmitted infection (STI) pathogens and non-STI causes, such as bacterial vaginosis and candidiasis (CA). We aimed to determine the relative prevalence of VDS etiologies in women presenting to sentinel primary health care clinics in South Africa. Secondary objectives were to ascertain the predictive value of speculum findings for the presence of STI pathogens and the proportion of women presenting with clinical features of CA who had identifiable yeast on vaginal smear microscopy. METHODS: Consecutive, consenting women with complaints of abnormal vaginal discharge were enrolled between January 1, 2019, and December 31, 2020. Genital discharge swab and blood specimens were collected and transported to a central STI reference laboratory in Johannesburg. RESULTS: A total of 364 women were enrolled at 3 sentinel sites. Bacterial vaginosis was the most common cause of VDS (163 of 361 [45.2%]; 95% confidence interval [CI], 40.1%-50.3%); however, a significant proportion had STI coinfection (71 of 163 [43.6%]; 95% CI, 35.8%-51.5%). The predominant STI etiology was Chlamydia trachomatis (73 [20.2%]; 95% CI, 16.4%-24.7%). An abnormal speculum finding had poor predictive value for STIs, and Gram stain microscopy showed yeast in only 37.2% of vaginal smears from women with CA symptoms. CONCLUSIONS: Bacterial vaginosis is the predominant cause of VDS in South Africa; however, STI coinfection is common. Clinical findings are poorly predictive of STI etiologies or candidiasis; therefore, a rapid and accurate STI point-of-care test would be useful in optimizing VDS management.

Demographic and Behavioral Risk Factors Associated with Reduced Susceptibility of Neisseria gonorrhoeae to First-Line Antimicrobials in South African Men with Gonococcal Urethral Discharge.

Neisseria gonorrhoeae is the predominant cause of male urethral discharge in South Africa, and escalating prevalence of gonococcal antimicrobial resistance (AMR) is a major health concern both in-country and globally. We analyzed the demographic, behavioral, and clinical characteristics of 685 men presenting with gonococcal urethral discharge to sentinel surveillance clinics over a 3-year period (2017 to 2019) to determine the burden of factors that are known to be associated with N. gonorrhoeae AMR to first-line therapy (defined as group 1 isolates exhibiting resistance or reduced susceptibility to extended-spectrum cephalosporins or azithromycin). Among 685 men with gonococcal urethral discharge, median age was 28 years (interquartile range [IQR], 24 to 32). Only two men (2/632; 0.3%) self-identified as homosexual; however, on further enquiry, another 16 (2%) confirmed that they had sex with men only. Almost 30% practiced oral sex and were at risk for pharyngeal gonococcal infection. In univariate analysis, male circumcision (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.49 to 0.99) and recent sex outside the country (OR, 1.83; 95% CI, 1.21 to 2.76) were significantly associated with having a category 1 N. gonorrhoeae isolate. In a multivariable model, only sex outside South Africa increased the odds of being infected with a decreased susceptible/resistant N. gonorrhoeae isolate (adjusted odds ratio [aOR], 1.64; 95% CI, 1.05 to 2.55). These findings warrant the intensification of N. gonorrhoeae AMR surveillance among recently arrived migrant and overseas traveler populations, as well as the inclusion of extragenital specimens for N. gonorrhoeae AMR surveillance purposes.

Congenital Syphilis Case Surveillance in South Africa 2017-19: Experience, Challenges and Opportunities.

BACKGROUND: Untreated or inadequately treated maternal syphilis infection may be transmitted from mother to child resulting in congenital syphilis (CS) infection. In South Africa (SA), CS is a notifiable medical condition (NMC). The NMC surveillance system (NMCSS) was improved by introducing an electronic notification application, a new case notification form and training resources in July 2017. We describe CS surveillance in SA and report on experiences from implementing an improved NMCSS from August 2017 to December 2019. METHODS: We present the CS case definition, data collected by the CS case investigation and notification forms and data flow through the NMCSS. Descriptive statistics were used to analyse CS notifications received from August 2017 to December 2019. Qualitative inductive analysis of the stakeholder communications diary was conducted to identify CS surveillance challenges. RESULTS: There were 418 CS notifications submitted from 80 facilities in 35 out of 52 districts. Of the notified cases, 194 (46.8%) were male and the median age at notification was 7 days (interquartile range: 3-16 days). The majority were diagnosed in hospital (98.6%). KwaZulu-Natal Province notified the most cases (52.9%) followed by Gauteng (28.0%). Challenges in CS surveillance included the lack of awareness of the CS case definition, completed paper-based notifications not reaching the NMCSS and the limited ability of the system to distinguish improved notifications from increase in disease burden. CONCLUSION: Improved CS surveillance through NMCSS was implemented in SA. Training, support and mentoring on CS and the notification system will be needed to inform elimination efforts.

Trends in RPR Seropositivity among Children Younger than 2 Years in South Africa, 2010-2019.

A positive rapid plasma reagin (RPR) result in children under the age of 2 years indicates either passive transplacental transfer of maternal antibodies or active infection with syphilis (possible congenital syphilis). We describe trends in RPR seropositivity in this population using centralized laboratory data. A secondary analysis of laboratory data collected through the National Health Laboratory Service, Corporate Data Warehouse from 2010 to 2019 was conducted. Of the 127 150 children <2 years included in the analysis, 10 969 [8.6%; 95% confidence interval (95% CI) 85-88]) were RPR seropositive. RPR seropositivity increased from 6.5% to 13.0% between 2010 and 2019. Overall, the annual rate of RPR seropositivity was relatively stable between 2010 and 2018 with a range of 89-127/100 000 live births, increasing sharply to 165/100 000 livebirths in 2019. KwaZulu-Natal and North West provinces recorded the largest increases in annual seropositivity rate, while Eastern Cape and Western Cape had the most significant declines. Although this analysis is limited to laboratory results, in the absence of major changes in testing practices, there may be a rise in the burden of antenatal syphilis exposure in utero indicating an increase in maternal syphilis and syphilis transmission in the general population. South Africa needs to intensify Mother-to-Child Transmission of syphilis elimination efforts to reach the WHO target of ≤50 cases per 100 live births by 2030.

Comparison of gentamicin MICs by agar dilution and Etest for clinical isolates of Neisseria gonorrhoeae.

BACKGROUND: In South Africa, Neisseria gonorrhoeae (NG) is the predominant cause of male urethritis syndrome (MUS). The national MUS treatment guidelines recommend gentamicin as salvage therapy for ceftriaxone treatment failures. We ascertained and compared gentamicin MICs obtained by agar dilution and Etest for clinical isolates of NG. METHODS: Gentamicin MICs for NG culture isolates obtained from 272 MUS cases in 2017 were determined using agar dilution, as per CLSI agar dilution methods, and Etest® (bioMérieux, Marcy-l'Étoile, France). Previously published interpretive criteria were used: MIC ≤4 mg/L, susceptible (S); MIC 8-16 mg/L, intermediately resistant (IR); and MIC ≥32 mg/L, resistant (R). WHO 2008 NG reference strains were used as comparison standards. RESULTS: Gentamicin agar dilution versus Etest MIC results (mg/L) were as follows: MIC50 = 16 versus 4; MIC90 = 16 versus 8; minimum MIC = 4 versus 1; and maximum MIC = 32 versus 16. Interpretive categories for agar dilution versus Etest were as follows: S, 4.4% versus 86.8%; IR, 86.0% versus 13.4%; and R, 9.6% versus 0%. The gentamicin MIC50 by agar dilution was significantly higher than by Etest (sign test P value <0.001); overall MIC agreement was 7.4% [kappa statistic (κ) = -0.014 (95% CI -0.039 to 0.010)]. Correlation with expected MICs for WHO reference strains was consistently better with Etest than with agar dilution. CONCLUSIONS: There was a significant discordance between NG gentamicin MICs by agar dilution versus Etest. NG gentamicin AST methodology must be standardized and interpretive criteria established to optimize the monitoring of susceptibility trends.

Medical Male Circumcision and Associations Among Sexually Transmitted Infections Service Attendees.

Medical male circumcision (MMC) is a proven intervention for preventing HIV acquisition among males. We describe the circumcision status, eligibility for MMC referral and associations with HIV positivity among symptomatic males attending sexually transmitted infections (STI) services. This study was a secondary analysis of cross-sectional data collected during sentinel surveillance for STI aetiologies. In the sentinel surveillance conducted at primary care facilities located in six South African provinces, an anonymous questionnaire was administered followed by collection of appropriate genital and blood specimens for laboratory testing including HIV, rapid plasma reagin (RPR) and HSV-2 serological testing. During analysis, multivariable logistic regression was used to determine association between prevalent HIV infection and male circumcision among males who were HSV-2 AND/OR RPR serology positive and among those who were negative. A total of 847 males were included the analysis, among whom the median age was 28 years (IQR 24-32 years) with 26.3% aged < 25 years. Of these, 166 (19.6%) were medically circumcised, 350 (41.4%) traditionally circumcised while 324 (39%) were not circumcised. The yield of assessment for MMC referral was 27.7%. Overall HIV positivity was 23.1%. Compared to no circumcision, MMC had a statistically insignificant 62% lower odds of being HIV positive -among males who were HSV-2 and RPR negative- adjusted odds ratio [aOR] 0.38 [95% confidence interval (CI) 0.12-1.18], p = 0.094. Among those HSV-2 AND/OR RPR positive, MMC had a statistically insignificant 26% lower odds of being HIV positive- aOR 0.74 (95% CI 0.41-1.36), p = 0.334. In both groups HIV positivity increased with age but was positively associated with condom use at last sexual encounter [aOR 3.41 (95% CI 1.43-8.15)] and previous treatment for an STI syndrome [aOR 3.81 (95% CI 1.60-9.05)] among those HSV-2 and RPR negative. High HIV positivity and high yield of eligibility for VMMC referral among males attending STI services points to the need for better integration of HIV prevention and treatment with STI care.

Feasibility of community-based HIV self-screening in South Africa: a demonstration project.

BACKGROUND: HIV diagnosis is a critical step in linking HIV-infected individuals to care and treatment and linking HIV-uninfected persons to prevention services. However, the uptake of HIV testing remains low in many countries. HIV self-screening (HIVSS) is acceptable to adults, but there is limited data on HIVSS feasibility in community programmes. This study aimed to evaluate the feasibility of HIVSS in South Africa. METHODS: We conducted a prospective study that enrolled participants through mobile site, homebased, workplace and sex worker programmes in two townships from May to November 2017. Following an information session on HIVSS, interested participants were offered one of three methods of HIVSS testing: supervised, semi-supervised, and unsupervised. Participants who opted for unsupervised testing and those who tested HIV positive after semi- or supervised HIVSS were followed up telephonically or with a home visit one week after receipt of the test kit to confirm results and linkages to care. Follow-up visits were concluded when the participant indicated that they had used the kit or had accessed a confirmatory HIV test. RESULTS: Of the 2061 people approached, 88.2% (1818/2061) received HIV testing information. Of this group, 89% (1618/1818) were enrolled in the study and 70.0% (1133/1618) were tested for HIV with the kit. The median age was 28 (IQR:23-33) years with an even gender distribution. Of those enrolled, 43.0% (696/1618) were identified through homebased outreach, 42.5% (687/1618) through mobile sites, 7.3% (118/1618) at their workplace and 7.2% (117/1618) from sex worker programmes. A total of 68.7% (1110/1616) selected unsupervised HIVSS, whereas 6.3% (101/1616) opted for semi-supervised and 25.0% ((405/1616) chose supervised HIVSS. Overall, the HIV prevalence using the HIVSS test was 8.2% (93/1129). Of those newly diagnosed with HIV, 16% (12/75) were initiated on ART. Almost half (48.0%; 543/1131) of those tested were linked to a primary HIV test as follows: supervised (85.2%; 336/394); semi-supervised (93.8%; 91/97) and unsupervised (18.1%; 116/640). CONCLUSION: Unsupervised HIVSS was by far the most selected and utilised HIVSS method. Linkages to primary and confirmatory testing for the unsupervised HIVSS and further care were low, despite home visits and telephonic reminders.

The incidence of tuberculosis among hiv-positive individuals with high CD4 counts: implications for policy.

BACKGROUND: Intensified case finding (ICF) and earlier antiretroviral therapy (ART) initiation are strategies to reduce burden of HIV-associated tuberculosis (TB). We describe incidence of and associated factors for TB among HIV-positive individuals with CD4 counts > 350 cells/µl in South Africa. METHODS: Prospective cohort study of individuals recruited for a TB vaccine trial. Eligible individuals without prevalent TB were followed up at 6 and 12 months after enrolment. Cox proportional hazards regression was used to determine factors associated with risk of incident TB. RESULTS: Six hundred thirty-four individuals were included in the analysis [80.9 % female, 57.9 % on ART, median CD4 count 562 cells/µl (IQR 466-694 cells/µl)]. TB incidence was 2.7 per 100 person-years (pyrs) (95 % CI 1.6-4.4 per 100 pyrs) and did not differ significantly between those on ART and those not on ART [HR 0.65 (95 % CI 0.24-1.81)]. Low body mass index (BMI <18.5 kg/m(2)) was associated with incident TB [HR 3.87 (95 % CI 1.09-13.73)]. Half of the cases occurred in the first 6 months of follow up and may have been prevalent or incubating cases at enrolment. CONCLUSIONS: TB incidence was high and associated with low BMI. Intensified case finding for TB should be strengthened for all HIV positive individuals regardless of their CD4 count or ART status.

Exploring the validity of routine individuated service data for antenatal HIV surveillance in the Western Cape.

Background: In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources through the Provincial Health Data Centre (PHDC). This enables the description of temporal changes in population-wide antenatal HIV seroprevalence. We evaluated the validity of these data compared to aggregated program data and population-wide sentinel antenatal HIV seroprevalence surveys for the Western Cape province. Methods: We conducted a retrospective cohort analysis of all pregnancies identified in the PHDC from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. HIV prevalence estimates were triangulated and compared with available survey estimates and aggregated programmatic data from registers as recorded in the District Health Information System. Provincial, district-level and age-group HIV prevalence estimates were compared between data systems using correlation coefficients, absolute differences and trend analysis. Results: Of the 977800 pregnancies ascertained, PHDC HIV prevalence estimates from 2011-2013 were widely disparate from aggregate and survey data (due to incomplete electronic data), whereas from 2014 onwards, estimates were within the 95% confidence interval of survey estimates, and closely correlated to aggregate data estimates (r = 0.8; p = 0.01), with an average prevalence difference of 0.4%. PHDC data show a slow but steady increase in provincial HIV prevalence from 16.7% in 2015 to 18.6% in 2020. The highest HIV prevalence was in the Cape Metro district (20.3%) Prevalence estimates by age group were comparable between sentinel surveys and PHDC from 2015 onwards, with prevalence estimates stable over time among younger age-groups (15-24 years) but increased among older age-groups (> 34 years). Conclusions: This study compares sentinel seroprevalence surveys with both register-based aggregate data and consolidated individuated administrative data. We show that in this setting linked individuated data may be reliably used for HIV surveillance and provide more granular estimates with greater efficiency than seroprevalence surveys and register-based aggregate data.

Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa.

BACKGROUND: Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women. METHODS: We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates. RESULTS: Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data. CONCLUSION: This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Trends in COVID-19 admissions and deaths among people living with HIV in South Africa: analysis of national surveillance data.

BACKGROUND: In 2021, the HIV prevalence among South African adults was 18% and more than 2 million people had uncontrolled HIV and, therefore, had increased risk of poor outcomes with SARS-CoV-2 infection. We investigated trends in COVID-19 admissions and factors associated with in-hospital COVID-19 mortality among people living with HIV and people without HIV. METHODS: In this analysis of national surveillance data, we linked and analysed data collected between March 5, 2020, and May 28, 2022, from the DATCOV South African national COVID-19 hospital surveillance system, the SARS-CoV-2 case line list, and the Electronic Vaccination Data System. All analyses included patients hospitalised with SARS-CoV-2 with known in-hospital outcomes (ie, who were discharged alive or had died) at the time of data extraction. We used descriptive statistics for admissions and mortality trends. Using post-imputation random-effect multivariable logistic regression models, we compared characteristics and the case fatality ratio of people with HIV and people without HIV. Using modified Poisson regression models, we compared factors associated with mortality among all people with COVID-19 admitted to hospital and factors associated with mortality among people with HIV. FINDINGS: Among 397 082 people with COVID-19 admitted to hospital, 301 407 (75·9%) were discharged alive, 89 565 (22·6%) died, and 6110 (1·5%) had no recorded outcome. 270 737 (68·2%) people with COVID-19 had documented HIV status (22 858 with HIV and 247 879 without). Comparing characteristics of people without HIV and people with HIV in each COVID-19 wave, people with HIV had increased odds of mortality in the D614G (adjusted odds ratio 1·19, 95% CI 1·09-1·29), beta (1·08, 1·01-1·16), delta (1·10, 1·03-1·18), omicron BA.1 and BA.2 (1·71, 1·54-1·90), and omicron BA.4 and BA.5 (1·81, 1·41-2·33) waves. Among all COVID-19 admissions, mortality was lower among people with previous SARS-CoV-2 infection (adjusted incident rate ratio 0·32, 95% CI 0·29-0·34) and with partial (0·93, 0·90-0·96), full (0·70, 0·67-0·73), or boosted (0·50, 0·41-0·62) COVID-19 vaccination. Compared with people without HIV who were unvaccinated, people without HIV who were vaccinated had lower risk of mortality (0·68, 0·65-0·71) but people with HIV who were vaccinated did not have any difference in mortality risk (1·08, 0·96-1·23). In-hospital mortality was higher for people with HIV with CD4 counts less than 200 cells per µL, irrespective of viral load and vaccination status. INTERPRETATION: HIV and immunosuppression might be important risk factors for mortality as COVID-19 becomes endemic. FUNDING: South African National Institute for Communicable Diseases, the South African National Government, and the United States Agency for International Development.