Clinic-based evaluation of point-of-care dual HIV/syphilis rapid diagnostic tests at primary healthcare antenatal facilities in South Africa and Zambia.

BACKGROUND: Southern African countries have the largest global burden of HIV and syphilis, with a high prevalence among women of reproductive age. Although antenatal screening is standard of care, syphilis screening has generally lagged behind HIV screening. We aimed to evaluate the performance and operational characteristics of two commercial dual HIV/syphilis point-of-care tests (POCTs) for simultaneous maternal HIV/syphilis screening. METHODS: A clinic-based evaluation of dual HIV/syphilis POCTs (SD Bioline and Chembio) was conducted at five primary healthcare centres (PHCs) in South Africa and Zambia. POCT results using capillary fingerprick blood were compared to reference laboratory syphilis and HIV serological assays. RESULTS: Three thousand four hundred twelve consenting pregnant women aged ≥ 18 years were enrolled. The prevalence of treponemal antibody seropositivity and HIV infection ranged from 3.7 to 9.9% (n = 253) and 17.8 to 21.3% (n = 643), respectively. Pooled sensitivity for syphilis compared to the reference assay was 66.0% (95%CI 57.7-73.4) with SD Bioline and 67.9% (95%CI 58.2-76.3) with Chembio. Pooled specificity for syphilis was above 98% with both POCTs. The sensitivities of SD Bioline and Chembio assays were 78.0% (95%CI 68.6-85.7) and 81.0% (95%CI 71.9-88.2), respectively compared to an active syphilis case definition of treponemal test positive with a rapid plasma reagin titre of ≥ 8. The negative predictive values (NPVs) based on various prevalence estimates for syphilis with both assays ranged from 97 to 99%. The pooled sensitivity for HIV was 92.1% (95%CI 89.4-94.2) with SD Bioline; and 91.5% (95%CI 88.2-93.9) with Chembio. The pooled specificities for HIV were 97.2% (95%CI 94.8-98.5) with SD Bioline and 96.7% (95%CI 95.1-97.8) with Chembio. The NPV based on various prevalence estimates for HIV with both assays was approximately 98%. Most participating women (91%) preferred dual POCTs over two single POCTs for HIV and syphilis, and healthcare providers gave favourable feedback on the utility of both assays at PHC level. CONCLUSIONS: Based on the need to improve antenatal screening coverage for syphilis, dual HIV/syphilis POCTs could be effectively incorporated into antenatal testing algorithms to enhance efforts towards elimination of mother-to-child transmission of these infections.

Genomic surveillance and antimicrobial resistance determinants in Neisseria gonorrhoeae isolates from Uganda, Malawi and South Africa, 2015-20.

OBJECTIVES: Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso. METHODS: Gonococcal isolates cultured in Uganda (n = 433), Malawi (n = 154) and South Africa (n = 99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n = 159), Burkina Faso (n = 52) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: Resistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n = 780) compared with the AMR lineage A (n = 141), and limited geographical phylogenomic signal was observed. CONCLUSIONS: We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.

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.

Hormonal contraception and risk of STIs and bacterial vaginosis in South African adolescents: secondary analysis of a randomised trial.

OBJECTIVES: Young women in sub-Saharan Africa are at high risk of STIs and unintended pregnancies, yet hormonal contraceptive (HC) use may affect STI risk. We compared the influence of three HCs on the incidence and prevalence of STIs and bacterial vaginosis (BV) in South African adolescents. METHODS: One hundred and thirty adolescents between 15 and 19 years were randomised to the injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) (Triphasil or Nordette) or a combined contraceptive vaginal ring (CCVR; NuvaRing) for 16 weeks (clinicaltrials.gov/NCT02404038). Vaginal samples were collected at baseline and 16 weeks post contraceptive initiation for STI and BV testing. RESULTS: In an intention-to-treat analysis, no significant differences in BV prevalence were found between study arms. The overall incidence of any STI at follow-up was high: 16.2% in the COC arm; 25.7% in the Net-En arm; and 37.1% in the CCVR arm. The incidence rate (IR) of any STI was similar between Net-En (IR 0.74 (95% CI 0.34 to 1.41)) and the oestrogen-containing contraceptives (IR 0.78 (95% CI 0.47 to 1.22)). A lower IR of Chlamydia trachomatis (incidence rate ratio (IRR) 0.68 (95% CI 0.19 to 1.99)) and Neisseria gonorrhoeae (IRR 0.25 (95% CI 0.01 to 1.35)) but a higher IR of Mycoplasma genitalium (IRR 16.0 (95% CI 2.96 to 400)), was observed in the Net-En arm compared with the oestrogen-containing contraceptives, although the overall incidence of M. genitalium was low (4.7%). In an exploratory analysis, the risk of any STI and N. gonorrhoeae was lower in the COC arm compared with CCVR. A per-protocol analysis yielded similar results. CONCLUSION: Our results suggest that use of Net-En may be associated with increased risk of M. genitalium compared with oestrogen-containing contraceptives but not with overall STI risk. COC use may decrease STI risk relative to CCVR.

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.

Prevalence and Antimicrobial Resistance of Mycoplasma genitalium Infection Among Women Living With Human Immunodeficiency Virus in South Africa: A Prospective Cohort Study.

This prospective cohort study of 622 women living with human immunodeficiency virus (HIV) from Johannesburg (2012) detected Mycoplasma genitalium in 7.4% (95% confidence interval [CI]: 5.5-9.7, 46/622), with detection more likely with lower CD4 counts(adjusted odds ratio [AOR] 1.02 per 10 cells/µL decrease, 95% CI: 1.00-1.03) and higher plasma HIV-1 RNA (AOR 1.15 per log copies/mL increase, 95% CI: 1.03-1.27). No mutations for macrolide/quinolone resistance was detected.

High in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among consecutive clinical Neisseria gonorrhoeae isolates from Thailand (2018) and South Africa (2015-2017).

We evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n=99; 2018) and South Africa (n=100; 2015-2017). Zoliflodacin was highly active in vitro against all tested isolates (MIC range: 0.004-0.25; MIC50: 0.064, MIC90: 0.125 µg/ml), with no cross-resistance to any of the seven comparator antimicrobials. Our data support the initiation of the global zoliflodacin phase 3 randomized controlled clinical trial for uncomplicated gonorrhea.

Clinical Characteristics of Mycoplasma genitalium and the Usefulness of Syndromic Management Among Women Living With Human Immunodeficiency Virus.

We report the clinical symptoms and examination findings of Mycoplasma genitalium (MG) in women living with human immunodeficiency virus in South Africa. If we relied on syndromic management alone to treat MG, only 15 of 46 MG-infected women would have received. appropriate treatment: sensitivity of 32.6% (95% confidence interval, 19.5-48.0) and specificity of 67.4% (95% confidence interval, 63.4-71.2).

Field evaluation of Standard Diagnostics' Bioline HIV/Syphilis Duo test among female sex workers in Johannesburg, South Africa.

BACKGROUND: Point-of-care tests provide immediate results with the opportunity for same-day interventions with improved public health outcomes. A dual HIV/syphilis test enables early treatment of both diseases. METHODS: We conducted a field evaluation of the Standard Diagnostics' SD Bioline HIV/Syphilis Duo test (SD Bioline) among female sex workers. SD Bioline was conducted on finger-prick blood according to manufacturer's instructions and compared with (i) Genscreen HIV1/2 (third generation) and Vironostika Ag/Ab (fourth generation) assays for HIV, and (ii) Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR) assays for syphilis. A negative TPPA test was considered negative, a TPPA-confirmed RPR titre ≤1:4 as past infection and a TPPA-confirmed RPR titre ≥1:8 as active syphilis. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Of 263 women recruited, 14 (5.3%) declined an HIV test. Among the remaining 249 women, 187 (75.1%) were HIV positive, 51 (20.5%) had syphilis antibodies with seven (2.8%) active infections. For HIV, the sensitivity and specificity were 98.9% (95% CI 95.8% to 99.8%) and 100% (95% CI 92.7% to 100%). For syphilis, the sensitivity and specificity were 66.7% (95% CI 52.0% to 78.9%) and 98.0% (95% CI 94.5% to 99.3%). Sera with high TPPA titres were more likely to test positive. CONCLUSIONS: In field conditions, while the SD Bioline test has high sensitivity and specificity for HIV and high specificity for syphilis, the test has lower sensitivity for syphilis than reported from laboratory evaluations. As the dual test detects only two thirds of syphilis cases, it should only be used in areas with weak screening programmes.

Etiology and antimicrobial susceptibility of pathogens responsible for urethral discharge among men in Harare, Zimbabwe.

BACKGROUND: Periodic etiological surveillance of sexually transmitted infection (STI) syndromes is required to validate treatment algorithms used to control STIs. However, such surveys have not been performed in Zimbabwe over the past decade. METHODS: A cross-sectional study design was used to determine the prevalence of the key STI etiological agents causing male urethral discharge (MUD). Urethral swab specimens were collected for molecular analysis and Neisseria gonorrhoeae isolation from consenting men 18 years and older who presented with MUD to the 12 clinics in Harare, Zimbabwe, between November 2010 and May 2011. A validated in-house multiplex polymerase chain reaction assay was used to detect the presence of N. gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. Gonococci were cultured on selective media, and antimicrobial susceptibilities were determined locally for ciprofloxacin, kanamycin, ceftriaxone, and cefixime using Etest strips, and minimum inhibitory concentrations were reported using defined breakpoints. RESULTS: Among 130 participants, N. gonorrhoeae was the most frequent pathogen detected (106; 82.8%), followed by C. trachomatis (15; 11.7%), M. genitalium (6; 4.7%), and T. vaginalis (2; 1.6%). Four (6.1%) of the 66 gonococci isolated were resistant to fluoroquinolones, whereas all viable isolates were susceptible to kanamycin, cefixime, and ceftriaxone. CONCLUSIONS: Gonorrhea is the most important cause of MUD in men in Harare, and our study highlights the emergence of fluoroquinolone-resistant N. gonorrhoeae. Further STI surveys are required in other regions of Zimbabwe to obtain a nationally representative picture of gonococcal burden and antimicrobial resistance among MUD patients.

Phenotypic and genetic characterization of the first two cases of extended-spectrum-cephalosporin-resistant Neisseria gonorrhoeae infection in South Africa and association with cefixime treatment failure.

OBJECTIVES: To describe the phenotypic and genetic characteristics of the first two cases of extended-spectrum cephalosporin (ESC)-resistant Neisseria gonorrhoeae in South Africa, one of which was associated with verified cefixime treatment failure. PATIENTS AND METHODS: Two ESC-resistant N. gonorrhoeae isolates were cultured from the urethral discharge of two men who have sex with men (MSM). One man reported a persistent urethral discharge that had failed to respond to previous therapy with oral cefixime. Agar dilution MICs were determined for eight antibiotics. ß-Lactam-associated resistance mutations were identified through PCR-based amplification and sequencing for several key genes: penA, mtrR and its promoter, porB1b (penB), ponA and pilQ. For molecular epidemiological characterization, full-length porB gene sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) were performed. RESULTS: Both isolates were resistant to cefixime, ciprofloxacin, penicillin and tetracycline and intermediate/resistant to azithromycin, but susceptible to ceftriaxone, gentamicin and spectinomycin. Both isolates had the type XXXIV penA mosaic allele in addition to previously described resistance mutations in the mtrR promoter (A deletion), porB1b (penB) (G101K and A102N) and ponA1 (L421P). Both isolates had an identical NG-MAST sequence type (ST4822) and MLST sequence type (ST1901). CONCLUSIONS: Both isolates were resistant to cefixime and possessed a number of identical mutations in key genes contributing to ESC resistance in N. gonorrhoeae. The two isolates contained the type XXXIV penA mosaic allele and belonged to a successful international MSM-linked multidrug-resistant gonococcal clone (MLST ST1901) associated with several cefixime treatment failures in Europe and North America.

Trends and associations of Trichomonas vaginalis infection in men and women with genital discharge syndromes in Johannesburg, South Africa.

OBJECTIVES: To better understand the epidemiology of Trichomonas vaginalis infection, we investigated the association between T vaginalis and demographic, clinical, microbiological and behavioural characteristics of patients presenting with genital discharges to a primary healthcare clinic in Johannesburg, South Africa. METHODS: During six annual surveys (2007-2012), 1218 cases of male urethral discharge syndrome and 1232 cases of vaginal discharge syndrome were consecutively recruited. Diagnostic methods included nucleic acid amplification (Neisseria gonorrhoeae, Chlamydia trachomatis, T vaginalis and Mycoplasma genitalium), microscopy (bacterial vaginosis and Candida) and serology (Treponema pallidum, herpes simplex virus type 2 (HSV-2) and HIV). Logistic regression analyses and χ2 tests were used to identify predictors of T vaginalis infection. RESULTS: The prevalence of T vaginalis decreased from 2007 to 2012 (men from 13.4% to 4.8%; women from 33.8 to 23.1%). Overall, 74 (6.1%) men and 291 (23.6%) women were T vaginalis positive, with the highest prevalence in those aged ≥40 years (men 13.6%; women 30.9%). T vaginalis infection occurred more often in pregnant women (adjusted OR (aOR) 2.67; 95% CI 1.29 to 5.54) and in women with serological evidence of T pallidum (aOR 1.63; 95% CI 1.08 to 2.45) or HSV-2 infections (aOR 1.75; 95% CI 1.16 to 2.64). T vaginalis infection occurred less often in men with coexistent gonorrhoea (aOR 0.35; 95% CI 0.21 to 0.57) and in women with either bacterial vaginosis (aOR 0.60; 95% CI 0.44 to 0.82) or Candida morphotypes (OR 0.61; 95% CI 0.43 to 0.86). CONCLUSIONS: Although the prevalence of T vaginalis infection has decreased over time, it remains an important cause of genital discharge in South Africa, particularly in older patients and pregnant women.

Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial.

Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15-19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.

Trends in Neisseria gonorrhoeae Antimicrobial Resistance over a Ten-Year Surveillance Period, Johannesburg, South Africa, 2008⁻2017.

BACKGROUND: In South Africa, sexually transmitted infections (STIs) are managed through a syndromic approach at primary healthcare centres (PHCs). Neisseria gonorrhoeae is the predominant cause of male urethritis syndrome. We describe antimicrobial resistance patterns and trends in Neisseria gonorrhoeae during a ten-year surveillance period at a large PHC in Johannesburg. METHODS: Neisseria gonorrhoeae was cultured from genital discharge swab specimens obtained from consenting adult patients presenting at the Alexandra Health Centre in Johannesburg between 2008 and 2017. Isolates were tested for antimicrobial susceptibility by Etest™ (cefixime, ceftriaxone, ciprofloxacin) or agar dilution (penicillin, tetracycline, azithromycin). RESULTS: During the period of surveillance, high-level resistance prevalence increased from 30% to 51% for penicillin (p-value for trend < 0.001), 75% to 83% for tetracycline (p-value for trend = 0.008), and 25% to 69% for ciprofloxacin (p-value for trend < 0.001). Analysis did not reveal high-level resistance to spectinomycin or a minimum inhibitory concentration (MIC) creep for extended-spectrum cephalosporins, and the prevalence of intermediate-resistance to azithromycin was less than 5%. CONCLUSIONS: High prevalence resistance to penicillin, tetracycline, and ciprofloxacin in N. gonorrhoeae obviates their use in future national treatment algorithms for genital discharge. It is essential to continue monitoring for emerging resistance to currently recommended antimicrobial therapy in this rapidly evolving pathogen.

Knowledge of HIV status and antiretroviral therapy use among sexually transmitted infections service attendees and the case for improving the integration of services in South Africa: A cross sectional study.

We describe knowledge of human immunodeficiency virus (HIV) status, correct report of HIV status and antiretroviral therapy (ART) use among sexually transmitted infection (STI) service attendees in South Africa.An anonymous questionnaire was administered and serological HIV testing done. Proportions of attendees reporting knowledge of HIV status and HIV status consistent with laboratory results and ART use (among HIV positives) were determined as were factors associated with knowledge and inconsistent report of HIV status.Of 1054 attendees, 288 (27.3%) were HIV positive and 830 (78.8%) self-reported knowledge of HIV status. Not knowing one's HIV status was associated with male gender [adjusted Odds Ratio (aOR) 2.66 (95% confidence interval (CI) 1.70-4.18] medical circumcision [aOR 0.48 (95% CI 0.24-0.95)] and site [Gauteng Province (GP)-aOR 6.20 (95% CI 3.51-10.95), Eastern Cape (EC)-aOR 17.29 (95% CI 10.08- 29.66) versus Free State (FS)/Western Cape (WC) sites]. Of 219 HIV positive attendees with knowledge of HIV status, 136 (62.1%) self-reported being HIV positive, of whom 80 (58.8%) reported taking ARVs in the preceding 3 days. Inconsistent report of status was associated with males [aOR 2.26 (95%CI 1.05-4.87)], prior STI treatment [aOR 0.33 (95% CI 0.16-0.69)], recent HIV testing (6months) [aOR 3.20 (95% CI 1.62-6.36)] and site [GP-aOR 6.89 (95% 3.21-14.82), EC-aOR 5.08 (95% CI 2.15-11.64) versus FS/WC sites]. Knowledge of HIV status was lower than targeted. HIV testing and linkage to care services are essential in STI-related care and validation of self-reported indicators in this population maybe necessary.

Endocervical and vaginal microbiota in South African adolescents with asymptomatic Chlamydia trachomatis infection.

Adolescent girls and young women represent a key risk group for sexually transmitted infections (STIs). The vaginal microbiota is thought to play an important role in susceptibility to STIs such as Chlamydia trachomatis. We compared the microbiota of the lateral vaginal wall and endocervix, and assessed associations with C. trachomatis infection in South African adolescents. The endocervical and vaginal lateral wall microbiota were characterized by amplifying and sequencing the V4 region of the 16S rRNA gene and C. trachomatis diagnosed using molecular methods. Of the 72 girls included, 30 had asymptomatic C. trachomatis infections. Three major vaginal community types were identified; one Lactobacillus crispatus, one L. iners and one diverse, Gardnerella vaginalis dominant. The microbiota of the endocervix was significantly different from that of the lateral wall in terms of diversity. There were many differentially abundant taxa between the endocervix and lateral vaginal wall, including Achromobacter spanius and Enterococcus faecium. Women with C. trachomatis had higher relative abundance of G. vaginalis and other anaerobes. In this African adolescent cohort, significant differences between the lateral vaginal wall and endocervical microbiota diversity and composition were evident, although neither were strongly associated with C. trachomatis infection.

Converging epidemics of sexually transmitted infections and bacterial vaginosis in southern African female adolescents at risk of HIV.

Adolescents in Africa are at high risk for HIV infection, other sexually transmitted infections (STIs) and bacterial vaginosis (BV). Since behavior and burden of STIs/BV may influence HIV risk, behavioral risk factors and prevalence of STIs/BV were compared in HIV-seronegative adolescent females (n = 298; 16-22 years) from two South African communities (Soweto and Cape Town). STIs ( Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus (HSV)-1, HSV-2, Treponema pallidum, and Haemophilus ducreyi) were detected by multiplex polymerase chain reaction, human papillomavirus (HPV) by Roche Linear Array, and BV by Nugent scoring. Rates of BV (Nugent ≥7; 46.6%) and HPV (66.8%) were high in both communities. Prevalence of C. trachomatis and N. gonorrhoeae were >2-fold higher in Cape Town than Soweto (Chlamydia: 42% [62/149] versus 18% [26/148], p < 0.0001; gonorrhoea 11% [17/149] versus 5% [7/148], p = 0.05). Only 24% of adolescents with vaginal discharge-causing STIs or BV were symptomatic. In South African adolescents, clinical symptoms compatible with vaginal discharge syndrome had a sensitivity of 23% and specificity of 85% for the diagnosis of discharge-causing STI or BV. In a region with high HIV prevalence and incidence, >70% of young women with treatable conditions that could enhance HIV risk would have been missed because they lacked symptoms associated with syndromic management.