Beyond syndromic management: Opportunities for diagnosis-based treatment of sexually transmitted infections in low- and middle-income countries

Introduction In light of the limited impact the syndromic management approach has had on the global sexually transmitted infection (STI) epidemic, we assessed a care model comprising point-of-care (POC) STI testing, immediate treatment, and expedited partner therapy (EPT) among a cohort of young women at high HIV risk in South Africa. Methods and findings HIV negative women presenting for STI care underwent POC testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV), and swabs were sent for NG culture and susceptibility testing. Results were available within 2 hours and women with STIs were immediately treated and offered EPT packs, including medication, condoms, and information for sexual partners. An EPT questionnaire was administered after one week, and women retested for STIs after 6 and 12 weeks. 267 women, median age 23 (IQR 21–26), were recruited and 88.4% (236/267) reported genital symptoms. STI prevalence was CT 18.4% (95%CI 13.7–23.0), NG 5.2% (95%CI 2.6–7.9) and TV 3.0% (95%CI 1.0–5.0). After 12 weeks, all but one NG and two CT infections were cleared. No cephalosporin-resistant NG was detected. Of 63/267 women (23.6%) diagnosed with STIs, 98.4% (62/63) were offered and 87.1% (54/62) accepted EPT. At one week 88.9% (48/54) stated that their partner had taken the medication. No allergic reactions or social harms were reported. Of 51 women completing 6-week follow up, detection rates were lower amongst women receiving EPT (2.2%, 1/46) compared to those who did not (40.0%, 2/5), p = 0.023. During focus group discussions women supported the care model, because they received a rapid, specific diagnosis, and could facilitate their partners’ treatment. Conclusions POC STI testing and EPT were acceptable to young South African women and their partners, and could play an important role in reducing STI reinfection rates and HIV risk. Larger studies should evaluate the feasibility and cost-effectiveness of implementing this strategy at population level

Testing the regulatory framework in South Africa – a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis

CITATION: Happel, A. U., et al. 2020. Testing the regulatory framework in South Africa – a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis. BMC Infectious Diseases, 20:491, doi:10.1186/s12879-020-05210-4.The original publication is available at https://bmcinfectdis.biomedcentral.comBackground: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment. Methods: Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7–10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment. Results: The South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24–1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product. Conclusion: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05210-4Publisher's versio

Characteristics of 267 young women attending STI care.

<p>Characteristics of 267 young women attending STI care.</p

Consort diagram of expedited partner therapy intervention for women in the CAPRISA 083 cohort study.

<p>Consenting women were offered participation in the CAPRISA 083 study and underwent point-of-care (POC) testing for sexually transmitted infections (STI). Those diagnosed with Chlamydia (CT), Gonorrhoea (NG) or Trichomoniasis (TV) were offered expedited partner therapy (EPT) to deliver to their partners. Women were contacted by phone one week later, and retested for STIs after six weeks. Some women were lost to follow-up (LTFU).</p

Prevalence of STIs, bacterial vaginosis and candidiasis at baseline in 267 young South African women.

<p>Prevalence of STIs, bacterial vaginosis and candidiasis at baseline in 267 young South African women.</p

STI detection after POC STI testing, immediate treatment and EPT intervention.

<p>STI detection after POC STI testing, immediate treatment and EPT intervention.</p

Whole-Genome Sequencing to Predict Antimicrobial Susceptibility Profiles in Neisseria gonorrhoeae.

BackgroundNeisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates.MethodsSusceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility.ResultsA total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL.ConclusionsSingle marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials