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Background. Nephroblastoma is a common childhood solid tumour in South Africa. Objective. The aim was to determine outcomes of patients diagnosed with nephroblastoma between 1990 and 2018 and compare outcomes of two cohorts treated with consecutive International Society of Paediatric Oncology (SIOP) nephroblastoma protocols. Methods. This was a retrospective, descriptive study of two cohorts in Tygerberg Hospital. Cohort 1 (1990 - 2007) was treated with the SIOP 9 and SIOP 93-01 protocols, and Cohort 2 (2008 - 2018) with the SIOP 2001 protocol. Data included demographic data (age at diagnosis, sex), HIV status, pre- and postoperative staging, surgical complications, histological types, lymph node sampling, overall survival (OS) and event-free survival (EFS) with the end point two years after diagnosis. Results. There were 60 children (M:F ratio 1:1.14) in Cohort 1 with an older mean age of 42 months (interquartile range (IQR) 16.25 - 56.5 months) v. 45 children (M:F ratio 1:0.8) in Cohort 2 with a mean age of 37 months (IQR 22 - 45.5 months). Cohort 2 had more patients with localised disease (76%) than Cohort 1 (55%) (trend towards significance p=0.076). Both cohorts had a good OS (respectively 88% and 93%) and EFS (respectively 82% and 80%). Half of Cohort 1 (50%; n=30/60) did not have lymph nodes sampled with four subsequent relapses, significantly associated with OS (p<0.001) and EFS (p=0.006). There was a significant association between OS and EFS and underlying histology (respectively p=0.006 and p=0.015) for Cohort 1, but only for EFS and histology (p=0.02) for Cohort 2. Conclusion. There was good OS for children with nephroblastoma treated with consecutive SIOP protocols in a single institution in South Africa. [ABSTRACT FROM AUTHOR]

The Consumer Protection Act (CPA) lays the basis for the protection of consumer rights in South Africa and comprehensively sets out obligations for "suppliers". There have been differing views expressed as to whether a student should be seen as a consumer. It is clear, however, that this Act applies to HEIs. This article, firstly, explores the concept of a student as "a customer/consumer". Secondly, it examines specific aspects of the CPA which will have an impact on HEIs as service providers in the education sector. It concludes that the impact of the CPA for business is far-reaching. It also directs that HEIs must take into account the provisions of this Act, particularly with respect to the rights to: equality, generally and with regard to access; disclosure and information; fair and equal marketing practices; and fair and reasonable terms and conditions, as well as fair value and good quality. HEIs are advised to scrutinize their current practices, policies, terms and conditions, in order to ensure that they comply with the Act.

The problem explored is the relatively low research output at a merged Higher Education Institution (HEI). The re-landscaping of how HEIs operate, has impacted on merged institutions, especially those of a comprehensive nature, that are facing the challenge of improving research output. This article is based on research conducted for a Master's study. In this article, the focus is on capacity building as a strategy to develop human resources in the field of research, using mentorship, with the aim of improving research output. The researchers explored a formal research mentorship programme (REMP) at tertiary institutions using a case study and adopting a mixed method approach. The case study was conducted at a merged HEI in Gauteng, viz. the University of Johannesburg (UJ). The study, via a survey and semi-structured interviews, obtained views and perceptions from academic staff members and deans, with regard to the implementation of a formal REMP. The results (from the interviews with the deans) reveal that an informal, spontaneous and collegial type of mentoring was preferred. However, these views differed with that of the findings of the survey (conducted among academic staff), which showed that a majority of the respondents favoured a formal REMP and they also believed that REMP guides young academics in terms of the research process and methodology. Based on some of these findings, a formal REMP is recommended. (Contains 7 figures.)

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences., (© 2024. The Author(s).)

We evaluated correlates of adherence to PrEP, including daily oral tenofovir disoproxil fumarate in combination emtricitabine (oral FTC/TDF) and the monthly dapivirine ring (ring)among adolescent girls and young women (AGYW) in the MTN-034/REACH study. We enrolled 247 AGYW aged 16-21 years in South Africa, Uganda and Zimbabwe (ClinicalTrials.gov: NCT03074786). Participants were randomized to the order of oral FTC/TDF or ring use for 6 months each in a crossover period, followed by a 6-month choice period. We assessed potential adherence correlates-individual, interpersonal, community, study, and product-related factors-quarterly via self-report. We measured biomarkers of adherence monthly; high adherence was defined as > 4 mg dapivirine released from returned rings or intracellular tenofovir diphosphate levels ≥ 700 fmol/punch from dried blood spots (DBS). We tested associations between correlates and objective measures of high adherence using generalized estimating equations. High adherence to oral FTC/TDF was significantly associated with having an older primary partner (p = 0.04), not having exchanged sex in the past 3 months (p = 0.02), and rating oral FTC/TDF as highly acceptable (p = 0.003). High ring adherence was significantly associated with unstable housing (p = 0.01), disclosing ring use to a male family member (p = 0.01), and noting a social benefit from study participation (p = 0.03). All associations were moderate, corresponding to about 6%-10% difference in the proportion with high adherence. In our multinational study, correlates of adherence among African AGYW differed for oral FTC/TDF and the ring, highlighting the benefit of offering multiple PrEP options., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hospitalized neonates are vulnerable to infection and have high rates of antibiotic utilization., Methods: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymized demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis., Findings: During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; P = 0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95% CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); P = 0·032)., Interpretation: This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis., Funding: A grant from Merck provided partial support., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: HIV incidence remains high in South Africa, with ~ 60% of all new HIV infections among adolescent girls and women (Country factsheets HIV and AIDS Estimates, 2022). Oral pre-exposure prophylaxis (PrEP), approved for HIV prevention in South Africa since 2015, is hampered by low uptake and adherence, particularly among adolescent girls and young women (AGYW). Combining oral PrEP with oral contraceptives could increase PrEP uptake, persistence and address unmet needs for contraception. We investigated the acceptability of a dual prevention pill (DPP), combining oral PrEP and a combined oral contraceptive (COC) for HIV and pregnancy prevention among women in Johannesburg, South Africa., Methods: Between March-July 2021, we conducted 12 focus group discussions (FGDs) with adolescent girls and women (n = 74) aged 16-40 stratified by ages (16-17, 18-24, 25-40), half of whom were COC users. We explored adolescent girls and women's opinions about the DPP concept, existing HIV and pregnancy prevention options, and input on perceived facilitators and barriers to DPP use. FGDs were conducted in English or isiZulu, using a standardized interview guide. FGDs were audio-recorded, transcribed to English and analyzed using ethnographic content analysis., Results: The majority viewed the DPP favorably as a multipurpose option preventing unplanned pregnancy and HIV. Most saw it as a convenient "two-in-one" solution, requiring one clinic visit for both PrEP and COCs. AGYW were viewed as the most likely to benefit from the DPP due to the likelihood of multiple partners and unplanned sex, possibly preventing school dropout from unplanned pregnancy or HIV acquisition. The DPP was perceived to be more reliable than condoms, especially when condom negotiation is limited. Benefits were also seen by participants in rape cases, protecting against pregnancy and HIV. DPP use barriers included side effect concerns, unsupportive partners and judgmental healthcare providers., Conclusions/significance: The DPP was perceived as acceptable for HIV and pregnancy prevention to AGYW in Johannesburg and its dual indications helpful in supporting improved PrEP uptake and persistence. DPP implementation programs need to consider solutions to potential barriers, like education on DPP benefits, coupled with reliable side effect support and healthcare provider sensitization as part of routine sexual health services to encourage uptake and adherence., (© 2024. The Author(s).)

Introduction: Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP with oral contraception (OC) may increase PrEP use and better meet women's sexual and reproductive health needs. We will gauge the DPP's acceptability in two cross-over clinical trials., Methods and Analysis: PC952 (Zimbabwe) and PC953 (South Africa) will compare acceptability, adherence and preference for an over-encapsulated DPP versus PrEP and OCs taken separately. HIV-negative, non-pregnant cisgender females in Johannesburg, South Africa (n=96, 16-40 years) and Harare, Zimbabwe (n=30, 16-24 years) will be randomised 1:1 to the order of regimens-DPP or two separate tablets-each used for three 28-day cycles, followed by a 6-month choice period in South Africa. Monthly clinic visits include HIV and pregnancy testing; safety assessments and risk reduction and adherence counselling. We will assess adherence (monthly) based on tenofovir diphosphate drug levels in dried blood spots and by self-report. We will evaluate acceptability (monthly) and preference (end of cross-over) via computer-assisted self-interviewing and in-depth interviews with a subset of participants. Data collection started in September 2022 and ended in January 2024., Ethics and Dissemination: PC952 was approved by the Ministry of Health and Child Care, Medical Research Council, Research Council and Medicines Control Authority of Zimbabwe; the Chitungwiza City Health Ethics Committee; and the Joint Research Ethics Committee for the University of Zimbabwe Faculty of Medicine and Health Sciences and Parirenyatwa Group of Hospitals. PC953 was approved by the South African Health Products Regulatory Authority and the University of the Witwatersrand's Human Research Ethics Committee. The Population Council IRB approved both studies. We will disseminate results in open-access journals, clinical trials registries, and at local and international meetings and conferences., Trial Registration Numbers: NCT04778514, NCT04778527., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: East and Southern Africa are the epicenter of the HIV epidemic. High HIV incidence rates among adolescent girls and young women (AGYW) remain stable over the last decade despite access to daily oral PrEP. Some settings have experienced high PrEP uptake among AGYW; however, discontinuation has been high. This review sought to understand drivers of PrEP discontinuation in this population in order to identify potential mechanisms to facilitate PrEP restart and optimize PrEP use., Recent Findings: Drivers of PrEP discontinuation included low perceived HIV acquisition risk, PrEP-associated side effects, pill burden, family/sexual partner disapproval, lack of/intermittent sexual activity, PrEP use stigma, fear of intimate partner violence, misinformation about long-term PrEP use, and limited/inconsistent access to PrEP. The most frequently reported driver of PrEP discontinuation was low perceived HIV acquisition risk. This indicates that innovative interventions to help AGYW recognize their HIV risk and make informed decisions about PrEP use are urgently needed., (© 2023. The Author(s).)

Background: Half of new HIV acquisitions in Africa occur in adolescent girls and young women. Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine or the monthly dapivirine vaginal ring is efficacious but has lower adherence and effectiveness among adolescent girls and young women. We aimed to assess product adherence, safety, and choice of oral PrEP compared with the dapivirine ring among African adolescent girls and young women., Methods: MTN-034/REACH was a randomised, open-label, phase 2a crossover trial among HIV-seronegative, non-pregnant adolescent girls and young women aged 16-21 years at four clinical research sites in South Africa, Uganda, and Zimbabwe. Participants were randomly assigned (1:1) to either the dapivirine ring or daily oral PrEP (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) for 6 months, then switched to the other product option for 6 months, followed by a third 6-month period in which participants were given a choice of oral PrEP, the dapivirine ring, or neither. Fixed block randomisation was used, stratified by site. The primary adherence endpoint was use of each product during the randomised periods, with high use defined as tenofovir-diphosphate concentrations greater than or equal to 700 fmol/punch (associated with taking an average of four or more tablets per week in the previous month) and greater than or equal to 4 mg dapivirine released from the returned ring (continuous use for 28 days in the previous month) based on residual drug concentrations. The primary safety endpoint was grade 2 or higher adverse events during each randomised period of 24 weeks of ring and oral PrEP. This trial is registered at ClinicalTrials.gov, NCT03593655., Findings: From Feb 6, 2019 to Sept 9, 2021, 396 adolescent girls and young women were screened, 247 of whom were enrolled and randomly assigned (6 months of the ring followed by 6 months of oral PrEP n=124; 6 months of oral PrEP followed by 6 months of the ring n=123). Median age was 18 years (IQR 17-19). 54 grade 2 or higher product-related adverse events were reported during oral PrEP and five during dapivirine ring use, with no product-related serious adverse events. High adherence was observed in 753 (57%) of the 1316 oral PrEP visits and 806 (57%) of the 1407 dapivirine ring visits. Four women acquired HIV during follow-up., Interpretation: Adherence was moderately high and similar between oral PrEP and the dapivirine ring with favourable safety and tolerability. Oral PrEP and the dapivirine ring are effective, safe, and well tolerated HIV prevention options for adolescent girls and young women who would benefit from a choice of PrEP formulations to meet their needs and preferences., Funding: National Institutes of Health., Competing Interests: Declaration of interests CC has received consulting fees from Gilead Sciences and Merck, and has been an expert witness for Gilead. SLH has received consulting fees and funds to her institution from Merck. KN has received research funds from Merck (Merck Sharpe & Dohme). JMB and JFR are employees of Gilead Sciences. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation., Methods: AGYW aged 16-21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months. Eligible AGYW were HIV-negative, not pregnant and using effective contraception for at least two months prior to enrollment. Descriptive statistics were used to summarize demographic and behavioral data while multinomial analysis was used to determine predictors of stated product preference (ring or oral PrEP)., Results: Of the 247 AGYW enrolled in REACH, 34% were aged 16-17 and 89% had a primary partner.The median age of sexual debut was 16 years and 40% had ever been pregnant. At screening, 35% of participants were diagnosed with a sexually transmitted infection (STI), 39% had an AUDIT-C score associated with harmful drinking and 11% reported intimate partner violence in the past 6 months. Overall, 28% of participants, had CESD-10 scores suggestive of depressive symptoms (≥12) in the past week. At baseline, similar proportions stated a preference for the ring and oral PrEP (38.1% and 40.5% respectively), with 19% of participants stating they preferred both products equally. Only study site was significantly associated with product preference (P<0.05) with AGYW from Johannesburg having higher odds of preferring the ring and those from Kampala having higher odds of preferring both options equally., Conclusions: We successfully enrolled African AGYW with a clear unmet need for HIV prevention. The balanced preference between the two products suggests that multiple biomedical prevention options may be appealing to this age group and could address their prevention needs., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Ngure et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. We evaluated post-randomization sexual behavior using an objective marker of condomless vaginal sex in a subset of participants. We conducted a sub-study among 458 ECHO participants at three sites (Cape Town, Johannesburg, Kisumu) to evaluate the frequency of condomless vaginal sex, measured by prostate specific antigen (PSA) detection in vaginal swabs, collected at the month 6 and final visit and the concordance of self-reported condomless vaginal sex with PSA detection, by randomized arm. We compared PSA detection frequency and concordance of PSA and self-reported condomless vaginal sex, by randomized group using Cochran-Mantel-Haenszel tests and adjusted generalized logistic growth curve models. PSA was detected less frequently in the DMPA-IM (16%), compared to the Cu-IUD (21%) and LNG implant (24%) groups, although results were not statistically significant in the unadjusted model when accounting for pre-specified multiple-testing criteria. There were significant differences in PSA detection between the DMPA-IM and LNG-implant groups (odds ratio 0.61 (95% CI 0.40, 0.94) in the adjusted model. There was moderate discordance between self-reported condomless vaginal sex and detection of PSA that was similar across randomized groups. These data suggest that women randomized to Cu-IUD and LNG implant may have had condomless sex more frequently than women randomized to DMPA-IM. The discordance between detectable PSA and self-reported sexual behaviour has important implications for design of future HIV prevention studies., (© 2022. The Author(s).)

Background: Persistent use of HIV prevention methods can be a challenge, particularly for some younger women. The long-acting, discreet, woman-centric dapivirine vaginal ring offers promise as a prevention method with less user burden, which could support continued use. We assessed dapivirine vaginal ring use to understand adherence patterns and identify characteristics influencing patterns., Setting: Participants enrolled in South Africa in the MTN-020/ASPIRE randomized placebo-controlled trial., Methods: We used group-based trajectory modeling to identify clusters of participants with similar longitudinal patterns of adherence in the last year of participation and potential predictors of group membership. Women with at least 1 year of follow-up were included (n = 626)., Results: Five adherence patterns were identified: (1) consistently high, 34%, (2) consistently moderate, 34%, (3) consistently low, 16%, (4) decreasing, 9%, and (5) increasing, 7%. Women younger than 22 years [adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI): 1.0 to 3.0], using an intrauterine device (AOR 3.3, 95% CI: 1.4 to 7.8) or oral contraceptives (AOR 3.9, 95% CI: 1.7 to 8.9), experiencing menses (AOR 1.8, 95% CI: 1.1 to 3.0), and who reported inconsistent condom use (AOR 1.8, 95% CI: 1.0 to 3.3) were more likely to be classified as consistently low compared to consistently high (referent)., Conclusions: Most South African women successfully persisted with a moderate or high level of use. Encouraging ring replacement with completion of menses may help to decrease concerns about hygiene and improve persistence. Associations between contraception and persistent low adherence suggest efforts may be needed to ensure contraceptive method choice does not interfere with ring use., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Consistent use of oral pre-exposure prophylaxis (PrEP) has been a challenge among women, particularly when in relationships with lack of partner support or intimate partner violence (IPV)., Methods: We conducted a randomized controlled trial (RCT) of an empowerment counseling intervention called "CHARISMA" delivered to women within a PrEP demonstration project in Johannesburg, South Africa. The trial tested the effectiveness of CHARISMA to increase PrEP adherence; decrease social harms and IPV; and improve partnership dynamics (eg, communication, disclosure and support) compared with those who received the standard of care counselling support and referrals. Four hundred seven HIV-seronegative, nonpregnant women aged 18-45 years were enrolled for 6 months of PrEP use, with 203 randomized (1:1) to the intervention. All participants reporting IPV received counseling and referrals that followed the WHO five-step Listen, Inquire, Validate, Enhance Safety, and Support approach., Results: This RCT did not identify statistically significant differences between study arms for PrEP adherence or relationship dynamics, with the exception of an increase in PrEP disclosure among intervention arm women. In our study, we cannot determine whether the lack of detectable findings may have been because of lack of intervention effect, strength of standard of care services, low risk in the study population, or other factors., Conclusions: Addressing IPV and relationship dynamics remain important factors influencing HIV risk, and addressing these within the context of PrEP delivery is an important synergistic opportunity. CHARISMA was highly acceptable to participants, and further adaptation and testing of the intervention to other populations and settings will augment the evidence base., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: GK has a family financial interest in a global health technology company, Dimagi. KR receives royalties from UpToDate, for authorship of an article about electronic cigarettes. NAR receives royalties from UpToDate for writing about smoking cessation topics and is a consultant for Achieve Life Sciences regarding an investigational smoking cessation medication.

Introduction: South Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition., Methods: During December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16-35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12-18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection., Results: 5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05-5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV., Conclusions: HIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population., Clinical Trial Registration: ClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites., Competing Interests: The authors have declared that no competing interests exist.

Women who acquire HIV during the pregnancy and breastfeeding periods have a higher risk of transmitting the virus to their child than women who become infected with HIV before pregnancy. We explore the context of sexual beliefs and practices that may shape both HIV risk and willingness to use HIV prevention products during pregnancy and postpartum in Malawi, South Africa, Uganda and Zimbabwe. Twenty-three single sex focus group discussions and 36 in-depth interviews took place between May and November 2018 with recently pregnant or breastfeeding women, men, mothers and mothers-in-law of pregnant or breastfeeding women, and key informants. Participants across study groups and sites (N = 232) reported various perceived benefits and harms of sex during pregnancy and postpartum. Participants discussed reasons why men might seek sex outside of the relationship. There is a critical need for alternative prevention options to protect pregnant and breastfeeding women from HIV., (© 2021. The Author(s).)

Biomedical, female-initiated HIV prevention methods can help reduce disproportionately high HIV rates among women in sub-Saharan Africa, but male partner resistance and intimate partner violence (IPV) may impact ability to ensure effective use. To support consistent use of the dapivirine vaginal ring (VR), we pilot-tested the impact of the CHARISMA relationship counseling intervention ("CHARISMA") with women enrolled in the multi-site open-label Microbicide Trials Network (MTN) 025/HOPE trial at the Wits Reproductive Health and HIV Research Institute (Wits RHI) site in Johannesburg, South Africa. Lay counselors used a 42-item tool with five subscales to assess relationships and IPV and provide tailored counseling at enrolment, followed by a booster counselling session at Month 1 and follow-up checks at Months 3 and 6. We evaluated potential impact by examining self-reported ring disclosure to partners, partner clinic attendance, self-reported incident social harms (SH) and IPV, and biomarkers of ring adherence at Wits RHI. We subsequently compared these outcomes at three comparator HOPE study sites using multivariable regression models. Comparator study sites were purposively selected as those most similar to Wits RHI for baseline characteristics identified a priori. At Wits RHI, 95 of 96 (99%) HOPE participants enrolled into the CHARISMA pilot study. Mean age was 30, 36.8% lived with a partner, and 85.3% received their partner's financial support. During the six months of pilot study follow-up, participants reported: ring use disclosure to partners at 72.7% visits; 4.3% partners attending the research clinic; one partner-related SH; and 9.5% experienced incident IPV. The mean level of dapivirine released from returned used rings was 3.4 mg (SD 1.56), suggesting moderate adherence. Participants in the CHARISMA pilot had high background prevalence and incidence of IPV but were nevertheless able to adhere to ring use, and some male partners came to the research clinic. In adjusted regression models, compared to Wits RHI, partner clinic attendance was lower at all comparator sites; and significantly so at Site A (aRR 0.12, 95% CI 0.00-0.98). Sites B and C had lower levels of dapivirine released (suggesting lower adherence), but this difference was not significant. Site B women were more likely to report ring disclosure to partners at FU visits (aRR 1.12, 95% CI 1.00-1.25). IPV reported during follow-up was significantly lower at Site B (aRR 0.20, 95% CI 0.04-0.98, p = 0.047). CHARISMA taught women skills to decide on levels of ring-use disclosure to partners or others; therefore it is difficult to interpret differences in ring disclosure to partners with other sites. Similarly, CHARISMA heightened participants' awareness of abuse, possibly increasing IPV reports. Testing CHARISMA under fully-powered controlled conditions will improve understanding of its impact on women's relationships and ability to use female-initiated HIV prevention methods., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe the anthropometry, socioeconomic circumstances, diet and screen time usage of adolescents in India and Africa as context to a qualitative study of barriers to healthy eating and activity., Design: Cross-sectional survey, including measured height and weight and derived rates of stunting, low BMI, overweight and obesity. Parental schooling and employment status, household assets and amenities, and adolescents' dietary diversity, intake of snack foods, mobile/smartphone ownership and TV/computer time were obtained via a questionnaire., Setting: Four settings each in Africa (rural villages, West Kiang, The Gambia; low-income urban communities, Abidjan, Cote D'Ivoire; low/middle-class urban communities, Jimma, Ethiopia; low-income township, Johannesburg, South Africa) and India (rural villages, Dervan; semi-rural villages, Pune; city slums, Mumbai; low-middle/middle-class urban communities, Mysore)., Participants: Convenience samples (n 41-112 per site) of boys and girls, half aged 10-12 years and another half aged 15-17 years, were recruited for a qualitative study., Results: Both undernutrition (stunting and/or low BMI) and overweight/obesity were present in all settings. Rural settings had the most undernutrition, least overweight/obesity and greatest diet diversity. Urban Johannesburg (27 %) and Abidjan (16 %), and semi-rural Pune (16 %) had the most overweight/obesity. In all settings, adolescents reported low intakes of micronutrient-rich fruits and vegetables, and substantial intakes of salted snacks, cakes/biscuits, sweets and fizzy drinks. Smartphone ownership ranged from 5 % (West Kiang) to 69 % (Johannesburg), higher among older adolescents., Conclusions: The 'double burden of malnutrition' is present in all TALENT settings. Greater urban transition is associated with less undernutrition, more overweight/obesity, less diet diversity and higher intakes of unhealthy/snack foods.

Background: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD., Objectives:  To evaluate whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be applied in the context of MSMD in SA., Methods: This study is a retrospective review of an SA PIDD cohort. Patients aged 0 - 15 years with SPUR TB infections, assessed between 2013 and 2018, were identified using a proposed algorithm. HIV infection or other secondary causes for immunodeficiency were excluded. Basic investigations, then focused immunophenotyping and next-generation sequencing, were performed., Results:  A total of 20 patients with a clinical diagnosis of MSMD were identified. A further two, forming part of a family cohort, had pathogenic variants but remain asymptomatic. Infection with Mycobacterium tuberculosis complex predominated (64%), while 27% had BCG infection or non-tuberculous mycobacteria (NTM) infection. Molecular analysis revealed pathogenic variants in 41% of patients with SPUR mycobacterial infection, mainly in those with BCG/NTM infection., Conclusions:  In the SA paediatric population, SPUR TB infections, particularly BCG/NTM, in the absence of secondary immunodeficiency, can alert to possible MSMD. The molecular diagnosis is pivotal, guiding disease classification and influencing clinical approach and management. The diagnosis is complex and requires a multidisciplinary approach with close collaboration between clinical immunologists, bioinformaticians, immunologists, clinical geneticists and genetic counsellors.

Background: We aimed to describe the epidemiology of candidemia among children in South Africa., Methods: We conducted laboratory-based surveillance among neonates (≤28 days), infants (29 days to <1 year), children (1-11 years) and adolescents (12-17 years) with Candida species cultured from blood during 2012-2017. Identification and antifungal susceptibility of viable isolates were performed at a reference laboratory. We used multivariable logistic regression to determine the association between Candida parapsilosis candidemia and 30-day mortality among neonates., Results: Of 2996 cases, neonates accounted for 49% (n = 1478), infants for 27% (n = 806), children for 20% (n = 589) and adolescents for 4% (n = 123). The incidence risk at tertiary public sector hospitals was 5.3 cases per 1000 pediatric admissions (range 0.39-119.1). Among 2943 cases with single-species infections, C. parapsilosis (42%) and Candida albicans (36%) were most common. Candida auris was among the 5 common species with an overall prevalence of 3% (n = 47). Fluconazole resistance was more common among C. parapsilosis (55% [724/1324]) versus other species (19% [334/1737]) (P < 0.001). Of those with known treatment (n = 1666), 35% received amphotericin B deoxycholate alone, 32% fluconazole alone and 30% amphotericin B deoxycholate with fluconazole. The overall 30-day in-hospital mortality was 38% (n = 586) and was highest among neonates (43% [323/752]) and adolescents (43% [28/65]). Compared with infection with other species, C. parapsilosis infection was associated with a reduced mortality among neonates (adjusted odds ratio 0.41, 95% confidence interval: 0.22-0.75, P = 0.004)., Conclusions: Candidemia in this setting mainly affected neonates and infants and was characterized by fluconazole-resistant C. parapsilosis with no increased risk of death., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Empirical antibiotic strategies in the treatment of chronic osteomyelitis should ideally be based on local microbiological antibiograms., Objectives: To review the antibiogram profiles of bacterial isolates of patients undergoing surgical treatment for chronic osteomyelitis and identify the most appropriate empirical antibiotic strategy., Methods: A retrospective review of clinical records and microbial culture reports was performed for all patients who underwent treatment for chronic osteomyelitis at two orthopaedic units in Western Cape Province, South Africa, between March 2016 and December 2019. Reported antibiotic susceptibility data were used to predict the potential efficacy of different empirical antibiotic regimens, according to underlying aetiology (fracture related, contiguous, haematogenous)., Results: Two hundred patients with chronic osteomyelitis of the appendicular skeleton underwent surgical management. Antibiogram profiles for 218 organisms, isolated from 169 patients, were evaluated. Staphylococcus aureus (41%) and Enterobacterales (30%) were the most common organisms isolated. The combinations of meropenem plus vancomycin, and piperacillin-tazobactam plus amikacin plus vancomycin, as empirical postoperative antibiotics would both effectively treat 78% of chronic osteomyelitis cases overall. The most effective practical oral combinations were co-amoxiclav plus ciprofloxacin (61%) and co-trimoxazole plus ciprofloxacin (61%)., Conclusions: This study reports antibiogram profiles in the developing-world setting that could potentially guide empirical antibiotic choices in the management of chronic osteomyelitis.

Background: Empirical broad-spectrum antibiotics are frequently prescribed to patients with severe COVID-19, motivated by concern about bacterial coinfection. There is no evidence of benefit from such a strategy, while the dangers of inappropriate antibiotics are well described., Objectives: To investigate the frequency, profile and related outcomes of infections by bacterial pathogens in patients admitted to an intensive care unit (ICU) with severe COVID-19 pneumonia., Methods: This was a prospective, descriptive study in a dedicated COVID-19 ICU in Cape Town, South Africa, involving all adult patients admitted to the ICU with confirmed COVID-19 pneumonia between 26 March and 31 August 2020. We collected data on patient comorbidities, laboratory results, antibiotic treatment, duration of admission and in-hospital outcome., Results: We included 363 patients, who collectively had 1 199 blood cultures, 308 tracheal aspirates and 317 urine cultures performed. We found positive cultures for pathogens in 20 patients (5.5%) within the first 48 hours of ICU admission, while 73 additional patients (20.1%) had positive cultures later during their stay. The most frequently isolated pathogens at all sites were Acinetobacter baumannii (n=54), Klebsiella species (n=13) and coagulase-negative staphylococci (n=9). Length of ICU stay (p&lt;0.001) and intubation (p&lt;0.001) were associated with positive cultures on multivariate analysis. Disease severity (p=0.5), early antibiotic use (p=0.5), diabetes mellitus (p=0.1) and HIV (p=0.9) were not associated with positive cultures. Positive cultures, particularly for tracheal aspirates (p&lt;0.05), were associated with longer ICU length of stay and mortality. Early empirical antibiotic use was not associated with mortality (odds ratio 2.5; 95% confidence interval 0.95 - 6.81)., Conclusions: Bacterial coinfection was uncommon in patients at the time of admission to the ICU with severe COVID-19. Avoiding early empirical antibiotic therapy is therefore reasonable. Strategies to avoid coinfection and outbreaks in hospital, such as infection prevention and control, as well as the strict use of personal protective equipment, are important to improve outcomes.

Background: Positive blood cultures showing Gram positive cocci in clusters signifies either Staphylococcus aureus or the less-virulent coagulase-negative staphylococci. Rapid identification and methicillin susceptibility determination with the Xpert MRSA/SA BC assay can improve management of S. aureus bloodstream infection and reduce inappropriate antibiotic use., Methods: We prospectively evaluated the Xpert MRSA/SA BC assay in comparison with culture, on samples referred to our laboratory in the Western Cape, South Africa. We interviewed attending clinicians upon culture result availability, to assess antibiotic choices and estimate potential impact of the assay., Results: Of the 231 samples included, there was 100% concordance between the Xpert MRSA/SA BC assay and culture (methicillin-resistant S. aureus 15/15, methicillin-susceptible S. aureus 42/42, coagulase-negative staphylococci 170/170). Time to final result could be reduced by approximately 30 h with the assay. Of the 178 patients with adequate antibiotic history, optimisation of antistaphylococcal therapy could have occurred more than 1 day sooner in 68.9% with S. aureus bloodstream infection (31/45, 95% CI 53.2-81.4%). Six of the 11 patients with methicillin-resistant S. aureus bloodstream infection (54.5%) could have received anti-MRSA cover sooner. Fifty-four days of antibiotic therapy could have been spared, equating to 0.3 days (95% CI, 0.2-0.4) saved per patient, driven by broad-spectrum beta-lactams (32 days, in 18.0% of the cohort)., Conclusion: This assay has potential as an antimicrobial stewardship tool; costing and impact on clinical outcome in patients with S. aureus bloodstream infection should be assessed.

Background: People with disabilities (PWDs) continue to experience challenges with access to healthcare. Community-based rehabilitation (CBR) is an approach that advocates for equal opportunities and social inclusion of PWDs to enhance their quality of daily life. Healthcare professionals are crucial in the implementation of CBR. However, little is known about the perception of healthcare professionals on this approach to rehabilitation in South Africa., Aim: This study sought to explore perceptions of healthcare professionals on CBR in the province of KwaZulu-Natal, South Africa., Setting: This study was located across four public healthcare facilities spanning districts to tertiary levels care in KwaZulu-Natal, situated in rural and peri-urban areas., Methods: An explorative qualitative approach using focus group discussions was used to collect data from healthcare professionals employed at these public hospitals in the province. Twenty-five healthcare workers participated in four focus group discussions, with four to eight participants per group. Data were transcribed and analysed using thematic analysis., Results: The findings revealed four dominant themes, namely, the CBR conundrum, CBR enablers, perceived impediments to CBR implementation and a proposal for the implementation of CBR., Conclusion: Continual promotion of, as well as education and training on, CBR for healthcare professionals, was understood as an imperative for the development and roll-out of CBR programmes in South African communities. Excellent communication about CBR programmes was described as key to ensuring social inclusion, quality of life and access to services for PWDs.

Background: Analysis of hospital-acquired bloodstream infection (HA-BSI) trends is important to monitor emerging antimicrobial resistance (AMR) threats and guide empiric antibiotic choices., Methods: A retrospective 10-year review of neonatal HA-BSI was performed at Tygerberg Hospital's neonatal unit in Cape Town, South Africa. Neonatal clinical and laboratory data from 2014 to 2018 (Period 2) was compared with published data from 2009 to 2013 (Period 1)., Results: The neonatal unit's HA-BSI rate declined between periods from 3.9/1000 inpatient-days in Period 1 to 3.3/1000 inpatient-days in Period 2 (p = 0.002). Pathogen yield and blood culture contamination rate were unchanged (11.0% to 10.4%, p = 0.233; 5.1% to 5.3%, p = 0.636 respectively). Gram-negative pathogens predominated (1047/1636; 64.0%); Klebsiella species, Staphylococcus aureus, Serratia marcescens, Enterococcus species and Acinetobacter baumannii were the most frequent pathogens. Extended spectrum beta-lactamase production was observed in 319/432 (73.8%) of Klebsiella species, methicillin resistance in 171/246 (69.5%) of Staphylococcus aureus and extensive drug resistance in 115/137 (83.9%) of Acinetobacter species (2009-2018). The crude mortality rate of neonatal HA-BSI episodes increased from Period 1 to Period 2 from 139/717 (19.4%) to 179/718 (24.9%) (p = 0.014), but HA-BSI attributable mortality remained unchanged (97/139 [69.8%] vs 118/179 [65.9%], p = 0.542). The in-vitro activity of piperacillin-tazobactam and amikacin declined during Period 2 (74.6% to 61.4%; p<0.001)., Conclusion: Although HA-BSI rates declined in the neonatal unit, antimicrobial resistance rates in BSI pathogens remained high. Continuous BSI surveillance is a valuable tool to detect changes in pathogen and AMR profiles and inform empiric antibiotic recommendations for neonatal units in resource-limited settings., Competing Interests: The authors have declared that no competing interests exist.

Background: HIV-1 risk scoring tools could help target provision of prevention modalities such as pre-exposure prophylaxis. Recent research suggests that risk scores for women aged 18-45 may not predict risk well among young women aged 18-24. We evaluated the predictive performance of age-specific risk scores compared with the existing non-age-specific VOICE risk score, developed for women aged 18-45., Methods: We conducted a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes Trial to develop and internally validate HIV-1 risk scores for women aged 18-24 and 25-35 in South Africa. Candidate predictors included baseline demographic, clinical, behavioral, and contextual characteristics readily available in clinical settings. The VOICE risk score was applied to women aged 18-35. We evaluated predictive performance of each risk score by area under the receiver operating characteristic curve (AUC)., Results: Predictive performance of all risk scores was moderate, with AUC (95% confidence interval) of 0.64 (0.60 to 0.67) among women aged 18-24, 0.68 (0.62 to 0.73) among those aged 25-35, and 0.61 (0.58 to 0.65) for the VOICE risk score applied to women aged 18-35; The AUC was similar in internal validation. Among women aged 18-24, HIV-1 incidence was high even at low risk scores, at 3.9 per 100 person-years (95% confidence interval: 3.2 to 4.7)., Conclusions: All risk scores were moderately predictive of HIV-1 acquisition, and age-specific risk scores performed only marginally better than the VOICE non-age-specific risk score. Approaches for targeted pre-exposure prophylaxis provision to women in South Africa may require more extensive data than are currently available to improve prediction.

Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women's willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women's adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64-80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03-1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38-35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70-6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36-10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.

Background: Fluconazole is used in combination with amphotericin B for induction treatment of cryptococcal meningitis and as monotherapy for consolidation and maintenance treatment. More than 90% of isolates from first episodes of cryptococcal disease had a fluconazole minimum inhibitory concentration (MIC) ≤4 μg/ml in a Gauteng population-based surveillance study of Cryptococcus neoformans in 2007-2008. We assessed whether fluconazole resistance had emerged in clinical cryptococcal isolates over a decade., Methodology and Principal Findings: We prospectively collected C. neoformans isolates from 1 January through 31 March 2017 from persons with a first episode of culture-confirmed cryptococcal disease at 37 South African hospitals. Isolates were phenotypically confirmed to C. neoformans species-complex level. We determined fluconazole MICs (range: 0.125 μg/ml to 64 μg/ml) of 229 C. neoformans isolates using custom-made broth microdilution panels prepared, inoculated and read according to Clinical and Laboratory Standards Institute M27-A3 and M60 recommendations. These MIC values were compared to MICs of 249 isolates from earlier surveillance (2007-2008). Clinical data were collected from patients during both surveillance periods. There were more males (61% vs 39%) and more participants on combination induction antifungal treatment (92% vs 32%) in 2017 compared to 2007-2008. The fluconazole MIC50, MIC90 and geometric mean MIC was 4 μg/ml, 8 μg/ml and 4.11 μg/ml in 2017 (n = 229) compared to 1 μg/ml, 2 μg/ml and 2.08 μg/ml in 2007-2008 (n = 249) respectively. Voriconazole, itraconazole and posaconazole Etests were performed on 16 of 229 (7%) C. neoformans isolates with a fluconazole MIC value of ≥16 μg/ml; only one had MIC values of >32 μg/ml for these three antifungal agents., Conclusions and Significance: Fluconazole MIC50 and MIC90 values were two-fold higher in 2017 compared to 2007-2008. Although there are no breakpoints, higher fluconazole doses may be required to maintain efficacy of standard treatment regimens for cryptococcal meningitis., Competing Interests: The authors have declared that no competing interests exist.

Gender roles and imbalances in sexual power contribute to the heightened HIV-1 risk faced by women in Sub-Saharan Africa. This has led prevention research to focus on the development of female controlled methods. Despite the design of products such as vaginal rings to be used autonomously by women, male partners and women's perceptions of relationships influence HIV prevention choices. To understand the influences that male partners and dyadic dynamics had on the use of the Dapivirine Vaginal Ring in the ASPIRE trial, this analysis of qualitative data explored the types of intimate partner relationships that women engaged in. This paper describes how partners facilitated or challenged women's ring use and how women dealt with these challenges within six different types of relationships characterized by power dynamics and commitment levels. We offer insights into how future use of female-initiated HIV prevention products can be promoted through recognition of different relationship types.

We assessed the interference between vaginal ring use and menses among women who participated in the qualitative component of the MTN-020/ASPIRE vaginal ring trial in Malawi, South Africa, Uganda and Zimbabwe (N = 214). A common reason for imperfect ring adherence and premature removal of the vaginal ring cited by participants related to vaginal bleeding or menses. Whereas self-reporting via survey questions suggested that the majority (60%) of women did not mind wearing the ring while menstruating, and did not remove it (91%) during menses, in the qualitative interviews women frequently described removing the ring during menses. Their reasons included hygiene, beliefs that the ring blocked the flow of menstrual blood, fears that the ring would come out with blood or during tampon removal, and concerns around an 'overburdened' vagina. Examining women's narratives and subjective experiences related to menstruation helps build a better understanding of factors affecting ring use and adherence.

Rumours may influence health-related behaviours, including the uptake of and adherence to HIV prevention products. This study assessed the safety and effectiveness of a vaginal ring delivering the antiretroviral dapivirine for HIV prevention in Africa. We explored negative rumours about study participation and the vaginal ring amongst study participants and their communities in Malawi, Uganda, South Africa and Zimbabwe. In total 214 women participated in either single or serial in-depth interviews, or a focus group discussion. Three key findings emerged in the data. Firstly, rumours reflected fears concerning the ring and trial participation. Given the historical-political context of the countries in which the trial was conducted, the ring's investigational nature and its foreign origin, ring use was rumoured to cause negative health outcomes such as cancer and infertility and to be associated with practices such as witchcraft or Satanism. The salience of these rumours varied by country. Secondly, rumours reportedly affected participants' adherence to the ring, and other women's willingness to participate in the study. Finally, participants reported that participant engagement activities helped address rumours, resulting in enhanced trust and rapport between staff and participants.

Little is known about the genotypic make-up of HIV-1 DNA genomes during the earliest stages of HIV-1 infection. Here, we use near-full-length, single genome next-generation sequencing to longitudinally genotype and quantify subtype C HIV-1 DNA in four women identified during acute HIV-1 infection in Durban, South Africa, through twice-weekly screening of high-risk participants. In contrast to chronically HIV-1-infected patients, we found that at the earliest phases of infection in these four participants, the majority of viral DNA genomes are intact, lack APOBEC-3G/F-associated hypermutations, have limited genome truncations, and over one year show little indication of cytotoxic T cell-driven immune selections. Viral sequence divergence during acute infection is predominantly fueled by single-base substitutions and is limited by treatment initiation during the earliest stages of disease. Our observations provide rare longitudinal insights of HIV-1 DNA sequence profiles during the first year of infection to inform future HIV cure research.

Background: A countrywide epidemic of Listeria monocytogenes (LM) in South Africa began in the first quarter of 2017, rapidly becoming the world's largest LM outbreak to date., Methods: We describe the clinical course of neonates with culture-confirmed LM infection admitted to a tertiary neonatal unit at Tygerberg Hospital, Cape Town (1 January 2017 - 31 January 2018). Current epidemic LM cases were compared with a historical cohort of sporadic neonatal LM cases at our institution (2006 - 2016). The global literature on epidemic neonatal LM outbreaks (1 January 1978 - 31 December 2017) was reviewed., Results: Twelve neonates (median gestational age 35 weeks, median birth weight 2 020 g) were treated for confirmed LM bacteraemia in 2017/18, presenting at a median age of 0.5 days. In 5 cases, neurolisteriosis was suspected. Three neonates died (25.0%) v. 8/13 neonatal deaths (61.6%) in the sporadic listeriosis cohort (2006 - 2016) (p=0.075). The institution's neonatal LM infection incidence increased significantly in 2017 from a historical rate of 0.17/1 000 live births to 1.4/1 000 (p&lt;0.001). During the current LM epidemic, the crude neonatal fatality rate exceeded the average calculated global epidemic neonatal LM mortality (3/12 (25.0%) v. 50/290 (17.2%); p=0.448). Possible factors contributing to the high mortality rate in this epidemic LM neonatal cohort may include more virulent disease associated with sequence type 6 and the predominance of early-onset disease., Conclusions: Epidemic neonatal listeriosis at Tygerberg Hospital was associated with a predominance of bacteraemic, early-onset disease. Listeriosis-associated mortality rates were higher than previously published, but lower than the rate in a historical institutional cohort.

Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants' sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners' interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners' discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves.

Introduction: This audit examines our total experience with penetrating thoracic trauma. It reviews all the patients who were brought alive to our surgical service and all who were taken directly to the mortuary. The group of patients who underwent emergency operation for penetrating thoracic trauma is examined in detail., Methodology: A prospective trauma registry is maintained by the Pietermaritzburg Metropolitan Complex. This database was retrospectively interrogated for all patients requiring an emergency thoracic operation for penetrating injury from July 2006 till July 2009. A retrospective review of mortuary data for the same period was undertaken to identify patients with penetrating thoracic trauma who had been taken to the forensic mortuary., Results: Over the 3-year period July 2006 to July 2009, a total of 1186 patients, 77 of whom were female, were admitted to the surgical services in Pietermaritzburg with penetrating thoracic trauma. There were 124 gunshot wounds and 1062 stab wounds. A total of 108 (9%) patients required emergency operation during the period under review. The mechanism of trauma in the operative group was stab wounds (n = 102), gunshot wound (n = 4), stab with compass (n = 1), and impalement by falling on an arrow (n = 1). Over the same period 676 persons with penetrating thoracic trauma were taken to the mortuary. There were 135 (20%) gunshot wounds of the chest in the mortuary cohort. The overall mortality for penetrating thoracic trauma was 541 (33%) of 1603 for stab wounds and 135 (52%) of 259 for gunshot wounds of the chest. Among the 541 subjects with stab wounds from the mortuary cohort, there were 206 (38%) with cardiac injuries. In the emergency operation group there were 11 (10%) deaths. In 76 patients a cardiac injury was identified. The other injuries identified were lung parenchyma bleeding (n = 12) intercostal vessels (n = 10), great vessels of the chest (n = 6), internal thoracic vessel (n = 2), and pericardial injury with no myocardial injury (n = 2). Most patients reached the hospital within 60 minutes of sustaining their injury. A subset of 12 patients had much longer delays of 12 to 24 hours. Surgical access was via median sternotomy in 56 patients and lateral thoracotomy in 52. The overall mortality for penetrating cardiac trauma in our series was 217 (76%) of 282., Conclusions: Penetrating thoracic trauma has a high mortality rate of 30% for subjects with stab wounds and 52% for those with gunshot wounds. Less than a quarter of patients with a penetrating cardiac injury reach the hospital alive. Of those who do and who are operated on, about 90 percent will survive. Other injuries necessitating emergency operation are lung parenchyma, intercostal vessels and internal thoracic vessels, and great vessels of the thorax. Gunshot wounds of the thorax remain more lethal than stab wounds., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

In a random house-to-house study of 1 000 Indians the prevalence of essential hypertension according to the World Health Organization (WHO) criteria was 19% (females 22%; males 15%). The study revealed that the prevalence of hypertension was higher than in published data from India. Ethnicity in our study caused a significant variation in prevalence. Prevalence was lower than in our urban Zulu study. Blood pressure rose with age, but there was a greater rise in systolic than in diastolic blood pressure. Prevalence in males and females under 40 years were equal. There was an association between hypertension and diabetes mellitus. More effective screening and therapeutic programmes should be initiated in the Indian population because of the high prevalence of hypertension which may lead to complications if untreated, and because 58% of the hypertensive subjects were untreated or had discontinued therapy.