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Background: Tuberculosis (TB) incidence in South Africa is among the highest globally. Initial loss to follow-up (ILFU), defined as not starting on TB treatment within 28 days of testing positive, is undermining control efforts. We assessed the feasibility, acceptability, and potential of a mHealth application to reduce ILFU. Methods: An mHealth application was developed to capture patients TB investigation data, provide results and monitor treatment initiation. This was implemented in two primary health clinics (PHC) in inner-city Johannesburg. Feasibility was assessed by comparing documentation of personal details, specimen results for same individuals during implementation period (paper register and Mhealth application). Effectiveness was assessed by comparing proportion of patients with results within 48 hours, and proportion started on treatment within 28 days of testing TB positive during pre- implementation (paper register) and implementation (mHealth application) periods. In-depth interviews with patients and providers were conducted to assess acceptability of application. Results: Pre-implementation, 457 patients were recorded in paper registers [195 (42.7%) male, median age 34 years (interquartile range IQR (28–40), 45 (10.5%) sputum Xpert positive]. During implementation, 319 patients were recorded in paper register and the mHealth application [131 (41.1%) male, median age 32 years (IQR 27–38), 33 (10.3%) sputum Xpert positive]. The proportion with complete personal details: [mHealth 95.0% versus paper register 94.0%, (p = 0.54)] and proportion with documented results: [mHealth 97.4% versus paper register 97.8%, (p = 0.79)] were not different in the two methods. The proportion of results available within 48 hours: [mHealth 96.8% versus paper register 68.6%), (p <0.001)], and the proportion on treatment within 28 days [mHealth 28/33 (84.8%) versus paper register 30/44 (68.2%), (p = 0.08)] increased during implementation but was not statistically significant. In-depth interviews showed that providers easily integrated the mHealth application into routine TB investigation and patients positively received the delivery of results via text message. Time from sputum collection to TB treatment initiation decreased from 4 days (pre-implementation) to 3 days but was not statistically significant. Conclusions: We demonstrated that implementation of the mHealth application was feasible, acceptable to health care providers and patients, and has potential to reduce the time to TB treatment initiation and ILFU in PHC settings. [ABSTRACT FROM AUTHOR]

TB is rated as one of the world’s deadliest diseases and South Africa ranks 9th out of the 22 countries with hardest hit of TB. Although many pieces of research have been carried out on this subject, this paper steps further by inculcating past knowledge into the model, using Bayesian approach with informative prior. Bayesian statistics approach is getting popular in data analyses. But, most applications of Bayesian inference technique are limited to situations of non-informative prior, where there is no solid external information about the distribution of the parameter of interest. The main aim of this study is to profile people living with TB in South Africa. In this paper, identical regression models are fitted for classical and Bayesian approach both with non-informative and informative prior, using South Africa General Household Survey (GHS) data for the year 2014. For the Bayesian model with informative prior, South Africa General Household Survey dataset for the year 2011 to 2013 are used to set up priors for the model 2014. [ABSTRACT FROM AUTHOR]

Voluntary medical male circumcision is an integral part of the South African government’s response to the HIV and AIDS epidemic. Following circumcision, it is recommended that patients abstain from sexual activity for six weeks, as sex may increase the risk of female-to-male HIV transmission and prolong the healing period. This paper investigates the resumption of sexual activity during the healing period among a cohort of school-going males in the KwaZulu-Natal province of South Africa. The analysis for this paper compares two groups of sexually active school-going males: the first group reported having sex during the healing period (n = 40) and the second group (n = 98) reported no sex during the healing period (mean age: 17.7, SD: 1.7).The results show that 29% (n = 40) of young males (mean age: 17.9, SD: 1.8) who were previously sexually active, resumed sexual activity during the healing period, had on average two partners and used condoms inconsistently. In addition, those males that engage in sexual activity during the healing period were less inclined to practice safe sex in the future (AOR = 0.055, p = 0.002) than the group of males who reported no sex during the healing period. These findings suggest that a significant proportion of young males may currently and in the future, subject themselves to high levels of risk for contracting HIV post circumcision. Education, as part of a VMMC campaign, must emphasize the high risk of HIV transmission for both the males their partners during the healing period. [ABSTRACT FROM AUTHOR]

Introduction: HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST. Methods: Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available. Results: Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS. Conclusions: HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration. [ABSTRACT FROM AUTHOR]

Introduction: The increasing number of people requiring HIV treatment in South Africa calls for efficient use of its human resources for health in order to ensure optimum treatment coverage and outcomes. This paper describes an innovative public-private partnership model which uses private sector doctors to treat public sector patients and ascertains the model’s ability to maintain treatment outcomes over time. Methods: The study used a retrospective design based on the electronic records of patients who were down-referred from government hospitals to selected private general medical practitioners (GPs) between November 2005 and October 2012. In total, 2535 unique patient records from 40 GPs were reviewed. The survival functions for mortality and attrition were calculated. Cumulative incidence of mortality for different time cohorts (defined by year of treatment initiation) was also established. Results: The median number of patients per GP was 143 (IQR: 66–246). At the time of down-referral to private GPs, 13.8% of the patients had CD4 count <200 cell/mm3, this proportion reduced to 6.6% at 12 months and 4.1% at 48 months. Similarly, 88.4% of the patients had suppressed viral load (defined as HIV-1 RNA <400 copies/ml) at 48 months. The patients’ probability of survival at 12 and 48 months was 99.0% (95% CI: 98.4%–99.3%) and 89.0% (95% CI: 87.1%–90.0%) respectively. Patient retention at 48 months remained high at 94.3% (95% CI: 93.0%–95.7%). Conclusions: The study findings demonstrate the ability of the GPs to effectively maintain patient treatment outcomes and potentially contribute to HIV treatment scale-up with the relevant support mechanism. The model demonstrates how an assisted private sector based programme can be effectively and efficiently used to either target specific health concerns, key populations or serve as a stop-gap measure to meet urgent health needs. [ABSTRACT FROM AUTHOR]

Introduction: Health Care Workers (HCWs) are among the highest risk groups for contracting tuberculosis (TB), which is ranked the third most common occupational health disease in South Africa. Little is known about the true extent of the burden of TB among South African HCWs and current surveillance approaches are inadequate. The study aimed to determine the feasibility of using postal and web-based surveys accessed through registries of registered professionals to estimate the prevalence of TB among HCWs in South Africa. Materials and methods: We conducted a cross sectional survey on a sample of professional nurses and doctors (general practitioners) registered on the Medpages database platform; a subscription based registry for practising health care professionals. The survey included professionals who were actively involved in the clinical management of patients, either in public or private health care facilities. The paper based survey, including pre-paid return envelopes, was distributed via the post office and web-based surveys were distributed via e-mail through a hyperlink. Descriptive statistics were used to summarize the data and the Chi-square test to determine associations between categorical variables. Active TB was defined as any history of TB Results: Out of a total of 3,400 health care professionals contacted, 596 (18%) responses were received: 401 (67%) web-based and 195 (33%) postal. A significantly higher percentage of complete forms were from postal compared to web-based (97% [189/195] versus 87% [348/401], p<0.001). Younger (<60 years) professionals were more likely to use the web-based compared to postal (87% [236/270] versus 71% [134/189], p<0.001). Overall, the prevalence of active TB infection was 8.7%, (95%CI: 6.3%–11.7%) and there was no difference observed between doctors and nurses (10.8% [18/167] versus 7.5% [22/292], p = 0.236). Conclusion: This novel approach demonstrated the feasibility of using an existing registry of professionals to conduct surveys to estimate the prevalence of TB. Our findings showed a high TB prevalence; however the estimate might have been biased by the low response rate. Further research to optimise our approach could lead to a viable option in improving surveillance among health care professionals. [ABSTRACT FROM AUTHOR]

This paper analyses the transfer and implementation of two internationally formulated infectious disease strategies in South Africa, namely, directly observed therapy (DOTS) for TB and syndromic management (SM) for sexually transmitted infections (STIs). Using the tools of policy analysis, this paper seeks to draw conclusions from contrasting experiences with the two strategies. DOTS and SM differ with respect to styles of engagement by World Health Organization (WHO), the international agency promoting the ideas, in the following ways: continuity and networking between policy makers, practitioners and researchers nationally; and approaches to sub-national implementation. We show how these factors may have been important to national uptake, and conclude on the need for a context sensitive approach to policy transfer and a balance between bottom-up and top-down implementation strategies. These insights may have relevance for the current global wave of treatment programmes for HIV and other infectious diseases. [ABSTRACT FROM AUTHOR]

The series, 'Mastering your Fellowship', provides examples of the question formats encountered in the written and clinical examinations, Part A of the Fellowship of the College of Family Physicians (South Africa) (FCFP [SA]) examination. The series is aimed at helping family medicine registrars (and their supervisors) in preparing for this examination. [ABSTRACT FROM AUTHOR]

Background: Empirical studies and population-level policy simulations show the importance of voluntary medical male circumcision (VMMC) in generalized epidemics. This paper complements available scenario-based studies (projecting costs and outcomes over some policy period, typically spanning decades) by adopting an incremental approach-analyzing the expected consequences of circumcising one male individual with specific characteristics in a specific year. This approach yields more precise estimates of VMMC's cost-effectiveness and identifies the outcomes of current investments in VMMC (e.g., within a fiscal budget period) rather than of investments spread over the entire policy period.Methods/findings: The model has three components. We adapted the ASSA2008 model, a demographic and epidemiological model of the HIV epidemic in South Africa, to analyze the impact of one VMMC on HIV incidence over time and across the population. A costing module tracked the costs of VMMC and the resulting financial savings owing to reduced HIV incidence over time. Then, we used several financial indicators to assess the cost-effectiveness of and financial return on investments in VMMC. One circumcision of a young man up to age 20 prevents on average over 0.2 HIV infections, but this effect declines steeply with age, e.g., to 0.08 by age 30. Net financial savings from one VMMC at age 20 are estimated at US$617 at a discount rate of 5% and are lower for circumcisions both at younger ages (because the savings occur later and are discounted more) and at older ages (because male circumcision becomes less effective). Investments in male circumcision carry a financial rate of return of up to 14.5% (for circumcisions at age 20). The cost of a male circumcision is refinanced fastest, after 13 y, for circumcisions at ages 20 to 25. Principal limitations of the analysis arise from the long time (decades) over which the effects of VMMC unfold-the results are therefore sensitive to the discount rate applied, and more generally to the future course of the epidemic and of HIV/AIDS-related policies pursued by the government.Conclusions: VMMC in South Africa is highly effective in reducing both HIV incidence and the financial costs of the HIV response. The return on investment is highest if males are circumcised between ages 20 and 25, but this return on investment declines steeply with age. [ABSTRACT FROM AUTHOR]

The article examines the effectiveness of sequential aerosol technique (SAT) against riverine tsetse flies in southern Africa. An overview on the tuning control operations concerning the reproduction of tsetse flies, is highlighted. Also emphasized are the tsetse species' challenging habitats in the adaptation of SAT, is also emphasized.

The phylogenetic signal of transmissibility (competence) and attack severity among hosts of generalist pests is poorly understood. In this study, we examined the phylogenetic effects on hosts differentially affected by an emergent generalist beetle–pathogen complex in California and South Africa. Host types (non‐competent, competent and killed‐competent) are based on nested types of outcomes of interactions between host plants, the beetles and the fungal pathogens. Phylogenetic dispersion analysis of each host type revealed that the phylogenetic preferences of beetle attack and fungal growth were a nonrandom subset of all available tree and shrub species. Competent hosts were phylogenetically narrower by 62 Myr than the set of all potential hosts, and those with devastating impacts were the most constrained by 107 Myr. Our results show a strong phylogenetic signal in the relative effects of a generalist pest–pathogen complex on host species, demonstrating that the strength of multi‐host pest impacts in plants can be predicted by host evolutionary relationships. This study presents a unifying theoretical approach to identifying likely disease outcomes across multiple host‐pest combinations. [ABSTRACT FROM AUTHOR]

Objective: This is the first large-scale assessment of the implementation of HIV Rapid Test Quality Improvement Initiative in South Africa. Methods: We used a quasi-experimental one group post-test only design. The intervention implemented starting April 2014 comprised health-care worker training on quality assurance (QA) of HIV rapid testing and enrolment of the facilities in proficiency testing (PT), targeting 2,077 healthcare facilities in 32 high HIV burden districts. Following the intervention, two consecutive rounds of site assessments were undertaken. The first, conducted after a median of 7.5 months following the training, included 1,915 facilities that participated in the QA training, while the second, conducted after a median of one-year following the first-round assessment included 517 (27.0%) of the 1,915 facilities. In both assessments, the Stepwise-Process-for-Improving-the-quality-of-HIV-Rapid-Testing (SPI-RT) checklist was used to score facilities’ performance in 7 domains: training, physical facility, safety, pre-testing, testing, post-testing and external quality assessment. Facilities’ level of readiness for national certification was assessed. Result: Between 2016 and 2017, there were four PT cycles. PT participation increased from 32.4% (620/1,915) in 2016 to 91.5% (1,753/1,915) in 2017. In each PT cycle, PT results were returned by 76%–87% of facilities and a satisfactory result (>80%) was achieved by ≥95% of facilities. In the SPI-RT assessment, in round-one, 22.3% of facilities were close to or eligible for national certification—this significantly increased to 38.8% in round-two (P-value<0.001). The median SPI-RT score for the domains HIV pre-testing (83.3%) and post-testing (72.2%) remained the same between the two rounds. The median score for the testing domain increased by 5.6% (to 77.8%). Conclusion: Facilities performance on the domains that are critical for accuracy of diagnosis (i.e. pre-testing, testing and post-testing) remained largely unchanged. This study provided several recommendations to improve QA implementation in South Africa, including the need to improve routine use of internal quality control for corrective actions. [ABSTRACT FROM AUTHOR]

Background: Ensuring effective clinical management and continuity of TB care across hospital and primary health-care services remains challenging in South Africa. The high burden of TB, coupled with numerous health system problems, influence the TB care delivered by hospital staff. Objective: To understand factors from the perspectives of hospital staff that influence the clinical management and discharge of TB patients, and to elicit recommendations to improve continuity of care for TB patients. Design: Participatory action research was used to engage hospital staff working with TB patients admitted to a central public hospital in the Western Cape province, South Africa. Data were collected through eight focus group discussions with nurses, junior doctors and ward administrators. Data analysis was done using Miles and Huberman’s framework to identify emerging patterns and to develop categories with themes and sub-themes. The participants influenced all phases of the research process to inform better practices in TB clinical management and discharge planning at the hospital. Results: The emerging themes and sub-themes were categorized into two overall sections: The clinical care management process and the discharge and referral process. Nurses expressed a fear of exposure to TB and MDR-TB due to challenges in clinical and infection-prevention control. Clinical hierarchies, poor interdisciplinary teamwork, limited task shifting and poor communication interfered with effective clinical and discharge processes. A high workload, staff shortages and inadequate skills resulted in insufficient information and health education for TB patients and their caregivers. Despite awareness of the patients’ socio-economic challenges, some aspects of care were not patient-centered, and caregivers were not included in discharge planning. Communication between the hospital and referral points was inefficient and poorly supported by information systems. Hospital staff recommended improved infection prevention and control practices and interdisciplinary teamwork in the hospital, that TB education for patients be integrated with hospital staff functions, with more patient-centered discharge planning, and improved communication across hospitals and primary health care levels. Conclusions: Interdisciplinary teamwork, more patient-centered care, and better communication within the hospital and with primary health-care services are needed for improved continuity of care for TB patients. Further studies on factors contributing to, and interventions to improve, continuity of TB care in similar hospital settings are needed. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends "same-day" initiation of antiretroviral therapy (ART) for HIV patients who are eligible and ready. Identifying efficient, safe, and feasible procedures for determining same-day eligibility and readiness is now a priority. The Simplified Algorithm for Treatment Eligibility (SLATE) study evaluated a clinical algorithm that allows healthcare workers to determine eligibility for same-day treatment and to initiate ART at the patient's first clinic visit.Methods and Findings: SLATE was an individually randomized trial at three outpatient clinics in urban settlements in Johannesburg, South Africa and three hospital clinics in western Kenya. Adult, nonpregnant, HIV-positive, ambulatory patients presenting for any HIV care, including HIV testing, but not yet on ART were enrolled and randomized to the SLATE algorithm arm or standard care. The SLATE algorithm used four screening tools-a symptom self-report, medical history questionnaire, physical examination, and readiness assessment-to ascertain eligibility for same-day initiation or refer for further care. Follow-up was by record review, and analysis was conducted by country. We report primary outcomes of 1) ART initiation ≤28 days and 2) initiation ≤28 days and retention in care ≤8 months of enrollment. From March 7, 2017 to April 17, 2018, we enrolled 600 patients (median [IQR] age 34 [29-40] and CD4 count 286 [128-490]; 63% female) in South Africa and 477 patients in Kenya (median [IQR] age 35 [29-43] and CD4 count 283 [117-541]; 58% female). In the intervention arm, 78% of patients initiated ≤28 days in South Africa, compared to 68% in the standard arm (risk difference [RD] [95% confidence interval (CI)] 10% [3%-17%]); in Kenya, 94% of intervention-arm patients initiated ≤28 days compared to 89% in the standard arm (6% [0.5%-11%]). By 8 months in South Africa, 161/298 (54%) intervention-arm patients had initiated and were retained, compared to 146/302 (48%) in the standard arm (6% [(2% to 14%]). By 8 months in Kenya, the corresponding retention outcomes were identical in both arms (137/240 [57%] of intervention-arm patients and 136/237 [57%] of standard-arm patients). Limitations of the trial included limited geographic representativeness, exclusion of patients too ill to participate, missing viral load data, greater study fidelity to the algorithm than might be achieved in standard care, and secular changes in standard care over the course of the study.Conclusions: In South Africa, the SLATE algorithm increased uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eight-month retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic.Trial Registration: Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya. [ABSTRACT FROM AUTHOR]

Background: Differentiated antiretroviral therapy (ART) delivery models, in which patients are provided with care relevant to their current status (e.g., newly initiating, stable on treatment, or unstable on treatment) has become an essential part of patient-centered health systems. In 2015, the South African government implemented Chronic Disease Adherence Guidelines (AGLs), which involved five interventions: Fast Track Initiation Counseling for newly initiating patients, Enhanced Adherence Counseling for patients with an unsuppressed viral load, Early Tracing of patients who miss visits, and Adherence Clubs (ACs) and Decentralized Medication Delivery (DMD) for stable patients. We evaluated two of these interventions in 24 South African facilities: ACs, in which patients meet in groups outside usual clinic procedures and receive medication; and DMD, in which patients pick up their medication outside usual pharmacy queues.Methods and Findings: We compared those participating in ACs or receiving DMD at intervention sites to those eligible for ACs or DMD at control sites. Outcomes were retention and sustained viral suppression (<400 copies/mL) 12 months after AC or DMD enrollment (or comparable time for controls). 12 facilities were randomly allocated to intervention and 12 to control arms in four provinces (Gauteng, North West, Limpopo, and KwaZulu Natal). We calculated adjusted risk differences (aRDs) with cluster adjustment using generalized estimating equations (GEEs) using difference in differences (DiD) with patients eligible for ACs/DMD prior to implementation (Jan 1, 2015) for comparison. For DMD, randomization was not preserved, and the analysis was treated as observational. For ACs, 275 intervention and 294 control patients were enrolled; 72% of patients were female, 61% were aged 30-49 years, and median CD4 count at ART initiation was 268 cells/μL. AC patients had higher 1-year retention (89.5% versus 81.6%, aRD: 8.3%; 95% CI: 1.1% to 15.6%) and comparable sustained 1-year viral suppression (<400 copies/mL any time ≤ 18 months) (80.0% versus 79.6%, aRD: 3.8%; 95% CI: -6.9% to 14.4%). Retention associations were apparently stronger for men than women (men RD: 13.1%, 95% CI: 0.3% to 23.5%; women RD: 6.0%, 95% CI: -0.9% to 12.9%). For DMD, 232 intervention and 346 control patients were enrolled; 71% of patients were female, 65% were aged 30-49 years, and median CD4 count at ART initiation was 270 cells/μL. DMD patients had apparently lower retention (81.5% versus 87.2%, aRD: -5.9%; 95% CI: -12.5% to 0.8%) and comparable viral suppression versus standard of care (77.2% versus 74.3%, aRD: -1.0%; 95% CI: -12.2% to 10.1%), though in both cases, our findings were imprecise. We also noted apparently increased viral suppression among men (RD: 11.1%; 95% CI: -3.4% to 25.5%). The main study limitations were missing data and lack of randomization in the DMD analysis.Conclusions: In this study, we found comparable DMD outcomes versus standard of care at facilities, a benefit for retention of patients in care with ACs, and apparent benefits in terms of retention (for AC patients) and sustained viral suppression (for DMD patients) among men. This suggests the importance of alternative service delivery models for men and of community-based strategies to decongest primary healthcare facilities. Because these strategies also reduce patient inconvenience and decongest clinics, comparable outcomes are a potential success. The cost of all five AGL interventions and possible effects on reducing clinic congestion should be investigated.Clinical Trial Registration: NCT02536768. [ABSTRACT FROM AUTHOR]

Background: Expanded HIV prevention options are needed to increase uptake of HIV prevention among women, especially in generalized epidemics. As the dapivirine vaginal ring moves forward through regulatory review and open-label extension studies, the potential public health impact and cost-effectiveness of this new prevention method are not fully known. We used mathematical modeling to explore the impact and cost-effectiveness of the ring in different implementation scenarios alongside scale-up of other HIV prevention interventions. Given the knowledge gaps about key factors influencing the ring’s implementation, including potential uptake and delivery costs, we engaged in a stakeholder consultation process to elicit plausible parameter ranges and explored scenarios to identify the possible range of impact, cost, and cost-effectiveness. Methods and findings: We used the Goals model to simulate scenarios of oral and ring pre-exposure prophylaxis (PrEP) implementation among female sex workers and among other women ≤21 years or >21 years with multiple male partners, in Kenya, South Africa, Uganda, and Zimbabwe. In these scenarios, we varied antiretroviral therapy (ART) coverage, dapivirine ring coverage and ring effectiveness (encompassing efficacy and adherence) by risk group. Following discussions with stakeholders, the maximum level of PrEP coverage (oral and/or ring) considered in each country was equal to modern contraception use minus condom use in the two age groups. We assessed results for 18 years, from 2018 to 2035. In South Africa, for example, the HIV infections averted by PrEP (ring plus oral PrEP) ranged from 310,000 under the highest-impact scenario (including ART held constant at 2017 levels, high ring coverage, and 85% ring effectiveness) to 55,000 under the lowest-impact scenario (including ART reaching the UNAIDS 90-90-90 targets by 2020, low ring coverage, and 30% ring effectiveness). This represented a range of 6.4% to 2.2% of new HIV infections averted. Given our assumptions, the addition of the ring results in 11% to 132% more impact than oral PrEP alone. The cost per HIV infection averted for the ring ranged from US$13,000 to US$121,000. Conclusions: This analysis offers a wide range of scenarios given the considerable uncertainty over ring uptake, consistency of use, and effectiveness, as well as HIV testing, prevention, and treatment use over the next two decades. This could help inform donors and implementers as they decide where to allocate resources in order to maximize the impact of the dapivirine ring in light of funding and implementation constraints. Better understanding of the cost and potential uptake of the intervention would improve our ability to estimate its cost-effectiveness and assess where it can have the most impact. [ABSTRACT FROM AUTHOR]

Introduction: South Africa is considered highly endemic for hepatitis A virus (HAV) although few seroprevalence studies have been conducted over the past two decades. The World Health Organization recommends integrating HAV vaccination into national childhood immunization schedules where there is transition from high to intermediate endemicity. As a means of gauging age-specific rates of infection, we report HAV seroprevalence rates among specimens tested for HAV serology within South Africa’s public health sector from 2005–2015. Materials and methods: Hepatitis A serology results (Anti-HAV IgM, IgG and total antibody) from 2005–2015 were extracted from South Africa’s National Health Laboratory Service’s Corporate Data Warehouse (NHLS CDW), the central data repository of all laboratory test-sets within the public health sector. Results were extracted according to test-set, result, date of testing, health facility, name, surname, age, and sex. Anti-HAV IgG results were merged with total antibody results to reflect anti-HAV seroprevalence. Testing volume, positivity rates and age-specific anti-HAV seroprevalence rates by year and geographic distribution are described. Results and discussion: A total of 501 083 HAV IgM results were retrieved, of which 16 423 (3.3%) were positive, 484 259 (96.6%) negative and 401 (0.1%) equivocal; and 34 710 HAV total antibody/IgG tests of which 30 675 (88.4%) were positive, 4 020 (11.6%) negative and 15 equivocal. Whereas IgM positivity was highest among the 1–4 year age group (33.5%) and lowest among patients >45 years (<0.5%), total antibody positivity ranged from its lowest level of 52.7% in the 1–4 year age group increasing to levels of >90% only after 25 years of age. Conclusion: Anti-HAV total antibody testing within the South African public health sector demonstrates seroprevalence rates reach levels >90% only in adulthood, suggesting South Africa could be in transition from high to intermediate endemicity. Prospective studies with geographically representative sampling are required to confirm these findings and evaluate provincial and urban/rural heterogeneity. [ABSTRACT FROM AUTHOR]

Background: TB persists despite being relatively easy to detect and cure because the journey from the onset of symptoms to cure involves a series of steps, with patients being lost to follow-up at each stage and delays occurring among patients not lost to follow-up. One cause of drop-off and delay occurs when patients delay or avoid returning to clinic to get their test results and start treatment. Methods: We fielded two SMS interventions in three Cape Town clinics to see their effects on whether people returned to clinic, and how quickly. One was a simple reminder; the other aimed to overcome “optimism bias” by reminding people TB is curable and many millions die unnecessarily from it. Recruits were randomly assigned at the clinic level to a control group or one of the two SMS groups (1:2:2). In addition to estimating effects on the full sample, we also estimated effects on HIV-positive patients. Results: SMS recipients were more likely to return to clinic in the requested two days than the control group. The effect was smaller in the intent-to-treat analysis (52/101 or 51.5% vs. 251/405 or 62.0%, p = 0.05) than in the per-protocol analysis (50/97 or 51.5% vs. 204/318 or 64.2%, p = 0.03). The effect was larger among HIV-positives (10/35 or 28.6% vs. 97/149 or 65.1%, p<0.01). The effects of SMS messages diminished as the interval increased: significant effects at the 5% level were found at five and 10 days only among HIV-positives. The second SMS message had larger effects, albeit not significantly larger, likely due in part to lack of statistical power. Conclusions: At 2 U.S. cents per message, SMS reminders are an inexpensive option to encourage TB testers to return to clinic, especially when worded to counter optimism bias. [ABSTRACT FROM AUTHOR]

South Africa ranks third among 22 high burden countries in the world. TB which remains a leading cause of death causes one in five adult deaths in South Africa. An in-depth understanding of knowledge, attitudes and practices of young people towards TB is required to implement meaningful interventions. We analysed young men and women (18–24 years)'s TB knowledge including TB/HIV coinfections, testing rates and factors associated with them. A cross sectional cluster-based household survey was conducted in two provinces. Participants completed computer-assisted self-interviews on TB knowledge, testing history and TB/HIV coinfections. A participant was regarded as knowledgeable of TB if s/he correctly answered the WHO-adopted TB knowledge questions. We built three multivariate regression models in Stata 13.0 to assess factors associated with knowing TB alone, testing alone and both knowing and testing for TB. 1955 participants were interviewed (89.9% response rate). Their median age was 20 years (IQR19-22). Sixteen percent (16.2%) of the participants were social grant recipients, 55% were enrolled in a school/college and 5% lived in substandard houses. A total of 72% had knowledge of TB, 21% underwent screening tests for TB and 14.7% knew and tested for TB. Factors associated with TB knowledge were being female, younger, a student, social grant recipient, not transacting sex and having positive attitudes towards people living with HIV (PLWH). Factors associated with TB testing were being a student, receiving a social grant, living in OR Tambo district, HIV knowledge and having a family member with TB history. Factors associated with both TB knowledge and testing were being female, a student, using the print media, living in OR Tambo district and having a family member with a TB history. The study demonstrates the importance of demographic factors (gender, economic status, family TB history, and location) and HIV factors in explaining TB knowledge and testing. We recommend extending community TB testing services to increase testing. [ABSTRACT FROM AUTHOR]

We propose a method for analyzing repeated residential movements based on graphical loglinear models. This method allows an explicit representation of residential presence and absence patterns from several areas without defining mobility measures. We make use of our method to analyze data from one of the most comprehensive demographic surveillance sites in Africa that is characterized by high adult HIV prevalence, high levels of poverty and unemployment and frequent residential changes. Between 2004 and 2016, residential changes were recorded for 8,857 men over 35,500.01 person-years, and for 12,158 women over 57,945.35 person-years. These individuals were HIV negative at baseline. Over the study duration, there were a total of 806 HIV seroconversions in men, and 2,458 HIV seroconversions in women. Our method indicates that establishing a residence outside the rural study area is a strong predictor of HIV seroconversion in men (OR = 2.003, 95% CI = [1.718,2.332]), but not in women. Residing inside the rural study area in a single or in multiple locations is a less significant risk factor for HIV acquisition in both men and women compared to moving outside the rural study area. [ABSTRACT FROM AUTHOR]

Introduction and methods: Hepatitis B is a vaccine preventable disease and is notifiable in South Africa. Hepatitis B vaccination was incorporated into the Expanded Programme on Immunisation in South Africa in 1995. We used a convenience sample from community-based febrile rash surveillance in 2013 to estimate hepatitis B sero-prevalence. Of samples serologically negative for acute measles infection, 450 samples spanning nine provinces of South Africa were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Results: Two children (2/450; 0.4%) tested positive for HBsAg. Three hundred and three children (67.3%) had evidence of vaccine induced immunity. Vaccine induced immunity was present in 80.2% of 1–5 year olds, but only 60.3% of 10–14 year olds. Natural immunity, indicating exposure to circulating hepatitis B, was present in 13/450 (2.9%) children. Conclusion: Chronic hepatitis B in South African has decreased in prevalence from highly endemic levels prior to vaccine introduction to approximately 0.4% in this sample, demonstrating impact of a successful vaccination programme 18 years after introduction. Decreased vaccine-induced immunity with increasing age may reflect waning antibody titres over time. [ABSTRACT FROM AUTHOR]

We present a new modeling tool that can be used to maximize the impact of canine rabies management resources that are available at the local level. The model is accessible through a web-based interface that allows for flexibility in the management strategies that can be investigated. Rabies vaccination, sterilization, chemo-contraception, and euthanasia can be specified and limited to specific demographic groups. Additionally, we allowed for considerable complexity in the specification of management costs. In many areas, the costs of contacting additional dogs increases as management effort increases, and this can have important strategic implications. We illustrated the application of the model by examining several alternative management strategies in an area of Mpumalanga Province, South Africa. Our results based on this dog population suggested that puppies should be vaccinated and sterilization would not be optimal if the spatial extent of management is not large (and perhaps not even then). Furthermore, given a sufficient budget, it was evident that vaccination campaigns should be repeated annually. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized in South Africa by large epidemics amongst ruminant livestock at very long, irregular intervals, mainly in the central interior. However, the presence and patterns of occurrence of the virus in the eastern parts of the country are poorly known. This study aimed to detect the presence of RVF virus (RVFV) in cattle and goats in far northern KwaZulu-Natal province and to estimate the prevalence of antibodies to the virus and the incidence rate of seroconversion. Methodology: Cross-sectional studies were performed in communally farmed cattle (n = 423) and goats (n = 104), followed by longitudinal follow-up of seronegative livestock (n = 253) 14 times over 24 months, representing 160.3 animal-years at risk. Exposure to RVFV was assessed using an IgG sandwich ELISA and a serum neutralization test (SNT) and seroconversion was assessed using SNT. Incidence density was estimated and compared using multivariable Poisson models and hazard of seroconversion was estimated over time. Principal findings: Initial overall seroprevalence was 34.0% (95%CI: 29.5–38.8%) in cattle and 31.7% (95%CI: 22.9–41.6%) in goats, varying by locality from 18–54%. Seroconversions to RVFV based on SNT were detected throughout the year, with the incidence rate peaking during the high rainfall months of January to March, and differed considerably between years. Overall seroconversion rate in cattle was 0.59 per animal-year (95% CI: 0.46–0.75) and in goats it was 0.41 per animal-year (95% CI: 0.25–0.64), varying significantly over short distances. Conclusions/Significance: The high seroprevalence in all age groups and evidence of year-round viral circulation provide evidence for a hyperendemic situation in the study area. This is the first study to directly estimate infection rate of RVFV in livestock in an endemic area in the absence of reported outbreaks and provides the basis for further investigation of factors affecting viral circulation and mechanisms for virus survival during interepidemic periods. [ABSTRACT FROM AUTHOR]

Objectives: To estimate trends in prevalence and incidence of syphilis, gonorrhea and chlamydia in adult men and women in South Africa. Methods: The Spectrum-STI tool estimated trends in prevalence and incidence of active syphilis, gonorrhea and chlamydia, fitting South African prevalence data. Results were used, alongside programmatic surveillance data, to estimate trends in incident gonorrhea cases resistant to first-line treatment, and the reporting gap of symptomatic male gonorrhea and chlamydia cases treated but not reported as cases of urethritis syndrome. Results: In 2017 adult (15–49 years) the estimated female and male prevalences for syphilis were 0.50% (95% CI: 0.32–0.80%) and 0.97% (0.19–2.28%), for gonorrhea 6.6% (3.8–10.8%) and 3.5% (1.7–6.1%), and for chlamydia 14.7% (9.9–21%) and 6.0% (3.8–10.4%), respectively. Between 1990 and 2017 the estimated prevalence of syphilis declined steadily in women and men, probably in part reflecting improved treatment coverage. For gonorrhea and chlamydia, estimated prevalence and incidence showed no consistent time trend in either women or men. Despite growing annual numbers of gonorrhea cases − reflecting population growth − the estimated number of first line treatment-resistant gonorrhea cases did not increase between 2008 and 2017, owing to changes in first-line antimicrobial treatment regimens for gonorrhea in 2008 and 2014/5. Case reporting completeness among treated male urethritis syndrome episodes was estimated at 10–28% in 2017. Conclusion: South Africa continues to suffer a high STI burden. Improvements in access and quality of maternal, STI and HIV health care services likely contributed to the decline in syphilis prevalence. The lack of any decline in gonorrhea and chlamydia prevalence highlights the need to enhance STI services beyond clinic-based syndromic case management, to reinvigorate primary STI and HIV prevention and, especially for women, to screen for asymptomatic infections. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer incidence is significant in countries, such as South Africa, with high burdens of both HIV and human papillomavirus (HPV). Cervical cancer is largely preventable if dysplasia is diagnosed and treated early, but there is debate regarding the best approaches for screening and treatment, especially for low-resource settings. Currently South Africa provides Pap smears followed by colposcopic biopsy and LEEP if needed in its public health facilities. We estimated the costs and cost-effectiveness of two approaches for treating cervical intraepithelial neoplasia grade 2 or higher (CIN2+) among HIV-infected women, most of whom were taking antiretroviral treatment, at a public HIV treatment facility in Johannesburg, South Africa. Methods: Method effectiveness was derived from an intention-to-treat analysis of data gathered in a clinical trial completed previously at the study facility. In the trial, women who were diagnosed with CIN2+ and eligible for cryotherapy were randomized to cryotherapy or LEEP. If women were CIN2+ at six months as determined via Pap smear and colposcopic biopsy, all women—regardless of their original treatment assignment—received LEEP. “Cure” was then defined as the absence of disease at 12 months based on Pap smear and colposcopic biopsy. Health service costs were estimated using micro-costing between June 2013 and April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered, and results from an as-treated analysis were considered in sensitivity analysis. Results: In total, 166 women with CIN2+ were enrolled (86 had LEEP; 80 had cryotherapy). At 12 months, cumulative loss to follow-up was 12.8% (11/86) for the LEEP group and 13.8% (11/80) for cryotherapy. Based on the unadjusted intention-to-treat analysis conducted for this economic evaluation, there was no significant difference in efficacy. At 12 months, 83.8% (95% CI 73.8–91.1) of women with CIN2+ at baseline and randomized to cryotherapy were free of CIN2+ disease. In contrast, 76.7% (95% CI 66.4–85.2) of women assigned to LEEP were free from disease. On average, women initially treated with cryotherapy were less costly per patient randomized at US$ 118.00 (113.91–122.10), and per case “cured” at US$ 140.90 (136.01–145.79). Women in the LEEP group cost US$ 162.56 (157.90–167.22) per patient randomized and US$ 205.59 (199.70–211.49) per case cured. In the as-treated analysis, which was based on trial data, LEEP was more efficacious than cryotherapy; however, the difference was not significant. Cryotherapy remained more cost-effective than LEEP in all sensitivity and scenario analyses. Conclusions: For this cost-effectiveness analysis, using an intention-to-treat approach and taking into consideration uncertainty in the clinical and cost outcomes, a strategy involving cryotherapy plus LEEP if needed at six months was dominant to LEEP plus LEEP again at six months if needed for retreatment. However, compared to other studies comparing LEEP and cryotherapy, the efficacy results were low in both treatment groups–possibly due to the HIV-positivity of the participants. Further research is needed, but at present choosing the “right” treatment option may be less important than ensuring access to treatment and providing careful monitoring of treatment outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Cryptococcal meningitis (CM) is an opportunistic fungal disease with a high mortality among HIV-positive patients with severe immunosuppression (CD4 count <100 cells/μl). Reflexed screening for cryptococcal antigen (CrAg) in remnant blood samples was initially piloted at selected CD4 testing laboratories of the National Health Laboratory Service (NHLS) prior to the implementation of a national screening programme using a lateral flow assay (LFA) (IMMY, Norman, OK, USA). The aim of this study was to assess CrAg positivity nationally, per province and district in combination with the percentage of CD4 samples tested with a CD4 count <100 cells/μl to identify areas with advanced HIV/CrAg disease burden. Methods: CrAg and CD4 laboratory result data were extracted from the NHLS corporate data warehouse. Monthly test volumes were used to assess CrAg test volumes and coverage, while bubble charts were used to display the relationship between CD4 <100 cells/μl, CrAg positivity and number of positive CrAg samples by district. ArcGIS software was used to spatially report CrAg positivity. Results: CrAg screening coverage was stable at around 96% after November 2016. Samples with a CD4 <100 cell/μl and CrAg positivity were also stable over the study period at 10% and ~5% respectively. The highest CrAg positivity was reported for the Kwa-Zulu Natal province (7.3%), which also had the lowest percentage of samples with a CD4 <100 cells/μl (7.2%). Uthungulu and Umkhanyakude districts had the highest CrAg positivity (9.3% and 8.9% respectively). Ethekwini and Johannesburg Metro districts contributed to 22% of the total number of CrAg-positive samples tested across South Africa for the period reported. Conclusion: Existing CD4 testing services were used to rapidly scale up CrAg reflex testing in South Africa. Districts with advanced HIV and CrAg disease burden were identified that need further investigation of patient management interventions. [ABSTRACT FROM AUTHOR]

South Africa has a Universal Test and Treat (UTT) policy in place to ensure that everyone tests for HIV and can access treatment if they test positive. The aim of this study is to document the pathways that older South Africans who are living with HIV take to access testing and treatment in this context. Despite the aging of the HIV epidemic in South Africa and clear evidence that testing older persons (over age 50) is necessary, very little is known about the circumstances under which older persons test for HIV or their motivations for doing so. In this study, we analyze 21 qualitative, in-depth interviews with women and men aged 50 and over who are living with HIV from two townships outside of Cape Town. Using grounded theory to specify emerging themes, we find similarities and differences between older men and women in their pathways to testing. Men primarily test for HIV when their spouse is diagnosed or in connection with TB testing and treatment. Older women, who are more likely to be widowed or divorced, often test for HIV only when they are symptomatic or not responding appropriately to care for non-communicable diseases. Most importantly, we find that older South Africans do not seek testing as a response to risk. Instead, older men and women test only once they are symptomatic and referred by a provider, or as a result of a partner’s status. Our respondents, particularly the women, expressed “shock” and confusion at learning they were HIV-positive because they do not see themselves as at risk of acquiring HIV. Because the benefits of UTT are greatest with early detection and treatment, older persons’ tendency to test at such a late stage of illness decreases the individual and population level advantages of UTT. More research is needed to understand older persons’ risk and testing behavior so that policy and programs include HIV testing messages that reach this population. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15-24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa.Methods and Findings: A total of 1,342 young people, stratified by age (15-19 and 20-24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home.Conclusions: A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is endemic in Africa and parts of the Middle East. It is an emerging zoonotic disease threat to veterinary and public health. Outbreaks of the disease have severe socio-economic impacts. RVF virus emergence is closely associated with specific endorheic wetlands that are utilized by the virus’ mosquito vectors. Limited botanical vegetation surveys had been published with regard to RVF virus (RVFV) ecology. We report on a phytosociological classification, analysis and description of wetland vegetation and related abiotic parameters to elucidate factors possibly associated with the 2010–2011 RVFV disease outbreak in South Africa. The study sites were located in the western Free State and adjacent Northern Cape covering an area of ~40,000 km2 with wetlands associated with high RVF mortality rates in livestock. Other study sites included areas where no RVF activity was reported during the 2010–11 RVF outbreak. A total of 129 plots (30 m2) were selected where a visible difference could be seen in the wetland and upland vegetation. The Braun-Blanquet method was used for plant sampling. Classification was done using modified Two-Way Indicator Species Analysis. The vegetation analysis resulted in the identification of eight plant communities, seven sub-communities and two variants. Indirect ordination was carried out using CANOCO to investigate the relationship between species and wetland ecology. The study also identified 5 categories of wetlands including anthropogenic wetlands. Locations of reported RVF cases overlapped sites characterized by high clay-content soils and specific wetland vegetation. These findings indicate ecological and environmental parameters that represent preferred breeding habitat for RVFV competent mosquito vectors. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the field experiences and recommendations of clinic-based health care providers (HCP) regarding the implementation of universal antiretroviral therapy (ART) in rural KwaZulu-Natal, South Africa. Methods: In Hlabisa sub-district, the local HIV programme of the Department of Health (DoH) is decentralized in 18 clinics, where ART was offered at a CD4 count ≤500 cells/μL from January 2015 to September 2016. Within the ANRS 12249 TasP trial, implemented in part of the sub-district, universal ART (no eligibility criteria) was offered in 11 mobile clinics between March 2012 and June 2016. A cross-sectional qualitative survey was conducted in April–July 2016 among clinic-based nurses and counsellors providing HIV care in the DoH and TasP trial clinics. In total, 13 individual interviews and two focus groups discussions (including 6 and 7 participants) were conducted, audio-recorded, transcribed, and thematically analyzed. Results: All HCPs reported an overall good experience of delivering ART early in the course of HIV infection, with most patients willing to initiate ART before being symptomatic. Yet, HCPs underlined that not feeling sick could challenge early ART initiation and adherence, and thus highlighted the need to take time for counselling as an important component to achieve universal ART. HCPs also foresaw logistical challenges of universal ART, and were especially concerned about increasing workload and ART shortage. HCPs finally recommended the need to strengthen the existing model of care to facilitate access to ART, e.g., community-based and integrated HIV services. Conclusions: The provision of universal ART is feasible and acceptable according to HCPs in this rural South-African area. However their experiences suggest that universal ART, and more generally the 90-90-90 UNAIDS targets, will be difficult to achieve without the implementation of new models of health service delivery. [ABSTRACT FROM AUTHOR]

Background: Retention in care is an essential component of meeting the UNAIDS "90-90-90" HIV treatment targets. In Khayelitsha township (population ~500,000) in Cape Town, South Africa, more than 50,000 patients have received antiretroviral therapy (ART) since the inception of this public-sector program in 2001. Disengagement from care remains an important challenge. We sought to determine the incidence of and risk factors associated with disengagement from care during 2013-2014 and outcomes for those who disengaged.Methods and Findings: We conducted a retrospective cohort study of all patients ≥10 years of age who visited 1 of the 13 Khayelitsha ART clinics from 2013-2014 regardless of the date they initiated ART. We described the cumulative incidence of first disengagement (>180 days not attending clinic) between 1 January 2013 and 31 December 2014 using competing risks methods, enabling us to estimate disengagement incidence up to 10 years after ART initiation. We also described risk factors for disengagement based on a Cox proportional hazards model, using multiple imputation for missing data. We ascertained outcomes (death, return to care, hospital admission, other hospital contact, alive but not in care, no information) after disengagement until 30 June 2015 using province-wide health databases and the National Death Registry. Of 39,884 patients meeting our eligibility criteria, the median time on ART to 31 December 2014 was 33.6 months (IQR 12.4-63.2). Of the total study cohort, 592 (1.5%) died in the study period, 1,231 (3.1%) formally transferred out, 987 (2.5%) were silent transfers and visited another Western Cape province clinic within 180 days, 9,005 (22.6%) disengaged, and 28,069 (70.4%) remained in care. Cumulative incidence of disengagement from care was estimated to be 25.1% by 2 years and 50.3% by 5 years on ART. Key factors associated with disengagement (age, male sex, pregnancy at ART start [HR 1.58, 95% CI 1.47-1.69], most recent CD4 count) and retention (ART club membership, baseline CD4) after adjustment were similar to those found in previous studies; however, notably, the higher hazard of disengagement soon after starting ART was no longer present after adjusting for these risk factors. Of the 9,005 who disengaged, the 2 most common initial outcomes were return to ART care after 180 days (33%; n = 2,976) and being alive but not in care in the Western Cape (25%; n = 2,255). After disengagement, a total of 1,459 (16%) patients were hospitalized and 237 (3%) died. The median follow-up from date of disengagement to 30 June 2015 was 16.7 months (IQR 11-22.4). As we included only patient follow-up from 2013-2014 by design in order to maximize the generalizability of our findings to current programs, this limited our ability to more fully describe temporal trends in first disengagement.Conclusions: Twenty-three percent of ART patients in the large cohort of Khayelitsha, one of the oldest public-sector ART programs in South Africa, disengaged from care at least once in a contemporary 2-year period. Fifty-eight percent of these patients either subsequently returned to care (some "silently") or remained alive without hospitalization, suggesting that many who are considered "lost" actually return to care, and that misclassification of "lost" patients is likely common in similar urban populations. A challenge to meeting ART retention targets is developing, testing, and implementing program designs to target mobile populations and retain them in lifelong care. This should be guided by risk factors for disengagement and improving interlinkage of routine information systems to better support patient care across complex care platforms. [ABSTRACT FROM AUTHOR]

Background: In South Africa, roughly half of the drug-resistant TB cases diagnosed are reported to have been started on treatment. We determined the proportion of persons diagnosed with rifampicin resistant (RR-) TB who initiated treatment in Johannesburg after the introduction of decentralized RR-TB care in 2011. Methods: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 with records of patients initiating RR-TB treatment at one of the city’s four public sector treatment sites (one centralized, three decentralized). Patients were followed from date of diagnosis until the earliest of RR-TB treatment initiation, death, or 6 months’ follow-up. We report diagnostic methods and outcomes, proportions initiating treatment, and median time from diagnosis to treatment initiation. Results: 594 patients were enrolled (median age 34 (IQR 29–42), 287 (48.3%) female). Diagnosis was by GenoType MTBDRplus (Hain-Life-Science) line probe assay (LPA) (281, 47.3%), Xpert MTB/RIF (Cepheid) (258, 43.4%), or phenotypic drug susceptibility testing (DST) (30, 5.1%) with 25 (4.2%) missing a diagnosis method. 320 patients (53.8%) had multi-drug resistant TB, 158 (26.6%) rifampicin resistant TB by Xpert MTB/RIF, 102 (17.2%) rifampicin mono-resistance, and 14 (2.4%) extensively drug-resistant TB. 256/594 (43.0%) patients initiated treatment, representing 70.7% of those who were referred for treatment (362/594). 338/594 patients (57.0%) did not initiate treatment, including 104 (17.5%) who died before treatment was started. The median time from sputum collection to treatment initiation was 33 days (IQR 12–52). Conclusion: Despite decentralized RR-TB treatment, fewer than half the patients diagnosed in Johannesburg initiated appropriate treatment. Offering treatment at decentralized sites alone is not sufficient; improvements in linking patients diagnosed with RR-TB to effective treatment is essential. [ABSTRACT FROM AUTHOR]

Background & aims: Elimination of HIV and syphilis mother-to-child transmission (MTCT) has received much attention but little consideration has been given to the possibility of elimination of HBV MTCT. In sub-Saharan Africa, HBV vertical transmission continues to be reported and it remains an important public health problem. This study aimed to assess the feasibility of screening pregnant women for HBV using a point-of-care (POC) test and implementing interventions to prevent HBV MTCT. Methods: In this observational prospective cohort study, HIV-uninfected pregnant women who consented to testing were screened for HBV using a rapid POC test for HBsAg. Positive results were laboratory-confirmed and tested for HBV DNA and serological markers. Women with viral loads ≥ 20 000 IU/ml received tenofovir (TDF) treatment and all infants received birth-dose HBV vaccine. Two blood samples collected six months apart from HBV-exposed infants within their first year of life were tested for HBV DNA. Results: Of 144 women who were approached, 134 consented to participating (93% acceptance rate of HBV POC test). Six women tested positive for HBsAg (4.5%; 95% CI 0.99%–8.01%), all confirmed by laboratory testing. Two mothers, M1 and M4, were treated with TDF during their third trimester of pregnancy. Six HBV-exposed infants received the HBV vaccine within 24 hours of birth, of whom two were lost to follow-up and four (including the two born to M1 and M4) had undetectable levels of HBV DNA when tested at the two time points. Conclusion: We found that HBV screening using POC testing fulfilled the criteria considered necessary for implementation. It has acceptable performance, is inexpensive, reliable, and was well accepted by the study participants. Screening pregnant women as part of the HBV MTCT prevention strategy is therefore feasible in a South African clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. Methods: We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005–2008) and post-PCV introduction (2012–2013) in children aged 0–59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. Results: In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000–140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000–50,000) severe pneumococcal disease cases were estimated in 2012–2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000–6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000–2500) in 2012–2013, a mortality rate difference of 61 per 100,000 child-years. Conclusions: While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0–59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) aims to reduce tuberculosis (TB) deaths by 95% by 2035; tracking progress requires accurate measurement of TB mortality. International Classification of Diseases (ICD) codes do not differentiate between HIV-associated TB and HIV more generally. Verbal autopsy (VA) is used to estimate cause of death (CoD) patterns but has mostly been validated against a suboptimal gold standard for HIV and TB. This study, conducted among HIV-positive adults, aimed to estimate the accuracy of VA in ascertaining TB and HIV CoD when compared to a reference standard derived from a variety of clinical sources including, in some, minimally-invasive autopsy (MIA). Methods and findings: Decedents were enrolled into a trial of empirical TB treatment or a cohort exploring diagnostic algorithms for TB in South Africa. The WHO 2012 instrument was used; VA CoD were assigned using physician-certified VA (PCVA), InterVA-4, and SmartVA-Analyze. Reference CoD were assigned using MIA, research, and health facility data, as available. 259 VAs were completed: 147 (57%) decedents were female; median age was 39 (interquartile range [IQR] 33–47) years and CD4 count 51 (IQR 22–102) cells/μL. Compared to reference CoD that included MIA (n = 34), VA underestimated mortality due to HIV/AIDS (94% reference, 74% PCVA, 47% InterVA-4, and 41% SmartVA-Analyze; chance-corrected concordance [CCC] 0.71, 0.42, and 0.31, respectively) and HIV-associated TB (41% reference, 32% PCVA; CCC 0.23). For individual decedents, all VA methods agreed poorly with reference CoD that did not include MIA (n = 259; overall CCC 0.14, 0.06, and 0.15 for PCVA, InterVA-4, and SmartVA-Analyze); agreement was better at population level (cause-specific mortality fraction accuracy 0.78, 0.61, and 0.57, for the three methods, respectively). Conclusions: Current VA methods underestimate mortality due to HIV-associated TB. ICD and VA methods need modifications that allow for more specific evaluation of HIV-related deaths and direct estimation of mortality due to HIV-associated TB. [ABSTRACT FROM AUTHOR]

Background: South Africa has a large burden of rifampicin-resistant tuberculosis (RR-TB), with 18,734 patients diagnosed in 2014. The number of diagnosed patients has increased substantially with the introduction of the Xpert MTB/RIF test, used for tuberculosis (TB) diagnosis for all patients with presumptive TB. Routine aggregate data suggest a large treatment gap (pre-treatment loss to follow-up) between the numbers of patients with laboratory-confirmed RR-TB and those reported to have started second-line treatment. We aimed to assess the impact of Xpert MTB/RIF implementation on the delay to treatment initiation and loss to follow-up before second-line treatment for RR-TB across South Africa.Methods and Findings: A nationwide retrospective cohort study was conducted to assess second-line treatment initiation and treatment delay among laboratory-diagnosed RR-TB patients. Cohorts, including approximately 300 sequentially diagnosed RR-TB patients per South African province, were drawn from the years 2011 and 2013, i.e., before and after Xpert implementation. Patients with prior laboratory RR-TB diagnoses within 6 mo and currently treated patients were excluded. Treatment initiation was determined through data linkage with national and local treatment registers, medical record review, interviews with health care staff, and direct contact with patients or household members. Additional laboratory data were used to track cases. National estimates of the percentage of patients who initiated treatment and time to treatment were weighted to account for the sampling design. There were 2,508 and 2,528 eligible patients in the 2011 and 2013 cohorts, respectively; 92% were newly diagnosed with RR-TB (no prior RR-TB diagnoses). Nationally, among the 2,340 and 2,311 new RR-TB patients in the 2011 and 2013 cohorts, 55% (95% CI 53%-57%) and 63% (95% CI 61%-65%), respectively, started treatment within 6 mo of laboratory receipt of their diagnostic specimen (p < 0.001). However, in 2013, there was no difference in the percentage of patients who initiated treatment at 6 mo between the 1,368 new RR-TB patients diagnosed by Xpert (62%, 95% CI 59%-65%) and the 943 diagnosed by other methods (64%, 95% CI 61%-67%) (p = 0.39). The median time to treatment decreased from 44 d (interquartile range [IQR] 20-69) in 2011 to 22 d (IQR 2-43) in 2013 (p < 0.001). In 2013, across the nine provinces, there were substantial variations in both treatment initiation (range 51%-73% by 6 mo) and median time to treatment (range 15-36 d, n = 1,450), and only 53% of the 1,448 new RR-TB patients who received treatment were recorded in the national RR-TB register. This retrospective study is limited by the lack of information to assess reasons for non-initiation of treatment, particularly pre-treatment mortality data. Other limitations include the use of names and dates of birth to locate patient-level data, potentially resulting in missed treatment initiation among some patients.Conclusions: In 2013, there was a large treatment gap for RR-TB in South Africa that varied significantly across provinces. Xpert implementation, while reducing treatment delay, had not contributed substantially to reducing the treatment gap in 2013. However, given improved case detection with Xpert, a larger proportion of RR-TB patients overall have received treatment, with reduced delays. Nonetheless, strategies to further improve linkage to treatment for all diagnosed RR-TB patients are urgently required. [ABSTRACT FROM AUTHOR]

Background: The first policy action outlined in the Sustainable Development Goals (SDGs) is the implementation of national social protection systems. This study assesses whether social protection provision can impact 17 indicators of five key health-related SDG goals amongst adolescents in South Africa. Methods: We conducted a longitudinal survey of adolescents (10–18 years) between 2009 and 2012. Census areas were randomly selected in two urban and two rural health districts in two South African provinces, including all homes with a resident adolescent. Household receipt of social protection in the form of ‘cash’ (economic provision) and ‘care’ (psychosocial support) social protection, and health-related indicators within five SDG goals were assessed. Gender-disaggregated analyses included multivariate logistic regression, testing for interactions between social protection and socio-demographic covariates, and marginal effects models. Findings: Social protection was associated with significant adolescent risk reductions in 12 of 17 gender-disaggregated SDG indicators, spanning SDG 2 (hunger); SDG 3 (AIDS, tuberculosis, mental health and substance abuse); SDG 4 (educational access); SDG 5 (sexual exploitation, sexual and reproductive health); and SDG 16 (violence perpetration). For six of 17 indicators, combined cash plus care showed enhanced risk reduction effects. Two interactions showed that effects of care varied by poverty level for boys’ hunger and girls’ school dropout. For tuberculosis, and for boys’ sexual exploitation and girls’ mental health and violence perpetration, no effects were found and more targeted or creative means will be needed to reach adolescents on these challenging burdens. Interpretation: National social protection systems are not a panacea, but findings suggest that they have multiple and synergistic positive associations with adolescent health outcomes. Such systems may help us rise to the challenges of health and sustainable development. [ABSTRACT FROM AUTHOR]

Background: South African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure. Methods: We include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second-line. Results: 5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1–8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment ≤100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6–12 months vs. 0–1.5 months = 1.47 (95% CI: 0.94–2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3–6 months vs. 0–1.5 months = 2.13 (95% CI: 1.01–4.47)). Conclusions: Even small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly. [ABSTRACT FROM AUTHOR]

Background: Age-disparate partnerships are hypothesized to increase HIV-risk for young women. However, the evidence base remains mixed. Most studies have focused only on unprotected sex among women in the partnership. Consequently, little is known about other risky behaviours, such as transactional sex, alcohol use, and concurrency, as well as the behaviours of the men who partner with young women. We therefore examined differences in various sexual behaviours of both young women and their male partners by partnership age difference. Methods: We used nationally representative data from South Africa (2012) on partnerships reported by 16–24 year old black African women (n = 818) and by black African men in partnerships with 16–24 year old women (n = 985). We compared sexual behaviours in age-disparate partnerships and age-similar partnerships, using multiple logistic regression to control for potential confounders and to assess rural/urban differences. Results: Young women in age-disparate partnerships were more likely to report unprotected sex than young women in similar-aged partnerships (aOR:1.51; p = 0.014; 95%CI:1.09–2.11). Men in partnerships with young women were more likely to report unprotected sex (aOR:1.92; p<0.01; 95%CI:1.31–2.81), transactional sex (aOR:2.73; p<0.01; 95%CI:1.64–4.56), drinking alcohol before sex (aOR:1.60; p = 0.062; 95%CI:0.98–2.61), and concurrency (aOR:1.39; p = 0.097; 95%CI:0.94–2.07) when their partners were five or more years younger. The association between age-disparate partnerships and transactional sex (aOR:4.14; p<0.01; 95%CI: 2.03–8.46) and alcohol use (aOR:2.24; p<0.013; 95%CI:1.20–4.19) was only found in urban areas. Conclusions: Results provide evidence that young women’s age-disparate partnerships involve greater sexual risk, particularly through the risky behaviours of their male partners, with the risk amplified for young women in urban areas. [ABSTRACT FROM AUTHOR]

Background: WHO recommends a male circumcision (MC) prevalence rate higher than 80% to have a substantial impact on the HIV-AIDS epidemic in Eastern and Southern Africa. Orange Farm, a township in South Africa, has a free-for-service voluntary medical male circumcision (VMMC) clinic in operation since 2008. Following an intense campaign from 2008 to 2010, MC prevalence rate increased to 55.4% (ANRS-12126). Ongoing and past VMMC campaigns focused on youths, through school talks, and adults at a community level. The main objective of the study was to assess the change in MC prevalence rate among adults aged 18–19 and 18–49 years in the past 5 years. Methods: A cross-sectional survey (ANRS-12285) was conducted among a random sample of 522 adult men in 2015. MC status and characteristics of participants were collected through a genital examination and a face-to-face questionnaire. Results: MC prevalence rate among young adult men aged 18–19 years increased markedly from 61.2% (95%CI: 57.4% to 65.0%) in 2010 to 87.5% (76.0% to 94.6%) in 2015 (p<0.001). In the same period, among men aged 18–49 years, MC prevalence rate varied slightly from 55.4% (53.6% to 57.1%) to 56.7% (52.4% to 60.9%). In 2015, 84.9% (79.2% to 89.5%) of uncircumcised adult men reported that they were willing to be circumcised. However, we estimated that only 4.6% (11/237; 2.5% to 7.9%) of the uncircumcised men underwent circumcision in 2015, despite 117/185 (63.2%; 95%CI: 56.1% to 69.9%) who reported that they were definitely willing to become circumcised. Conclusions: In Orange Farm, VMMC campaigns were successful among the youth and led to a sufficiently high MC prevalence rate to have a substantial impact in the future on the HIV-AIDS epidemic. However, despite high acceptability and a free VMMC service, VMMC campaigns since 2010 have failed to increase MC prevalence rate among adults to above 80%. These campaigns should be revisited. [ABSTRACT FROM AUTHOR]

Background: In 2012, South Africa set a goal of circumcising 4.3 million men ages 15–49 by 2016. By the end of March 2014, 1.9 million men had received voluntary medical male circumcision (VMMC). In an effort to accelerate progress, South Africa undertook a modeling exercise to determine whether circumcising specific client age groups or geographic locations would be particularly impactful or cost-effective. Results will inform South Africa’s efforts to develop a national strategy and operational plan for VMMC. Methods and Findings: The study team populated the Decision Makers’ Program Planning Tool, Version 2.0 (DMPPT 2.0) with HIV incidence projections from the Spectrum/AIDS Impact Module (AIM), as well as national and provincial population and HIV prevalence estimates. We derived baseline circumcision rates from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey. The model showed that circumcising men ages 20–34 offers the most immediate impact on HIV incidence and requires the fewest circumcisions per HIV infection averted. The greatest impact over a 15-year period is achieved by circumcising men ages 15–24. When the model assumes a unit cost increase with client age, men ages 15–29 emerge as the most cost-effective group. When we assume a constant cost for all ages, the most cost-effective age range is 15–34 years. Geographically, the program is cost saving in all provinces; differences in the VMMC program’s cost-effectiveness across provinces were obscured by uncertainty in HIV incidence projections. Conclusion: The VMMC program’s impact and cost-effectiveness vary by age-targeting strategy. A strategy focusing on men ages 15–34 will maximize program benefits. However, because clients older than 25 access VMMC services at low rates, South Africa could consider promoting demand among men ages 25–34, without denying services to those in other age groups. Uncertainty in the provincial estimates makes them insufficient to support geographic targeting. [ABSTRACT FROM AUTHOR]

Background: We assessed the diagnostic accuracy of Determine TB-LAM (LF-LAM) to screen for tuberculosis among ambulatory adults established in HIV care in South Africa. Methods: A systematic sample of adults attending for HIV care, regardless of symptomatology, were enrolled in the XPHACTOR study, which tested a novel algorithm for prioritising investigation with Xpert MTB/RIF. In this substudy, restricted to participants with enrolment CD4<200x106/l, urine was stored at enrolment for later testing with LF-LAM. Sputum was sent for immediate Xpert MTB/RIF if any of: current cough, fever ≥3 weeks, body mass index (BMI)<18.5kg/m2, CD4<100x106/l (or <200x106/l if pre-ART), weight loss ≥10% or strong clinical suspicion were present; otherwise, sputum was stored for Xpert testing at study completion. Participants were reviewed monthly, with reinvestigation if indicated, to 3 months, when sputum and blood were taken for mycobacterial culture. We defined tuberculosis as “confirmed” if Xpert, line probe assay or culture for M. tuberculosis within six months of enrolment were positive, and “clinical” if tuberculosis treatment started without microbiological confirmation. Results: Amongst 424 participants, 61% were female and 57% were taking ART (median duration 22 months); median age, CD4 and BMI were 39 years, 111x106/l, and 23 kg/m2. 56/424 (13%) participants had tuberculosis (40 confirmed, 16 clinical). 24/424 (5.7%) vs. 8/424 (1.9%) were LAM-positive using grade 1 vs. grade 2 cut-off. Using grade 1 cut-off, sensitivity for confirmed TB (all clinical TB excluded) was 12.5% (95% CI 4.2%, 26.8%) and in CD4<100x106/l vs. CD4 ≥100x106/l was 16.7% (95% CI 4.7%, 37.4%) vs. 6.3% (95% CI 0.2%, 30.2%). Specificity was >95% irrespective of diagnostic reference standard, CD4 stratum, or whether grade 1 or grade 2 cut-off was used. Conclusion: Sensitivity of LF-LAM is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care. [ABSTRACT FROM AUTHOR]

Background: In high HIV prevalence settings, offering HIV testing may be a reasonable part of contact tracing of index tuberculosis (TB) patients. We evaluated the uptake of HIV counselling and testing (HCT) among household contacts of index TB patients and the proportion of newly diagnosed HIV-infected persons linked into care as part of a household TB contact tracing study. Methods: We recruited index TB patients at public health clinics in two South African provinces to obtain consent for household contact tracing. During scheduled household visits we offered TB symptom screening to all household members and HCT to individuals ≥14years of age. Factors associated with HCT uptake were investigated using a random effects logistic regression model. Results & Discussion: Out of 1,887 listed household members ≥14 years old, 984 (52%) were available during a household visit and offered HCT of which 108 (11%) self-reported being HIV infected and did not undergo HCT. Of the remaining 876, a total of 304 agreed to HCT (35%); 26 (8.6%) were newly diagnosed as HIV positive. In multivariable analysis, factors associated with uptake of HCT were prior testing (odds ratio 1.6; 95% confidence interval [CI]: 1.1–2.3) and another member in the household testing (odds ratio 2.4; 95% CI: 1.7–3.4). Within 3 months of testing HIV-positive, 35% reported initiating HIV care. Conclusion: HCT as a component of household TB contact tracing reached individuals without prior HIV testing, however uptake of HIV testing was poor. Strategies to improve HIV testing in household contacts should be evaluated. [ABSTRACT FROM AUTHOR]

Background: High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.Methods and Findings: RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm") received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study ("standard arm") followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05-1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24-1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain.Conclusions: Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa.Trial Registration: ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary tuberculosis (TB) remains a major public health challenge in South Africa. However, little attention is paid to the impact of health related quality of life (HRQL) among TB patients at the beginning and at the end of TB treatment. This study assesses factors associated with HRQL among tuberculosis patients in three high risk provinces in South Africa. Methods: A prospective cohort study was conducted at primary health care settings. Patients completed the HRQL social functioning (SF)-12 health survey. Comparison of Physical Health Summary Score (PCS) and Mental Health Summary Score (MCS) was assessed at 6 months after treatment. Generalized estimating equations (GEEs) were used to examine the factors associated with changes in HRQL. Results: In all patients, after 6 months of treatment there was a significant improvement in HRQL with the biggest increase in the PCS. A higher educational qualification had a strong significant positive effect on the mental HRQL. Psychological distress showed a significant negative association with physical and mental HRQL after six months. Permanent residence showed a significant positive association with mental HRQL among TB patients compared to those living in shack/traditional dwellings. Rating ones health as being good and fair/poor was significantly associated with poor physical HRQL. Twenty drinks or more in the past month had a significant negative effect on the physical HRQL. Conclusion: The findings suggest that programmes targeted at improving TB treatment success should have specific interventions for patients with low educational background, impoverished households/communities and those with hazardous or harmful alcohol use. [ABSTRACT FROM AUTHOR]

African horse sickness (AHS) is a severe, often fatal, arbovirus infection of horses, transmitted by Culicoides spp. midges. AHS occurs in most of sub-Saharan Africa and is a significant impediment to export of live horses from infected countries, such as South Africa. A stochastic risk model was developed to estimate the probability of exporting an undetected AHS-infected horse through a vector protected pre-export quarantine facility, in accordance with OIE recommendations for trade from an infected country. The model also allows for additional risk management measures, including multiple PCR tests prior to and during pre-export quarantine and optionally during post-arrival quarantine, as well as for comparison of risk associated with exports from a demonstrated low-risk area for AHS and an area where AHS is endemic. If 1 million horses were exported from the low-risk area with no post-arrival quarantine we estimate the median number of infected horses to be 5.4 (95% prediction interval 0.5 to 41). This equates to an annual probability of 0.0016 (95% PI: 0.00015 to 0.012) assuming 300 horses exported per year. An additional PCR test while in vector-protected post-arrival quarantine reduced these probabilities by approximately 12-fold. Probabilities for horses exported from an area where AHS is endemic were approximately 15 to 17 times higher than for horses exported from the low-risk area under comparable scenarios. The probability of undetected AHS infection in horses exported from an infected country can be minimised by appropriate risk management measures. The final choice of risk management measures depends on the level of risk acceptable to the importing country. [ABSTRACT FROM AUTHOR]

Almost 30% of pregnant women attending public health clinics in South Africa are HIV positive; which represents approximately 280,000 women each year. South Africa has the largest antiretroviral therapy programme in the world, with over 2.7 million people on treatment in 2013. Since its belated and controversial beginning, the Prevention of Mother-to-Child Transmission programme has achieved a substantial reduction in vertical transmission. South Africa is justifiably proud of this success. However, the history of Prevention of Mother-to-Child Transmission (PMTCT) and antiretroviral therapy programmes in South Africa has been fraught with delays and political intervention. South Africa could have started both PMTCT and antiretroviral therapy programmes in 2000. Instead, the AIDS denialist views of the government allowed the HIV epidemic to spiral out of control. Roll-out of a national PMTCT programme began in 2002, but only after the government was forced to do so by a Constitutional Court ruling. Now, a decade later, HIV treatment and prevention programmes have been completely transformed. This article will discuss the evolution of the HIV epidemic in South Africa, and give a historical overview of the struggle to establish a national PMTCT, and the impact of delaying PMTCT and treatment programmes on infant and maternal health. [ABSTRACT FROM AUTHOR]

HIV prevention trials have demonstrated the effectiveness of a number of behavioral and biomedical interventions. HIV prevention packages are combinations of interventions and offer potential to significantly increase the effectiveness of any single intervention. Estimates of the effectiveness of prevention packages are important for guiding the development of prevention strategies and for characterizing effect sizes before embarking on large scale trials. Unfortunately, most research to date has focused on testing single interventions rather than HIV prevention packages. Here we report the results from agent-based modeling of the effectiveness of HIV prevention packages for men who have sex with men (MSM) in South Africa. We consider packages consisting of four components: antiretroviral therapy for HIV infected persons with CD4 count <350; PrEP for high risk uninfected persons; behavioral interventions to reduce rates of unprotected anal intercourse (UAI); and campaigns to increase HIV testing. We considered 163 HIV prevention packages corresponding to different intensity levels of the four components. We performed 2252 simulation runs of our agent-based model to evaluate those packages. We found that a four component package consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART coverage over and above persons already receiving ART at baseline, could prevent 33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3). The package components with the largest incremental prevention effects were UAI reduction and PrEP coverage. The impact of increased HIV testing was magnified in the presence of PrEP. We find that HIV prevention packages that include both behavioral and biomedical components can in combination prevent significant numbers of infections with levels of coverage, acceptance and adherence that are potentially achievable among MSM in South Africa. [ABSTRACT FROM AUTHOR]

: Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03–0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04–0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13–5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies. Trial Registration: ClinicalTrials.gov: [ABSTRACT FROM AUTHOR]

Setting: Multidrug-resistant tuberculosis (MDR-TB) unit in KwaZulu-Natal, South Africa. Objective: To develop and evaluate a nurse case management model and intervention using the tenets of the Chronic Care Model to manage treatment for MDR-TB patients with a high prevalence of human immunodeficiency virus (HIV) co-infection. Design: A quasi-experimental pilot programme utilizing a nurse case manager to manage care for 40 hospitalized MDR-TB patients, 70% HIV co-infected, during the intensive phase of MDR-TB treatment. Patients were followed for six months to compare proximal outcomes identified in the model between the pre- and post-intervention period. Results: The greatest percent differences between baseline and six-month MDR-TB proximal outcomes were seen in the following three areas: baseline symptom evaluation on treatment initiation (95% improvement), baseline and monthly laboratory evaluations completed per guidelines (75% improvement), and adverse drug reactions acted upon by medical and/or nursing intervention (75% improvement). Conclusion: Improvements were identified in guideline-based treatment and monitoring of adverse drug reactions following implementation of the nurse case management intervention. Further study is required to determine if the intervention introduced in this model will ultimately result in improvements in final MDR-TB treatment outcomes. [ABSTRACT FROM AUTHOR]