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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]

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]

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: 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]

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]

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]

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: 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: 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]