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Introduction: Treatment success rates of rifampicin resistant (RR)/multi-drug resistant (MDR) tuberculosis (TB) in South Africa range from 43–48%, falling short of the World Health Organization’s target of ≥75%. We present rates and assess predictors of attrition by 12 months on treatment. Methods: Prospective observational cohort analysis of adults (≥18 years) initiating RR/MDR-TB treatment from 01 March 2013 to 30 September 2016. Attrition was defined as a combination of death and loss to follow-up (LTFU; treatment interruption ≥2 months) by 12 months on treatment. Predictors of attrition were identified using Cox Proportional Hazards models to estimate crude (HR) and adjusted hazard ratios (aHR) with corresponding 95% confidence intervals. Results: By 12 months on treatment, 75/240 (31.3%) patients had either died (37/240; 15.4%) or been LTFU (38/240; 15.8%). Patients with moderate/severe anaemia (aHR: 2.10; 95% CI 1.00–4.39), and those who were smear positive at baseline (aHR: 2.04; 95% CI 1.01–4.12) were significantly more likely to die or be lost from care. Conclusion: At this outpatient DR-TB treatment site, there was a high rate of attrition halfway through the standard treatment course at 12 months of 31%. High rates of attrition by 12 months on treatment may continue during the second-half of therapy. [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]

Objective: We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB). Methods: Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months), transfer out, or a final outcome (loss from treatment (LFT) or death). Results: 214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186), followed by direct PCR on AFB positive specimen in 14 (7%) and indirect PCR on cultured isolate in 5 (2%). Median time between sputum testing and treatment initiation was 10 days (IQR 6–21). Interim outcomes were available in 148 patients of whom 78% (n = 115) were still on treatment, 9% (n = 13) had died, and 14% (n = 20) were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9%) were culture negative at 6 months, 12 were still sputum culture positive (9.2%) and 34 had no culture documented or contaminated culture (26%). Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09–0.98). HIV co-infection occurred in 178 patients (83%) with a median CD4 count 88 cells/ml3 (IQR 27–218). Conclusions: Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care. [ABSTRACT FROM AUTHOR]

Background: According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa. Methods: We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment. Results: Across the two sites, 578 eligible patient files were reviewed. 36.7% were categorized as low weight (=50 kg) at DR-TB initiation. 76.0% had no history of TB treatment prior to the current episode of RR TB. 26.8% were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5% of patients were also HIV positive, of whom 43. 8% were on ART prior to RR TB treatment and 32.1% initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3%) and 110 patients (19.0%) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts =100 cells/mm³ and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95% CI: 1.30-5.84 and sHR: 3.07, 95% CI: 1.46-6.46, respectively). Conclusion: Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment. [ABSTRACT FROM AUTHOR]

Background: Gauteng Province has the second lowest tuberculosis (TB) incidence rate in South Africa but the greatest proportion of TB/HIV co-infection, with 68% of TB patients estimated to have HIV. TB treatment outcomes are well documented at the national and provincial level; however, knowledge gaps remain on how outcomes differ across detailed age groups.Methods: Using data from South Africa's National Electronic TB Register (ETR), we assessed all-cause mortality and loss to follow-up (LTFU) among patients initiating treatment for TB between 01/2010 and 12/2015 in the metropolitan municipalities of Ekurhuleni Metropolitan Municipality and the City of Johannesburg in Gauteng Province. We excluded patients who were missing age, had known drug-resistance, or transferred into TB care from sites outside the two metropolitan municipalities. Among patients assigned a treatment outcome, we investigated the association between age group at treatment initiation and mortality or LTFU (treatment interruption of ≥2 months) within 10 months after treatment initiation using Cox proportional hazard models and present hazard ratios and Kaplan-Meier survival curves.Results: We identified 182,890 children (<10 years), young adolescent (10-14), older adolescent (15-19), young adult (20-24), adult (25-49), and older adult (≥50) TB cases without known drug-resistance. ART coverage among HIV co-infected patients was highest for young adolescents (64.3%) and lowest for young adults (54.0%) compared to other age groups (all over 60%). Treatment success exceeded 80% in all age groups (n = 170,017). All-cause mortality increased with age. Compared to adults, young adults had an increased hazard of LTFU (20-24 vs 25-49 years; aHR 1.43 95% CI: 1.33, 1.54) while children, young adolescents, and older adults had lower hazard of LTFU. Patients with HIV on ART had a lower risk of LTFU, but greater risk of death when compared to patients without HIV.Conclusions: Young adults in urban areas of Gauteng Province experience a disproportionate burden of LTFU and low coverage of ART among co-infected patients. This group should be targeted for interventions aimed at improving clinical outcomes and retention in both TB and HIV care. [ABSTRACT FROM AUTHOR]

Background: Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL.Methods: We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015-01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults.Results: We enrolled 149 DR-TB patients (median age 36 years IQR 29-43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6 months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4 weeks, of these the most common were joint pain (n = 22), peripheral neuropathy (n = 16), hearing loss (n = 15), nausea and vomiting (n = 12) and dizziness or vertigo (n = 11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53-3.27) and PCS (aRR 1.52 95% CI 1.07-2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6 months or less.Conclusion: Results show that DR-TB had a substantial impact on patients' quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment. [ABSTRACT FROM AUTHOR]

Background: In 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes.Methods: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 (early cohort) and 07/2013-06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city's four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes.Results: Five hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n = 256) to 60.3% (n = 430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high. Although TTI reduced by a median of 19 days, from 33 days (IQR 12-52) in the early cohort to 14 days (IQR 7-31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation.Conclusion: Pre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical. [ABSTRACT FROM AUTHOR]

Summary Background The South African Electronic Drug-Resistant Tuberculosis Register (EDRweb) is the national database of registered drug-resistant tuberculosis (DR-TB) cases. Methods This study was a retrospective, de-identified secondary analysis of EDRweb patients initiating treatment for rifampicin-resistant TB (January 2009 to September 2011). The relative risks of death and treatment success were estimated using modified Poisson regression with robust error estimation. Results Seventeen thousand six hundred and ninety-seven cases of DR-TB were registered and met the inclusion criteria; 52.0% ( n = 9207) were male and the median age was 35 years (interquartile range 27–43 years). Of the 9419 cases with HIV infection (53.2%), 7157 (76.0%) were on antiretroviral therapy. Most had undergone previous TB treatment (76.5%, n = 13 531). Multidrug-resistant TB was the most common diagnosis, at 80.6% ( n = 14 272). No treatment outcome was available for 6934 patients (39.2%). For patients with outcomes, 4227 (39.4%) were successfully treated, 2987 (27.8%) died, 2533 (23.7%) were lost to follow-up, and 996 (9.3%) failed. Second-line drug resistance was the strongest predictor of death during DR-TB treatment; extensively drug-resistant TB patients were more likely to have died during treatment (adjusted relative risk 2.63, 95% confidence interval 2.45–2.84). Conclusions Testing for second-line drug resistance at initiation of DR-TB treatment can identify patients most at risk of treatment failure and death and most in need of individualized treatment. [ABSTRACT FROM AUTHOR]