Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study.

CAPRISA, 2014.Abstract available in pdf

Survival from XDR-TB Is Associated with Modifiable Clinical Characteristics in Rural South Africa

Drug-resistant tuberculosis (TB) is a major threat to global public health. Patients with extensively drug-resistant TB (XDR-TB), particularly those with HIV-coinfection, experience high and accelerated mortality with limited available interventions. To determine modifiable factors associated with survival, we evaluated XDR-TB patients from a community-based hospital in rural South Africa where a large number of XDR-TB cases were first detected.A retrospective case control study was conducted of XDR-TB patients diagnosed from 2005-2008. Survivors, those alive at 180 days from diagnostic sputum collection date, were compared with controls who died within 180 days. Clinical, laboratory and microbiological correlates of survival were assessed in 69 survivors (median survival 565 days [IQR 384-774] and 73 non-survivors (median survival 34 days [IQR 18-90]). Among 129 HIV+ patients, multivariate analyses of modifiable factors demonstrated that negative AFB smear (AOR 8.4, CI 1.84-38.21), a lower laboratory index of routine laboratory findings (AOR 0.48, CI 0.22-1.02), CD4>200 cells/mm(3) (AOR 11.53, 1.1-119.32), and receipt of antiretroviral therapy (AOR 20.9, CI 1.16-376.83) were independently associated with survival from XDR-TB.Survival from XDR-TB with HIV-coinfection is associated with less advanced stages of both diseases at time of diagnosis, absence of laboratory markers indicative of multiorgan dysfunction, and provision of antiretroviral therapy. Survival can be increased by addressing these modifiable risk factors through policy changes and improved clinical management. Health planners and clinicians should develop programmes focusing on earlier case finding and integration of HIV and drug-resistant TB diagnostic, therapeutic, and preventive activities

Extensively Drug-Resistant Tuberculosis in Women, KwaZulu-Natal, South Africa

To determine whether women in KwaZulu-Natal, South Africa, with drug-resistant tuberculosis (TB) were more likely than men to have extensively drug-resistant TB, we reviewed 4,514 adults admitted during 2003–2008 for drug-resistant TB. Female sex independently predicted extensively drug-resistant TB, even after we controlled for HIV infection. This association needs further study

Comparing early treatment outcomes of MDR-TB in a decentralised setting with a centralised setting in KwaZulu-Natal, South Africa.

Setting—In KwaZulu-Natal, South Africa, a TB and HIV endemic setting, prolonged hospitalisation for the treatment of the growing number of MDR-TB patients is not possible or effective. Objective—We compared early treatment outcomes in patients with MDR-TB, with and without HIV co infection, at a central, urban, referral hospital with four decentralised rural sites. Design—This is an operational, prospective cohort study of patients between 1 July 2008 to 30 November 2009, where culture conversion, time-to-culture-conversion, survival and predictors of these outcomes were analysed. Results—Of the 860 patients with MDR-TB, 419 were at the decentralised sites and 441 at the central hospital. Overall, 71% were HIV co-infected

Community-based care vs. centralised hospitalisation for MDR-TB patients, KwaZulu-Natal, South Africa.

CAPRISA, 2015.Abstract available in pdf

MDR-TB patients in KwaZulu-Natal, South Africa: cost-effectiveness of 5 models of care.

CAPRISA, 2018.Abstract available in pdf

High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria. PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27–42). 134 (67.0%) were living with HIV; the median CD4+ count was 281 cells·μL−1 (IQR 130–467) and all were on antiretroviral therapy. 16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1). Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.http://erj.ersjournals.com2020-06-01hj2019Medical Microbiolog

Surgical treatment of complications of pulmonary tuberculosis, including drug-resistant tuberculosis.

CAPRISA, 2015.Abstract available in pdf

Treatment outcomes for extensively drug-resistant tuberculosis and HIV co-infection.

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3–9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) defaulted from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome

Association between health systems performance and treatment outcomes in patients co-infected with MDR-TB and HIV in KwaZulu-Natal, South Africa: implications for TB programmes.

CAPRISA, 2014.Objective: To improve the treatment of MDR-TB and HIV co-infected patients, we investigated the relationship between health system performance and patient treatment outcomes at 4 decentralised MDR-TB sites. Methods: In this mixed methods case study which included prospective comparative data, we measured health system performance using a framework of domains comprising key health service components. Using Pearson Product Moment Correlation coefficients we quantified the direction and magnitude of the association between health system performance and MDR-TB treatment outcomes. Qualitative data from participant observation and interviews analysed using systematic text condensation (STC) complemented our quantitative findings. Findings: We found significant differences in treatment outcomes across the sites with successful outcomes varying from 72% at Site 1 to 52% at Site 4 (p<0.01). Health systems performance scores also varied considerably across the sites. Our findings suggest there is a correlation between treatment outcomes and overall health system performance which is significant (r = 0.99, p<0.01), with Site 1 having the highest number of successful treatment outcomes and the highest health system performance. Although the 'integration' domain, which measured integration of MDR-TB services into existing services appeared to have the strongest association with successful treatment outcomes (r = 0.99, p<0.01), qualitative data indicated that the 'context' domain influenced the other domains. Conclusion: We suggest that there is an association between treatment outcomes and health system performance. The chance of treatment success is greater if decentralised MDR-TB services are integrated into existing services. To optimise successful treatment outcomes, regular monitoring and support are needed at a district, facility and individual level to ensure the local context is supportive of new programmes and implementation is according to guidelines