Tuberculosis Epidemiology and Intervention Research Unit

Pretoria, South Africa

Tuberculosis Epidemiology and Intervention Research Unit

Pretoria, South Africa

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Dheda K.,University of Cape Town | Dheda K.,University College London | Shean K.,University of Cape Town | Zumla A.,University College London | And 23 more authors.
The Lancet | Year: 2010

Background: Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes. Methods: In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion. Findings: 195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0·13). Treatment with moxifloxacin (hazard ratio 0·11, 95% CI 0·01-0·82; p=0·03), previous culture-proven multidrug-resistant tuberculosis (5·21, 1·93-14·1; p=0·001), and number of drugs used in a regimen (0·59, 0·45-0·78, p<0·0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0·38, 0·18-0·80; p=0·01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment. Interpretation: In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity. Funding: South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership. © 2010 Elsevier Ltd. All rights reserved.


Finlay A.,Centers for Disease Control and Prevention | Lancaster J.,Tuberculosis Epidemiology and Intervention Research Unit | Holtz T.H.,Centers for Disease Control and Prevention | Weyer K.,World Health Organization | And 2 more authors.
BMC Public Health | Year: 2012

Background. Persons who default from tuberculosis treatment are at risk for clinical deterioration and complications including worsening drug resistance and death. Our objective was to identify risk factors associated with tuberculosis (TB) treatment default in South Africa. Methods. We conducted a national retrospective case control study to identify factors associated with treatment default using program data from 2002 and a standardized patient questionnaire. We defined default as interrupting TB treatment for two or more consecutive months during treatment. Cases were a sample of registered TB patients receiving treatment under DOTS that defaulted from treatment. Controls were those who began therapy and were cured, completed or failed treatment. Two respective multivariable models were constructed, stratified by history of TB treatment (new and re-treatment patients), to identify independent risk factors associated with default. Results. The sample included 3165 TB patients from 8 provinces; 1164 were traceable and interviewed (232 cases and 932 controls). Significant risk factors associated with default among both groups included poor health care worker attitude (new: AOR 2.1, 95% CI 1.1-4.4; re-treatment: AOR 12, 95% CI 2.2-66.0) and changing residence during TB treatment (new: AOR 2.0, 95% CI 1.1-3.7; re-treatment: AOR 3.4, 95% CI 1.1-9.9). Among new patients, cases were more likely than controls to report having no formal education (AOR 2.3, 95% CI 1.2-4.2), feeling ashamed to have TB (AOR 2.0, 95% CI 1.3-3.0), not receiving adequate counseling about their treatment (AOR 1.9, 95% CI 1.2-2.8), drinking any alcohol during TB treatment (AOR 1.9, 95% CI 1.2-3.0), and seeing a traditional healer during TB treatment (AOR 1.9, 95% CI 1.1-3.4). Among re-treatment patients, risk factors included stopping TB treatment because they felt better (AOR 21, 95% CI 5.2-84), having a previous history of TB treatment default (AOR 6.4, 95% CI 2.9-14), and feeling that food provisions might have helped them finish treatment (AOR 5.0, 95% CI 1.3-19). Conclusions. Risk factors for default differ between new and re-treatment TB patients in South Africa. Addressing default in both populations with targeted interventions is critical to overall program success. © 2011 Finlay et al; licensee BioMed Central Ltd.


Mazinyo E.W.,Tuberculosis HIV AIDS Treatment Support and Integrated Therapy thatSit | Kim L.,Centers for Disease Control and Prevention | Masuku S.,Tuberculosis Epidemiology and Intervention Research Unit | Lancaster J.L.,Tuberculosis Epidemiology and Intervention Research Unit | And 4 more authors.
PLoS ONE | Year: 2016

Background Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. Methods A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008-31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking 80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with nonadherence. Results Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Nonadherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). Conclusions The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment. © 2016 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.


Bastos M.L.,Federal University of Rio de Janeiro | Hussain H.,Interactive Research and Development | Weyer K.,World Health Organization | Garcia-Garcia L.,Instituto Nacional Of Salud Publica | And 83 more authors.
Clinical Infectious Diseases | Year: 2014

Background: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drugresistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.Methods: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis.We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.Results: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for secondline injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.Conclusions: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis. © The Author 2014.


Farley J.E.,Johns Hopkins University | Kelly A.M.,Michigan State University | Reiser K.,Johns Hopkins University | Brown M.,Johns Hopkins University | And 4 more authors.
PLoS ONE | Year: 2014

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. Copyright: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. © 2014 Farley et al.


Van der Walt M.,Tuberculosis Epidemiology and Intervention Research Unit | Lancaster J.,Tuberculosis Epidemiology and Intervention Research Unit | Odendaal R.,Tuberculosis Epidemiology and Intervention Research Unit | Davis J.G.,Johns Hopkins University | And 2 more authors.
PLoS ONE | Year: 2013

Background: Globally treatment outcomes for multidrug-resistant Mycobacterium tuberculosis (MDR-TB) remain poor and this is compounded by high drug toxicity. Little is known about the influence of adverse drug reactions (ADRs) on treatment outcomes in South Africa. Methods: We evaluated the impact of severe ADRs among a prospective cohort of MDR-TB patients in South Africa (2000-2004). The HIV-infected study participants were anti-retroviral naïve. Results: Of 2,079 patients enrolled, 1,390 (66.8%) were included in this analysis based on known HIV test results (39.1% HIV-infected). At least one severe ADR was reported in 83 (6.9%) patients with ototoxicity being the most frequent ADR experienced (38.9%). Conclusions: We found that being HIV-infected but antiretroviral naïve did not increase occurrence of SADRs in patients on second-line anti-tuberculosis drugs. Early screening and proactive management of ADRs in this patient population is essential, especially given the rollout of decentralized care and the potential for overlapping toxicity of concomitant MDR-TB and HIV treatment. © 2013 Van der Walt et al.


O'Donnell M.R.,Yeshiva University | Jarand J.,University of Calgary | Loveday M.,Medical Research Council of South Africa | Padayatchi N.,University of KwaZulu - Natal | And 11 more authors.
Annals of Internal Medicine | Year: 2010

Background: Nosocomial transmission has been described in extensively drug-resistant tuberculosis (XDR-TB) and HIV co-infected patients in South Africa. However, little is known about the rates of drug-resistant tuberculosis among health care workers in countries with high tuberculosis and HIV burden. Objective: To estimate rates of multidrug-resistant tuberculosis (MDR-TB) and XDR-TB hospitalizations among health care workers in KwaZulu-Natal, South Africa. Design: Retrospective study of patients with drug-resistant tuberculosis who were admitted from 2003 to 2008 for the initiation of drug-resistant tuberculosis therapy. Setting: A public tuberculosis referral hospital in KwaZulu-Natal, South Africa. Participants: 231 health care workers and 4151 non-health care workers admitted for initiation of MDR-TB or XDR-TB treatment. Measurements: Hospital admission rates and hospital admission incidence rate ratios. Results: Estimated incidence of MDR-TB hospitalization was 64.8 per 100 000 health care workers versus 11.9 per 100 000 non-health care workers (incidence rate ratio, 5.46 [95% CI, 4.75 to 6.28]). Estimated incidence of XDR-TB hospitalizations was 7.2 per 100 000 health care workers versus 1.1 per 100 000 non-health care workers (incidence rate ratio, 6.69 [CI, 4.38 to 10.20]). A higher percentage of health care workers than non-health care workers with MDR-TB or XDR-TB were women (78% vs. 47%; P < 0.001), and health care workers were less likely to report previous tuberculosis treatment (41% vs. 92%; P < 0.001). HIV infection did not differ between health care workers and non-health care workers (55% vs. 57%); however, among HIV-infected patients, a higher percentage of health care workers were receiving antiretroviral medications (63% vs. 47%; P < 0.001). Limitation: The study had an observational retrospective design, is subject to referral bias, and had no information on type of health care work or duration of occupational exposure to tuberculosis. Conclusion: Health care workers in this HIV-endemic area were substantially more likely to be hospitalized with either MDR-TB or XDR-TB than were non-health care workers. The increased risk may be explained by occupational exposure, underlining the urgent need for tuberculosis infection-control programs. Primary Funding Source: None. © 2010 American College of Physicians.

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