Drug-resistant tuberculosis in patients with minimal symptoms: favourable outcomes in the absence of treatment.

SETTING: Referral hospital for drug-resistant tuberculosis (DR-TB) in KwaZulu-Natal Province, South Africa. OBJECTIVE: To review the clinical outcomes of patients (age  14 years) with a laboratory-confirmed diagnosis of DR-TB who had minimal symptoms and/or did not have chest radiographic evidence of active disease at referral. These patients were not started on treatment, but were enrolled in an observation programme with follow-up at 2, 6 and 12 months. RESULTS: Of 3345 referred patients diagnosed with DR-TB, 192 (6%) were enrolled in the observation programme. The median duration from initial sputum collection in primary care to examination at our hospital was 92 days (IQR 64-124). After 12 months, 120 (62%) patients were well, 36 (19%) were lost to follow-up, 30 (16%) had deteriorated and were started on second-line anti-tuberculosis treatment and 6 (3%) had died. Bilateral disease (OR 4.25, 95%CI 1.14-15.77, P = 0.030) and previous TB (OR 2.14, 95%CI 1.10-4.19, P = 0.026) were independent predictors of an unfavourable end result in a multivariate model. CONCLUSION: In our high-burden setting, most patients diagnosed with DR-TB who had minimal symptoms at referral remained well without treatment. Longitudinal observation, coupled with symptom checking and chest radiograph, is a viable strategy.

High treatment failure and default rates for patients with multidrug-resistant tuberculosis in KwaZulu-Natal, South Africa, 2000-2003.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a significant public health threat in South Africa. OBJECTIVE: To describe treatment outcomes and determine risk factors associated with unfavorable outcomes among MDR-TB patients admitted to the provincial TB referral hospital in KwaZulu-Natal Province, South Africa. DESIGN: Retrospective observational study of MDR-TB patients admitted from 2000 to 2003. RESULTS: Of 1209 MDR-TB patients with documented treatment outcomes, 491 (41%) were cured, 35 (3%) completed treatment, 208 (17%) failed treatment, 223 (18%) died and 252 (21%) defaulted. Of the total number of patients with known human immunodeficiency virus (HIV) status, 52% were HIV-infected. Treatment failure, death and default each differed in their risk factors. Greater baseline resistance (aOR 2.3-3.0), prior TB (aOR 1.7), and diagnosis in 2001, 2002 or 2003 (aOR 1.9-2.3) were independent risk factors for treatment failure. HIV co-infection was a risk factor for death (aOR 5.6), and both HIV (aOR 2.0) and male sex (aOR 1.9) were risk factors for treatment default. CONCLUSION: MDR-TB treatment outcomes in KwaZulu-Natal were substantially worse than those published from other MDR-TB cohorts. Interventions such as concurrent antiretroviral therapy and decentralized MDR-TB treatment should be considered to improve MDR-TB outcomes in this high HIV prevalence setting.

Improved early results for patients with extensively drug-resistant tuberculosis and HIV in South Africa.

SETTING: A public tuberculosis (TB) referral hospital in KwaZulu-Natal, South Africa. OBJECTIVE: To present treatment outcomes of patients with extensively drug-resistant tuberculosis (XDR-TB) patients and human immunodeficiency virus (HIV) coinfection with and without highly active antiretroviral therapy. METHODS: Retrospective cohort study. Eligible patients had drug susceptibility testing that met a consensus definition for XDR-TB, and agreed to treatment. Therapy was based on drug susceptibilities, available medications and patient tolerance. RESULTS: Overall, 60 XDR-TB patients initiated therapy with a median number of 5.5 drugs. Of these, 43 (72%) were HIV-positive, and 21 (49%) were on antiretroviral therapy; 29 HIV-infected patients (67%) had available CD4 counts, with a median CD4 count of 200.5 cells/mm(3) (standard deviation 127.4 cells/mm(3)). Of 60 patients, 31 (52%) had adverse events (AEs), and 17/60 patients (28%) had severe AEs. During follow-up, 12/60 (20%) experienced sputum culture conversion, while 25/60 (42%) patients died. None of the following was significantly associated with mortality: HIV status, previous MDR diagnosis or severe AEs. DISCUSSION: In this study, it was possible to treat HIV-XDR-TB coinfected patients and prolong survival in a resource-limited setting. We highlight the challenges in treatment, including high frequencies of AEs and death. Expanded identification of cases, prompt referral for treatment, and attention to management of comorbidities may facilitate successful treatment of XDR-TB in HIV-infected patients.