Treatment Outcomes for Patients with Extensively Drug-Resistant Tuberculosis, KwaZulu-Natal and Eastern Cape Provinces, South Africa.

We analyzed data for a retrospective cohort of patients treated for extensively drug-resistant tuberculosis in 2 provinces in South Africa and compared predictors of treatment outcome in HIV-positive patients who received or had not received antiretroviral drugs with those for HIV-negative patients. Overall, 220 (62.0%) of 355 patients were HIV positive. After 2 years, 34 (10.3%) of 330 patients with a known HIV status and known outcome had a favorable outcome. Multivariate analysis showed that predictors of favorable outcome were negative results for acid-fast bacilli by sputum microscopy at start of treatment and weight >50 kg. HIV-positive patients were more likely to have an unfavorable outcome. The strongest predictor of unfavorable outcome was weight <50 kg. Overall outcomes were poor. HIV status was not a predictor of favorable outcome, but HIV-positive patients were more likely to have an unfavorable outcome. These results underscore the need for timely and adequate treatment for tuberculosis and HIV infection.

Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008-2010.

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 non-adherence. RESULTS: Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent 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.

Occupational Risk Factors for Tuberculosis Among Healthcare Workers in KwaZulu-Natal, South Africa.

BACKGROUND: Tuberculosis is a known occupational hazard for healthcare workers (HCWs), especially in countries with a high burden of tuberculosis. It is estimated that HCWs have a 2- to 3-fold increased risk of developing tuberculosis compared with the general population. The objective of this study was to identify occupational risk factors for tuberculosis among HCWs in 3 district hospitals with specialized multidrug-resistant tuberculosis wards in KwaZulu-Natal, South Africa. METHODS: We conducted a case-control study of HCWs diagnosed with tuberculosis between January 2006 and December 2010. Cases and controls were asked to complete a self-administered questionnaire regarding potential risk factors for tuberculosis. RESULTS: Of 307 subjects selected, 145 (47%) HCWs responded to the questionnaire; 54 (37%) tuberculosis cases and 91 (63%) controls. Cases occurred more frequently among clinical staff 46% (n = 25) and support staff 35% (n = 19). Thirty-two (26% [32/125]) HCWs were known to be infected with human immunodeficiency virus (HIV), including 45% (21/54) of cases. HCWs living with HIV (odds ratio [OR], 6.35; 95% confidence interval [CI], 3.54-11.37) and those who spent time working in areas with patients (OR, 2.24; 95% CI, 1.40-3.59) had significantly greater odds of developing tuberculosis, controlling for occupation, number of wards worked in, and household crowding. CONCLUSIONS: HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients.

Risk of Death among HIV Co-Infected Multidrug Resistant Tuberculosis Patients, Compared To Mortality in the General Population of South Africa.

BACKGROUND: Even though highly effective drugs are available in South Africa, multidrug resistant tuberculosis (MDR-TB) patients with HIV infection have higher mortality compared to HIV-uninfected MDR-TB patients. This trend has been observed in similar countries with high HIV prevalence. This study sought to determine excess mortality attributable to HIV among MDR-TB patients in South Africa using relative survival methods. METHODS: Data available were from a cohort of 2079 MDR-TB patients enrolled in a Standardized Programmatic Management of MDR-TB from 2000 to 2004 in South Africa. A Poisson-based model adjusted for age, gender, year of diagnosis, TB history, and resistance to ethambutol, anti-TB injectable drugs and fluoroquinolones antibiotics was constructed to assess the excess mortality among HIV co-infected MDR-TB patients. Excess hazard ratios (EHRs) were used to describe the effect of the predictors on net mortality, controlling for the general mortality in the South African population. RESULTS: Death was recorded on 1619 patients, of whom 367 (22.7%) had died within 2 years. Out of the 1413 patients that tested for HIV infection, 554 (39.2%) tested positive. Excess mortality was higher in HIV infected, compared to HIV uninfected, MDR-TB patients (adjusted excess hazard ratio, 5.6 [95% CI, 3.2-9.7]); in patients whose TB isolates' resistance to ethambutol and kanamycin was unknown (3.7 [2.1-6.2] and 4.87 [1.9-13.3], respectively) vs. known. There were no differences in excess mortality between age and gender of the patient, year of diagnosis and TB history. CONCLUSION: Adjusting for some important predictors, MDR-TB patients with HIV infection experienced higher excess mortality compared to HIV-uninfected MDR-TB patients, after accounting for the general mortality in South Africa. An appropriate, though complex method has produced predictor effect estimates similar to those obtained from classical methods. Thus, the use of relative survival methods should be encouraged in the analysis of causespecific mortality, when ascertainment of cause of death is inaccurate or unknown.

Natural infection of guinea pigs exposed to patients with highly drug-resistant tuberculosis.

A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant Mycobacterium tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6 mm], only 12% had histopathologic evidence of active disease. Reversions (≥6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6-13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease.