TB prevalence in Zimbabwe: a national cross-sectional survey, 2014.

BACKGROUND: We conducted the first national TB prevalence survey to provide accurate estimates of bacteriologically confirmed pulmonary TB disease among adults aged ≥15 years in 2014.METHODS: A TB symptoms screen and chest X-ray (CXR) were used to identify presumptive TB cases who submitted two sputum samples for smear microscopy, liquid and solid culture. Bacteriological confirmation included acid-fast bacilli smear positivity confirmed using Xpert® MTB/RIF and/or culture. Prevalence estimates were calculated using random effects logistic regression with multiple imputations and inverse probability weighting.RESULTS: Of 43,478 eligible participants, 33,736 (78%) were screened; of these 5,820 (17%) presumptive cases were identified. There were 107 (1.9%) bacteriologically confirmed TB cases, of which 23 (21%) were smear-positive. The adjusted prevalences of smear-positive and bacteriologically confirmed TB disease were respectively 82/100,000 population (95% CI 47-118/100,000) and 344/100,000 (95% CI 268-420/100,000), with an overall all-ages, all-forms TB prevalence of 275/100,000 population (95% CI 217-334/100,000). TB prevalence was higher in males, and age groups 35-44 and ≥65 years. CXR identified 93/107 (87%) cases vs. 39/107 (36%) using the symptom screen.CONCLUSION: Zimbabwe TB disease prevalence has decreased relative to prior estimates, possibly due to increased antiretroviral therapy coverage and successful national TB control strategies. Continued investments in TB diagnostics for improved case detection are required.

Xpert(®) MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe.

BACKGROUND: Patients at elevated risk of drug-resistant tuberculosis (TB) are prioritized for Xpert(®) MTB/RIF testing; however, the clinical usefulness of the test in this population is understudied. DESIGN: From November 2011 to June 2014, consecutive out-patients with a history of previous TB in high-density suburbs of Harare, Zimbabwe, were tested using Xpert, solid and liquid culture, and the microscopic observation drug susceptibility assay. Diagnostic accuracy for rifampin (RMP) resistance and time to initiation of second-line regimens were ascertained. The rpoB gene was sequenced in cases with culture-confirmed RMP resistance and genotypic susceptibility. RESULTS: Among 352 retreatment patients, 71 (20%) were RMP-resistant, 98 (28%) RMP-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative. Xpert had a sensitivity of 86% (95%CI 75-93) and a specificity of 98% (95%CI 92-100) for RMP-resistant TB. The positive predictive value of Xpert-determined RMP resistance for multidrug-resistant TB (MDR-TB) was 82% (95%CI 70-91). Of 71 (83%) participants, 59 initiated treatment with second-line drugs, with a median time to treatment initiation of 18 days (IQR 10-44). CONCLUSION: The diagnostic accuracy of Xpert for RMP resistance is high, although the predictive value for MDR-TB was lower than anticipated. Xpert allows for faster initiation of second-line treatment than culture-based drug susceptibility testing under programmatic conditions.

Re-inventing adherence: toward a patient-centered model of care for drug-resistant tuberculosis and HIV.

BACKGROUND: Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE: To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION: Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION: It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

Elucidating the role of clofazimine for the treatment of tuberculosis.

Clofazimine (CFZ), a riminophenazine and a key component of the treatment regimen for lepromatous leprosy, has been rehabilitated clinically for the treatment of multidrug-resistant tuberculosis (MDR-TB). Observational studies and a randomized control trial suggest efficacy in the treatment of MDR-TB and the potential for treatment shortening. Animal and translational research have shown mixed results. In this article, we review key clinical, animal, and translational data to better understand the potential role of CFZ in the treatment of MDR-TB and in shortening anti-tuberculosis treatment.

Impact of Xpert MTB/RIF on Antiretroviral Therapy-Associated Tuberculosis and Mortality: A Pragmatic Randomized Controlled Trial.

INTRODUCTION: GeneXpert® MTB/RIF (Xpert) is now widely distributed in high human immunodeficiency virus (HIV)/tuberculosis (TB)-burden countries. Yet, whether the test improves patient-important outcomes within HIV treatment programs in limited resource settings is unknown. METHODS: To investigate whether use of Xpert for TB screening prior to initiation of antiretroviral treatment (ART) improves patient-important outcomes, in a pragmatic randomized controlled trial we assigned 424 patients to Xpert or fluorescence sputum smear microscopy (FM) at ART initiation. The primary endpoint was a composite of 3-month mortality and ART-associated TB. RESULTS: There was no difference in overall TB diagnosis at ART initiation (20% [n = 43] Xpert vs 21% [n = 45] FM; P = .80), with most patients in both groups treated empirically. There was no difference in time to TB treatment initiation {5 days (interquartile range [IQR], 3-13) vs 8 days [IQR, 3-23; P = .26]} or loss to follow-up (32 [15%] vs 38 [18%]; P = 0.38). Although a nonsignificant reduction in mortality occurred in the Xpert group (11 [6%] vs 17 [10%]; 95% CI, -9% to 2%; P = .19), there was no difference in the composite outcome (9% [n = 17] Xpert vs 12% [n = 21] FM; difference -3%; 95% CI, -9% to 4%). CONCLUSIONS: Among HIV-infected initiating ART, centralized TB screening with Xpert did not reduce the rate of ART-associated TB and mortality, compared with fluorescence microscopy.

Systematic review of clofazimine for the treatment of drug-resistant tuberculosis.

The increased incidence of drug-resistant tuberculosis has created an urgent necessity for the development of new and effective anti-tuberculosis drugs and for alternative therapeutic regimens. Clofazimine (CFZ) is a fat-soluble riminophenazine dye used in the treatment of leprosy worldwide. CFZ has also been used as a Group 5 drug in the treatment of tuberculosis (TB). A large cohort study from Bangladesh published in 2010 described a treatment regimen for multidrug-resistant tuberculosis (MDR-TB) including CFZ as being highly effective against MDR-TB. We searched multiple databases for studies published through February 2012 that reported use of CFZ in MDR- and extensively drug-resistant TB (XDR-TB) treatment regimens. We identified nine observational studies (6 MDR-TB and 3 XDR-TB) including patients with drug-resistant TB treated with CFZ. Overall, 65% (95% confidence interval [95%CI] 54-76) of the patients experienced favorable outcomes, defined as either cure or treatment completion. Using random effects meta-analysis, 65% (95%CI 52-79) of those with MDR-TB and 66% (95%CI 42-89) of those with XDR-TB experienced favorable treatment outcomes. High-quality prospective cohort studies and clinical trials examining the effect of CFZ as part of drug-resistant TB treatment regimens are needed.