• Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multi-country Study.

      Franke, MF; Khan, P; Hewison, C; Khan, U; Huerga, H; Seung, KJ; Rich, ML; Zarli, K; Samieva, N; Oyewusi, L; et al. (ATS Journals, 2020-07-24)
      Background Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion. Methods We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups. Findings 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion. Interpretation Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
    • Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection

      Rangaka, M X; Wilkinson, K A; Seldon, R; Van Cutsem, G; Meintjes, G A; Morroni, C; Mouton, P; Diwakar, L; Connell, T G; Maartens, G; et al. (2007-12-07)
      RATIONALE: Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). Interpretation: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis.
    • Eligibility for the Shorter Multidrug-Resistant Tuberculosis Regimen: Ambiguities in the World Health Organization Recommendations

      Varaine, F; Guglielmetti, L; Huerga, H; Bonnet, M; Kiria, N; Sitienei, JK; Rich, M; Mitnick, CD (American Thoracic Society, 2016-10-15)
    • New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations

      Harausz, E; Garcia-Prats, A; Seddon, J; Schaaf, H; Hesseling, A; Achar, J; Bernheimer, J; Cruz, A; D'Ambrosio, L; Detjen, A; et al. (American Thoracic Society, 2017-05-15)
      It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.
    • Reply from the Authors of Eligibility for the Shorter MDR-TB Regimen: Ambiguities in the WHO Recommendations

      Varaine, F; Guglielmetti, L; Mitnick, C (American Thoracic Society, 2017-07-17)