• What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?

      Bastard, M; Sanchez-Padilla, E; Hayrapetyan, A; Kimenye, K; Khurkhumal, S; Dlamini, T; Fadul Perez, S; Telnov, A; Hewison, C; Varaine, F; et al. (International Union Against Tuberculosis and Lung Disease, 2019-10-01)
      INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration. METHODS: We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted. RESULTS: This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1–95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains. CONCLUSION: Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.
    • "When Treatment Is More Challenging than the Disease": A Qualitative Study of MDR-TB Patient Retention

      Shringarpure, K S; Isaakidis, P; Sagili, K D; Baxi, R K; Das, M; Daftary, A (Public Library of Science, 2016-03-09)
      One-fifth of the patients on multidrug-resistant tuberculosis treatment at the Drug-Resistant-TB (DR-TB) Site in Gujarat are lost-to-follow-up(LFU).
    • Where There is Hope: A Qualitative Study Examining Patients' Adherence to Multi-Drug Resistant Tuberculosis Treatment in Karakalpakstan, Uzbekistan

      Horter, S; Stringer, B; Greig, J; Amangeldiev, A; Tillashaikhov, MN; Parpieva, N; Tigay, Z; du Cros, P (BioMed Central, 2016-07-28)
      Treatment for multi-drug resistant tuberculosis (MDR-TB) is lengthy, has severe side effects, and raises adherence challenges. In the Médecins Sans Frontières (MSF) and Ministry of Health (MoH) programme in Karakalpakstan, Uzbekistan, a region with a high burden of MDR-TB, patient loss from treatment (LFT) remains high despite adherence support strategies. While certain factors associated with LFT have been identified, there is limited understanding of why some patients are able to adhere to treatment while others are not. We conducted a qualitative study to explore patients' experiences with MDR-TB treatment, with the aim of providing insight into the barriers and enablers to treatment-taking to inform future strategies of adherence support.
    • WHO Clinical Staging of HIV Infection and Disease, Tuberculosis and Eligibility for Antiretroviral Treatment: Relationship to CD4 Lymphocyte Counts.

      Teck, R; Ascurra, O; Gomani, P; Manzi, M; Pasulani, O; Kusamale, J; Salaniponi, F M L; Humblet, P; Nunn, P; Scano, F; et al. (International Union Against TB and Lung Disease, 2005-03)
      SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy.
    • WHO Recommendations For Multidrug-Resistant Tuberculosis

      Berry, C; Achar, J; du Cros, P (Elsevier, 2016-11-05)
    • Whole Genome Sequencing Reveals Complex Evolution Patterns of Multidrug-Resistant Mycobacterium tuberculosis Beijing Strains in Patients

      Merker, M; Kohl, T A; Roetzer, A; Truebe, L; Richter, E; Rüsch-Gerdes, S; Fattorini, L; Oggioni, M R; Cox, H; Varaine, F; et al. (Public Library of Science, 2013-12)
      Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR) variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS) to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and molecular drug resistance tests. Furthermore, high resolution WGS analysis is necessary to accurately detect exogenous re-infection as classical genotyping lacks discriminatory power in high incidence settings.
    • Wind-driven roof turbines: a novel way to improve ventilation for TB infection control in health facilities

      Cox, H; Escombe, R; McDermid, C; Mtshemla, Y; Spelman, T; Azevedo, V; London, L; Medecins Sans Frontieres, Cape Town, South Africa; Burnet Institute for Medical Research, Melbourne, Australia; Department of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; City of Cape Town Health Department, Cape Town, South Africa; University of Cape Town, Cape Town, South Africa (Public Library of Science (PLoS), 2012-01-09)
      Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa.
    • XDR-TB in South Africa: detention is not the priority.

      Goemaere, E; Ford, N; Berman, D; McDermid, C; Cohen, R; PLOS Medicine (2007-04)
    • Xpert(®) MTB/RIF for Detection of Mycobacterium Tuberculosis From Frozen String and Induced Sputum Sediments

      Atwebembeire, J; Orikiriza, P; Bonnet, M; Atwine, D; Katawera, V; Nansumba, M; Nyehangane, D; Bazira, J; Mwanga-Amumpaire, J; Byarugaba, F; et al. (International Union Against Tuberculosis and Lung Disease, 2016-08-01)
      Although it is now widely used for tuberculosis (TB) diagnosis, Xpert(®) MTB/RIF availability remains inadequate in low-resource settings. Moreover, its accuracy in testing stored samples from non-expectorating patients has not been evaluated.
    • Xpert® MTB/RIF under routine conditions in diagnosing pulmonary tuberculosis: a study in two hospitals in Pakistan [Short communication]

      Shah, S K; Kumar, A M V; Dogar, O F; Khan, M A; Qadeer, E; Tahseen, S; Masood, F; Chandio, A K; Edginton, M E (International Union Against TB and Lung Disease, 2013-03)