• Upholding Tuberculosis Services during the 2014 Ebola Storm: An Encouraging Experience from Conakry, Guinea

      Ortuno-Gutierrez, N; Zachariah, R; Woldeyohannes, D; Bangoura, A; Chérif, GF; Loua, F; Hermans, V; Tayler-Smith, K; Sikhondze, W; Camara, LM (Public Library of Science, 2016-08-17)
      Ten targeted health facilities supported by Damien Foundation (a Belgian Non Governmental Organization) and the National Tuberculosis (TB) Program in Conakry, Guinea.
    • Use of Colorimetric Culture Methods for Detection of Mycobacterium Tuberculosis Complex Isolates from Sputum Samples in Resource-Limited Settings

      Boum, Y; Orikiriza, P; Rojas-Ponce, G; Riera-Montes, M; Atwine, D; Nansumba, M; Bazira, J; Tuyakira, E; De Beaudrap, P; Bonnet, M; et al. (2013-07)
      Despite recent advances, tuberculosis (TB) diagnosis remains imperfect in resource-limited settings due to its complexity and costs, poor sensitivity of available tests, or long times to reporting. We present a report on the use of colorimetric methods, based on the detection of mycobacterial growth using colorimetric indicators, for the detection of Mycobacterium tuberculosis in sputum specimens. We evaluated the nitrate reductase assay (NRA), a modified NRA using para-nitrobenzoic acid (PNB) (NRAp), and the resazurin tube assay using PNB (RETAp) to differentiate tuberculous and nontuberculous mycobacteria. The performances were assessed at days 18 and 28 using mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen (LJ) medium culture methods as the reference standards. We enrolled 690 adults with suspected pulmonary tuberculosis from a regional referral hospital in Uganda between March 2010 and June 2011. At day 18, the sensitivities and specificities were 84.6% and 90.0% for the NRA, 84.1% and 92.6% for the NRAp, and 71.2% and 99.3% for the RETAp, respectively. At day 28, the sensitivity of the RETAp increased to 82.6%. Among smear-negative patients with suspected TB, sensitivities at day 28 were 64.7% for the NRA, 61.3% for the NRAp, and 50% for the RETAp. Contamination rates were found to be 5.4% for the NRA and 6.7% for the RETAp, compared with 22.1% for LJ medium culture and 20.4% for MGIT culture. The median times to positivity were 10, 7, and 25 days for colorimetric methods, MGIT culture, and LJ medium culture,respectively. Whereas the low specificity of the NRA/NRAp precludes it from being used for TB diagnosis, the RETAp might provide an alternative to LJ medium culture to decrease the time to culture results in resource-poor settings.
    • Voluntary Counselling, HIV Testing and Sexual Behaviour Among Patients with Tuberculosis in a Rural District of Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Salaniponi, F M L; Médecins sans Frontières, Thyolo, Malawi. zachariah@internet.lu (International Union Against TB and Lung Disease, 2003-01)
      OBJECTIVES: A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi in order to 1) verify the acceptability of voluntary counselling and testing for human immunodeficiency virus (HIV) infection; 2) describe sexual behaviour and condom use; and 3) identify socio-demographic and behavioural risk factors associated with 'no condom use'. DESIGN: Cross-sectional study. METHODS: Consecutive patients diagnosed with TB between January and December 2000 were offered voluntary counselling and HIV testing (VCT) and were subsequently interviewed. RESULTS: There were 1,049 new TB patients enrolled in the study. Of these, 1,007 (96%) were pre-test counselled, 955 (91%) underwent HIV testing and 912 (87%) were post-test counselled; 43 (4%) patients refused HIV testing. The overall HIV infection rate was 77%. Of all HIV-positive TB patients, 691 (94%) were put on cotrimoxazole. There were 479 (49%) TB patients who reported sexual encounters, of whom only 6% always used condoms. Unprotected sex was associated with having TB symptoms for over 1 month, having had less than 8 years of school education, being single, divorced or widowed or having sex with the same partner. CONCLUSIONS: Offering VCT to TB patients in this setting has a high acceptance rate and provides an opportunity to strengthen and integrate TB and HIV programmes.
    • 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)