• A Randomised Phase II Trial to Evaluate the Toxicity of High-Dose Rifampicin to Treat Pulmonary Tuberculosis

      Jindani, A; Borgulya, G; de Patiño, I W; Gonzales, T; de Fernandes, RA; Shrestha, B; Atwine, D; Bonnet, M; Burgos, M; Dubash, F; et al. (International Union Against Tuberculosis and Lung Disease, 2016-06-01)
      Randomised Phase IIB clinical trial.
    • Randomized trials to optimize treatment of multidrug-resistant tuberculosis

      Mitnick, C D; Castro, K G; Harrington, M; Sacks, L V; Burman, W; Harvard Medical School, Boston, MA, USA; Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA; Treatment Action Group, New York, NY, USA; Food and Drug Administration, Rockville, MD, USA; Denver Public Health and University of Colorado Health Sciences Center, Denver, CO, USA (2007-11-06)
    • Rapid culture-based methods for drug-resistance detection in Mycobacterium tuberculosis.

      Palomino, J C; Martin, A; Von Groll, A; Portaels, F; Mycobacteriology Unit, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. (Elsevier, 2008-10)
      Tuberculosis still represents a major public health problem, especially in low-resource countries where the burden of the disease is more important. Multidrug-resistant and extensively drug drug-resistant tuberculosis constitute serious problems for the efficient control of the disease stressing the need to investigate resistance to first- and second-line drugs. Conventional methods for detecting drug-resistance in Mycobacterium tuberculosis are slow and cumbersome. The most commonly used proportion method on Löwenstein-Jensen medium or Middlebrook agar requires a minimum of 3-4 weeks to produce results. Several new approaches have been proposed in the last years for the rapid and timely detection of drug-resistance in tuberculosis. This review will address phenotypic culture-based methods for rapid drug susceptibility testing in M. tuberculosis.
    • Rapid detection of Mycobacterium tuberculosis resistance to second-line drugs by use of the manual mycobacterium growth indicator tube system.

      Martin, A; von Groll, A; Fissette, K; Palomino, J C; Varaine, F; Portaels, F; Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium. amartin@itg.be (2008-12)
      The objective of this study was to evaluate the manual mycobacterium growth indicator tube (MGIT) system for the testing of Mycobacterium tuberculosis susceptibility to second-line drugs compared to the proportion method. One hundred eighty-eight M. tuberculosis isolates were tested for susceptibility to ofloxacin, kanamycin, ethionamide, and capreomycin by the manual MGIT, and results were compared to those obtained with the proportion method on 7H11 agar, considered a reference method. Results for ofloxacin and capreomycin were excellent, with 100% accuracy, and a result of 99.4% accuracy was achieved for kanamycin. For ethionamide, accuracy was lower, with a result of 86.7% compared to that of the proportion method. We proposed the following critical concentrations for the drugs: for ofloxacin, 2.0 microg/ml; for kanamycin, 2.5 microg/ml; for ethionamide, 5 microg/ml; and for capreomycin, 2.5 microg/ml. The time required to obtain results was an average of 8 days by the manual MGIT and 3 weeks by the reference method. Our results show that the manual MGIT is an accurate method for the rapid susceptibility testing of M. tuberculosis to second-line drugs. There is no need for a machine when using the manual MGIT, and results can be read with a simple UV lamp or with a semiquantitative reader, which considerably reduces the cost of the method.
    • Rational use of moxifloxacin for tuberculosis treatment

      Cox, H; Ford, N; Keshavjee, S; McDermid, C; von Schoen-Angerer, T; Mitnick, C; Goemaere, E; Burnet Institute, Melbourne, Australia; Médecins Sans Frontières, Johannesburg, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Harvard Medical School, Boston, USA; Partners in Health, Boston, USA; Médecins Sans Frontières Campaign for Access to Essential Medicines, Geneva, Switzerland (2011-04-01)
    • Re-Inventing Adherence: Toward a Patient-Centered Model of Care for Drug-Resistant Tuberculosis and HIV

      O'Donnell, M R; Daftary, A; Frick, M; Hirsch-Moverman, Y; Amico, K R; Senthilingam, M; Wolf, A; Metcalfe, J Z; Isaakidis, P; Davis, J L; et al. (International Union Against TB and Lung Disease, 2016-04-01)
      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.
    • Reasons for defaulting from drug-resistant tuberculosis treatment in Armenia: a quantitative and qualitative study

      Sanchez-Padilla, E; Marquer, C; Kalon, S; Qayyum, S; Hayrapetyan, A; Varaine, F; Bastard, M; Bonnet, M (The Union, 2014-02)
      Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB).
    • Reduced tuberculosis case notification associated with scaling up antiretroviral treatment in rural Malawi.

      Zachariah, R; Bemelmans, M; Akesson, A; Gomani, P; Phiri, K; Isake, B; Van den Akker, T; Philips, M; Mwale, A; Gausi, F; et al. (2011-07)
      To report on the trends in new and recurrent tuberculosis (TB) case notifications in a rural district of Malawi that has embarked on large-scale roll-out of antiretroviral treatment (ART).
    • Reducing the Number of Sputum Samples Examined and Thresholds for Positivity: An Opportunity to Optimise Smear Microscopy.

      Bonnet, M; Ramsay, A; Gagnidze, L; Githui, W; Guerin, P J J; Varaine, F; Epicentre, Paris, France. maryline.bonnet@geneva.msf.org (International Union Against TB and Lung Disease, 2007-09)
      SETTING: Urban health clinic, Nairobi. OBJECTIVE: To evaluate the impact on tuberculosis (TB) case detection and laboratory workload of reducing the number of sputum smears examined and thresholds for diagnosing positive smears and positive cases. DESIGN: In this prospective study, three Ziehl-Neelsen stained sputum smears from consecutive pulmonary TB suspects were examined blind. The standard approach (A), > or = 2 positive smears out of 3, using a cut-off of 10 acid-fast bacilli (AFB)/100 high-power fields (HPF), was compared with approaches B, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3, one of which is > or = 10 AFB/100 HPF; C, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3; D, > or = 1 positive smear (> or = 10 AFB/100 HPF) out of 2; and E, > or = 1 positive smear (> or = 4 AFB/100 HPF) out of 2. The microscopy gold standard was detection of at least one positive smear (> or = 4 AFB/100 HPF) out of 3. RESULTS: Among 644 TB suspects, the alternative approaches detected from 114 (17.7%) (approach B) to 123 cases (19.1%) (approach E) compared to 105 cases (16.3%) for approach A (P < 0.005). Sensitivity ranged between 82.0% (105/128) for A and 96.1% (123/128) for E. The single positive smear approaches reduced the number of smears by 36% compared to approach A. CONCLUSION: Reducing the number of specimens and the positivity threshold to define a positive case increased the sensitivity of microscopy and reduced laboratory workload.
    • Relationship between education and training activities and tuberculosis case detection in Fiji, 2008–2011 [Short communication]

      Delai, M Y; Gounder, S; Tayler-Smith, K; Van den Bergh, R; Harries, A D (The TB Union, 2012-12)
    • 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)
    • Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Greater Metropolitan Mumbai: Trends over Time

      Dalal, A; Pawaskar, A; Das, M; Desai, R; Prabhudesai, P; Chhajed, P; Rajan, S; Reddy, D; Babu, S; Jayalakshmi, T K; et al. (Public Library of Science, 2015-01-21)
      While the high burden of multidrug-resistant tuberculosis (MDR-TB) itself is a matter of great concern, the emergence and rise of advanced forms of drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug-resistant TB (XXDR-TB) is more troubling. The aim of this study was to investigate the trends over time of patterns of drug resistance in a sample of MDR-TB patients in greater metropolitan Mumbai, India.
    • Resistance to Second-line Drugs in Multidrug-resistant Tuberculosis

      Nyang'wa, B-T; Brigden, G; du Cros, P; Shanks, L (2013-02-23)
    • Response to antiretroviral therapy: improved survival associated with CD4 above 500 cells/μl.

      Maman, D; Pujades-Rodriguez, M; Nicholas, S; McGuire, M; Szumilin, E; Ecochard, R; Etard, J-F; Epicentre, 8 rue saint Sabin, Paris, France; bHospices Civils de Lyon, Service de Biostatistique, cUniversite´ de Lyon, Lyon, France; Me´decins Sans Frontie`res, Paris, France. (2012-07-17)
      We investigated the association between immune response and mortality in four HIV African programs supported by Médecins Sans Frontières.
    • A retrospective study of tuberculosis outcomes in Gulf Province, Papua New Guinea

      Moses, I; Main, S; Commons, RJ; Robertson, B; Mek, A; Gale, M (International Union Against Tuberculosis and Lung Disease, 2019-09-21)
      Setting: Gulf Province, a rural area of mainland Papua New Guinea, is known to have one of the highest burdens of tuberculosis (TB) in the country. Objectives: To describe the characteristics and outcomes of TB patients registered for first-line treatment in Kerema General Hospital in Gulf Province between January and December 2016. Design: This was a retrospective cohort study using routinely collected programme data. Results: Of 347 cases with a recorded TB site, 54% were male and 32% were aged <15 years. No human immunodeficiency virus (HIV) status was recorded for 51% of cases. TB was bacteriologically confirmed in 23% of cases. Among the cohort, there were 145 extrapulmonary TB cases (42%); the site of disease was unknown in 56% of these cases. Of the 297 cases with treatment outcome evaluated, 56% had a favourable outcome and 26% were lost to follow-up. On multivariable analysis, extrapulmonary TB (adjusted OR [aOR] 0.51, 95%CI 0.30–0.88, P = 0.02) and bacteriologically confirmed TB (aOR 0.40, 95%CI 0.21–0.77, P < 0.01) were associated with decreased odds of an unfavourable treatment outcome. Conclusion: The study findings highlight the need to improve TB diagnosis, access to HIV testing, treatment adherence, patient support and the quality of TB programme data in Gulf Province.
    • Risk factors associated with default from multi- and extensively drug-resistant tuberculosis treatment, uzbekistan: a retrospective cohort analysis.

      Lalor, M K; Greig, J; Allamuratova, S; Althomsons, S; Tigay, Z; Khaemraev, A; Braker, K; Telnov, O; du Cros, P; Médecins Sans Frontières, Nukus, Karakalpakstan, Uzbekistan. (PLoS, 2013)
      The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010.
    • Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

      Cox, H; Niemann, S; Ismailov, G; Doshetov, D; Orozco, J D; Blok, L; Rüsch-Gerdes, S; Kebede, Y; Australian International Health Institute, University of Melbourne, Australia. (Infectious Disease Society of America, 2007-06-01)
      BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance.
    • Risk of Tuberculosis Infection and Disease for Health Care Workers: An Updated Meta-Analysis

      Uden, L; Barber, E; Ford, N; Cooke, G (Oxford University Press, 2017-08-29)
      Tuberculosis (TB) remains a major challenge to global health. Healthcare workers (HCWs) appear to be at increased risk of TB compared with the general population, despite efforts to scale up infection control and reduce nosocomial TB transmission. This review aims to provide an updated estimate of the occupational risk of latent TB infection (LTBI) and active TB among HCWs compared with the general population.