• Tackling mortality due to childhood tuberculosis

      Godreuil, S; Marcy, O; Wobudeya, E; Bonnet, M; Solassol, J (Elsevier, 2018-03-23)
    • Taking on the diabetes-tuberculosis epidemic in India: paving the way through operational research

      Satyanarayana, S; Kumar, A M V; Wilson, N; Kapur, A; Harries, A D; Zachariah, R (International Union Against Tuberculosis and Lung Disease, 2014-03-25)
    • Target Product Profile of a Molecular Drug-Susceptibility Test for Use in Microscopy Centers

      Denkinger, C M; Dolinger, D; Schito, M; Wells, W; Cobelens, F; Pai, M; Zignol, M; Cirillo, D M; Alland, D; Casenghi, M; et al. (Oxford University Press, 2015-04-01)
      Current phenotypic testing for drug resistance in patients with tuberculosis is inadequate primarily with respect to turnaround time. Molecular tests hold the promise of an improved time to diagnosis.
    • TB in disasters.

      Ford, N; Sizaire, V; Mills, E; Médecins Sans Frontières, Braamfontein, Johannesburg, South Africa. (2008-10)
    • TB treatment in a chronic complex emergency: treatment outcomes and experiences in Somalia

      Liddle, K F; Elema, R; Thi, S S; Greig, J; Venis, S; Médecins Sans Frontières (MSF), Amsterdam, The Netherlands (Oxford University Press, 2013-09-29)
      Médecins Sans Frontières (MSF) provides TB treatment in Galkayo and Marere in Somalia. MSF international supervisory staff withdrew in 2008 owing to insecurity but maintained daily communication with Somali staff. In this paper, we aimed to assess the feasibility of treating TB in a complex emergency setting and describe the programme adaptations implemented to facilitate acceptable treatment outcomes.
    • Thin layer agar compared to BACTEC MGIT 960 for early detection of Mycobacterium tuberculosis

      Martin, A; Fissette, K; Varaine, F; Portaels, F; Palomino, J C; Institute of Tropical Medicine, Mycobacteriology Unit, Antwerp, Belgium; Médecins Sans Frontières, Paris, France (2009-07-05)
      We compared the sensitivity and time to detection of growth of Mycobacterium tuberculosis in the thin layer agar (TLA) compared to BACTEC MGIT960. The average time for growth of M. tuberculosis in TLA and BACTEC MGIT960 was 10.6 and 9.6 days, respectively. The sensitivity of detection of M. tuberculosis was 97.3% on TLA and 97% on BACTEC MGIT960 for smear positive samples. TLA showed comparable results to BACTEC MGIT960 and could be an alternative method for low-income countries.
    • Thin-layer agar for detection of resistance to rifampicin, ofloxacin and kanamycin in Mycobacterium tuberculosis isolates

      Martin, A; Paasch, F; Von Groll, A; Fissette, K; Almeida, P; Varaine, F; Portaels, F; Palomino, J-C; Institute of Tropical Medicine, Mycobacteriology Unit, Antwerp, Belgium; Laboratory of Mycobacteriology, Universidade Federal do Rio Grande, Rio Grande do Sul, Brazil; Médecins Sans Frontières, Paris, France (2009-10-01)
      BACKGROUND: In low-income countries there is a great need for economical methods for testing the susceptibility of Mycobacterium tuberculosis to antibiotics. OBJECTIVE: To evaluate the thin-layer agar (TLA) for rapid detection of resistance to rifampicin (RMP), ofloxacin (OFX) and kanamycin (KM) in M. tuberculosis clinical isolates and to determine the sensitivity, specificity and time to positivity compared to the gold standard method. METHODS: One hundred and forty-seven clinical isolates of M. tuberculosis were studied. For the TLA method, a quadrant Petri plate containing 7H11 agar with RMP, OFX and KM was used. Results were compared to the Bactec MGIT960 for RMP and the proportion method for OFX and KM. RESULTS: The sensitivity and specificity for RMP and OFX were 100% and for KM they were 100% and 98.7%, respectively. The use of a TLA quadrant plate enables the rapid detection of resistance to the three anti-tuberculosis drugs RMP, OFX and KM in a median of 10 days. CONCLUSION: TLA was an accurate method for the detection of resistance in the three drugs studied. This faster method is simple to perform, providing an alternative method when more sophisticated techniques are not available in low-resource settings.
    • The timing of death in patients with tuberculosis who die during anti-tuberculosis treatment in Andhra Pradesh, South India

      Jonnalagada, S; Harries, A D; Zachariah, R; Satyanarayana, S; Tetali, S; Keshav Chander, G; Rao, S; Rao, R; Peri, S; Anchala, R; et al. (BioMed Central, 2011-12-13)
      Background: India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TBrelated deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with “early” death, occurring in the initial 8 weeks of treatment. Methods: This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results: There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with “early death”. Conclusion: In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/ AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed.
    • To treat or not to treat? Implementation of DOTS in Central Asia.

      Cox, H; Hargreaves, S; Médecins Sans Frontières, Uzbekistan and Turkmenistan, PO Box 333, 700000, Tashkent, Uzbekistan. hom@msfh-tashkent.uz (Elsevier, 2003-03-01)
    • Towards Early Inclusion of Children in Tuberculosis Drugs Trials: A Consensus Statement

      Nachman, S; Ahmed, A; Amanullah, F; Becerra, M C; Botgros, R; Brigden, G; Browning, R; Gardiner, E; Hafner, R; Hesseling, A; et al. (Elsevier, 2015-06)
      Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.
    • Towards the WHO target of zero childhood tuberculosis deaths: an analysis of mortality in 13 locations in Africa and Asia

      Russell, G K; Merle, C S; Cooke, G S; Casas, E C; da Fonseca, M; du Cros, P (International Union Against Tuberculosis and Lung Disease, 2013-12)
      Achieving the World Health Organization (WHO) target of zero paediatric tuberculosis (TB) deaths will require an understanding of the underlying risk factors for mortality.
    • Towards tuberculosis elimination: an action framework for low-incidence countries

      Lönnroth, K; Migliori, G B; Abubakar, I; D'Ambrosio, L; de Vries, G; Diel, R; Douglas, P; Falzon, D; Gaudreau, M-A; Goletti, D; et al. (European Respiratory Society, 2015-03-18)
      This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.
    • Translational Research for Tuberculosis Elimination: Priorities, Challenges, and Actions

      Lienhardt, C; Lönnroth, K; Menzies, D; Balasegaram, M; Chakaya, J; Cobelens, F; Cohn, J; Denkinger, C M; Evans, T G; Källenius, G; et al. (Public Library of Science, 2016-03-02)
      Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035.
    • Treating All Multidrug-Resistant Tuberculosis Patients, Not Just Bacteriologically Confirmed Cases

      Das, M; Isaakidis, P; Van den Bergh, R; Kumar, A M V; Sharath, B N; Mansoor, H; Saranchuk, P (International Union Against TB and Lung Disease, 2016-06-21)
    • Treating drug-resistant tuberculosis in a low-intensity chronic conflict setting in India

      Armstrong, E; Das, M; Mansoor, H; Babu, R B; Isaakidis, P (BioMed Central (Springer Science), 2014-12-01)
    • Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis

      Harausz, EP; Garcia-Prats, AJ; Law, S; Schaaf, HS; Kredo, T; Seddon, JA; Menzies, D; Turkova, A; Achar, J; Amanullah, F; et al. (Public Library of Science, 2018-07-11)
      An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children.
    • Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

      Ahmad, N; Ahuja, SD; Akkerman, OW; Alffenaar, JC; Anderson, LF; Bahgaei, P; Bang, D; Barry, PM; Bastos, ML; Behera, D; et al. (Elsevier, 2018-09-08)
      BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition.
    • Treatment of Drug-resistant Tuberculosis with Bedaquiline in a High HIV Prevalence Setting: An Interim Cohort Analysis

      Ndjeka, N; Conradie, F; Schnippel, K; Hughes, J; Bantubani, N; Ferreira, H; Maartens, G; Mametja, D; Meintjes, G; Padanilam, X; et al. (International Union Against Tuberculosis and Lung Disease, 2015-08-01)
      South Africa has a large burden of extensively drug-resistant tuberculosis (XDR-TB); only 15% of XDR-TB patients have successful outcomes.
    • Treatment of multidrug-resistant tuberculosis in a remote, conflict-affected area of the Democratic Republic of Congo.

      Shanks, L; Masumbuko, E W; Ngoy, N M; Maneno, M; Bartlett, S; Thi, S S; Shah, T; Médecins Sans Frontières, Amsterdam, The Netherlands; Medecins (2012-05-04)
      The Democratic Republic of Congo is a high-burden country for multidrug-resistant tuberculosis. Médecins Sans Frontières has supported the Ministry of Health in the conflict-affected region of Shabunda since 1997. In 2006, three patients were diagnosed with drug-resistant TB (DR-TB) and had no options for further treatment. An innovative model was developed to treat these patients despite the remote setting. Key innovations were the devolving of responsibility for treatment to non-TB clinicians remotely supported by a TB specialist, use of simplified monitoring protocols, and a strong focus on addressing stigma to support adherence. Treatment was successfully completed after a median of 24 months. This pilot programme demonstrates that successful treatment for DR-TB is possible on a small scale in remote settings.
    • Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

      Bonnet, M; Pardini, M; Meacci, F; Orrù, G; Yesilkaya, H; Jarosz, T; Andrew, P W; Barer, M; Checchi, F; Rinder, H; et al. (Public Library of Science, 2011-08-23)
      Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals.