• Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

      Pardini, M; Niemann, S; Varaine, F; Iona, E; Meacci, F; Orrù, G; Yesilkaya, H; Jarosz, T; Andrew, P; Barer, M; et al. (2009-06-18)
      Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community.
    • Identification of Patients Who Could Benefit from Bedaquiline or Delamanid: a Multisite MDR-TB Cohort Study

      Bonnet, M; Bastard, M; du Cros, P; Khamraev, A; Kimenye, K; Khurkhumal, S; Hayrapetyan, A; Themba, D; Telnov, A; Sanchez-Padilla, E; et al. (International Union Against TB and Lung Disease, 2016-02-01)
      The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome.
    • Impact of Introducing the Line Probe Assay on Time to Treatment Initiation of MDR-TB in Delhi, India

      Singla, N; Satyanarayana, S; Sachdeva, K S; Van den Bergh, R; Reid, T; Tayler-Smith, K; Myneedu, V P; Ali, E; Enarson, D A; Behera, D; et al. (Public Library of Science, 2014-07-24)
      National Institute of Tuberculosis and Respiratory Diseases (erstwhile Lala Ram Sarup Institute) in Delhi, India.
    • Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis [Review article].

      Cox, H; Ford, N; Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; Monash University, Melbourne, Victoria, Australia; ‡ Médecins Sans Frontières, London, UK; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa (Publisher International Union Against Tuberculosis and Lung Disease, 2012-02-08)
      BACKGROUND: Current treatment for drug-resistant tuberculosis (DR-TB) is inadequate, and outcomes are significantly poorer than for drug-susceptible TB, particularly for patients previously treated with second-line drugs, treatment failures or extensively drug-resistant (XDR-) TB patients (complicated DR-TB). Linezolid is not recommended for routine DR-TB treatment due to the lack of efficacy data, but is suggested for patients where adequate second-line regimens are difficult to design.OBJECTIVE: To conduct a systematic review and metaanalysis to assess existing evidence of efficacy and safety of linezolid for DR-TB treatment.METHODS: We searched PubMed, Embase and abstracts from World Conferences of The Union for studies published through February 2011. We included all studies in which linezolid was given systematically to DR-TB patients and where treatment outcomes were reported.RESULTS: A total of 11 studies were included in our review, representing 148 patients. The pooled proportion for treatment success was 67.99% (95%CI 58.00-78.99, τ2 129.42). There were no significant differences in success comparing daily linezolid dose (≤600 vs. >600 mg) and mean linezolid duration (≤7 vs. >7 months). The pooled estimate for the frequency of any adverse events was 61.48% (95%CI 40.15-82.80), with 36.23% (95%CI 20.67-51.79) discontinuing linezolid due to adverse events.CONCLUSION: Treatment success with linezolid was equal to or better than that commonly achieved for uncomplicated DR-TB, and better than previous reports for previously treated patients and those with XDR-TB. While data are limited, linezolid appears be a useful drug, albeit associated with significant adverse events, and should be considered in the treatment of complicated DR-TB.
    • Lowenstein-Jensen Selective Medium for Reducing Contamination in Mycobacterium tuberculosis Culture

      Kassaza, K; Orikiriza, P; Llosa, A; Bazira, J; Nyehangane, D; Page, A-L; Boum, Y (2014-07)
      We compared Mycobacterium tuberculosis sputum culture recovery and contamination rates between Lowenstein-Jensen medium (LJ) containing the following decontaminants and LJ alone: (i) PANTA (n = 299), (ii) Selectatab-MB (n = 299), and (iii) penicillin G (n = 234). The contamination rate for LJ alone was approximately 31%, versus 5.0% for PANTA-containing, 2% for Selectatab-containing, and 9% for penicillin-containing media (P < 0.001). M. tuberculosis isolation rates were 9.8%, 17%, 18%, and 12% for standard LJ, PANTA, Selectatab, and penicillin cultures, respectively.
    • New opportunities in tuberculosis prevention: implications for people living with HIV.

      Gonzalez Fernandez, L; Casas, EC; Singh, S; Churchyard, GJ; Brigden, G; Gotuzzo, E; Vandevelde, W; Sahu, S; Ahmedov, S; Kamarulzaman, A; et al. (Wiley Open Access, 2020-01-01)
      INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
    • Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis

      Mbuagbaw, L; Guglielmetti, L; Hewison, C; Bakare, N; Bastard, M; Caumes, E; Frechet-Jachym, M; Robert, J; Veziris, N; Khachatryan, N; et al. (Centers for Disease Control and Prevention, 2019-05-01)
      Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%-81.9%), and the treatment success rate was 65.8% (95% CI 59.9%-71.3%). Death rate was 11.7% (95% CI 7.0%-19.1%). Up to 91.1% (95% CI 82.2%-95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%-23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.
    • Preventing tuberculosis in children: A global health emergency

      Reuter, A; Seddon, JA; Marais, BJ; Furin, J (Elsevier, 2020-03-05)
      It is estimated that 20 million children are exposed to tuberculosis (TB) each year, making TB a global paediatric health emergency. TB preventative efforts have long been overlooked. With the view of achieving “TB elimination” in “our lifetime”, this paper explores challenges and potential solutions in the TB prevention cascade, including identifying children who have been exposed to TB; detecting TB infection in these children; identifying those at highest risk of progressing to disease; implementing treatment of TB infection; and mobilizing multiple stakeholders support to successfully prevent TB.