• Compassionate Use of New Drugs in Children and Adolescents with Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Early Experiences and Challenges

      Tadolini, M; Garcia-Prats, AJ; D'Ambrosio, L; Hewison, C; Centis, R; Schaaf, HS; Marais, BJ; Ferreira, H; Caminero, JA; Jonckheere, S; et al. (European Respiratory Society, 2016-06-23)
    • Correspondence regarding "Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa".

      Mohr-Holland, E; Reuter, A; Hughes, J; Daniels, J; Beko, B; Makhanda, G; De Avezedo, V; Kock, Y; Cox, H; Furin, J; et al. (European Respiratory Society, 2020-07-23)
    • Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa.

      Mohr, E; Hughes, J; Reuter, A; Trivino Duran, L; Ferlazzo, G; Daniels, J; De Azevedo, V; Kock, Y; Steele, SJ; Shroufi, A; et al. (European Respiratory Society, 2018-06-14)
      Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa. This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF). Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred. This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.
    • Diagnostic sensitivity of SILVAMP TB-LAM (FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV

      Kerkhoff, AD; Sossen, B; Schutz, C; Reipold, EI; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Nicol, MP; et al. (European Respiratory Society, 2019-11-07)
    • Effectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analyses

      Ahmad Khan, F; Salim, M; du Cros, P; Casas, E; Khamraev, A; Sikhondze, W; Benedetti, A; Bastos, M; Lan, Z; Jaramillo, E; et al. (European Respiratory Society, 2017-07-27)
      We assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.
    • Efficacy, Safety and Tolerability of Linezolid for the Treatment of XDR-TB: a Study in China

      Berry, C; Yates, TA; Seddon, JA; Phillips, PP; du Cros, P (European Respiratory Society, 2016-05-01)
    • High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

      Ndjeka, N; Schnippel, K; Master, I; Meintjes, G; Maartens, G; Romero, R; Padanilam, X; Enwerem, M; Chotoo, S; Singh, N; et al. (European Respiratory Society, 2018-10-25)
      Background: South African patients with rifampicin-resistant tuberculosis and resistance to fluoroquinolones and/or injectables (pre/XDR-TB) were granted access to bedaquiline through a Clinical Access Programme with strict inclusion and exclusion criteria.Methods: Pre/XDR-TB and XDR-TB patients were treated with 24 weeks bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed.Results: 200 patients were enrolled: 87 (43.9%) with XDR-TB, 99 (49.3%) were female, median age 34 years (IQR 27, 42). 134 (67.0%) were living with HIV; median CD4+ 281 (IQR 130; 467) and all on antiretroviral therapy.16/200 patients (8.0%) did not complete 6 months of bedaquiline of which 8 were lost to follow up, 6 died, 1 stopped for side effects and 1 patient was diagnosed with drug-sensitive TB.146/200 (73.0%) patients had favourable outcomes: 139/200 were cured (69.5%) and 7 completed treatment (3.5%). 25 died (12.5%), were lost from treatment (10.0%), 9 had treatment failure (4.5%).22 adverse events were attributed to bedaquiline: including QTcF >500 ms (n=5), QTcF increase >50 ms from baseline (n=11), paroxysmal atrial flutter (n=1).Conclusion: Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this MDR-TB and XDR-TB cohort.
    • Multidrug-Resistant Tuberculosis Treatment Failure Detection Depends on Monitoring Interval and Microbiological Method

      Mitnick, CD; White, RA; Lu, C; Rodriguez, CA; Bayona, J; Becerra, MC; Burgos, M; Centis, R; Cohen, T; Cox, H; et al. (European Respiratory Society, 2016-09-01)
      Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
    • Responding to SARS-CoV-2 in South Africa: what can we learn from drug-resistant tuberculosis?

      Ndjeka, N; Conradie, F; Meintjes, G; Reuter, A; Hughes, J; Padanilam, X; Ismail, N; Kock, Y; Master, I; Romero, R; et al. (European Respiratory Society, 2020-07-23)
      Rapid adoption of new diagnostic tools, parallel process of research and implementation, decentralisation of services, the use of personal protective equipment, as well as strong partnership and collaboration, could strengthen the fight against COVID-19
    • Shortened Multidrug-Resistant Tuberculosis Treatment in Settings with a High Prevalence of Ofloxacin Resistance

      Guglielmetti, L; Varaine, F; Huerga, H; Bonnet, M; Rich, M; Mitnick, C (European Respiratory Society, 2017-07-20)
    • 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.
    • WHO 2019 guidelines on drug-resistant tuberculosis treatment: based on evidence or expert opinion?

      Guglielmetti, L; Huerga, H; Khan, U; Varaine, F (European Respiratory Society, 2020-03-05)