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Extensively drug-resistant tuberculosis (XDR TB) is a public health emergency that threatens global TB control. Multidrug-resistant TB (MDR TB) is caused by Mycobacterium tuberculosis that shows resistance to isoniazid and [...]

Abstract Introduction: Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic [...]

Background Tuberculosis (TB) drugs and their import are costly. We assessed how shorter TB drug regimens, which were non-inferior or superior in recent TB trials, can affect the costs for purchasing and importing TB drugs. Methods We estimated the drug costs and import costs of 39 longer and shorter TB drug regimens using TB drug prices from the Global Drug Facility and import cost estimates for a TB program in Karakalpakstan, Uzbekistan. Drug regimens from recent TB trials were compared with TB drug regimens following present or past World Health Organization recommendations. Results We estimated an import cost of $4.19 and a drug cost of $43 per standard 6-month drug-sensitive (DS)-TB regimen. A new 17-week DS-TB regimen from the TBTC Study 31 currently requires more tablets and is more expensive to import ($6.08) and purchase ($233). The TB program can substantially decrease import costs ($2.26–14) and drug costs ($391–2308) per multidrug-resistant (MDR)-TB regimen when using new 6-month or shorter drug regimens from the Nix-TB, NExT, TB PRACTECAL, ZeNix, or BEAT TB trials instead of 9–20-month regimens with import costs of $9.96–507 and drug costs of $354–15 028. For a commonly used 20-month all-oral, bedaquiline-containing MDR-TB regimen, we estimated costs of $41 for drug import and $1773 for drug purchase. Conclusions The implementation of a new and shorter DS-TB regimen may increase the costs for drug purchase and import. The implementation of new and shorter MDR-TB regimens may decrease the costs for drug purchase and/or drug import. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) estimated that nearly half a million persons became infected with multidrug-resistant (MDR) tuberculosis (TB), defined as disease caused by Mycobacterium tuberculosis strains resistant to rifampin [...]

Background 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. Methods and findings To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged Conclusions This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated., Author(s): Elizabeth P. Harausz 1,2,*, Anthony J. Garcia-Prats 1, Stephanie Law 3, H. Simon Schaaf 1, Tamara Kredo 4, James A. Seddon 5, Dick Menzies 3, Anna Turkova 6, Jay [...]

To the Editor: Approximately 480,000 persons acquired multidrug-resistant tuberculosis (MDR TB) in 2013 (1). Of the 32,000 children who acquire MDR TB annually, few are identified and administered appropriate treatment [...]

By November 2015, the West Africa Ebola epidemic had caused 28598 infections and 11299 deaths in the three countries most affected. The outbreak required rapid innovation and adaptation. Médecins sans Frontières (MSF) scaled up its usual 20-30 bed Ebola management centres (EMCs) to 100-300 beds with over 300 workers in some settings. This brought challenges in patient and clinical data management resulting from the difficulties of working safely with high numbers of Ebola patients. We describe a project MSF established with software developers and the Google Social Impact Team to develop context-adapted tools to address the challenges of recording Ebola clinical information. We share the outcomes and key lessons learned in innovating rapidly under pressure in difficult environmental conditions. Information on adoption, maintenance, and data quality was gathered through review of project documentation, discussions with field staff and key project stakeholders, and analysis of tablet data. In March 2015, a full prototype was deployed in Magburaka EMC, Sierra Leone. Inpatient data were captured on 204 clinical interactions with 34 patients from 5 March until 10 April 2015. Data continued to also be recorded on paper charts, creating theoretically identical record “pairs” on paper and tablet. 83 record pairs for 33 patients with 22 data items (temperature and symptoms) per pair were analysed. The overall Kappa coefficient for agreement between sources was 0.62, but reduced to 0.59 when rare bleeding symptoms were excluded, indicating moderate to good agreement. The time taken to deliver the product was more than that anticipated by MSF (7 months versus 6 weeks). Deployment of the tablet coincided with a dramatic drop in patient numbers and thus had little impact on patient care. We have identified lessons specific to humanitarian-technology collaborative projects and propose a framework for emergency humanitarian innovation. Time and effort is required to bridge differences in organisational culture between the technology and humanitarian worlds. This investment is essential for establishing a shared vision on deliverables, urgency, and ownership of product.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities., Competing Interests: The endTB Consortium coordinated donations of delamanid (Otsuka Pharmaceutical) and bedaquiline (Janssen) to be used for treatment by some of the patients included in the endTB Observational Study. All authors report no additional potential conflicts of interest. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Rodriguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9-12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan., Methods: Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion., Results: Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8-44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression., Conclusions: Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility., Competing Interests: Conflict of interest: P. du Cros reports other funded work from TB Alliance for introduction of pretomanid, outside the submitted work. Conflict of interest: A. Khamraev has nothing to disclose. Conflict of interest: Z. Tigay has nothing to disclose. Conflict of interest: T. Abdrasuliev has nothing to disclose. Conflict of interest: J. Greig has nothing to disclose. Conflict of interest: G. Cooke has nothing to disclose. Conflict of interest: K. Herboczek has nothing to disclose. Conflict of interest: T. Pylypenko has nothing to disclose. Conflict of interest: C. Berry has nothing to disclose. Conflict of interest: A. Ronnachit has nothing to disclose. Conflict of interest: D. Lister has nothing to disclose. Conflict of interest: S. Dietrich has nothing to disclose. Conflict of interest: C. Ariti has nothing to disclose. Conflict of interest: K. Safaev has nothing to disclose. Conflict of interest: B-T. Nyang'wa has nothing to disclose. Conflict of interest: N. Parpieva has nothing to disclose. Conflict of interest: M. Tillashaykhov has nothing to disclose. Conflict of interest: J. Achar has nothing to disclose., (Copyright ©ERS 2021.)

We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9-12 months (the "shorter regimen") and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing., Competing Interests: Conflict of interest: S. Abidi has nothing to disclose. Conflict of interest: J. Achar has nothing to disclose. Conflict of interest: M.M. Assao Neino has nothing to disclose. Conflict of interest: D. Bang has nothing to disclose. Conflict of interest: A. Benedetti has nothing to disclose. Conflict of interest: S. Brode reports grants from Insmed and the Canadian Institutes for Health Research, personal fees for educational presentations from Boehringer Ingelheim and AstraZeneca, outside the submitted work. Conflict of interest: J.R. Campbell has nothing to disclose. Conflict of interest: E. Casas has nothing to disclose. Conflict of interest: F. Conradie has nothing to disclose. Conflict of interest: G. Dravniece has nothing to disclose. Conflict of interest: P. du Cros reports he was previously a member of the steering committee and protocol writing committee for the PRACTECAL randomised controlled trial of three novel 6-month MDR-TB regimens; and has undertaken a paid consultancy between TB Alliance and Burnet Institute to investigate applicability of the TB-Nix regimen (a novel short MDR-TB regimen) to Papua New Guinea. Conflict of interest: D. Falzon has nothing to disclose. Conflict of interest: E. Jaramillo has nothing to disclose. Conflict of interest: C. Kuaban has nothing to disclose. Conflict of interest: Z. Lan has nothing to disclose. Conflict of interest: C. Lange reports personal fees for lectures from Chiesi, Gilead, Janssen, Lucane, Novartis, Oxoid, Berlin-Chemie and Thermo Fisher, outside the submitted work. Conflict of interest: P.Z. Li has nothing to disclose. Conflict of interest: M. Makhmudova has nothing to disclose. Conflict of interest: A.K.J. Maug has nothing to disclose. Conflict of interest: D. Menzies has nothing to disclose. Conflict of interest: G.B. Migliori has nothing to disclose. Conflict of interest: A. Miller reports that The Eli Lilly Foundation MDR-TB Partnership provided partial salary support in 2015–2016 through a grant to Salmaan Keshavjee, Harvard Medical School, although none of the work in the current paper or analysis was supported through that mechanism; the grant also paid for travel to a meeting in July of 2016. Conflict of interest: B. Myrzaliev has nothing to disclose. Conflict of interest: N. Ndjeka has nothing to disclose. Conflict of interest: J. Noeske has nothing to disclose. Conflict of interest: N. Parpieva has nothing to disclose. Conflict of interest: A. Piubello has nothing to disclose. Conflict of interest: V. Schwoebel has nothing to disclose. Conflict of interest: W. Sikhondze has nothing to disclose. Conflict of interest: R. Singla has nothing to disclose. Conflict of interest: M.B. Souleymane has nothing to disclose. Conflict of interest: A. Trébucq has nothing to disclose. Conflict of interest: A. Van Deun has nothing to disclose. Conflict of interest: K. Viney has nothing to disclose. Conflict of interest: K. Weyer has nothing to disclose. Conflict of interest: B.J. Zhang has nothing to disclose. Conflict of interest: F. Ahmad Khan reports grants from the World Health Organization during the conduct of the study., (The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2020.)