LogoLogoMSF Science Portal
  • My saved items
logo

© Médecins Sans Frontières

MSF Science Portal
About MSF Science Portal
About MSF
Contact Us
Frequently Asked Questions (FAQs)
Privacy Policy
Terms of Use

v2.1.4829.produseast1

23 result(s)
Filter and sort
23 result(s)
Journal Article > ResearchFull Text

Protecting the safe water chain in refugee camps: An exploratory study of water handling practices, chlorine decay, and household water safety in South Sudan, Jordan, and Rwanda

Journal of the American Medical Association (JAMA). 3 December 2024; Online ahead of print; DOI:10.4269/ajtmh.24-0221
Ali SI, De Santi M, Monette G, Khan UT, Fesselet JF,  et al.
Journal of the American Medical Association (JAMA). 3 December 2024; Online ahead of print; DOI:10.4269/ajtmh.24-0221

In refugee and internally displaced person settlements, hygienic water handling and free residual chlorine (FRC) are crucial for protecting water against recontamination after distribution up to the household point-of-consumption. We conducted a secondary analysis of water quality and water handling data collected in refugee camps in South Sudan, Jordan, and Rwanda using statistical and process-based modeling to explore how water handling practices affect FRC decay and household FRC outcomes. The two practices that consistently produced a significant effect on FRC decay and household FRC were storing water in direct sunlight and transferring water between containers during household storage. Samples stored in direct sunlight had 0.22–0.31 mg/L lower household FRC and had FRC decay rates between 2 and 3.7 times higher than samples stored in the shade, and samples that were transferred between containers had 0.031–0.51 mg/L lower household FRC and decay rates 1.65–3 times higher than non-transferred samples in sites in which the effect was significant, suggesting that humanitarian responders should aim to provide additional water storage containers to prevent water transferring in households and encourage water-users not to store water in direct sunlight. By contrast, the effect of the three recommended hygienic water handling behaviors (clean, covered containers and drawing by tap or pouring) was mixed or inconclusive. These inconclusive results were likely due to imbalanced or unreliable approaches to gathering the data, and we recommend that hygienic water handling practices that mechanistically provide a physical barrier against recontamination should always be promoted in humanitarian settings.

More
Journal Article > ResearchFull Text

Estimating post-treatment recurrence after multidrug-resistant tuberculosis treatment among patients with and without HIV: the impact of assumptions about death and missing follow-up

Clin Infect Dis. 25 January 2024; Volume 78 (Issue 1); 164-171.; DOI:10.1093/cid/ciad589
Sauer SM, Mitnick CD, Khan UT, Hewison CCH, Bastard M,  et al.
Clin Infect Dis. 25 January 2024; Volume 78 (Issue 1); 164-171.; DOI:10.1093/cid/ciad589
BACKGROUND
Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up.

METHODS
We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights.

RESULTS
The estimated TB recurrence risk was 7.4 per 1000 (95% confidence interval (CI): 3.5,12.9) when deaths were handled as non-recurrences, and 7.6 per 1000 (95% CI: 3.6,13.1) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 25.5 (95% CI: 15.4,38.1), 11.7 (95% CI: 6.5,18.3), and 8.6 (95% CI: 4.2,14.6) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small impact on estimates.

CONCLUSIONS
The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.
More
Journal Article > Short ReportFull Text

Pregnancy and birth outcomes in patients with multidrug-resistant tuberculosis treated with regimens that include new and repurposed drugs

Clin Infect Dis. 25 January 2024; Volume 78 (Issue 1); 144-148.; DOI:10.1093/cid/ciad445
Lotia Farrukh I, Lachenal N, Adenov MM, Ahmed SM, Algozhin Y,  et al.
Clin Infect Dis. 25 January 2024; Volume 78 (Issue 1); 144-148.; DOI:10.1093/cid/ciad445
Among 43 pregnant women receiving multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment with bedaquiline and/or delamanid, 98% had favorable treatment outcomes. Of 31 continued pregnancies, 81% had live births with no reported malformations, and 68% of neonates had normal birth weights. Effective MDR/RR-TB treatment during pregnancy can improve maternal outcomes without harming neonates.More
Journal Article > ResearchFull Text

Standards for clinical trials for treating TB

Int J Tuberc Lung Dis. 1 December 2023; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
du Cros PAK, Greig J, Cross GB, Cousins C, Berry C,  et al.
Int J Tuberc Lung Dis. 1 December 2023; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
English
Français
BACKGROUND
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.

METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.

RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.

CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
More
Journal Article > ProtocolFull Text

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial

Trials. 30 November 2023; Volume 24 (Issue 1); 773.; DOI:10.1186/s13063-023-07701-6
Patil SB, Tamirat M, Khazhidinov K, Ardizzoni E, Atger M,  et al.
Trials. 30 November 2023; Volume 24 (Issue 1); 773.; DOI:10.1186/s13063-023-07701-6
BACKGROUND
Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients.

METHODS
endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations.

DISCUSSION
This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen.
More
Journal Article > ResearchFull Text

Effectiveness of bedaquiline use beyond six months in patients with multidrug-resistant tuberculosis

Am J Respir Crit Care Med. 1 June 2023; Volume 207 (Issue 11); 1525-1532.; DOI:10.1164/rccm.202211-2125OC
Trevisi L, Hernán MA, Mitnick CD, Khan UT, Seung KJ,  et al.
Am J Respir Crit Care Med. 1 June 2023; Volume 207 (Issue 11); 1525-1532.; DOI:10.1164/rccm.202211-2125OC
RATIONALE
Current recommendations for the treatment of rifampin- and multidrug-resistant tuberculosis include bedaquiline used for six months or longer. Evidence is needed to inform the optimal duration of bedaquiline.

OBJECTIVES
We emulated a target trial to estimate the effect of three bedaquiline duration treatment strategies (6 months, 7-11 months, ≥ 12 months) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis.

METHODS
To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse-probability weighting.

MAIN RESULTS
The 1,468 eligible individuals received a median of four (IQR: 4-5) likely effective drugs. In 87.1% and 77.7%, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment (95% CI) was 0.85 (0.81, 0.88) for 6 months of BDQ, 0.77 (0.73, 0.81) for 7-11 months, and 0.86 (0.83, 0.88) for > 12 months. Compared with 6 months of bedaquiline, the ratio of treatment success (95% CI) was 0.91 (0.85, 0.96) for 7-11 months and 1.01 (0.96, 1.06) for > 12 months. Analyses that did not account for immortal time bias found a higher probability of successful treatment with > 12 months: ratio 1.09 (1.05, 1.14).

CONCLUSIONS
Bedaquiline use beyond six months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time can bias estimate of effects of treatment duration. Future analyses should explore the effect of duration of bedaquiline and other drugs in subgroups with advanced disease and/or receiving less potent regimens.
More
Journal Article > ResearchFull Text

Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications

Int J Tuberc Lung Dis. 1 June 2023; Volume 27 (Issue 6); 451-457.; DOI:10.5588/ijtld.22.0613
Rich ML, Khan UT, Zeng C, LaHood AN, Franke MF,  et al.
Int J Tuberc Lung Dis. 1 June 2023; Volume 27 (Issue 6); 451-457.; DOI:10.5588/ijtld.22.0613
English
Français
BACKGROUND
Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.

OBJECTIVES
To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015–2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.

METHODS
We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.

RESULTS
Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0–82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.

CONCLUSIONS
Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.
More
Journal Article > Research

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective

PLOS Glob Public Health. 28 April 2023; Volume 3 (Issue 4); e0000818.; DOI:10.1371/journal.pgph.0000818
Rodriguez CA, Lodi S, Horsburgh CR, Mitnick CD, Bastard M,  et al.
PLOS Glob Public Health. 28 April 2023; Volume 3 (Issue 4); e0000818.; DOI:10.1371/journal.pgph.0000818
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.More
Journal Article > ResearchFull Text

Concordance of three approaches for operationalizing outcome definitions for multidrug-resistant TB

Int J Tuberc Lung Dis. 1 January 2023; Volume 27 (Issue 1); 34-40.; DOI:10.5588/ijtld.22.0324
Zeng C, Mitnick CD, Hewison CCH, Bastard M, Khan PY,  et al.
Int J Tuberc Lung Dis. 1 January 2023; Volume 27 (Issue 1); 34-40.; DOI:10.5588/ijtld.22.0324
BACKGROUND
The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).

METHODS
Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.

RESULTS
Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.

CONCLUSION
High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
More
Journal Article > ResearchFull Text

Safety and effectiveness outcomes from a 14-country cohort of patients with multi-drug resistant tuberculosis treated concomitantly with bedaquiline, delamanid and other second-line drugs

Clin Infect Dis. 15 October 2022; Volume 75 (Issue 8); 1307-1314.; DOI:10.1093/cid/ciac176
Huerga H, Khan UT, Bastard M, Mitnick CD, Lachenal N,  et al.
Clin Infect Dis. 15 October 2022; Volume 75 (Issue 8); 1307-1314.; DOI:10.1093/cid/ciac176
BACKGROUND
Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet, this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs.

METHODS
We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented.

RESULTS
Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died and 7.2% experienced treatment failure.

CONCLUSIONS
Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.
More