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JMIR Human Factors May 2024Complementing digital adherence technologies (DATs) with mobile money incentives may improve their utility in supporting tuberculosis medication adherence, yet the...
Digital Adherence Technologies Linked to Mobile Money Incentives for Medication Adherence Among People Living With Tuberculosis: Mixed Methods Feasibility and Acceptability Study.
BACKGROUND
Complementing digital adherence technologies (DATs) with mobile money incentives may improve their utility in supporting tuberculosis medication adherence, yet the feasibility and acceptability of this integrated approach remain unclear.
OBJECTIVE
This study aims to describe the feasibility and acceptability of a novel DAT intervention called My Mobile Wallet composed of real-time adherence monitoring, SMS text message reminders, and mobile money incentives for tuberculosis medication adherence in a low-income setting.
METHODS
We purposively recruited people living with tuberculosis from the Mbarara Regional Referral Hospital in Mbarara, Uganda, who (1) were starting tuberculosis treatment at enrollment or within the past 4 weeks, (2) owned a mobile phone, (3) were able to use SMS test messaging, (4) were aged ≥18 years, and (5) were living in Mbarara district. At study exit (month 6), we used interviews and questionnaires informed by the unified theory of acceptance and use of technology (UTAUT) to collect feasibility and acceptability data, reflecting patients' experiences of using each component of My Mobile Wallet. Feasibility also included tracking the functionality of the adherence monitor (ie, an electronic pillbox) as well as SMS text message and mobile money delivery. We used a content analytical approach to inductively analyze qualitative data and Stata (version 13; StataCorp LLC) to analyze quantitative data.
RESULTS
All 39 participants reported that the intervention was feasible because it was easy for them to use (eg, access and read SMS text messages) and worked as expected. Almost all SMS text messages (6880/7064, 97.4%) were sent as planned. The transmission of adherence data from the monitor worked well, with 98.37% (5682/5776) of the data transmitted as planned. All participants additionally reported that the intervention was acceptable because it helped them take their tuberculosis medication as prescribed; the mobile money incentives relieved them of tuberculosis-related financial burdens; SMS text message reminders and electronic pillbox-based alarms reminded them to take their medication on time; and participants perceived real-time adherence monitoring as "being watched" while taking their medication, which encouraged them to take their medication on time to demonstrate their commitment. The intervention was perceived as a sign of care, which eventually created emotional support and a sense of connectedness to health care. Participants preferred daily SMS text message reminders (32/39, 82%) to reminders linked to missed doses (7/39, 18%), citing the fact that tuberculosis medication is taken daily.
CONCLUSIONS
The use of real-time adherence monitoring linked to SMS text message reminders and mobile money incentives for tuberculosis medication adherence was feasible and acceptable in a low-resource setting where poverty-based structural barriers heavily constrain tuberculosis treatment and care.
Topics: Humans; Medication Adherence; Feasibility Studies; Male; Female; Adult; Tuberculosis; Uganda; Motivation; Text Messaging; Reminder Systems; Middle Aged; Surveys and Questionnaires; Cell Phone; Qualitative Research; Antitubercular Agents
PubMed: 38819905
DOI: 10.2196/47996 -
Therapeutic Advances in Respiratory... 2024Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more... (Observational Study)
Observational Study
Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.
BACKGROUND
Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together.
OBJECTIVES
The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens.
DESIGN
A prospective observational cohort study.
METHODS
From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
RESULTS
A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens ( < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine.
CONCLUSION
Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.
Topics: Humans; Prospective Studies; Adult; Ukraine; Rifampin; Male; Middle Aged; Tuberculosis, Multidrug-Resistant; Female; Mycobacterium tuberculosis; Young Adult; Aged; Adolescent; Antitubercular Agents; Microbial Sensitivity Tests; Aged, 80 and over; Antibiotics, Antitubercular; Predictive Value of Tests; Precision Medicine; Reproducibility of Results
PubMed: 38817020
DOI: 10.1177/17534666241249841 -
Scientific Reports May 2024Tuberculosis (TB), caused by Mycobacterium tuberculosis, has a significant impact on global health worldwide. The development of multi-drug resistant strains that are...
Tuberculosis (TB), caused by Mycobacterium tuberculosis, has a significant impact on global health worldwide. The development of multi-drug resistant strains that are resistant to the first-line drugs isoniazid and rifampicin threatens public health security. Rifampicin and isoniazid resistance are largely underpinned by mutations in rpoB and katG respectively and are associated with fitness costs. Compensatory mutations are considered to alleviate these fitness costs and have been observed in rpoC/rpoA (rifampicin) and oxyR'-ahpC (isoniazid). We developed a framework (CompMut-TB) to detect compensatory mutations from whole genome sequences from a large dataset comprised of 18,396 M. tuberculosis samples. We performed association analysis (Fisher's exact tests) to identify pairs of mutations that are associated with drug-resistance, followed by mediation analysis to identify complementary or full mediators of drug-resistance. The analyses revealed several potential mutations in rpoC (N = 47), rpoA (N = 4), and oxyR'-ahpC (N = 7) that were considered either 'highly likely' or 'likely' to confer compensatory effects on drug-resistance, including mutations that have previously been reported and validated. Overall, we have developed the CompMut-TB framework which can assist with identifying compensatory mutations which is important for more precise genome-based profiling of drug-resistant TB strains and to further understanding of the evolutionary mechanisms that underpin drug-resistance.
Topics: Mycobacterium tuberculosis; Mutation; Genome, Bacterial; Drug Resistance, Multiple, Bacterial; Rifampin; Antitubercular Agents; Isoniazid; Tuberculosis, Multidrug-Resistant; Humans; Bacterial Proteins; Whole Genome Sequencing; Microbial Sensitivity Tests
PubMed: 38811658
DOI: 10.1038/s41598-024-62946-8 -
PloS One 2024To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency...
To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs.
Topics: Mycobacterium tuberculosis; Microbial Sensitivity Tests; China; Antitubercular Agents; Humans; Laboratory Proficiency Testing; Reproducibility of Results; Phenotype; Amikacin; Pyrazinamide
PubMed: 38809914
DOI: 10.1371/journal.pone.0304265 -
Jornal Brasileiro de Pneumologia :... May 2024
Topics: Brazil; Humans; Tuberculosis; Antitubercular Agents; Tuberculosis, Pulmonary
PubMed: 38808837
DOI: 10.36416/1806-3756/e20240121 -
Scientific Reports May 2024Tuberculosis (TB) continues to be a global health crisis, necessitating urgent interventions to address drug resistance and improve treatment efficacy. In this study, we...
Tuberculosis (TB) continues to be a global health crisis, necessitating urgent interventions to address drug resistance and improve treatment efficacy. In this study, we validate lumazine synthase (RibH), a vital enzyme in the riboflavin biosynthetic pathway, as a potential drug target against Mycobacterium tuberculosis (M. tb) using a CRISPRi-based conditional gene knockdown strategy. We employ a high-throughput molecular docking approach to screen ~ 600,000 compounds targeting RibH. Through in vitro screening of 55 shortlisted compounds, we discover 3 compounds that exhibit potent antimycobacterial activity. These compounds also reduce intracellular burden of M. tb during macrophage infection and prevent the resuscitation of the nutrient-starved persister bacteria. Moreover, these three compounds enhance the bactericidal effect of first-line anti-TB drugs, isoniazid and rifampicin. Corroborating with the in silico predicted high docking scores along with favourable ADME and toxicity profiles, all three compounds demonstrate binding affinity towards purified lumazine synthase enzyme in vitro, in addition these compounds exhibit riboflavin displacement in an in vitro assay with purified lumazine synthase indicative of specificity of these compounds to the active site. Further, treatment of M. tb with these compounds indicate reduced production of flavin adenine dinucleotide (FAD), the ultimate end product of the riboflavin biosynthetic pathway suggesting the action of these drugs on riboflavin biosynthesis. These compounds also show acceptable safety profile in mammalian cells, with a high selective index. Hence, our study validates RibH as an important drug target against M. tb and identifies potent antimycobacterial agents.
Topics: Mycobacterium tuberculosis; Antitubercular Agents; Molecular Docking Simulation; Multienzyme Complexes; Drug Discovery; Bacterial Proteins; Humans; Tuberculosis; Microbial Sensitivity Tests; Animals
PubMed: 38806590
DOI: 10.1038/s41598-024-63051-6 -
BMC Infectious Diseases May 2024Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various...
BACKGROUND
Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.
CASE PRESENTATION
The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.
CONCLUSION
Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.
Topics: Humans; Male; Middle Aged; Cryptococcosis; Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Liver Failure; Acquired Immunodeficiency Syndrome; Hepatitis B, Chronic; Coinfection; Antitubercular Agents; HIV Infections; AIDS-Related Opportunistic Infections
PubMed: 38802753
DOI: 10.1186/s12879-024-09431-9 -
BMC Infectious Diseases May 2024Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors...
INTRODUCTION
Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil.
METHODS
We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment.
RESULTS
Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT).
CONCLUSION
The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.
Topics: Humans; Brazil; Male; Female; Adult; Middle Aged; Antitubercular Agents; Treatment Failure; Young Adult; Adolescent; Tuberculosis; Aged; Directly Observed Therapy; Child; Child, Preschool; Risk Factors; Infant; HIV Infections; Treatment Outcome; Aged, 80 and over
PubMed: 38802744
DOI: 10.1186/s12879-024-09417-7 -
Tuberculosis (Edinburgh, Scotland) Jul 2024To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance.
OBJECTIVE
To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance.
METHODS
122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score.
RESULTS
The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579-0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756-1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6-98.2%) and specificity was 81.3% (95% CI: 70.0-88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2.
CONCLUSION
Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.
Topics: Humans; Tuberculosis, Pulmonary; Male; Female; Adult; Middle Aged; Antitubercular Agents; Mycobacterium tuberculosis; Sputum; Predictive Value of Tests; Drug Monitoring; Treatment Outcome; Reproducibility of Results; Aged; Tuberculosis, Multidrug-Resistant; Time Factors; Biomarkers; Gene Expression Profiling; Young Adult
PubMed: 38801793
DOI: 10.1016/j.tube.2024.102521 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Facile access to some novel biologically relevant dihydrotriazolopyrimidine carboxylic acid-derived amide analogues using NMI/SOCl, and aromatic and aliphatic primary...
Facile access to some novel biologically relevant dihydrotriazolopyrimidine carboxylic acid-derived amide analogues using NMI/SOCl, and aromatic and aliphatic primary and secondary amines, is reported herein. The role of -methylimidazole (NMI) as the base and sulfuryl chloride (SOCl) as the coupling reagent has been effectively realized in accessing these molecules in good to excellent yields. The feasibility of the developed protocol has also been extended to the gram-scale synthesis of -benzylbenzamide in a 75% yield from benzoic acid and benzyl amine. The newly synthesized compounds were tested via in vitro anti-inflammatory and anti-tubercular activity studies. The compounds and were found to be the most active anti-inflammatory agents, whereas and were found to exhibit promising anti-tubercular potency when compared to other synthesized molecules. The structure-activity relationship (SAR) studies revealed the importance of the presence of electron-donating functionalities in enhancing the anti-inflammatory potential of the newly synthesized molecules. However, the presence of electron-withdrawing substituents was found to be significant for improving their anti-tubercular potency.
PubMed: 38794119
DOI: 10.3390/ph17050548