Rapid, Quantitative Point-of-Care Measurement of Tuberculosis Treatment Adherence

快速、定量的护理点测量结核病治疗依从性

• 批准号: 10065420
• 负责人: George W Jackson
• 金额: $ 22.1万
• 依托单位: BASE PAIR BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10065420
• 关键词: Address; Adherence; Adverse drug effect; Alcohol abuse; Americas; Antibiotic Resistance; Antitubercular Agents; Area; Arkansas; Base Pairing; Bedside Testings; Biological Assay; Blood; Cause of Death; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinic; Clinical; Code; Color; Combined Modality Therapy; Communicable Diseases; Communication; Communities; Cyanides; DNA; Data; Deductibles; Detection; Devices; Diagnostic; Directly Observed Therapy; Disease; Doctor of Medicine; Doctor of Philosophy; Dose; Drug Kinetics; Drug Monitoring; Drug resistance; Electrodes; Epidemic; Ethambutol; Gifts; HIV; HIV Seronegativity; HIV Seropositivity; Health; Health Professional; Health Sciences; Health care facility; Health system; Home environment; Human; Immobilization; Impairment; In Vitro; Incentives; Individual; Infectious Agent; Inferior; Knowledge; Lateral; Legal patent; Measurement; Measures; Mediator of activation protein; Medicine; Metabolism; Methodology; Methods; Monitor; Morbidity - disease rate; Multidrug-Resistant Tuberculosis; Optics; Patient Monitoring; Patients; Pharmaceutical Preparations; Pharmacogenomics; Pharmacotherapy; Phase; Population; Public Health; Pyrazinamide; Reader; Reagent; Regimen; Relapse; Rifampin; Risk; Running; Sampling; Small Business Innovation Research Grant; Streptomycin; Surveillance Program; Symptoms; System; Techniques; Technology; Testing; Texas; Therapeutic; Transportation; Treatment Failure; Treatment Protocols; Treatment outcome; Tuberculosis; Uganda; Universities; Urine; Work; absorption; accurate diagnosis; analog; aptamer; base; chemotherapy; comorbidity; compliance behavior; cost; diabetic; digital; drug development; experience; family support; glucose monitor; innovation; isoniazid; medication compliance; molecular recognition; mortality; mouse model; national surveillance; non-compliance; novel therapeutics; pill; point of care; premature; prevent; prototype; rapid diagnosis; resistance mutation; resistant strain; response; sensor; side effect; small molecule; smartphone Application; tool; treatment adherence; treatment duration; tuberculosis drugs; tuberculosis treatment

Project Summary/Abstract Tuberculosis (TB) continues to be a major health concern worldwide and is the leading cause of death worldwide from a single infectious agent. Globally, an estimated 10 million people fell ill with TB in 2018, and there were an estimated 1.2 million TB deaths among HIV- negative people in 2018 and an additional 251,000 deaths among HIV positive people. In the U.S. there were 9,029 new TB confirmed by the CDC’s national surveillance program in 2018, the lowest on record, yet there are an estimated 13 million in the U.S. living with latent TB infection, and an estimated 290,000 new cases each year in the Americas indicating a significant remaining regional burden. The emergence of drug resistant strains of TB is considered a global threat to the control of TB. Despite this threat, TB is a curable disease if treatment is received quickly and appropriately. Thus, rapid and accurate diagnosis and the use of effective anti-TB treatments not only minimize morbidity and mortality, but also mitigate the spread of TB among the population. Nevertheless, TB patients who are not cured or non-adherent to their treatment pose a serious risk both for individuals and their community. Non-adherence to anti-TB treatment may result in the emergence of multidrug resistant TB (MDR-TB), prolonged infectiousness and poor TB treatment outcomes. Even in the U.S., adherence to treatment through to completion is poor and challenging due to a number of factors – the duration of treatment is long (usually six months or longer), combination therapy is required, and side effects may be unpleasant. Cost of medications (even relatively small copays or deductibles) can be a serious barrier to adherence if not covered by the public health system. Furthermore, patients often experience rapid improvement in symptoms, which may obfuscate the importance of continuing prolonged treatment with drugs that may be perceived as unnecessary. Worldwide, there are often even more obstacles to adherence including: access to transportation for directly observed therapy (DOT), lack of knowledge on the benefits of completing a treatment course, running out of drugs at home, distance to the health facility, HIV seropositivity, alcohol abuse, and use of herbal medication. Non-adherence was also significantly associated with drug side effects, being in the continuation phases of chemotherapy, pill burden, lack of adequate communication with health professionals and lack of family support. Finally, there is wide variability in absorption and metabolism of the anti-TB drugs, and low drug concentrations in blood are associated with inferior TB treatment outcomes, including treatment failure and relapse. Pharmacokinetic variability has been identified as a key mediator of the rate of sterilizing effect and the emergence of new drug resistance mutations during anti-TB therapy. In summary, there is still a desperate need for rapid, quantitative assessment of TB drug dosing and adherence to treatment, preferably at the point of care. In this SBIR project, we will develop a new sensor platform that can be used to quickly measure the primary TB drugs in urine. The system will resemble a personal glucose meter for diabetics in that there is a small handheld reader and a test strip (screen-printed electrode). DNA aptamers will be immobilized on the electrode in order to provide specific molecular recognition in a sensitive format that we have already proven for other analytes in urine. This approach has the promise to educate clinicians on proper dosing and monitor patient adherence to treatment which remains a significant hurdle to ultimately eradicating TB.

项目摘要/摘要 结核病（TB）在全球范围内仍然是主要健康问题，是领先的 全世界死亡的原因。在全球范围内，估计有1000万 2018年有TB的人民院士，艾滋病毒中估计有120万TB死亡 - 2018年负面的人，艾滋病毒阳性人群又有251,000人死亡。在 美国疾病预防控制中心（CDC）的国家监视计划在2018年确认了9,029个新结核病 记录下最低，但估计有1300万居住在潜在结核病 感染，估计在美洲每年有290,000例新病例表明 剩下的重大区域负担。 结核病抗药性菌株的出现被认为是对控制的全球威胁 结核病。尽管有这种威胁，但如果迅速接受治疗，结核病还是可治愈的疾病 适当。这是快速准确的诊断和使用有效的抗TB治疗 不仅可以最大程度地减少发病率和死亡率，还可以减轻结核病在 人口。然而，未治愈或不遵守治疗的结核病患者 对个人及其社区构成严重风险。不遵守抗TB 治疗可能会导致耐多药TB（MDR-TB）的出现，延长 传染性和结核病治疗结果不良。即使在美国，也要坚持治疗 到完成是由于许多因素 - 持续时间 治疗时间长（通常六个月或更长时间），需要组合疗法，侧面 效果可能是不愉快的。药物成本（甚至相对较小的共付额或免赔额） 如果公共卫生系统不涵盖，可能会严重遵守。此外， 患者经常在症状上迅速改善，这​​可能会掩盖重要性 继续长时间使用可能被认为是不必要的药物的治疗。 在全球范围内，通常会有更多的遵守障碍，包括： 直接观察到的治疗（DOT）的运输，缺乏对 完成一门治疗课程，在家中用尽毒品，距离卫生设施的距离，艾滋病毒 血清毒性，酗酒和使用草药药物。不遵守也是如此 与药物副作用显着相关，处于 化学疗法，药丸伯恩，与卫生专业人员缺乏足够的沟通，缺乏 家庭支持。最后，抗TB的滥用和代谢有很大的变化 药物，血液中的药物浓度低与结核病下等级有关， 包括治疗失败和缓解。药代动力学变异性已被确定为关键 灭菌作用速率和新药耐药性突变的出现的介体 在抗TB治疗期间。 总而言之，仍然迫切需要对结核病药物进行快速定量评估 在护理点优先考虑治疗的剂量和依从性。 在这个SBIR项目中，我们将开发一个新的传感器平台，可用于快速 测量尿液中的主要结核病药物。该系统将类似于个人葡萄糖表 糖尿病患者是一个小的手持式读取器和一个测试条（屏幕打印电极）。 DNA适体将被固定在电极上，以提供特定的分子 我们已经为尿液中其他分析物证明了敏感格式的识别。 方法有望对临床医生进行适当的给药和监测患者的依从性教育 对于最终消除结核病仍然是一个重大障碍的治疗。