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.

项目概要/摘要 结核病 (TB) 仍然是全世界的主要健康问题，也是导致结核病的主要疾病 世界范围内由单一传染源导致的死亡原因。全球范围内估计有 1000 万 2018 年，有 120 万人感染了结核病，艾滋病毒感染者中估计有 120 万人死于结核病。 2018 年，艾滋病毒呈阴性者人数增加，艾滋病毒呈阳性者死亡人数增加 251,000 人。在 2018 年，美国 CDC 国家监测计划确认了 9,029 例新增结核病病例， 创历史新低，但美国估计仍有 1300 万人患有潜伏性结核病 感染，估计美洲每年有 290,000 例新病例，这表明 剩余的重大区域负担。 结核病耐药菌株的出现被认为是对控制的全球性威胁 结核病。尽管存在这种威胁，如果迅速接受治疗，结核病是一种可以治愈的疾病。 适当地。因此，快速准确的诊断以及有效的抗结核治疗的使用 不仅可以最大限度地降低发病率和死亡率，还可以减少结核病在人群中的传播 人口。然而，未治愈或不坚持治疗的结核病患者 对个人及其社区都构成严重风险。不坚持抗结核治疗 长期治疗可能会导致耐多药结核病 (MDR-TB) 的出现 传染性和结核病治疗效果不佳。即使在美国，坚持治疗 由于多种因素，从完成到完成的过程都很糟糕并且充满挑战—— 治疗时间长（通常为六个月或更长），需要联合治疗，并且需要联合治疗 效果可能会令人不快。药物费用（即使是相对较小的自付额或免赔额） 如果公共卫生系统不承保，可能会严重阻碍依从性。此外， 患者经常会经历症状的快速改善，这​​可能会混淆重要性 继续使用可能被认为不必要的药物进行长期治疗。 在世界范围内，遵守规定往往面临更多障碍，包括： 直接观察治疗 (DOT) 的交通、缺乏对其益处的了解 完成治疗过程、家中药物用完、距医疗机构的距离、艾滋病毒 血清阳性、酗酒和使用草药。不遵守规定也 与药物副作用显着相关，处于持续阶段 化疗、药物负担、与卫生专业人员缺乏充分沟通以及缺乏 家庭的支持。最后，抗结核药物的吸收和代谢存在很大差异。 药物和血液中药物浓度低与结核病治疗结果较差有关， 包括治疗失败和复发。药代动力学变异性已被确定为关键 灭菌效果率和新耐药突变出现的中介因素 在抗结核治疗期间。 总之，仍然迫切需要对结核病药物进行快速、定量评估 剂量和治疗依从性，最好是在护理时。 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 测量尿液中的原发结核药物。该系统将类似于个人血糖仪 糖尿病患者的特点是有一个小型手持式阅读器和一个测试条（丝网印刷电极）。 DNA适体将被固定在电极上，以提供特定的分子 我们已经证明可以以灵敏的方式识别尿液中的其他分析物。这 该方法有望教育临床医生正确剂量并监测患者依从性 治疗仍然是最终根除结核病的重大障碍。