Rapid Monitoring and Assessment of Tubercuolosis Treatment at the Point of Care Using Breath

使用呼吸在护理点快速监测和评估结核病治疗

• 批准号: 8952361
• 负责人: Swomitra Kumar Mohanty
• 金额: $ 22.48万
• 依托单位: NANOSYNTH MATERIALS AND SENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8952361
• 关键词: Address; Africa South of the Sahara; Aftercare; Age; Air; Area; Bacillus (bacterium); Back; Bacteria; Binding; Biological; Biological Markers; Breath Tests; Breathing; Cellular Phone; Centers for Disease Control and Prevention (U.S.); China; Chronic Disease; Clinic; Clinical; Communicable Diseases; Complex; Computer software; Controlled Environment; Coughing; Country; Data; Data Collection; Data Set; Databases; Detection; Devices; Diagnosis; Disease; Disease Outbreaks; Drug resistance; Drug usage; Effectiveness; Electronics; Epidemiology; Extreme drug resistant tuberculosis; Fluorescent Antibody Technique; Gas Chromatography; Gases; Genus Mycobacterium; Gold; Health; Health Personnel; Health Professional; Healthcare; Human; India; Individual; Infection; Information Dissemination; Life; Location; Low Income Population; Lung; Maps; Mass Spectrum Analysis; Measures; Metals; Methodology; Methods; Monitor; Multi-Drug Resistance; Multidrug-Resistant Tuberculosis; Mycobacterium tuberculosis; Nanotubes; Occupations; Patients; Performance; Peru; Pharmaceutical Preparations; Phenylacetates; Physicians; Population; Prevalence; Public Health; Reading; Reagent; Research; Research Support; Resources; Rural; Sampling; Sensitivity and Specificity; Signal Transduction; Site Visit; Small Business Technology Transfer Research; Sneezing; Sputum; Staging; Symptoms; Technology; Time; Training; Treatment Effectiveness; Treatment Efficacy; Treatment Protocols; Tuberculosis; Work; base; cost; demographics; design; health care service organization; interest; killings; nicotinate; operation; point of care; point-of-care diagnostics; public health relevance; rapid technique; resistant strain; sensor; sex; social; solid state; statistics; tool; tuberculosis treatment; volatile organic compound

 DESCRIPTION (provided by applicant): Problem and Significance: According to the CDC global statistics, nearly 1/3 of the world is infected with Tuberculosis (TB). In 2012 8.6 million f peopled infected lived in what is considered a high burden country. Countries such as India, Peru, China, sub Saharan Africa and others have significant regions endemic for TB, particularly among the lower income population. This represents a significant health problem that needs to be addressed. Objective: The objective of this proposal is to characterize and assess a rapid and portable TB treatment monitoring technology based on a solid-state TB sensor that detects volatile organic biomarkers (VOBs) given off by the mycobacterium that cause TB. VOBs are typically found in the breath of human beings and have known associations with many chronic and infectious diseases including TB. The following VOBs are associated with TB: methyl phenylacetate, methyl p-anisate, methyl nicotinate, and o-phenylanisole. Our prior supported research (NSF-STTR) has shown that our newly developed sensor is capable of detecting these VOBs associated in a controlled environment. The sensing material is made up of metal functionalized 3D TiO2 nanotube arrays that bind specific VOBs of interest based on the type of metal present. The readout for the end-user is an electronic signal that gives a rapid, yes/no answer based on change in current (orders of magnitude change). The sensor is simple to use, completely inorganic requiring no specialized biological reagents for sensing (i.e. antibodies, fluorescent tags, etc.), has a long shelf life (over 18 months), uses a simple potentiostat for operation, and is portable. The intended use for this technology is for monitoring TB treatment at the point of care (POC) in a rapid manner to help ascertain if a treatment is working, or help determine if a patient is subject to a drug resistant strain of TB. In addition this sensing platfom integrates a data analytics platform that utilizes the electronics that operate the sensors (smartphone, potentiostat) to collect patient demographics including time and geolocation of the diagnosis to allow health care workers and health departments to map out where TB is located in a population and where it could possibly spread. This type of information in real-time could be invaluable to health departments trying to manage a TB outbreak in a particular region. Using VOBs for monitoring TB treatment is an attractive alternative to traditional methods (i.e. sputum analysis, clinical symptoms), as it is can be detected using non-invasive methods in a rapid manner. Our preliminary results suggest a relationship between levels of VOBs present and if a medication is effective in treating a TB infection (levels appear to reduce in 7-10 days after treatment). Ideally if this relationship holds true, physicians could ascertain if a patient has a drug resistant strain of TB by simply measuring VOBs levels after a week of treatment instead of waiting several weeks for cultures results to get back as is currently done. However, VOBs have seen limited use in POC diagnostics settings since current technology (Gas Chromatography/Mass Spec) for detection of VOBs is expensive and not suitable for low resource setting field use. The technology presented here is low cost and can be tailored to detect VOBs of interest via specific metal functionalization, and can overcome traditional technological hurdles associated with breath analysis. To further develop this technology or TB treatment monitoring and provide comprehensive data analytics to healthcare workers, the following hypothesis and specific aims must be looked at: Hypothesis 1: We hypothesize that the levels of VOBs for TB will decrease if drugs used to treat the infection are effective. Hypothesis 2: We also hypothesize that if the levels of VOBs are not reduced after administering treatment, then this is indicative of multi-drug resistant TB. Specific Aim 1: Determine the analytical validity the TB Breathalyzer device, and determine the sensitivity and specificity of the sensor in reference to the "gold standard" used to monitor TB. Hypothesis 3: We hypothesize an integrated sensor and smartphone package will integrate into the flow of healthcare for physicians and analysis can be done quickly and easily with an intuitive app for operation and data collection. Specific Aim 2: Integrate sensor into a smartphone package and assess its performance including evaluating the user interface with clinicians to determine how the technology integrates into the flow of health care with physicians. Hypothesis 4: Integration of the sensor with a smartphone controller will allow healthcare professionals to collect data about patient demographics in real time which could provide important information for health care organization in regards to disease prevalence, location, stage of diseases, and effectiveness of treatment. Specific Aim 3: Develop methods for real-time data collection, analysis, and dissemination of the information for epidemiological tracking.

 描述（申请人提供）：问题和意义：根据CDC全球统计，全球近1/3的人感染结核病（TB）。2012年，860万感染者生活在被认为是高负担的国家。诸如印度、秘鲁、中国、撒哈拉以南非洲等国家有结核病流行的重要地区，特别是在低收入人群中。这是一个需要解决的重大健康问题。目的：该提案的目的是描述和评估一种快速便携的结核病治疗监测技术，该技术基于固态结核病传感器，可检测导致结核病的分枝杆菌释放的挥发性有机生物标志物（VOB）。VOB通常存在于人类的呼吸中，并且已知与包括结核病在内的许多慢性和传染性疾病有关。以下VOB与TB相关：苯乙酸甲酯、对茴香酸甲酯、烟酸甲酯和邻苯基苯甲醚。我们先前支持的研究（NSF-STTR）表明，我们新开发的传感器能够检测到这些VOB在受控环境中。传感材料由金属功能化的3D TiO 2纳米管阵列组成，这些纳米管阵列基于存在的金属类型结合感兴趣的特定VOB。最终用户的读数是一个电子信号，根据电流的变化（数量级变化）给出快速的是/否答案。该传感器使用简单，完全是无机的，不需要专门的生物试剂（即抗体、荧光标记等）进行传感，保质期长（18个月以上），使用简单的恒电位仪操作，便于携带。 该技术的预期用途是在护理点（POC）快速监测结核病治疗，以帮助确定治疗是否有效，或帮助确定患者是否患有耐药结核病菌株。此外，该传感平台集成了一个数据分析平台，该平台利用操作传感器（智能手机，恒电位仪）的电子设备收集患者人口统计数据，包括诊断的时间和地理位置，以允许医护人员和卫生部门绘制出结核病在人群中的位置以及可能传播的位置。这种实时信息对于试图管理特定地区结核病爆发的卫生部门来说可能是非常宝贵的。 使用VOB监测TB治疗是传统方法（即痰液分析，临床症状）的一种有吸引力的替代方法，因为它可以使用非侵入性方法快速检测。我们的初步结果表明，VOB水平与药物是否有效治疗结核病感染（水平似乎在治疗后7-10天内降低）之间存在关系。理想情况下，如果这种关系成立，医生可以通过简单地测量治疗一周后的VOB水平来确定患者是否患有耐药结核菌株，而不是像目前这样等待几周的培养结果。然而，VOB在POC诊断设置中的使用有限，因为用于检测VOB的当前技术（气相色谱/质谱）是昂贵的并且不适合于低资源设置现场使用。本文提出的技术成本低，可以通过特定的金属功能化来检测感兴趣的VOB，并且可以克服与呼吸分析相关的传统技术障碍。为了进一步发展这项技术或结核病治疗监测，并为医疗工作者提供全面的数据分析，必须考虑以下假设和具体目标：假设1：我们假设，如果用于治疗感染的药物有效，结核病的VOB水平将降低。假设二：我们还假设，如果VOB的水平在给予治疗后没有降低，则这指示多药耐药TB。具体目标1：确定TB呼吸测醉器设备的分析有效性，并参照用于监测TB的“金标准”确定传感器的灵敏度和特异性。假设三：我们假设集成的传感器和智能手机包将集成到医生的医疗保健流程中，并且可以通过直观的应用程序进行操作和数据收集来快速轻松地进行分析。具体目标二：将传感器集成到智能手机包中并评估其性能，包括评估与临床医生的用户界面，以确定该技术如何与医生整合到医疗保健流程中。假设4：传感器与智能手机控制器的集成将允许医疗保健专业人员真实的时间收集关于患者人口统计学的数据，这可以为医疗保健组织提供关于疾病患病率、位置、疾病阶段和治疗有效性的重要信息。具体目标3：制定实时数据收集、分析和传播流行病学跟踪信息的方法。