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（由应用程序提供）：问题和意义：根据CDC全球统计数据，世界上近1/3感染了结核病（TB）。 2012年，有860万f被感染的人居住在一个高燃烧国家。印度，秘鲁，中国，撒哈拉以南非洲和其他国家的国家对结核病有重要区域，尤其是在较低收入人口中。这代表了需要解决的重大健康问题。目的：该提案的目的是根据固态结核病传感器来表征和评估快速，便携式的结核病治疗监测技术，该技术检测到导致TB的分枝杆菌发出的挥发性有机生物标志物（VOB）。 VOB通常在人类的呼吸中发现，并与包括结核病在内的许多慢性和传染病有所了解。以下VOB与TB有关：苯基苯基苯甲酸甲酯，甲基二甲酸甲酯，甲基烟酸甲酯和O-苯基甲酯。我们先前的支持研究（NSF-STTR）表明，我们新开发的传感器能​​够检测到受控环境中相关的这些VOB。感官材料由金属功能化的3D TiO2纳米管阵列组成，该阵列根据存在的金属类型结合了感兴趣的特定VOB。最终用户的读数是一个电子信号，它基于当前的变化（数量级变化阶）给出了快速，是/否答案。该传感器易于使用，完全无机，不需要专门的生物学试剂进行感测（即抗体，荧光标签等），具有长长的保质期（超过18个月），使用了一个简单的电位仪进行操作，并且是便携式的。该技术的预期用途是在医疗点（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受到TB的耐药性菌株。此外，这种感应的Platfom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，Potentiostat）的电子设备收集患者人口统计数据，包括时间和地理位置诊断，以允许卫生保健工作者和卫生部门绘制TB的位置，并可能扩散在何处以及可能扩散的位置。这种实时的信息对于试图管理特定地区的结核病暴发的卫生部门可能是无价的。使用VOB来监测结核病治疗是传统方法（即痰分析，临床症状）的一种有吸引力的替代方法，因为可以快速使用非侵入性方法检测到它。我们的初步结果表明，存在的VOB水平与药物有效治疗结核病感染之间存在关系（在治疗后7-10天内似乎降低了水平）。理想情况下，如果这种关系成立，医生可以通过简单地测量一周的治疗后的VOBS水平，而不是等待数周的培养结果，从而确定患者是否患有耐药性结核病，以便像目前这样做。但是，VOB在POC诊断设置中的使用有限，因为当前技术（气相色谱/质量规格）检测VOB是昂贵的，并且不适合低资源设置现场使用。此处介绍的技术是低成本，可以量身定制以通过特定的金属功能化来检测有趣的VOB，并可以克服与呼吸分析相关的传统技术障碍。为了进一步开发这项技术或结核病治疗监测并向医护人员提供全面的数据分析，必须研究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，则TB的VOB水平将降低。假设2：我们还假设，如果在治疗后没有降低VOB的水平，则表明多药耐药性结核病。具体目标1：确定TB呼气器设备的分析有效性，并根据用于监视TB的“金标准”确定传感器的灵敏度和特异性。假设3：我们假设一个集成的传感器和智能手机软件包将集成到医生的医疗保健流中，并且可以通过直观的应用程序快速轻松地进行分析，以进行操作和数据收集。具体目标2：将传感器集成到智能手机包装中并评估其性能，包括评估与临床医生的界面，以确定技术如何通过假设将传感器集成到医疗保健流中4：将传感器与智能手机控制器集成在一起，允许医疗保健专业人员允许医疗保健专业人员在治疗中为患者人群提供有关患者人口统计学的数据，从而为疾病预防疾病的疾病预防和疾病治疗中的重要信息提供了疾病，并为疾病的效率提供了疾病，阶段，阶段，阶段，阶段，阶段，阶段。特定目的3：开发用于实时数据收集，分析和传播信息的方法的方法，以进行流行病学跟踪。