RAPID AFFORDABLE TB DRUG SUSCEPTIBILITY TESTING

快速、经济实惠的结核病药物敏感性测试

• 批准号: 7482188
• 负责人: HOWARD M. SHAPIRO
• 金额: $ 29.92万
• 依托单位: HOWARD M. SHAPIRO, MD, P.C.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482188
• 关键词: Accounting; Africa; Age; American; Aminoglycoside Antibiotics; Antibiotic susceptibility; Antimicrobial susceptibility; Appearance; Area; Attention; Back; Biological Assay; Burial; Calculi; Capromycin; Cessation of life; China; Class; Count; Country; Culture Techniques; Cycloserine; Developed Countries; Developing Countries; Diagnosis; Diagnostic; Discrimination; Disease; Drug resistance; Dyes; Epidemic; Equipment; European; Extreme drug resistant tuberculosis; Fluoroquinolones; Growth; HIV; High Prevalence; Hour; Human; Image; Image Cytometry; Incidence; India; Individual; Liquid substance; Methods; Microscope; Microscopic; Multi-Drug Resistance; Multidrug-Resistant Tuberculosis; Mummies; Mycobacterium tuberculosis; Neurofibrillary Tangles; Optics; Organism; Pharmaceutical Preparations; Predisposition; Property; Public Health; Resistance; Resolution; Resources; Rifampin; Sampling; Sputum; Testing; Thioamides; Time; Training; Tuberculosis; Virulent; World Health Organization; day; digital; fluorescence imaging; isoniazid; p-Aminosalicylic Acid; tuberculosis drugs

DESCRIPTION (provided by applicant): The World Health Organization (WHO) estimates that 8.9 million cases of TB occurred in 2004, with 3.9 million of these representing the most infectious, smear-positive, form. Of the estimated 1.7 million deaths, over 260,000 occurred in HIV-infected individuals; the increasing incidence of TB worldwide is due almost entirely to cases in areas of Africa with a high prevalence of HIV. Over 424,000 of the 2004 cases were multidrug resistant (MDR), i.e., resistant to isoniazid (INH) and rifampin (RIF); most occurred in China, India, and the Russian Federation. Among MDR cases, approximately 10% are extensively drug resistant (XDR), i.e., also resistant to three or more of the six classes of second-line drugs. MDR- and XDR-TB pose the greatest threats to public health in the resource-poor areas mentioned above, and WHO has recently emphasized the need for inexpensive, rapid, and simple TB diagnostic and antimicrobial susceptibility tests suitable for use in such areas. The microscopic observation direct susceptibility (MODS) assay has attracted considerable attention in this context. Decontaminated sputum is inoculated into multiwell plates containing liquid medium, with first-line drugs (typically INH and RIF) in some wells, and the wells are observed over a period of days. Growth of Mycobacterium tuberculosis (MTB) is detected by the cordlike appearance of colonies under a low-power microscope. The assay, uses inexpensive consumables and simple equipment, and determines culture positivity and antibiotic susceptibility at a median of 7 days; modern automated methods, employing expensive equipment and consumables, and classical culture techniques are less sensitive and take longer. This project will investigate the use of a small, simple, extremely inexpensive fluorescence image cytometer to automate the readout of the MODS assay or develop a functional equivalent, in either case eliminating the need for a trained microscopist, with the anticipated result being an accurate, rapid, and sensitive apparatus and method for detecting TB and determining antibiotic susceptibility, suitable for use in developed as well as developing countries. PUBLIC HEALTH RELEVANCE: An estimated 8.9 million cases of tuberculosis (TB) occurred in 2004; of the estimated 1.7 million deaths, over 260,000 occurred in HIV-infected individuals. Multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) TB are a significant threat to public health in resource- poor areas such as Africa, China, India, and the Russian Federation, where epidemics of TB and HIV-AIDS interact in a negative fashion. The World Health Organization has recently emphasized the need for inexpensive, rapid, and simple TB diagnostic and drug susceptibility tests suitable for use in such areas. One such test, the MODS assay, is rapid and inexpensive, but requires readout by a skilled microscopist. This project will attempt to develop an inexpensive apparatus, using simple optics, light-emitting diodes, and a digital camera chip, that could be used for an automated MODS assay or its functional equivalent, meeting diagnostic needs in both resource-poor and affluent countries.

描述（由申请人提供）：世界卫生组织 (WHO) 估计 2004 年发生了 890 万例结核病病例，其中 390 万例是传染性最强的涂片阳性结核病病例。在估计的 170 万人死亡中，超过 26 万人是艾滋病毒感染者；全球结核病发病率不断上升，几乎完全是由于非洲艾滋病毒高发地区的病例所致。 2004年病例中超过424,000例具有多重耐药性（MDR），即对异烟肼（INH）和利福平（RIF）耐药；大多数发生在中国、印度和俄罗斯联邦。在 MDR 病例中，大约 10% 具有广泛耐药性 (XDR)，即对六类二线药物中的三种或更多药物也具有耐药性。耐多药结核病和广泛耐药结核病对上述资源匮乏地区的公共卫生构成最大威胁，世界卫生组织最近强调需要适合这些地区使用的廉价、快速和简单的结核病诊断和抗菌药物敏感性测试。显微镜观察直接敏感性（MODS）测定在这方面引起了相当大的关注。将净化后的痰液接种到含有液体培养基的多孔板中，一些孔中含有一线药物（通常是INH和RIF），并对孔进行几天的观察。结核分枝杆菌 (MTB) 的生长可通过低倍显微镜下菌落的索状外观来检测。该检测使用廉价的耗材和简单的设备，平均 7 天即可确定培养物阳性和抗生素敏感性；现代自动化方法采用昂贵的设备和耗材，而经典培养技术则不太敏感且需要更长的时间。该项目将研究使用小型、简单、极其便宜的荧光图像细胞仪来自动读取 MODS 测定或开发功能等效物，在任何一种情况下都不需要经过培训的显微镜师，预期结果是准确的、用于检测结核病和确定抗生素敏感性的快速、灵敏的设备和方法，适合在发达国家和发展中国家使用。公共卫生相关性：2004 年估计发生了 890 万例结核病 (TB)；在估计的 170 万人死亡中，超过 26 万人死于艾滋病毒感染者。耐多药结核病（MDR-TB）和广泛耐药结核病（XDR-TB）对非洲、中国、印度和俄罗斯联邦等资源匮乏地区的公共卫生构成重大威胁，这些地区结核病和艾滋病毒流行-艾滋病以消极的方式相互作用。世界卫生组织最近强调需要适合在这些领域使用的廉价、快速和简单的结核病诊断和药物敏感性测试。 MODS 测定是此类测试之一，快速且廉价，但需要熟练的显微镜人员进行读数。该项目将尝试开发一种廉价的设备，使用简单的光学器件、发光二极管和数码相机芯片，可用于自动 MODS 测定或其功能等效物，满足资源匮乏和富裕国家的诊断需求。