TB Diagnostics at the Point of Care

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DESCRIPTION (provided by applicant): Of all diseases, tuberculosis (TB) represents one of, if not, the greatest health disparity between whites and minorities [1]. For every TB-infected white person in the United States, there are an estimated 9 African- Americans, 8 Latinos, 6 Native Americans, 23 Asians, and 21 Native Hawaiian/Pacific Islanders with this disease [2]. Compounded with this disparity is the prevalence of drug-resistant mutations of TB, which have an associated 1000 polymorphisms that span 36 genes, two promoter regions, and one ribosomal RNA coding region [3]. Current methodologies, available primarily to affluent healthcare communities, utilize microbial cultures, which require sophisticated laboratories and weeks before a result can be determined. Difficulties for minorities in a low socioeconomic class to commute and/or follow up with their physicians can result in a lack of appropriate treatment. A low-cost, simple, and rapid point-of-care (POC) test that detects TB and its resistance to first-line drugs (isoniazid, rifampin, ethambutol,and pyrazinamide) would improve TB diagnostics for these minority communities. However, current technologies lack sensitivity, specificity, and/or multiplexing capacity to achieve this goal. We, therefore, propose to develop a POC device that offers the sensitivity of culture methods, specificity of nucleic acid methods, and a broad coverage of mutations. To accomplish this, we will advance our TruArray platform (hemispherical porous gel drop microarrays) for TB diagnostics using on-chip PCR and our existing MDR-TB PCR-microarray biochips. During Phase 1 we demonstrated feasibility of our sample preparation approach, our PCR-micorarray biochips, and prototype POC instrument. For Phase 2 we propose to expand the coverage of our test to include additional mutations that confer resistance to all first-line drugs, integrate this test onto our POC instrument, and translae this system to Laboratorios Medicos Especializados in Juarez, Mexico.