title: Evaluation of a lens-free imager to facilitate tuberculosis diagnostics in MODS.
abstract: Tuberculosis (TB) control efforts are hampered by a mismatch in diagnostic technology. Lack of adequate early diagnostics and Multi-drug resistant (MDR) detection is a critical problem in control efforts. Alternate and novel diagnostic approaches are required, especially in low-resources settings where they are needed most. The Microscopic Observation Drug Susceptibility (MODS) assay is a cost-effective, highly sensitive, and specific method based on the detection of characteristic cording growth patterns of Mycobacterium tuberculosis (MTB), in microscopic examination of a liquid culture under an inverted microscope. By adding antimicrobials to the wells, MODS also determines antimicrobial susceptibility in both MDR and Extreme Drug Resistant (XDR) tuberculosis. The interpretation of a MODS culture performed in a 24 well plate, requires an extensive inspection over the entire surface to detect TB cords. This process requires significant time and effort from a trained microscopist. We evaluated a lens-free imager system, able to render microscopic images of live specimens, for the proof of principle to be used for MODS culture interpretation. The lens-free imager system is able to digitalize a 24-mm(2) surface with approximately 40X magnification in a single capture. The evaluation of the lens-free imager found that it produced microscopic images that were adequate for MODS interpretation by a human expert. Compared to the average time that takes a microscopist to completely examine a MODS culture sample, the lens free imager notably reduced the time of inspection. Therefore, lens-free imager variants may constitute promising systems to aid in the diagnostics of tuberculosis, by simplifying and reducing the time of inspection and permitting automatization of MODS interpretation.
authors.affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Solis
authors.affiliation: Laboratorio de Tuberculosis, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueda
authors.affiliation: Laboratorio de Tuberculosis, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru; Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Room 5515, Baltimore, MD 21205, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru; Laboratorio de Tuberculosis, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheen
authors.affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru; Laboratorio de Tuberculosis, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, Lima 31, Peru. Electronic address: mirko.zimic@upch.pe.
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D004867:Equipment Design; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000295:instrumentation*; D008853:Microscopy / Q000295:instrumentation*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D057188:Workflow
chemical_list: D000995:Antitubercular Agents
keywords: Diagnostics; Lens-free imager; Lens-free microscopy; MDR; MODS; Microscopy; Multi drug resistance; Tuberculosis; ePetri