title: Mobile digital fluorescence microscopy for diagnosis of tuberculosis.
abstract: Access to sputum smear microscopy in high-tuberculosis (TB)-burden regions is limited by a scarcity of microscopes and experienced technicians. We evaluated the accuracy of CellScope, a novel digital fluorescence microscope that may expand access to microscopy. The study utilized smear microscopy slides prepared from sputum specimens submitted by consecutive adults with ≥ 2 weeks of cough who were admitted to Mulago Hospital (Kampala, Uganda). Conventional light-emitting diode (LED) fluorescence microscopy (FM) and mycobacterial culture were performed by experienced technicians. Two U.S.-based postgraduate researchers without prior microscopy experience restained, imaged, and interpreted the slides using CellScope. We assessed whether sensitivity and specificity of CellScope-based LED FM was noninferior to conventional LED FM by using a preselected margin of inferiority of 15%. Of 525 patients included, 72% were HIV seropositive and 39% had culture-confirmed TB. The proportions of positive results were similar with CellScope and conventional LED FM (34% versus 32%, respectively; P = 0.32), and agreement was substantial. CellScope accuracy was within the noninferiority margin for both sensitivity (63% versus 70%; difference, -7%; 95% confidence interval [CI], -13% to -1%) and specificity (85% versus 92%; difference, -7%; 95% CI, -12% to -3%). A subanalysis of 43 slides evaluated by each CellScope reader found substantial interreader reliability (custom-weighted kappa, 0.65) and variable intrareader reliability (custom-weighted kappa, 0.11 versus 0.48). CellScope offers promise for expanding microscopy services. Future studies should evaluate the device when operated by health workers in low-resource settings, the feasibility of image transmission and analysis by experienced microscopists, and the accuracy of automated image analysis algorithms.
authors.affiliation: School of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Asa
authors.initials: A
authors.lastname: Tapley
authors.forename: Neil
authors.initials: N
authors.lastname: Switz
authors.forename: Clay
authors.initials: C
authors.lastname: Reber
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.forename: Cecily
authors.initials: C
authors.lastname: Miller
authors.forename: John Baptist
authors.initials: JB
authors.lastname: Matovu
authors.forename: William
authors.initials: W
authors.lastname: Worodria
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fletcher
authors.forename: Adithya
authors.initials: A
authors.lastname: Cattamanchi
mesh_terms: D000328:Adult; D001431:Bacteriological Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000175:diagnosis*; D014454:Uganda
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