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 (customweighted 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.T uberculosis (TB) continues to be responsible for more deaths than any other infectious disease besides HIV/AIDS (1). In Africa, where the burden of TB is greatest, approximately 40% of individuals who fall ill with the disease go undiagnosed (2). Sputum smear microscopy is capable of detecting the majority of infectious TB cases, and mathematical models suggest that expanding access to high-quality smear microscopy may improve individual outcomes (3) and reduce TB prevalence and incidence (4). Although recently developed molecular detection methods are becoming available in some diagnostic centers (5), the costs and infrastructure requirements of current tests are prohibitive for most peripheral clinics in high-burden countries (6). Therefore, efforts to improve the quality and expand the reach of microscopy continue to be a global priority (7).In low-income countries, smear microscopy typically involves direct visualization of stained smears by experienced laboratory technicians using conventional light microscopes. In contrast, in high-income countries, microscopy in the related discipline of pathology increasingly involves the use of digital images viewed on high-resol...

An Assemblable, Multi-Angle Fluorescence and Ellipsometric Microscope

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The Impact of Tuberculosis among Immigrants: Epidemiology and Strategies of Control in High-Income Countries—Current Data and Literature Review

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Review of Telemicrobiology

“…Tapley and colleagues developed a prototype system that acts similarly to a cellular phone's camera and display screen to capture and display a fluorescent microscopy live feed. (28) They demonstrated that minimally qualified individuals could effectively use the system to interpret sputa for the presence of mycobacteria, and the authors suggest that this method could be enhanced by transmitting some of the images to remote experts. In 2009, Zimic and coauthors described the use of cellular telephones to transmit images of mycobacteria grown in a drug susceptibility test system.…”