Mobile digital fluorescence microscopy for diagnosis of tuberculosis

Area of Science:

• Medical Diagnostics
• Microscopy Technology
• Infectious Disease Research

Background:

• Access to sputum smear microscopy for tuberculosis (TB) diagnosis is limited in high-burden regions due to equipment and expertise shortages.
• Digital microscopy offers a potential solution to expand diagnostic capabilities in resource-limited settings.

Purpose of the Study:

• To evaluate the diagnostic accuracy of the CellScope, a novel digital fluorescence microscope, compared to conventional light-emitting diode (LED) fluorescence microscopy for TB detection.
• To assess if CellScope-based LED fluorescence microscopy (FM) is non-inferior to conventional LED FM in sensitivity and specificity.

Main Methods:

• Sputum smear microscopy slides from 525 patients in Uganda were prepared and analyzed using both CellScope and conventional LED FM by experienced technicians.
• Two U.S.-based postgraduate researchers, new to microscopy, restained, imaged, and interpreted slides using the CellScope.
• Non-inferiority was assessed using a preselected margin of 15%.

Main Results:

• CellScope and conventional LED FM showed similar proportions of positive results (34% vs. 32%, P = 0.32) with substantial agreement.
• CellScope accuracy was within the non-inferiority margin for sensitivity (63% vs. 70%) and specificity (85% vs. 92%).
• Interreader reliability for CellScope was substantial (kappa=0.65), but intrareader reliability varied (kappa=0.11-0.48).

Conclusions:

• The CellScope digital fluorescence microscope demonstrates promising accuracy for TB diagnosis, comparable to conventional methods.
• The device has the potential to expand microscopy services, particularly in resource-limited settings.
• Further research is needed to evaluate CellScope with local health workers and explore automated image analysis.