Diagnostic value of microscopic blood smear examination using a digital cell morphology system for human granulocytic anaplasmosis

Background Human granulocytic anaplasmosis (HGA) is an emerging tick-borne zoonosis caused by Anaplasma phagocytophilum . HGA typically presents with flu-like symptoms and, in rare cases, can lead to life-threatening complications. Diagnosis relies on the polymerase chain reaction (PCR), which is the most sensitive, as well as serology or blood smear (BS) examination. However, PCR and serology are generally restricted to specialized laboratories and, depending on the organization and specialization of each laboratory, are often unsuitable for urgent diagnoses. Microscopic examination of BS can detect HGA by identifying intragranulocyte morulae but is time-consuming, requires trained microbiologists, and has limited sensitivity. This study evaluated the feasibility of morulae detection by BS analyzed with the CellaVision® system, a digital cell morphology platform for the automated classification of white blood cells and red blood cells, in patients with PCR-confirmed HGA. Methods Between 2019 and 2025, for each HGA PCR request at the Colmar Civil Hospitals, two May-Grünwald Giemsa-stained BS were prepared, digitized, and the cells preclassified using the CellaVision® System systematically. Retrospectively, two microbiologists performed a review of the recorded images for all positive HGA PCR results to identify intragranulocyte morulae independently and blinded to each other's findings. Results A total of 101 PCR tests for HGA were performed in 92 patients, with 5 patients testing positive (median time to results: 6 days). In all 5 patients, images of intragranulocyte morulae were obtained using the CellaVision® system, and the examination was completed in under 15 min. Conclusions Using the CellaVision® system for BS analysis with a standardized review protocol simplifies the reading process. The method successfully detected morulae in all confirmed cases included in this preliminary study though prospective validation is still required. However, a negative digitally assessed blood smear must not be interpreted as excluding HGA.