Hygiene INTRODUCTIONEarly detection of malaria in patients not suspected of having the disease is a potential novel application for modern hematology analyzers like the Sysmex XE-2100 (Sysmex Corporation, Kobe, Kansai, Japan). A prompt and accurate diagnosis is critical to reduce adverse outcomes associated with malaria, including death. 1 In endemic regions, malaria is a prime diagnostic concern in febrile patients, and expert thickfilm evaluation is usually available.2 However, the accuracy of microscopic malaria diagnosis in less experienced centers or in non-endemic regions may be lower, and health personnel is less likely to consider the disease, leading to delayed diagnoses.1 Automated full blood counts (FBC) are usually performed in patients with febrile illnesses, providing a unique opportunity to guide a timely parasitological malaria diagnosis.Hematology analyzers evaluated for malaria detection include the Cell-Dyn (Abbott Diagnostics, Santa Clara, CA), 3 the GEN.S and LH-750 (Beckman Coulter, Miami, FL), 4 and the XE-2100 and XS-1000 i (Sysmex Corporation, Kobe, Kansai, Japan). 5,6 The Sysmex XE-2100 is an automated hematology analyzer that uses flow cytometry, direct current (DC) impedanciometry, and radiofrequency conductance (RF) to detect and measure blood corpuscular elements.7 Flow cytometry may detect malaria parasites or parasite debris such as free hemozoin or hemozoin-laden macrophages as reported for Cell-Dyn instruments.8 For the Sysmex XE-2100, two case series reported a gap between the manual and automated eosinophil counts (pseudoeosinophilia) and abnormal granulocyte-coded events in the DIFF scatterplot used for white blood cell (WBC) separation based on fluorescence versus side-scatter signals in samples from Plasmodium vivaxinfected patients.9, 10 Later, Huh and others 5 found that the two previously reported abnormalities, compared with thick film, had a sensitivity of 69.4% and a specificity of 100% for P. vivax diagnosis. These findings suggest the potential clinical utility of malaria detection by the XE-2100. Ideally, to improve the clinical impact of this detection method, it should be an automated process relying on the analyzer's quantitative data and expressed as a "malaria alarm" that could motivate the microscopic search for malaria.The primary aim of this study was to develop, validate, and test the accuracy of one observer-dependent (OD) and two non-observer-dependent (N-OD) diagnostic prediction models for P. vivax and P. falciparum malaria. The approach for developing the OD models was similar to previous studies using the XE-2100 for malaria diagnosis 5 with the inclusion of other clinical and scatterplot variables not previously investigated. The N-OD models were developed to obtain a framework for an automated malaria-detection algorithm for the XE-2100. Secondary aims were to determine the occurrence of pseudoeosinophilia and to explore a possible cause for the XE-2100 FBC malaria-related abnormalities. MATERIALS AND METHODSStudy population. Blood samples were col...