Abstract
For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis. Although current haematology analysers are not specifically designed to detect malaria-related abnormalities, most studies have found sensitivities that comply with WHO malaria-diagnostic guidelines, i.e. ≥ 95% in samples with > 100 parasites/μl. Establishing a correct and early malaria diagnosis is a prerequisite for an adequate treatment and to minimizing adverse outcomes. Expert light microscopy remains the 'gold standard' for malaria diagnosis in most clinical settings. However, it requires an explicit request from clinicians and has variable accuracy. Malaria diagnosis with flow cytometry-based haematology analysers could become an important adjuvant diagnostic tool in the routine laboratory work-up of febrile patients in or returning from malaria-endemic regions. Haematology analysers so far studied for malaria diagnosis are the Cell-Dyn®, Coulter® GEN·S and LH 750, and the Sysmex XE-2100® analysers. For Cell-Dyn analysers, abnormal depolarization events mainly in the lobularity/granularity and other scatter-plots, and various reticulocyte abnormalities have shown overall sensitivities and specificities of 49% to 97% and 61% to 100%, respectively. For the Coulter analysers, a 'malaria factor' using the monocyte and lymphocyte size standard deviations obtained by impedance detection has shown overall sensitivities and specificities of 82% to 98% and 72% to 94%, respectively. For the XE-2100, abnormal patterns in the DIFF, WBC/BASO, and RET-EXT scatter-plots, and pseudoeosinophilia and other abnormal haematological variables have been described, and multivariate diagnostic models have been designed with overall sensitivities and specificities of 86% to 97% and 81% to 98%, respectively. The accuracy for malaria diagnosis may vary according to species, parasite load, immunity and clinical context where the method is applied. Future developments in new haematology analysers such as considerably simplified, robust and inexpensive devices for malaria detection fitted with an automatically generated alert could improve the detection capacity of these instruments and potentially expand their clinical utility in malaria diagnosis.
Highlights
For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis
In a Canadian study, in patients with imported malaria, 45% infected with P. vivax, 33% with Plasmodium falciparum, 22% with other species or mixed malaria, 59% cases were missed on first presentation and 16% had ≥3 physician-contacts before malaria smears were ordered [15]
A study evaluating 185 malaria-related fatalities in travellers returning to the United States, of which 92.7% were caused by P. falciparum, 3.3% by P. vivax and the remainder by other species, found that 67.8% of these patients were not diagnosed in the first visit, 17.9% were diagnosed at autopsy, and 66.7% of preventable deaths were attributed to management failure upon presentation [14]
Summary
The early detection of malaria is life-saving. Most health personnel are trained to consider malaria in febrile patients arriving from endemic regions; in settings with low pre-test probability for malaria, the diagnosis may be initially overlooked. Malaria detection with haematology analysers, as a by-product of its main purpose, the CBC analysis, can be useful as an adjuvant diagnostic tool in the work-up of febrile patients. All authors have read and approved the final version of the paper
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