Automated Detection of Malaria-Associated Pseudoeosinophilia and Abnormal WBC Scattergram by the Sysmex XE-2100 Hematology Analyzer: A Clinical Study with 1,801 Patients and Real-Time Quantitative PCR Analysis in Vivax Malaria-Endemic Area
Abstract:Abstract. Recently, the XE-2100 hematology analyzer was investigated in a rather small patient group; pseudoeosinophilia or abnormal white blood cell (WBC) scattergrams reported by this instrument were considered as significantly valuable diagnostic parameters in detecting vivax malaria. This study was conducted not only to assess the usefulness of pseudoeosinophilia or abnormal WBC scattergram in vivax malaria-endemic areas with large patient groups ( N = 1,801) but also to investigate the correlation of para… Show more
“…3,4 Notwithstanding the widespread availability of specific external quality assessment programs (EQAs), the low incidence of new diagnoses in Western countries does not allow to maintain a satisfactory degree of expertise for identifying Malaria parasites with microscopic revision of blood smears, so that screening techniques for a targeted microscopic review may be necessary for enabling an early and accurate diagnosis of this infection, especially in nonendemic countries. 3 Recent evidence attests that the latest generation of hematological analyzers may be a valid support for the screening of patients with suspected Malaria, [5][6][7][8][9][10][11][12][13][14][15] although the diagnostic sensitivity and specificity of abnormal findings were found to be strictly dependent on the instrumentation, the parasitic index, and the stage of Plasmodium maturation. The most suggestive findings that have been described so far include abnormalities of leukocyte differential scattergram and reticulocyte (RET) count, which may indicate the presence of parasites at various stages of maturation (i.e.…”
Section: Introductionmentioning
confidence: 99%
“…trophozoites, schizos, and gametocytes). [5][6][7][8][9][10][11][12][13][14][15] The new hematological analyzer Sysmex XN-module (Sysmex Co., Kobe, Japan) enumerates and classifies blood cells, RET, immature leukocytes (White Precursors Cell; WPC), and platelets (PLT) with a combination of optical fluorescence technique (PLT-F), flow cytometry, and laser-optical recognition. The XN-module also provides a variety of innovative cell population data (CPD) parameters, which can be helpful for improving leukocyte differential count and for the more accurate identification of abnormal cells.…”
Section: Introductionmentioning
confidence: 99%
“…Therefore, identification and validation of putative laboratory hallmarks, such as specific anomalies generated by fully automated hematological analyzers in blood samples containing Malaria parasites, should be seen as an extremely valuable perspective for allowing rapid and accurate screening or diagnosing [6][7][8][9][10][11][12][13][14]. Notably, even in healthcare facilities using point of care (POC) analyzers and no…”
The peculiar abnormalities observed in CPDs, WDF, and WNR-scattergrams may raise a definite suspicion of Malaria infection. Further studies should then be planned for validating these preliminary findings and assessing whether these specific abnormalities may be incorporated in rapid and inexpensive Malaria diagnostic algorithms.
“…3,4 Notwithstanding the widespread availability of specific external quality assessment programs (EQAs), the low incidence of new diagnoses in Western countries does not allow to maintain a satisfactory degree of expertise for identifying Malaria parasites with microscopic revision of blood smears, so that screening techniques for a targeted microscopic review may be necessary for enabling an early and accurate diagnosis of this infection, especially in nonendemic countries. 3 Recent evidence attests that the latest generation of hematological analyzers may be a valid support for the screening of patients with suspected Malaria, [5][6][7][8][9][10][11][12][13][14][15] although the diagnostic sensitivity and specificity of abnormal findings were found to be strictly dependent on the instrumentation, the parasitic index, and the stage of Plasmodium maturation. The most suggestive findings that have been described so far include abnormalities of leukocyte differential scattergram and reticulocyte (RET) count, which may indicate the presence of parasites at various stages of maturation (i.e.…”
Section: Introductionmentioning
confidence: 99%
“…trophozoites, schizos, and gametocytes). [5][6][7][8][9][10][11][12][13][14][15] The new hematological analyzer Sysmex XN-module (Sysmex Co., Kobe, Japan) enumerates and classifies blood cells, RET, immature leukocytes (White Precursors Cell; WPC), and platelets (PLT) with a combination of optical fluorescence technique (PLT-F), flow cytometry, and laser-optical recognition. The XN-module also provides a variety of innovative cell population data (CPD) parameters, which can be helpful for improving leukocyte differential count and for the more accurate identification of abnormal cells.…”
Section: Introductionmentioning
confidence: 99%
“…Therefore, identification and validation of putative laboratory hallmarks, such as specific anomalies generated by fully automated hematological analyzers in blood samples containing Malaria parasites, should be seen as an extremely valuable perspective for allowing rapid and accurate screening or diagnosing [6][7][8][9][10][11][12][13][14]. Notably, even in healthcare facilities using point of care (POC) analyzers and no…”
The peculiar abnormalities observed in CPDs, WDF, and WNR-scattergrams may raise a definite suspicion of Malaria infection. Further studies should then be planned for validating these preliminary findings and assessing whether these specific abnormalities may be incorporated in rapid and inexpensive Malaria diagnostic algorithms.
“…Later, two studies in a malaria-endemic region in South Korea evaluated pseudoeosinophilia (>5% difference between the automated and manual eosinophil count) and DIFF scatter-plot abnormalities for P. vivax diagnosis against thick film [54], or against thick film and real-time polymerase chain reaction (RT-PCR) [55] (Table 4). In the first study by Huh and colleagues [54], pseudoeosinophilia and abnormal DIFF scatter-plot alone yielded sensitivities of 39% and 52%, respectively, with no change in specificity.…”
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.
“…[19] Spurious eosinophilia detected in malaria patients is also a fair indicator of the degree of parasitemia as indicated by Jong, et al [20] The sensitivity and specificity of spurious eosinophilia as a marker of Plasmodium infection in the present study were 61.5% and 100%, respectively. Lower sensitivity and comparable specificity were obtained in study by Jong-Ha, et al [20] with sensitivity and specificity of 39.0% and 99.7%, respectively.…”
Peripheral smears of the cases having inconsistent eosinophilia result with that of Sysmex XS-800i analyzer should be examined carefully for the presence of malaria parasites in the red blood cells. Sysmex XS-800i analyzers have moderate range of sensitivity and high degree of specificity in diagnosing malaria as spurious eosinophilia.
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