Performance of the hematology analyzer XN-31 prototype in the detection of Plasmodium infections in an endemic region of Colombia

Abstract

Early and accurate diagnosis is critical in reducing the morbidity and mortality associated with malaria. Microscopy (MI) is the current diagnostic gold standard in the field; however, it requires expert personnel, is time-consuming, and has limited sensitivity. Although rapid diagnostic tests for antigen detection (RDTs) are an alternative to diagnosis, they also have limited sensitivity and produce false positive results in detecting recent past infection. The automated hematology analyzer XN-31 prototype (XN-31p) (Sysmex Corporation, Kobe, Japan) is able to identify plasmodium-infected erythrocytes, count parasitemia and perform complete blood-cell counts within one minute. The performance of the XN-31p in diagnosing malaria was evaluated and compared with real-time polymerase chain reaction (qPCR), MI and RDT in an endemic area of Colombia where Plasmodium falciparum and Plasmodium vivax are present. Acute febrile patients were enrolled from July 2018 to April 2019 in Quibdó, Colombia. Malaria diagnoses were obtained from MI and RDT in the field and later confirmed by qPCR. Venous blood samples in EDTA were processed with an XN-31p in the field. Sensitivity, specificity, positive/negative predictive values, and the likelihood ratios of positive and negative tests were calculated with respect to the results from qPCR, MI and RDT. The intraclass correlation coefficient (ICC) and Bland–Altman plot were used to evaluate the concordance in the parasitemia with respect to MI. A total of 1,754 subjects were enrolled. The mean age was 27.0 years (IQR 14–44); 89.6% were Afro-Colombians, 94.3% lived in urban areas and 0.91% were pregnant. With respect to qPCR, the XN-31p showed a sensitivity of 90% (95% CI 87.24–92.34) and a specificity of 99.83% (95% CI 99.38–99.98) in detecting Plasmodium spp.; both parameters were equivalent to those for MI and RDT. Using MI as the reference, the XN-31p showed a sensitivity of 98.09% (95% CI 96.51–99.08), a specificity of 99.83% (95% CI 99.4–99.98), an ICC of 0.85 (95% CI 0.83–0.87) and an average difference of − 3096 parasites/µL when compared with thick-smear MI and an ICC of 0.98 (95% CI 0.97–0.98) and an average difference of − 0.0013% when compared with thin-smear MI. The XN-31p offers a rapid and accurate alternative method for diagnosing malaria in clinical laboratories in areas where P. falciparum and P. vivax cocirculate.

Fast detection and quantification of Plasmodium species infected erythrocytes in a non-endemic region by using the Sysmex XN-31 analyzer

“…In one study from Cameroon, it was found that 2 out of every 10 sickle cell patients who died had malaria [ 26 ]. To date, there have been preliminary studies done how interferences affect the results of the XN-31, but there is some discrepancy in the results and what conditions can trigger an abnormal scattergram on the XN-31 [ 14 , 15 ]. For the investigation of RBC abnormalities, abnormal samples were deliberately collected to determine the effect on the XN-31 result.…”

“…The XN-30, was approved for research purposes only, whereas the XN-31 is a CE marked in vitro diagnostic device with identical hardware, software, and user interface. The XN-31 has not been evaluated in clinical practice in non-endemic countries nor for Plasmodium species other than P. falciparum and P. vivax [ 13 , 14 , 16 ].…”

Fast Detection And Quantification of Plasmodium Species Infected Erythrocytes In A Non-Endemic Region By Using The Sysmex XN-31 Analyzer

“…26 To date, there have been preliminary studies done how interferences affect the results of the XN-31, but there is some discrepancy in the results and what conditions can trigger an abnormal scattergram on the XN-31. 14,15 Further need to be done in order to determine whether the XN-31 can properly detect Plasmodium infected RBC in patients with sickle cell disease and other diseases that significantly affect red blood cell morphology and/or erythropoiesis.…”

“…Using fluorescence flow cytometry (FFC) technology and a violet semiconductor laser with a 405 nm wavelength, this hemocytometer can detect, specify and quantitate malaria-infected red blood cells (MI-RBC) within a specific area of the scattergram known as the M-gating area. Previous studies on the XN-31 and its predecessor the XN-30 reported mainly data on P. falciparum infected patients in endemic countries [12][13][14][15][16] or on in vitro cultures 13,17,18 . The XN-30, was approved for research purposes only, whereas the XN-31 is a CE marked in vitro diagnostic device with identical hardware, software, and user interface.…”

“…The XN-31 has not been evaluated in clinical practice in non-endemic countries nor for Plasmodium species other than P. falciparum and P. vivax. 13,14,16 .…”