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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.

SUBMITTER: Zuluaga-Idarraga L

PROVIDER: S-EPMC7933134 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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

Zuluaga-Idárraga Lina L Rios Alexandra A Sierra-Cifuentes Verónica V Garzón Edwar E Tobón-Castaño Alberto A Takehara Ikki I Toya Yuji Y Izuka Munehisa M Uchihashi Kinya K Lopera-Mesa Tatiana M TM

Scientific reports 20210304 1

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- ...[more]

PMID: 33664389

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Project description:BackgroundThe Sysmex XN-V is derived from the new Sysmex XN series of human hematology analyzers. The main changes from the previously validated XT-2000iV analyzer include an optic-fluorescent analysis for platelets and nucleated RBC count.ObjectiveWe aimed to validate the Sysmex XN-V for canine blood according to American College for Veterinary Clinical Pathology and International Council for Standardization in Hematology recommendations.Materials and methodsCanine EDTA blood specimens and quality control material were analyzed on the Sysmex XN-V to evaluate imprecision, bias, linearity, a comparison with the XT-2000iV analyzer, interference effects, carry-over, and stability. We also verified previously established Sysmex XT-2000iV reference intervals (RIs).ResultsImprecision and bias were low (<5%) for most variables. Observed total error was lower than allowable total error for most measured variables except lymphocytes and monocytes. Visually determined linearity was excellent for all variables, except for lymphocytes. The correlation between the XN-V and XT-2000iV analyzers was high (>0.93) for all variables except MCHC and reticulocyte indices. Correlations between the Sysmex XN-V and manual differential counts were good for neutrophils and eosinophils, acceptable for lymphocytes, and fair for monocytes. Hemolysis, lipemia, and to a lesser extent icterus, had significant effects on measured hemoglobin concentration and associated variables. Carry-over was not visually observed for any variable. Changes in the Sysmex XN-V measurements after storage at 4℃ and 24℃ were similar to those described for the Sysmex XT-2000iV analyzer. The previously established Sysmex XT-2000iV RIs can be used to interpret results from the Sysmex XN-V analyzer for most variables except red blood cell distribution width and mean platelet volume.ConclusionsThe performance of the Sysmex XN-V analyzer was excellent and compared favorably with the Sysmex XT-2000iV analyzer.

Project description:BackgroundThe automated haematology analyzer XN-31 prototype (XN-31p) is a new flow cytometry-based device developed to measure the number and the ratio of malaria-infected red blood cells (MI-RBC) with a complete blood count (CBC). The XN-31p can provide results in about one minute and also can simultaneously provide information on the malaria parasite (Plasmodium) species. In this study, clinical testing of the XN-31p was performed using blood samples from patients with imported malaria in Japan.MethodsBlood samples were collected from 80 patients who visited the hospital of the National Center for Global Health and Medicine, Tokyo, Japan, for malaria diagnosis from January 2017 to January 2019. The test results by the XN-31p were compared with those by other standard methods, such as microscopic observation, rapid diagnostic tests and the nested PCR.ResultsThirty-three patients were diagnosed by the nested PCR as being malaria positive (28 Plasmodium falciparum, 2 Plasmodium vivax, 1 Plasmodium knowlesi, 1 mixed infection of P. falciparum and Plasmodium malariae, and 1 mixed infection of P. falciparum and Plasmodium ovale), and the other 47 were negative. The XN-31p detected 32 patients as "MI-RBC positive", which almost matched the results by the nested PCR and, in fact, completely matched with the microscopic observations. The ratio of RBCs infected with malaria parasites as determined by the XN-31p showed a high correlation coefficient of more than 0.99 with the parasitaemia counted under microscopic observation. The XN-31p can analyse the size and nucleic acid contents of each cell, and the results were visualized on a two-dimensional cytogram termed the "M scattergram". Information on species and developmental stages of the parasites could also be predicted from the patterns visualized in the M scattergrams. The XN-31p showed a positive coincidence rate of 0.848 with the nested PCR in discriminating P. falciparum from the other species.ConclusionsThe XN-31p could rapidly provide instructive information on the ratio of MI-RBC and the infecting Plasmodium species. It was regarded to be of great help for the clinical diagnosis of malaria.

Project description:BackgroundAccurate and timely diagnosis of malaria is essential for disease management and surveillance. Thin and thick blood smear microscopy and malaria rapid diagnostic tests (RDTs) are standard malaria diagnostics, but both methods have limitations. The novel automated hematology analyzer XN-30 provides standard complete blood counts (CBC) as well as quantification of malaria parasitemia at the price of a CBC. This study assessed the accuracy of XN-30 for malaria detection in a controlled human malaria infection (CHMI) study and a phase 3 diagnostic accuracy study in Burkina Faso.MethodsSixteen healthy, malaria-naive CHMI participants were challenged with five Plasmodium falciparum-infected mosquitoes. Blood was sampled daily for XN-30, blood smear microscopy, and malaria qPCR. The accuracy study included patients aged > 3 months presenting with acute febrile illness. XN-30, microscopy, and rapid diagnostic tests (HRP-2/pLDH) were performed on site; qPCR was done in retrospect. The malaria reference standard was microscopy, and results were corrected for sub-microscopic cases.ResultsAll CHMI participants became parasitemic by qPCR and XN-30 with a strong correlation for parasite density (R2 = 0.91; p < .0001). The XN-30 accurately monitored treatment and allowed detection of recrudescence. Out of 908 patients in the accuracy study, 241 had microscopic malaria (density 24-491,802 parasites/μL). The sensitivity and specificity of XN-30 compared to microscopy were 98.7% and 99.4% (PPV = 98.7%, NPV = 99.4%). Results were corrected for qPCR-confirmed sub-microscopic cases. Three microscopy-confirmed cases were not detected by XN-30. However, XN-30 detected 19/134 (14.2%) qPCR-confirmed cases missed by microscopy. Among qPCR-confirmed cases, XN-30 had a higher sensitivity (70.9% versus 66.4%; p = .0009) and similar specificity (99.6% versus 100%; p = .5) as microscopy. The accuracy of XN-30 for microscopic malaria was equal to or higher than HRP-2 and pLDH RDTs, respectively.ConclusionsThe XN-30 is a novel, automated hematology analyzer that combines standard hemocytometry with rapid, objective, and robust malaria detection and quantification, ensuring prompt treatment of malaria and malaria anemia and follow-up of treatment response.Trial registrationBoth trials were registered on clinicaltrials.gov with respective identifiers NCT02836002 (CHMI trial) and NCT02669823 (diagnostic accuracy study).

Project description:BackgroundSimple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results.MethodsPaired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15-25 °C) or chilled temperatures (2-8 °C).ResultsIdentical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p.ConclusionThese results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model.

Dataset Information

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

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

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