Evaluation of the Abbott Cell‐Dyn 4000 hematology analyzer for detection and therapeutic monitoring of Plasmodium vivax in the Republic of Korea

Abstract

SummaryThe Cell-Dyn 4000 automated hematology analyzer (CD4000) has the ability to detect malaria patients, but it remained unclear whether it could detect persistent malaria post-treatment. To investigate this, we used the CD4000 to evaluate 68 Korean patients with Plasmodium vivax malaria, and control groups of 50 patients with fever and 50 asymptomatic patients. The results from the instrument-generated scatter plot (derived by laser light depolarization) were compared with microscopy results. During the initial diagnosis, the sensitivity of the CD4000 in detecting malaria was 91.2%. On day 3 of follow-up, the CD4000 results matched those from microscopy by 96.7%. Malaria was not detected by either method beyond 14 days post-presentation. Interestingly, the atypical depolarizing events, which typify the presence of malaria in the analyzer, were highly correlated with the levels of parasitaemia in serially diluted samples of the leucocyte-depleted blood, and the CD4000 detected parasites down to the level of 288 ± 17.7 /ll. Our findings suggest that the phenomenon of atypical light depolarization could be influenced by parasitaemia levels, and be used as a screening method for P. vivax malaria patients, as well as for the therapeutic monitoring.

Automated haematology analysis to diagnose malaria

“…Interestingly, there is evidence that depolarizing material in intra-erythrocytic parasites could also be detected [31,32]. It appears that excitation light with a longer wavelength causes slightly stronger depolarization signals [29].…”

“…Using the CD 4000, in cases of P. vivax infections, large black-coded populations have been observed, which usually indicate non-leucocytic events (Figure 2). These events could be caused by parasites since these populations are much smaller in size than any of the leukocyte populations [32,35,37]. However, it is unclear if they represent lysis-resistant haemozoin-containing erythrocytes or perhaps large parasites seen in mature forms (mature trophozoites, schizonts).…”

“…However, the definition of what constitutes a Cell-Dyn malaria-positive sample varies between studies, especially regarding the position of the cut-off line and the fact that multiple reference diagnosis tests are used (Table 1). Sensitivity in 13 studies ranged from 48.6% to 100% [18,27,30,32-37,39-43] and specificities from 25.3% to 100% [18,27,30,32-37,39-43] (Table 1). Some studies on imported malaria showed rather low values for sensitivity (Table 1); for example 48.6% found in Germany [27], 55% found in South Africa [44], and 62% in The Netherlands [36].…”

“…Other malaria related abnormalities described only for the CD 4000 include abnormalities observed in other scatter-plots, especially the EOS-I scatter-plot, which shows granularity (depolarized side-scatter) versus size (0°-forward-scatter) [32,35,37,41]. Several studies reported the appearance of highly granular (depolarized side-scatter values above channel 50), green or black-coded events clustered (as opposed to random) in the small-size range (low forward-scatter) [32,35,37].…”

“…Several studies reported the appearance of highly granular (depolarized side-scatter values above channel 50), green or black-coded events clustered (as opposed to random) in the small-size range (low forward-scatter) [32,35,37]. Given the small size and high granularity of these events, they most likely correspond to haemozoin-laden mature parasites or haemozoin-rich red cell 'ghosts' [37].…”