Discrepancy Between White Blood Cell Count Channels as a Clue to Malaria Infection

A 40-year-old man with no underlying conditions was admitted to our hospital due to high fever and chills lasting for 3 weeks. He previously lived in southern Ethiopia and had arrived in Taiwan 3 months before symptom onset, working as a postdoctoral researcher at a university in Taipei. He had no travel history during his stay in Taiwan. Three weeks prior to admission, he developed fever, chills, myalgia, general malaise, nausea, and vomiting. He first visited a local hospital, where a diagnosis of common cold with gastrointestinal symptoms was considered. As his symptoms persisted, he sought further evaluation at our hospital. Upon arrival, his body temperature was 41°C; other physical findings were unremarkable. His fever was paroxysmal, recurring every 48 h. A venous blood sample was collected for complete blood count (CBC), including white blood cell (WBC) count and differential, using the Sysmex XN-10 analyzer (Sysmex, Kobe, Japan). The initial results showed hemoglobin 13.5 g/dL and platelet count 138 × 103/μL. Notably, a discrepancy was observed between the WBC differential channel (WBC-D: 5.86 × 103/μL) and the nucleated cell channel (WBC-N: 2.52 × 103/μL) (Figure 1). Manual blood films were prepared for review (Figure 2), revealing multiple gametocytes and early trophozoites with ring-form. The laboratory medicine team alerted clinicians to the presence of protozoa morphologically suspected to be Plasmodium vivax, which was later confirmed by PCR, as a rapid diagnostic test was not available at that time. The patient was treated with artemether-lumefantrine (20 mg/120 mg), and the follow-up blood film after 3 days showed clearance of the parasite (Figure S1). The scattergram returned to normal, and the discrepancy between WBC-N and WBC-D was rectified (Figure 1). He became afebrile and was discharged with a five-day course of primaquine (7.5 mg/day). In non-endemic areas, malaria is often overlooked, underscoring the need for accessible screening tools. Previous studies have reported malaria-related hematologic abnormalities, including leukopenia, pseudoreticulocytosis, and pseudoeosinophilia [1]. Abnormal scattergrams and cell population data have been proposed as cost-effective screening indicators [2]. The Sysmex XN-10 automated hematology analyzer detects WBC through two separate channels: WNR and WDF. In the WDF channel, the reagent perforates the WBC membrane, allowing a fluorescent dye to bind with nucleic acids. Flow cytometry is then used to differentiate four cell populations: lymphocytes, monocytes, eosinophils, and neutrophils/basophils. In contrast, the acid reagent of WNR channel preserves the morphology of basophils while denuding the nuclei of nucleated red blood cells and other WBC. After fluorescent staining, flow cytometry can distinguish among basophils, other WBC, and nucleated red blood cells. Generally, WBC counts from WNR and WDF channels correlate closely [3], and marked discrepancies are uncommon. In this case, we assume that gametocytes may have been misclassified within the neutrophil-eosinophil cluster in the WDF channel, producing an apparently normal WBC result (Figure 1). In previous literature, the presence of gametocytes in non-Plasmodium falciparum infections tended to result in larger delta WBC (WDF–WNR) values [2], consistent with the present case. In summary, this case highlights the diagnostic value of abnormal scattergrams, particularly when discrepancies between WBC channels are observed. Further samples should be collected to validate whether the delta WBC (WDF–WNR) flag can be incorporated into the screening flowchart for certain malaria species, such as Plasmodium vivax. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1: Follow-up peripheral blood film after 3 days. (A–B) The follow-up peripheral blood film after 3 days showed clearance of parasites (May-Grünwald Giemsa stain, 1000× magnification). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.