Plasma Soluble Progenitor Cell Receptors as Biomarkers for Severe Anemia Among Malaria-Infected Pediatrics: A Prospective Study in Ghana

Abstract

Background: Soluble forms of progenitor cell receptors may be implicated in the delayed erythropoietic response during severe anemia. In this study, plasma levels of soluble erythropoietin receptor (sEPO-R) and soluble granulocyte, macrophage-colony stimulating factor receptor (sGM-CSFR) were assessed in Plasmodium falciparum-infected children in Ghana. Methods: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty P. falciparum-infected, and 60 uninfected children aged 12–144 months were recruited from April to July, 2023. About 4 mL of blood was collected for malaria microscopy, full blood count using a haematology analyser, and sEPO-R, sGM-CSFR and erythropoietin (EPO) estimation using enzyme-linked immunosorbent assays. Data were analyzed using SPSS version 26.0. Results: Plasma levels of sEPO-R were higher among participants with severe malarial anemia (SMA) than those in the non-SMA and control groups (p < 0.001). Plasma sGM-CSFR levels were higher in P. falciparum-infected children than in controls, but the levels were similar between the SMA and non-SMA groups. Hemoglobin (r = −0.823, p < 0.001), RBC (r = −0.852, p < 0.001), HCT (r = −0.790, p < 0.001) and platelets (r = −0.810, p < 0.001) negatively correlated with sEPO-R. There was a strong positive correlation between sEPO-R and EPO in P. falciparum-infected children (r = 0.901, p < 0.001). Plasma sEPO-R better predicted severe anemia among malaria-infected children (cut-off point: 161.5 pg/mL, sensitivity: 96.0%, specificity: 82.9%, AUC: 0.964, p < 0.001). Conclusion: P. falciparum-infected children had higher plasma levels of sGM-CSFR, sEPO-R and EPO. Plasma sEPO-R correlated negatively with erythrocyte parameters, suggesting a possible contribution of the endogenous receptor to the development of severe anemia in children with malaria. Further studies to investigate the neutralizing effects of sEPO-R on erythropoietic response during malaria are recommended.