Soluble Urokinase Plasminogen Activator Receptor (Supar), Tumor Necrosis Factor Receptor-2 (Tnfr2), Neutrophil-to-lymphocyte Ratio (NLR) and Platelets-to-Lymphocyte Ratio (PLR) as markers of Severe Plasmodium Falciparum Malaria in Ghana

Introduction : Systemic inflammation, immune activation and endothelial damage contribute to the pathogenesis of malaria. Soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor-2 (TNFR-2), Neutrophil-to-lymphocyte Ratio (NLR) and Platelets-to-Lymphocyte Ratio (PLR) are markers of these pathways. The aim of this study was to determine the diagnostic value of suPAR, TNFR-2, NLR, PLR as markers of severe falciparum malaria. Methods : The current study recruited 168 participants comprising 128 malaria positive patients and 40 healthy controls. suPAR and TNFR-2 were determined by the ELISA technique. Full blood count was performed using Sysmex XN350 Hematology Analyzer from which NLR and PLR were determined by dividing the absolute neutrophil and platelet counts by the absolute lymphocyte count. Results : Out of the 128 cases, 11 (8.6%) had severe malaria. PLR [26.7 vs. 122.4, p =0.006] and suPAR [16.0 ng/mL vs. 18.0 ng/mL, p =0.033] demonstrated a significant drop in the severe malaria group compared to those without malaria. Median levels of suPAR [16.5 ng/mL vs. 18.0 ng/mL, p =0.006] and TNFR2 [67.3 ng/L vs. 74.0 ng/L, p =0.026] were significantly reduced in the uncomplicated malaria group compared to the control group. Increasing suPAR (R = 0.257, p = 0.003) showed a notable correlation with a significant rise in parasitemia. Increasing TNFR2 (R = 0.291, p <0.0001) was associated with a significant increase in parasitemia. At a cutoff value of ≤85.93, PLR was the best measure for detecting severe malaria with a sensitivity of 82.4% and a specificity of 77.5% with an AUC of 0.840. low PLR [aOR = 19.9, p =0.017] and low suPAR [aOR = 17.9, p =0.013] emerged as significant independent risk factors linked to severe malaria among the subjects. Conclusion : PLR is a good discriminatory test for the presence of severe falciparum malaria. A patient with low PLR and low suPAR has an increased chance of developing falciparum malaria. suPAR and TNFR-2 biomarkers correlated with malaria parasite density. Therefore, these biomarkers may be used in addition to clinical and laboratory markers to heighten the suspicion of severe falciparum malaria.