Low monocyte to neutrophil ratio in peripheral blood associated with disease complication in primary Plasmodium falciparum infection.

Immunity to malaria can be acquired but only after repeat exposures to polymorphic Plasmodium. However, the development of clinical outcomes during P. falciparum infection is not clearly understood. This study elucidated whether monocytes, neutrophils and pro/anti-inflammatory cytokines were associated with clinical outcomes in single infection and prior repeated malaria infections. Two hundred and seventy-nine patients with complicated and uncomplicated malaria were investigated. Peripheral blood IFN-gamma, TNF-alpha and IL-10 levels were measured by ELISA, and monocytes and neutrophils by an automated cell counter. On admission, in patients with uncomplicated malaria prior repeated infections, absolute neutrophil counts were positively and monocyte to neutrophil ratio negatively correlated significantly with parasitemia (r = 0.358, p = 0.000; r = -0.356, p = 0.000, respectively), while those with single infection absolute monocyte counts and monocyte to neutrophil ratio were significantly correlated negatively with IFN-gamma (r = -0.381, p = 0.001; r = -0.393, p = 0.000, respectively), and positively with TNF-alpha levels (r = 0.310, p = 0.007; r = 0.227, p = 0.017, respectively). In sharp contrast, in complicated malaria with single infection extremely high IFN-gamma and IL-10 levels but significantly low percent monocyte counts and monocyte to neutrophil ratio were seen. After 7 days of treatment, absolute monocyte counts and monocyte to neutrophil ratio were significantly increased, while absolute neutrophil counts significantly decreased (p = 0.000, 0.000, and 0.001, respectively), similarly after 28 days of treatment (p = 0.008, 0.000 and 0.000, respectively). These results suggest different functions of monocytes, neutrophils and pro/anti-inflammatory cytokines in complicated and uncomplicated malaria with single P. falciparum infection or prior repeated infections in the context of disease severity. Low monocyte to neutrophil ratio may be regarded as a risk factor in developing complication in primary malaria infection.