<b>HAEMATOLOGICAL AND BIOCHEMICAL RESPONSES IN CHILDREN WITH SEVERE MALARIA TREATED WITH ARTESUNATE/ARTEMETHER-LUMEFANTRINE COMBINATION THERAPY</b>

Severe malaria (SM) affects several haematological and biochemical parameters with vast clinical manifestations which may lead to death. However, the rate at which these parameters respond to artesunate/artemether-lumefantrine combination therapy (AALCT) as monitoring tools for therapeutic response in children with SM has not been established. The objectives of this study were to determine the: (i) responses of haematological indices to AALCT in children with SM; (ii) responses of serum oxidative, antioxidant and inflammatory markers to AALCT in children with SM; (iii) responses of serum electrolytes and biomolecules to AALCT in children with SM; (iv) responses of liver and kidney function indices to AALCT in children with SM; (v) malaria diagnostic potential of some haematological and biochemical parameters; and (vi) mathematical equation for predicting Plasmodium falciparum density. Blood was collected from ante-cubital vein of both clinically healthy children (control) and children with severe malaria (case). The serum was prepared by centrifuging the clotted blood samples. The level of haematological indices (packed cell volume [PCV], haemoglobin concentration [HbC], leucocytes counts [LC] and platelets count [PC]), oxidative biomarkers (malondialdehyde [MDA], protein carbonyls [PCO] and nitric oxide [NO]; antioxidant indices (catalase, superoxide dismutase [SOD], glutathione, glutathione reductase [GR], glutathione peroxidase [GPx] vitamins A, C and E); inflammatory markers (tumour necrosis factor-α [TNF-α], interferon-γ, interleukin-12, C-reactive proteins [CRP], interleukin-4 and interleukin-10), electrolytes and biomolecules (sodium, potassium, bicarbonate, chloride, calcium, inorganic phosphorous, zinc, copper, magnesium, iron, glucose and uric acid), liver function indices (bilirubin, total protein, albumin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and kidney function indices (creatinine and urea) were determined using standard methods in 200 control and 100 case children; before, during and after treatment with WHO recommended dose of AALCT. The mathematical equation for predicting the density of Plasmodium falciparum was determined using regression analysis. Data were analysed using one way analysis of variance at p &lt; 0.05. Findings in this study were that: i. SM significantly decreased (p &lt; 0.05) PCV, HbC and PC but significantly increased (p &lt; 0.05) LC. AALCT increased PCV, HbC and PC but decreased and normalized LC 48 hours after treatment; ii. SM significantly increased (p &lt; 0.05) serum concentrations of MDA, PCO, GR, GPx, interleukin-4, interleukin-12, TNF-α, interferon-γ and CRP but significantly decreased (p &lt; 0.05) NO, glutathione, catalase, SOD, vitamins A, C, E and interleukin-10. AALCT ameliorated the effects of the markers with GR, GPx, SOD, interleukin-4, TNF-α, PCO/SOD and CRP/SOD normalized 48 hours after treatment; iii. SM significantly decreased (p &lt; 0.05) serum levels of sodium, bicarbonate, inorganic phosphate, zinc, magnesium and iron but significantly increased (p &lt; 0.05) potassium, copper, glucose and uric acid levels. AALCT ameliorated the alterations in the electrolytes and biomolecules levels with sodium, bicarbonate, glucose and HCO3/glucose normalized 48 hours after treatment; iv. AALCT ameliorated alterations in liver and kidney function indices caused by SM with creatinine and urea levels normalized 48 hours after treatment; v. serum GR activity at cut-off values &gt;85.78U/l was indicative of presence of P. falciparum malaria; vi. serum GR had the highest diagnostic potentials, having high sensitivity (98.5%), specificity (96.0%), positive predictive value (98.01%), odds ratio (1576), area under curve (0.999) and low negative predictive value (4.04%); and vii. parasite density (x 103 parasites/µl) = 6.96[GR] - 433.1 - 0.01[GR]2 is the derived equation for predicting P. falciparum density in children. The study concluded that AALCT ameliorated haematological and biochemical alterations caused by SM while serum GR had the best malaria diagnostic potential. Serum GR can therefore be employed for monitoring therapeutic response in children with SM.