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ABSTRACT
Malaria is a leading cause of death in sub-Sahara Africa including Nigeria. The oxidative stress associated with malaria infection may affect the plasma protective proteins and trace elements which are involved in the antioxidant defensive system. The aim of this study was to assess the advanced metallothionein profile of malaria infected children in Benin metropolis and determine its association with parasite density. This case-control study has a total of 350 children between the age of 6months and 11years and consist 200 malaria infected and 150 non-malaria infected subjects. Semi-structured questionnaire was used to collect socio-demographic data. Blood sample was collected from each of the participants and malaria parasite density was assayed using thick film. Serum metallothionein (MT), glutathione (GSH) and ceruloplasmin (CP) were measured using Enzyme linked Immunosorbent assay (ELISA) techniques, while copper (Cu) and zinc (Zn) levels were determined using Atomic Absorption spectrometry. The data generated was analyzed using appropriate statistical tools. The mean values of metallothionein (118±4.54 vs 30.6±0.87 (pg/ml), ceruloplasmin (98.2±1.93 vs 44.7±2.45 (pg/ml), and glutathione (97.7±3.66 vs 65.8±2.75 (pg/ml) were significantly higher (p<0.001) among children infected with malaria parasite compared with non-malaria infected control subjects. Zinc (1.15±0.06 vs 1.23±0.11 (mg/l) was lower though not significantly (p>0.05) but copper (1.33±0.03 vs 1.49±0.05 (mg/l) was significantly lower (p<0.05) in malaria infected children than control subjects. Similarly, the means of MT/GSH (1.37±0.09 vs 0.54±0.04), MT/Zn (116.1±7.1 vs 31.84±1.8) and CP/Cu (81.5±3.6 vs 31.82±2.6) were significantly higher (p<0.001) while Cu/Zn ratio (1.3±0.05 vs 1.47±0.07) was significantly lower (p<0.003) among malaria infected children than controls. The mean parasite density of the malaria infected children was 716.75±61.14 parasites/µL of blood. Ceruloplasmin correlated inversely (r= -0.15, p=0.04) with malaria parasite density, while other parameters showed no association with parasite density. The odds of having elevated serum metallothionein 62.67 (95% C.I 30.89-127.15), ceruloplasmin 13.58(95% C.I 7.84-23.21) and glutathione 2.37 (95% C.I 1.48-3.81) was higher in malaria infected children than the control subjects. The area under curve (AUC) shows that metallothionein (AUC=0.98±0.01, p<0.05), ceruloplasmin(AUC=0.91±0.02, p<0.05) and glutathione (AUC=0.76±0.03, p<0.05) are useful antioxidant biomarkers in malaria infected children. The findings from this study indicates that marked changes occurred in advanced metallothionein profile of children with malaria infection and its inclusion in routine investigation may enhance early diagnosis and reduce mortality due to malaria infection.
