Determination of Tumor Necrosis factor-a, Interluekin-10, Interluekin-12, and Intercellular adhesion molecule-1 levels in relation to Malaria severity in children

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Sitali, Lungowe
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Malaria is highly prevalent in sub-Sahara Africa and is the leading cause of morbidity and mortality accounting for approximately one million deaths per annum. Disease severity and parasitaemia have been linked to cytokine levels, but their relationship requires further elucidation. Better understanding of these relationships would bear on the management of malaria. Potential associations between TNF-a, IL-10, IL-12 and ICAM-1 and malaria disease severity were investigated in the study. Children of ages 12 to 144 months presenting with severe or uncomplicated malaria were assessed as regards to the respective serum cytokine levels at enrollment and 3 days after treatment. There were 102 participants recruited into the study, of which 20 had severe malaria, 55 had uncomplicated malaria and 27 were healthy controls. Parasite densities were also determined using geimsa stained blood thick films. The study was conducted at UTH, Chongwe Clinic, Mpongwe Mission and Mpulungu Hospitals.The levels of parasitaemia were found to be relatively similar in children with severe malaria and those with uncomplicated malaria. The parasite densities were zero in all the patients after treatment. This study concluded that parasite densities did not correlate to disease severity.The levels of TNF-a (picogram per milliliter), were measured by ELISA and were found to be higher in patients than in the healthy controls (31.7±3.4/17.41±16-severe/uncomplicated malaria and 8.9±6.67 in the controls). No significant reduction in the levels was observed after three days of treatment. Levels of IL-10 in patients with uncomplicated malaria were not significantly higher as compared to those with severe malaria (602.56± 1,032.89 and 409.59±627.39 respectively). When compared to the healthy controls, the levels of IL-10 were significantly higher in the patients (602.56±1,032.89 and 409.59±627.39 (Uncomplicated /severe malaria) and 11.21±28.16 for the controls; P value <0.001). Furthermore, the levels of IL-10, after three days of treatment, significantly reduced. The levels of IL-12 were relatively similar in severe and uncomplicated malaria, and there was no significant difference when compared to the levels in the healthy controls. After treatment, the reduction in the levels of IL-12 was not significant. Finally, ICAM-1 (nanograms per milliliter) levels were significantly higher in the patients (447.43 ± 380.53 and 392.60 ±167.38) than in the healthy controls (196.06±125.19), P value < 0.001 and the levels in severe and uncomplicated malaria groups were.similar, P value was 0.88. After treatment, the levels of ICAM-1 remained unchanged in uncomplicated malaria, but not significantly reduced in severe malaria.In addition, there were correlations observed between serum cytokine (TNF-a, IL-10 and ICAM-I) levels and temperature as well as parasite density implying that cytokines may play an important role in the pathogenesis and diagnosis of malaria. These results also showed a significant association between parasite density and TNF- a (rho=0.23, p< 0.001), IL-10 (rho= 0.59, p< 0.05), IL-12 (rho= 0.21, p <0.05), ICAM-1 and parasite density (rho= 0.45, p=0.001), implying that when the parasite density was high, the mentioned cytokines were high. There was a significant association between TNF-a and Hb (rho= -024, p< 0.05), IL-10 (-0.43, p<0.001), showing that when Hb is low, the named cytokines were high.In conclusion, the null hypothesis of the study was rejected. This study has demonstrated relatively similar parasite densities in children with severe and uncomplicated malaria. The levels of TNF-a, IL-10, IL-12 and ICAM-1 were significantly raised in malaria as compared to the healthy controls. Finally, the observed correlations between cytokines and parasitaemia as well as temperature are suggestive of the pathogenetic role of cytokines in malaria.