Pathophysiology of Severe Malaria in Children: Clinical and Laboratory Correlations

Abstract

Background Despite the programmes of malaria control the incidence of mortality from severe malaria (SM) continues to rise. This is mainly attributable to the fact that the pathophysiological mechanisms are still not clearly defined. Objectives This project investigated the endocrine and paracrine aspects of the pathophysiology of SM in children. The study monitored relevant clinical and laboratory parameters of SM cases on admission so as to identify and correct life threatening changes. Patients and Methods This is a cross sectional study conducted at Wadmedani Paediatric Hospital from September 2007 to September 2008. Fifty six Children with SM, identified according to WHO criteria, were included in the study. Thirty one children with uncomplicated malaria (UM) were included for comparison. Both groups underwent a history and physical examination. Investigations included: parasitemia, Hb, RBG, TWBC, liver enzymes, bilirubin, urea, creatinine, sodium, potassium and cytokines (TNF-α, IFN-γ, IL-10). Statistical analysis was carried out with SPSS for windows. Means were analyzed by student’s T test. Correlations were analyzed using χ2 tests, Pearson's correlation coefficient and Spearman' rank correlation coefficient tests. Assessments of prognostic factors were conducted with regression model. P values < 0.05 were considered significant. Results Children with SM were younger than those with UM (mean age=56.75 months compared to 82.71 months, P value= 0.001). V A significant difference was found in the mean RBG between children with SM and UM (89.27±39.06 compared to 108.06±39.14 mg/dl respectively) P value= 0.035 as well as in the mean Hb (7.54±2.71 compared to 9.91±1.67 mg/dl respectively, P value= 0.000). The pattern and cytokines secretion levels showed higher mean TNF-α in children below 5 years old and in children with CM. Those above 5 years had higher IFN-γ which was found to correlate positively with Hb, RBG, splenomegaly and hepatomegaly. Children with SA had a lower IFN-γ and IL-10 when compared to UM. Conclusions SA may result from haemolysis of red blood cells, low level of IFN-γ and IL-10. Glucose consumption by the parasites and low IFN-γ may be the causes of hypoglycemia. CM, mixed presentation, young age and hyperkalaemia were independently associated with increased risk of morbidity and mortality. High bilirubin, high TWBCs counts, high urea, high creatinine, low Hb and low RBG were significantly associated with CM and mixed presentation.