Severe malaria in children Glucose homeostasis and laboratory indicators of patients at risk

Abstract

Back Ground Severe and complicated Plasmodium falciparum infections continue to threaten the survival of young children in sub-Saharan Africa. A reduction in the mortality and morbidity may only come about by better understanding of the pathophysiological processes that are responsible for the manifestation of severe malaria. Hypoglycemia is a frequently encountered complication in falciparum malaria that is usually ascribed to increased glucose uptake and impaired glucose production caused by the inhibition of gluconeogenesis. This study sets out to examine the pathophysiological aspects of severe malaria in children related to blood glucose homeostasis, prevalence and possible causes of hypoglycaemia in severe malaria. It also examines clinical indicators and laboratory parameters associated with severe malaria in children, so as to propose appropriate laboratory tests as indicators for high risk children with severe malaria. Patients and Methods This is a cross- sectional cohort study based on clinical presentations and laboratory findings. It was conducted at Khartoum Paediatric and Bashaeir Hospitals during the period September 2006 to September 2007. The total number of patients with malaria included in this study and confirmed by thin and thick blood films were 80 patients. Children from 0 to 12 years with Plasmodium falciparum infection were included in the study using the WHO inclusion criteria for severe malaria (45 children). For comparison a matched group of uncomplicated malaria was studied (35 children). All patients underwent a complete clinical examination with general and systemic examination by a medical doctor in hospital. Five ml of venous blood were taken from each patient in both groups on admission after informed consent. All laboratory investigations were done on blood samples collocted before treatment. Hb, K+, Random blood glucose, insulin, C-peptide, urea and the serum amino acids were measured in both groups of patients. Results 11 Children with severe malaria were younger (mean age, 4.7years) compared to those with uncomplicated malaria (mean age, 8.1years). Hypoglycaemia was an uncommon complication; it was found only in two patients, (4.4%) of patients with severe malaria. No difference was found in random blood glucose levels in children with severe and uncomplicated malaria (99.58 and 96.18 mg/dl respectively). The mean insulin level was significantly lower in patients with severe malaria 5.31 mIU/L, compared with the mean in the uncomplicated malaria group 8.59 mIU/L (P, 0.01). The mean of C-peptide was nearly equal between the two groups and no significant difference was found. However the incidence of hypoinsulinaemia in severe malaria was significantly higher (P, 0.002). Hypokalaemia was found to be common in both groups but the incidence was much higher in patients with uncomplicated malaria. Arginine concentrations were low in individuals with severe malaria (25.63μmol/l) and uncomplicated malaria (29.79μmol/l). Arginine was significantly lower in severely anaemic patients (19.3 μmol/l) compared with uncomplicated malaria (29.79μmol/l). But it was also found that most of the amino acids were consistently lower in patients with anaemia. Glucogenic amino acids did not show differences between the two groups. Phenylalanine was significantly higher in severe malaria than uncomplicated malaria (P =0.001), particularly in cerebral malaria. Large neutral amino acids (except tryptophane) were significantly higher in patients with cerebral malaria. Children who had convulsions did not show any significant difference in the mean of amino acids except for Phenylalanine which was significantly higher; but not to the extent found in cerebral malaria. Conclusions: Hypoglycaemia was an uncommon complication in this study. The study suggests unimpaired gluconeogenesis in severe and uncomplicated malaria except for the two patients with hypoglycaemia. Insulin levels were significantly low in the severe malaria group compared with uncomplicated malaria. As C-peptide did not show a difference between the two groups. This study suggests a decreased half life of insulin in severe malaria. Arginine concentrations were low in individuals with severe and 12 uncomplicated malaria which indicates reduced NO production and therefore reduced killing of patients. Large neutral amino acids and in particular phenylalanine were significantly higher in CNS involvement and may be part of the pathogenesis of cerebral malaria.