Abstract
BackgroundIn spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls.Methods and FindingsChildren with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later.ConclusionsIn children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative ‘cerebral malaria’ cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.
Highlights
Falciparum malaria is one of the commonest potentially fatal infections in sub-Saharan Africa
In children with malaria plasma von Willebrand factor (VWF) and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery
High levels of both markers occur in retinopathy-negative ‘cerebral malaria’ cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity
Summary
Falciparum malaria is one of the commonest potentially fatal infections in sub-Saharan Africa. Most deaths from malaria occur in young children living in areas of intense Plasmodium falciparum transmission. African children bear 90% of the brunt of mortality from falciparum malaria, with high case fatality rates in children with cerebral malaria even with good treatment [1]. Falciparum malaria is a major cause of morbidity and mortality in Malawi in children under the age of five. Children in Blantyre district, where transmission is stable and intense, suffer on average 2.8 symptomatic malaria episodes per year while adults, though still susceptible to infection, are less likely to have symptomatic disease [3]. In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls
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