Abstract
Over 90% of the world’s severe and fatal Plasmodium falciparum malaria is estimated to affect young children in sub-Sahara Africa, where it remains a common cause of hospital admission and inpatient mortality. Few children will ever be managed on high dependency or intensive care units and, therefore, rely on simple supportive treatments and parenteral anti-malarials. There has been some progress on defining best practice for antimalarial treatment with the publication of the AQUAMAT trial in 2010, involving 5,425 children at 11 centres across 9 African countries, showing that in artesunate-treated children, the relative risk of death was 22.5% (95% confidence interval (CI) 8.1 to 36.9) lower than in those receiving quinine. Human trials of supportive therapies carried out on the basis of pathophysiology studies, have so far made little progress on reducing mortality; despite appearing to reduce morbidity endpoints, more often than not they have led to an excess of adverse outcomes. This review highlights the spectrum of complications in African children with severe malaria, the therapeutic challenges of managing these in resource-poor settings and examines in-depth the results from clinical trials with a view to identifying the treatment priorities and a future research agenda.
Highlights
In many parts of the world malaria incidence has declined, in part due to substantial donor investment targeting the scaling up of insecticide-treated nets (ITN) and other vector control measures
The heaviest burden of P. falciparum malaria falls on sub-Saharan Africa, where children under five years old are disproportionately affected by this parasite (Figure 1)
Children typically present when they are critically ill with life-threatening complications yet, in most African hospitals, few will ever be managed on an intensive care unit or in a high dependency facility
Summary
Severe malaria is a complex multisystem disorder with a clinical presentation that has many similarities to severe bacterial sepsis, despite distinctive differences in pathogenesis. A prospective study of 1,844 paediatric hospital admissions with P. falciparum malaria in Kenya established that two clinical features, impaired consciousness (defined as coma or prostration) and respiratory distress (a clinical sign of metabolic acidosis), identified 84% of fatal cases. It is important to note that, in addition to those presenting with severe anaemia, this complication may develop during hospital admission especially in children with hyperparasitaemia [59], the frequent need to monitor Hb. The presence of respiratory distress increases case fatality (approximately 15%) rising to 40% if complicated by impaired consciousness [27,60]. High case fatalities of children with severe malaria anaemia has resulted in recommendations that the current transfusion guidelines be evidence-based and tested in a clinical trial [64,65]. The review concluded there was no evidence to support the use of dexamethasone in cerebral malaria, numbers involved were small and the assessment of complications in both trials was incomplete
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