Plasmodium falciparum appears to have a particular propensity to involve the brain but the burden, risk factors, and full extent of neurological involvement have not been systematically described. The objective of the study was to determine the incidence and describe the clinical phenotypes and outcomes of neurological involvement in African children with acute falciparum malaria. A review of records was done of all children younger than 14 years admitted to a Kenyan district hospital with malaria from January 1992 through December 2004. Neurological involvement was defined as convulsive seizures, agitation, prostration, or impaired consciousness or coma. The main outcome measures were the incidence, pattern, and outcome of neurological involvement. Of 58,239 children admitted, 19,560 (33.6%) had malaria as the primary clinical diagnosis. Neurological involvement was observed in 9313 children (47.6%) and manifested as seizures (6563/17,517 [37.5%]), agitation (316/11,193 [2.8%]), prostration (3223/15,643 [20.6%]), and impaired consciousness or coma (2129/16,080 [13.2%]). In children younger than 5 years, the mean annual incidence of admissions with malaria was 2694 per 100,000 persons and the incidence of malaria with neurological involvement was 1156 per 100,000 persons. However, readmissions may have led to a 10% overestimate in incidence. Children with neurological involvement were older (median, 26 [interquartile range {IQR}, 15-41] vs 21 [IQR, 10-40] months; P<.001), had a shorter duration of illness (median, 2 [IQR, 1-3] vs 3 [IQR, 2-3] days; P<.001), and a higher geometric mean parasite density (42.0 [95% confidence interval {CI}, 40.0-44.1] vs 30.4 [95% CI, 29.0-31.8] x 10(3)/microL; P<.001). Factors independently associated with neurological involvement included past history of seizures (adjusted odds ratio [AOR], 3.50; 95% CI, 2.78-4.42), fever lasting 2 days or less (AOR, 2.02; 95% CI, 1.64-2.49), delayed capillary refill time (AOR, 3.66; 95% CI, 2.40-5.56), metabolic acidosis (AOR, 1.55; 95% CI, 1.29-1.87), and hypoglycemia (AOR, 2.11; 95% CI, 1.31-3.37). Mortality was higher in patients with neurological involvement (4.4% [95% CI, 4.2%-5.1%] vs 1.3% [95% CI, 1.1%-1.5%]; P<.001). At discharge, 159 (2.2%) of 7281 patients had neurological deficits. Neurological involvement is common in children in Kenya with acute falciparum malaria, and is associated with metabolic derangements, impaired perfusion, parasitemia, and increased mortality and neurological sequelae. This study suggests that falciparum malaria exposes many African children to brain insults.

Many anti-bacterial drugs inhibit growth of malaria parasites by targeting their bacterium-derived endosymbiotic organelles, the mitochondrion and plastid. Several of these drugs are either in use or being developed as therapeutics or prophylactics, so it is paramount to understand more about their target of action and modality. To this end, the authors measured in vitro growth and visualized nuclear division and the development of the mitochondrion and apicoplast in Plasmodium falciparum treated with five drugs targeting bacterial housekeeping pathways. This revealed two distinct classes of drug effect. Ciprofloxacin, rifampicin, and thiostrepton had an immediate effect: slowing parasite growth, retarding organellar development and preventing nuclear division. Classic delayed-death, in which the drug has no apparent effect until division and reinvasion of a new host by the daughter merozoites, was only observed for two drugs: clindamycin and tetracycline. These cells had apparently normal division and segregation of organelles in the first cycle but severe defects in apicoplast growth, subtle changes in the mitochondrion and a failure to complete cytokinesis during the second cycle. In two cases, the drug response in P. falciparum directly conflicted with reported responses for the related parasite Toxoplasma gondii, suggesting significant differences in apicoplast biology between the two parasites.