Rethinking cerebral malaria pathology.
OBJECTIVE
Intense interventions are ongoing to combat malaria. Malaria mortality investigation remains as an intense area of study with controversies, competing models of pathogenesis, and a few carefully proceeding clinical trials. This review suggests a reframing of the question of cerebral malaria pathology in light of recent findings to focus on dissection of pathogenesis that will lead to effective treatments.


RESULTS
Pediatric and adult manifestations of cerebral malaria within the retina allows for intense study of the clinical defined patients including the advent of multiple imaging modalities in endemic regions. Basic pathogenesis in mouse models and human studies, focused on cytokines, inflammation, cytoadherence, and endothelial activation, continues to be elucidated molecule by molecule. Coagulation is variably important and may serve as one of several unifying principles of current pathogenesis models. Parasite-derived molecules - surface or soluble - remain necessary but not sufficient to explain pathologic manifestations.


CONCLUSIONS
As we close the gaps in the fight against global malaria, the question of cerebral malaria mortality remains a source of great concern. We currently have no effective means of reversal of coma or impacting mortality in the comatose patient. As transmission is broken, cerebral malaria will spread to older age groups in Africa where we expect mortality will be higher. Continued directed study of pathogenesis with the primary goal of efficacious interventions in the comatose is a necessity.
Milner
Danny A
DA
The Brigham and Women's Hospital, Boston, Massachusetts, USA. dmilner@partners.org
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D016779:Malaria, Cerebral / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D051379:Mice; D010961:Plasmodium / Q000276:immunology* / Q000472:pathogenicity*