Am. J. Trop. Med. Hyg., 76(5), 2007, pp. 793
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene
LETTER TO THE EDITOR
ROLE OF FOLATE DEFICIENCY IN THE PATHOGENESIS OF RETINAL AND CEREBRAL HEMORRHAGES IN CEREBRAL MALARIA
Michael Eisenhut
Luton and Dunstable Hospital
Lewsey Road
Luton LU40DZ, United Kingdom
Telephone: 44-804-5127-0127
E-mail: Michael_eisenhut{at}yahoo.com
Dear Sir:
A recent study reported that retinopathy is a characteristic feature of cerebral malaria caused by Plasmodium falciparum.1 Severity of retinopathy was related to risk of death and duration of coma in survivors. One characteristic feature of malaria related retinopathy were hemorrhages, which were present in 46% of patients with cerebral malaria. A previous study showed that the number of retinal hemorrhages correlated with the number of cerebral hemorrhages.2
Recently, a case of dietary folate deficiency associated with bilateral retinal hemorrhages was reported,3 which confirmed previous similar observations.4 Congenital folate deficiency due to a homozygous mutation in the methylenetetrahydro-folate reductase (MTHFR) gene has been associated with cerebral hemorrhages. Folate levels were significantly lower in patients homozygous for this mutation and cerebral hemorrhages compared with patients without and controls.5 An investigation of serum and cerebrospinal fluid (CSF) folate levels in patients with cerebral malaria showed significantly reduced levels compared with controls. After successful treatment of the acute malaria episode, CSF folate levels increased significantly.6 This may indicate that folic acid deficiency is involved in the pathogenesis of retinal and cerebral hemorrhages in cerebral malaria. The mechanism by which folic acid deficiency causes retinal and cerebral hemorrhages in malaria does not seem to involve anemia, which in itself is a well-established cause of retinal hemorrhages regardless of the etiology of anemia.7 Patients with retinal hemorrhages in cerebral malaria had the same packed red blood cell volume compared with patients with cerebral malaria without retinal hemorrhages,8 and patients with severe malarial anemia in another study had less severe retinopathy compared with patients with cerebral malaria.9 Electron microscopic studies of cerebrovascular endothelium in folate-deprived rats showed cytoplasmic swelling and mitochondrial degeneration in the endothelium and degenerative changes in the cerebrocortical microvascular wall,10 which may predispose to hemorrhages. Future research needs to investigate an association of folate deficiency and MRTHFR gene polymorphisms with retinal hemorrhages and disease severity in cerebral malaria.
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