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LETTER TO THE EDITOR

ROLE OF FOLATE DEFICIENCY IN THE PATHOGENESIS OF RETINAL AND CEREBRAL HEMORRHAGES IN CEREBRAL MALARIA

Dear Sir:

We thank Dr. Eisenhut for his interest in our review of malarial retinopathy¹ and for suggesting the hypothesis that reduced folate levels may contribute to the production of retinal hemorrhages in cerebral malaria. Retinal hemorrhages are one component of malarial retinopathy, the other main ones being retinal whitening, vessel changes, and papilledema.

The morphology of retinal hemorrhages is different in the two conditions. The retinal hemorrhages seen in folate deficiency are multiple blot and flame hemorrhages. In cerebral malaria, the retinal hemorrhages are predominantly white-centered round hemorrhages, similar to Roth spots. In cerebral malaria the retinal hemorrhages, and the typical cerebral ring hemorrhages, often have fibrin thrombi in the small vessel at their center.² It therefore seems unlikely that folate deficiency has a central role in the pathogenesis of retinal hemorrhages in cerebral malaria, although further research would be necessary to establish this.

We would like to clarify the relationship between anemia and cerebral malaria. Within the group of patients with strictly defined cerebral malaria (including severe anemia), the number of retinal hemorrhages correlates to the degree of anemia. However, within the group defined as severe malarial anemia (excluding cerebral malaria), there are far fewer retinal hemorhages.³ The pathogenesis of retinal hemorrhage in cerebral malaria seems to be associated with the presence of coma, and only then anemia. Because Olumese and others used fundoscopy through undilated pupils, they would have only been able to see a small proportion of the total number of retinal hemorrhages present in the patients they studied.⁴

Given the presence of sequestered parasitized red blood cells, vessel endothelial changes, and hematologic derangement in cerebral malaria, there are many predisposing factors for retinal and cerebral hemorrhage.

1. Beare NA, Taylor TE, Harding SP, Lewallen S, Molyneux ME, 2006. Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg 75: 790–797.[Abstract/Free Full Text]
2. White VA, Lewallen S, Beare N, Kayira K, Carr RA, Taylor TE, 2001. Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans R Soc Trop Med Hyg 95: 618–621.[Web of Science][Medline]
3. Beare NA, Southern C, Chalira C, Taylor TE, Molyneux ME, Harding SP, 2004. Prognostic significance and course of retinopathy in children with severe malaria. Arch Ophthalmol 122: 1141–1147.[Abstract/Free Full Text]
4. Olumese PE, Adeyemo AA, Gbadegesin RA, Walker O, 1997. Retinal haemorrhage in cerebral malaria. East Afr Med J 74: 285–287.[Web of Science][Medline]

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