Total depletion in liver store of vitamin a: a hitherto unrecognized nature of cerebral malaria

Abstract

Background Malaria accounts for more than one million deaths each year. We learn from textbook that Plasmodium falciparum sporozoites inoculated by Anophiline mosquito proliferate into schizonts inside liver cells, followed by hepatocyte eruption, releasing matured merozoites into circulation to parasitze erythrocytes. Little is ever questioned about role of vitamin A-storing hepatic stellate cells. Materials and Methods Fresh livers of patients (n=3) with cerebral malaria obtained from autopsy with informed consents were examined by fluorescence microscopy of 50 um-thick frozen sections for retinol contents, by Golgi silver impregnation for visualizing perisinusoidal stellate cells, and by oil red O for lipid stain. Control specimens (n=2) were derived from forensic autopsy without liver disorders. Results Under ultraviolet (330-385nm) exposure, normal human livers were observed with fluorescenc signals emitted from vitamin A storing stellate cells. They were uniformly bright and evenly distributed in the lobules, but absent in the portal and hepatic tracts. In malaria, autofluoresence was null; all liver sections of patients were nonfluorescent. Oil red O preparations demonstrated lipid droplets of stellate cells in control livers, but without lipid droplets in malarial livers. The latter exhibited stellate cells the appeared with abundant cytoplasmic processes, contrasting strongly with that of normal human. Discussion Without doubt, lack of autofluorescence in the livers reflects the absence of retinol storage in hepatic stellate cells. This study represents the first of its kind to examine malarial livers with fluorescence microscopy. Earlier studies reported that malaria patients have decreased serum retinol levels (Thurnham and Singkamani, 1991). Supplementation of vitamin A reduces morbidity due to P. falciparum (Shankar et al, 1999). Host resistance against malaria is potentiated with 9-cis-retinoic acid, a metabolite of vitamin A (Serghides and Kain, 2004). The body could be utilizing retinol rapidly to produce plasma membrane of red blood cells. Our study suggests strongly that liver store of vitamin A is probably a prime indicator in determining the resistance or tendency to develop sever malaria. This also implies the prophylactic/therapeutic use of vitamin A to safeguard susceptible population in endemic areas is justified. (Supported by RBD Project #4703).