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Pathological lesions observed in humans infected with Schistosoma mansoni are due to the eggs produced by the female parasite. Mevinolin, a potent inhibitor of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase, blocks egg production by this parasite. In this report, we demonstrate that cholesterol precursors, mevalonate and farnesol, stimulate egg production by the female parasite and that these precursors can reverse the mevinolin-induced inhibition of egg production. Because the parasite cannot synthesize cholesterol, we incubated parasites in a culture media containing radiolabeled acetate with and without mevinolin. We isolated nonsterol lipids from the parasite and observed that mevinolin dramatically reduced the conversion of acetate into the polyisoprenoid (dolichols) lipids of the parasite. Dolichols and other nonsterol lipids did not stimulate egg production. HMG-CoA reductase activity was observed in homogenates of the parasite and was inhibited by mevinolin (Ki = 52 nM), but its activity was tripled when the parasite was chronically exposed to low doses of the drug. Parasites with increased reductase activity produced five to six times more eggs. Lastly, chronic administration of large doses of mevinolin to infected mice resulted in a marked reduction of the pathology associated with the infection. These results suggest that egg production in S. mansoni is associated with the parasite's HMG-CoA reductase activity and that a nonsterol lipid produced in the biochemical pathway regulated by this enzyme stimulates egg production.

In a field study of two villages in the Gezira, an area of the Sudan endemic for Schistosoma mansoni, liver ultrasonography was used to detect subjects with Symmers' hepatic periportal fibrosis, some of whom underwent oesophagoscopy to detect oesophageal varices. The prevalence of oesophageal varices in subjects undergoing oesophagoscopy was 54 per cent and 67 per cent respectively, occurring mainly in males aged about 30 years. The varices were usually asymptomatic. Symptomatic varices (with a positive history of haematemesis) occurred in 4 per cent and 3 per cent respectively of subjects with sonographic evidence of liver periportal fibrosis. By detecting oesophageal varices in an asymptomatic phase, hepatic ultrasonography and fibreoptic oesophagoscopy may elucidate the natural history of the varices and their response to periodic anti-schistosomal chemotherapy.

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