New approach to the screening of drugs in experimental schistosomiasis mansoni in mice.

Abstract

Summary In mice experimentally infected with Schistosoma mansoni, oviposition starts round the 30th day of infection. Eggs are immature when laid and about 6 days are necessary for the embryo to reach the miracidial stage. A few days after maturation the eggs reach the intestinal lumen and are eliminated with the feces. Schistosomal elements (eggs, shell, parasitic nodules) found in the intestine of untreated mice infected with S. mansoni were described. When the percentage of schistosomal elements (oogram) between the 38th and the 70th day of infection was investigated, it was found that almost all of the elements were viable eggs (immature eggs of the 1st, 2nd. 3rd and 4th stages and mature ones). When mice infected with S. mansoni are given treatment with active drugs, there occurs, in the intestinal wall, a progressive change in the number of eggs and in the percentage of viable eggs of the different stages. This change is brought about by the interruption of oviposition in the intestinal wall and by the maturation of viable eggs already there. Changes in the oogram provide a simple, sensitive, and reliable criterion for the screening of drugs in schistosomiasis. The following method of screening drugs is recommended: (a) Mice weighing 16 to 18 g are infected subcutaneously with 80 to 100 S. mansoni cercariae; (b) from the 47th day of infection on, groups of four to six animals are given a 7-day treatment, using a daily dose-level of about ⅕ to ⅓ of LD50; (c) 3 days after completion of treatment, the animals are sacrificed and two or three fragments from the small intestine are microscopically examined. A drug is considered active when the corresponding oogram shows 50% or more mature eggs and absence of immature eggs of one or more developmental stages. The advantages of this method over the methods in current use for the screening of drugs in mice experimentally infected with S. mansoni are discussed.