The Oogram in the Study of Relapse in Experimental Chemotherapy of Schistosomiasis Mansoni

Abstract

The percentage of viable eggs in the different stages of development (oogram), as determined in intestinal fragments of mice experimentally infected with S. mansoni, proved a simple and reliable criterion for the study of relapse after chemotherapy. In mice treated with Ciba's 17'581 thioxanthone (300 mg/kg, orally, for 3 consecutive days), the percentage of immature eggs in the intestinal wall gradually decreased and from the 7th day on all viable eggs were mature. Eggs of the first stage were not found after the 2nd day of treatment. No resumption of egg laying was detected until the 20th day. In mice treated with Astiban (Antimony III, dimercaptosuccinate, sodium salt; 150 mg/kg, intraperitoneally, for 7 consecutive days), a gradual decrease in the percentage of immature eggs was also observed, and on the 9th day after start of treatment all viable eggs were mature. However, when treatment was discontinued, oviposition in the intestinal wall was resumed a few days later. On the 11th day, the percentage of immature eggs, mostly of the first stage, was about 40% and on the 21st day had reached 90%. It has been shown that Schistosoma mansoni eggs are immature when laid and that a period of about 6 days is needed for the embryo to develop (Gonnert, 1955; Prata, 1957; Pellegrino et al., 1962). Since egg laying begins approximately 30 days after infection, all the stages of viable eggs are found in the intestinal wall from the 40th to the 45th day. When mice infected with S. mansoni are treated with active drugs, there occurs in the intestinal wall a progressive decrease in the number of eggs as well as an alteration in the percentage of viable eggs in the different stages of development. These changes are brought about by the interruption of oviposition in the intestinal wall and by the maturation of viable eggs already present. It has also been shown that changes in the percentage of the different stages of viable eggs in the intestinal wall (oogram) provide a simple, sensitive, and Received for publication 15 January 1963. * The present study was aided by a grant from F. Hoffmann-La Roche & Company, Basle, Switzerland. t Address: Instituto de Biologia, Faculdade de Filosofia, Rua Carangola 288, Belo Horizonte, Brazil. 1 Fellow from the Conselho Nacional de Pesquisas, Brazil. reliable criterion for the screening of drugs in experimental schistosomiasis mansoni in mice (Pellegrino et al., 1962). When treatment does not succeed in killing the schistosomes, reappearance of eggs in the intestinal wall and feces is linked with a series of changes in the worms, including restoration of muscle tone, regeneration of the reproductive organs, pairing of males and females, and their migration from liver to mesenteric veins. The study of this relapse phenomenon is of great value in the chemotherapy of schistosomiasis and for the study of the mechanism of drug action. Changes in the distribution of schistosomes in the hepatic portal system and the presence of eggs of S. mansoni in the feces are the criteria generally used in experimental investigation of relapse (Standen, 1953). In the present paper, the value of the oogram method for such a study in mice experimentally infected with S. mansoni is discussed. MATERIALS AND METHODS Infection of animals: Laboratory-reared Australorbis glabratus, experimentally infected with S. mansoni, were placed in a beaker containing dechlorinated water and left under an electric lamp for about 1 hr, after which time the snails were removed. The water containing cercariae was filtered through surgical gauze to remove snail