Search

The efficacy of 3 doses (10, 15 and 20 mg/kg) of the new antischistosomal drug Ro 15-5458 (10-[2-(diethylamino)ethyl]-9-acridanone-(thiazolidin-2-ylidene)hy drazone, CAS 092928-47-7) against an Egyptian strain of S. mansoni was studied in mice. The effect of duration of infection on the response of mice to treatment with 20 mg/kg was evaluated at 7 and 12 weeks after infection. The criteria used for the assessment of drug efficacy were: worn count and distribution in the liver and portomesenteric system, oogram changes in the small intestine, estimation of the number of ova/g stood, liver and intestine and histopathological examination of mice liver. Data revealed a dose dependent decrease in number of adult worms and number of ova/g stool, liver and intestine. A reduction of 83.6, 89.4 and 94.9% in mean number of schistosomes compared to control was recorded following treatment with 10, 15 and 20 mg/ kg of the drug, respectively. Oogram changes were more remarkable following treatment with 20 mg/kg as evidenced by complete disappearance of all immature stages. Treatment with Ro 15-5458 in a dose of 20 mg/kg resulted in complete disappearance of couples and 100% shift or worms to the live. Examination of mice liver 2 weeks post treatment revealed on changes in pathology following treatment with 10 mg/kg compared to control. Treatment with 20 mg/kg gave better results comparable to 15 mg/kg, a decreased number and size of granulomas with minimal areas of necrosis was observed. Parasitological cure was effectively achieved when treatment was initiated 7 or 12 weeks post infection. However, histopathological data revealed that the earlier the treatment the better the results.

The in vivo effects of oxamniquine on the tegumental surface of adult Schistosoma mansoni were studied using scanning electron microscopy. Pronounced tegumental alterations were observed in all worms including marked oedema, wrinkling and distortion, atrophy, loss of tone and complete disorganization of suckers, blebbing, destruction of tubercles, collapse of sensory papillae and erosion or peeling of the surface layer. The amount of damage was more marked in males than females and varied considerably among worms recovered from the same host and even in different regions of the same worm. Damage was irreversible and all worms were eventually eliminated.

Levamisol which is highly effective against Ascaris infections, was shown to produce degenerative changes in the intestine and the reproductive system of the worm. Worms that were not expelled by treatment produced only nonviable eggs which could not develop in vitro. Levamisol is thus shown to be not only a highly curative drug, but a compound of significant epidemiological importance.

The response of mice infected with Schistosoma mansoni to a novel environment has been investigated in an attempt to study the effects of the disease on brain cognitive function by using opto-varimix instrument and autotrack computer program. Two to 18 weeks infected mice showed lower ambulatory activities than their matched controls with the largest reduction occurring between weeks 6 to 10. Maximum effects were observed in week 8. The first 5 minutes of ambulatory activities, designated as the "first session", were 22.3% lower in infected mice as compared with controls. The decline in the first session activities of infected mice was slower than the controls. Infected mice showed fewer stereotype movements with maximum reduction in week 16 of infection. There was no correlation between mice ambulatory activities or stereotype movements and infection duration. The importance of these findings in relation to the course of the disease and the underlying mechanism(s) are discussed.

By means of electrophoresis quantitative estimation of serum protein components were made at various intervals before and after treatment with oxamniquine. During infection of mice with S. mansoni serum protein fractions showed marked alterations. Significant increase of total protein, alpha-2 globulin and beta globulin started at week 4 and alpha-1 globulin and gamma globulin at week 6. The significant decrease of globulins at week 6 resulted in reduced albumin globulin ratios. Some of these changes developed during maturation of worms and became more evident with initiation of egg deposition. The possible cause of these variations and their significance were discussed. Oxamniquine treatment of infected mice inhibited such alterations. Administration of the drug to normal mice was followed by temporary increase of serum albumin.

The therapeutic efficiency of oxamniquine against the local strain of Schistosoma mansoni was investigated in experimentally infected mice. The drug was administered orally using a human-equivalent dose of 20 mg kg-1 day-1 for 3 consecutive days (total dose of 60 mg kg-1). Oxamniquine proved to be very effective as indicated by hepatic shift, oogram changes, complete elimination of adult worms and eradication of faecal eggs.