Research Project
3129656
The overall aim of the proposed study is to confirm and extend the study of the occurrence of drug-resistance involving schistosomiasis in Brazil as reported previously. Schistosoma Mansoni eggs will be obtained from feces collected previously by physicians from patients showing incomplete cures after therapy with antischistosomal drugs in clinics and hospitals in the BeloHorizonte region of Brazil. Miracidia from the isolated eggs will be used to expose Biomphalaria glabrata (BeloHorizonte strain) snails. Mice will be exposed to resultant cercariae. Mice with immature infections will be treated with either praziquantel, oxamniquin or oltipraz. From the efficacy of treatment in rodents, it can be ascertained what percentage of incomplete cures in patients are due to drug-resistant schistosomes and whether there is a direct correlation between percentage of cure and drug resistance, which would permit rapid surveys for resistance in the field. Since, however, there may no correlation and infection and treatment of rodents is time consuming and expensive, simpler tests for detection of drug-resistance in schistosomes which are currently under investigation will be evaluated as relevant. The response to other schistosomicides of any drug-resistant strains that are isolated in the present study will be determined to provide a logical basis for clinial therapy. The susceptability of two other species of Biomphalaria indigenous to Brazil will be determined. The data obtained may be useful in ascertaining if drug-resistant stains are capable of being transferred to other regions of Brazil by migrating persons. Isoenzyme patterns of drug-resistant and sensitive strains will be compared for purpose of detecting differences. To reduce the cost and labor of maintaining schistosome isolates that might be derived from the present study, an attempt will be made to cryopreserve schistosome sporocysts which could then be used to infect further snails by microsurgical transplantation. Cryopreserved, cloned sporocysts of drug-resistant schistosomes would be advantageous for future research concerning drug-resistance machanism from the genetical, pharmacological and biochemical aspects as well as evaluation of novel chemicals fo potential cross resistance.
