Genetic analysis of praziquantel resistance in Schistosoma mansoni.

To determine the genetic basis of the resistance of Schistosoma mansoni to praziquantel (PZQ) and to understand whether the resistance is dominant or recessive trait, a schistosome cross was undertaken between a PZQ-susceptible and a PZQ-resistant isolate using infections of the single-sex cercariae which were identified by a direct W1-specific PCR technique. The resistances of F1 and F2 generation to PZQ were evaluated using in vitro egg, miracidial and cercarial tests. The F1 hybrid progeny from crosses between the susceptible and resistant isolates were resistant to PZQ. The resistant phenotype reappeared in the F2 progeny. It can thus be considered that the PZQ resistance behaves like a dominant trait.

Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents

The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K) to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquire, and praziquantel) were evaluated in infected female Swiss albino mice. These schistosomal isolates had been maintained in the laboratory without further drug pressure for 20 to 30 generations. Multiple dosage regimens were used for each drug against each isolate of S. mansoni to generate ED50 (effective dose 50%) values. Results demonstrated that the K isolate is resistant to niridazole, the MPR-1 isolate to oxamniquine, and the MAP isolate to both hycanthone and oxamniquine. The BH isolate was susceptible to all drugs and was used as the reference isolate. All isolates were susceptible to praziquantel. The significance of the difference in response of the MPR-1 and MAP isolates is discussed. These results confirm the resistance of these isolates of S. mansoni of three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs

Rate of action of Schistosomicides in mice infected with Schistosoma mansoni

Camundongos infectados experimentalmente com Schistosoma mansoni foram tratados por via oral com dose única de 125 ou 250 mg/Kg de oltipraz, 50 ou 100mg/Kg de oxamniquine, e 200 ou 400mg/Kg de praziquantel. O número de vermes e alteraçäo do oograma foram determinado entre a 1ª e a16ª semanas após o tratamento. O tempo necessário para observar o máximo de atividade da droga foi de 1 semana para o praziquantel, 2 semanas para o oxamniquine e 8 semanas para o olipraz. Alteraçöes do oograma persistiram durante o período de observaçäo, embora recidiva tenha sido detectada, já na 4ª semana, com as drogas utilizadas

Variation in response of Schistosoma mansoni strains to Schistosomicides

A cepa BH de S. mansoni foi suscetível ao hycanthone (1 X 80 mg/Kg), oxamniquine (1 X 100 mg/Kg), niridazole (5 X 100 mg/Kg), praziquantel (1 X 100 mg/Kg), oltipraz (5 X 125 mg/Kg) e amoscanato (1 X 300 mg/Kg). Assim, essa cepa do trematódeo é importante como referência nos estudos de quimioterapia experimental. Por outro lado, a cepa MPR-1 apresentou resistência ao oxamniquine e/ou hycanthone. Foi possível constatar em uma cepa resistência parcial ao oltipraz

Strain variation in the infectivity of Schistosoma mansoni for Biomphalaria glabrata

Com duas linhagens de Biomphalaria glabrata foi estudada a suscetibilidade de cinco cepas de Schistosoma mansoni resistentes e suscetíveis a esquistossomicidas. Três cepas do trematódeo oriundas de Porto Rico apresentaram desenvolvimento mais lento e menor índice de infecçäo em B. glabrata brasileira quando comparados com o comportamento de duas cepas de S. mansoni provenientes do Brasil. Por outro lado, as cepas brasileiras do parasita desenvolveram bem e infectaram mais de 90% dos exemplares de B. glabrata portorriquenhos. Entre os resultados, ressalta-se que cepas resistentes a esquistossomicidas poderäo ser utilizadas por pacientes em diferentes áreas geográficas como Brasil e Porto Rico

Drug resistance in Schistosomiasis: a review

Drug resistance associated with the treatment of human schistosomiasis appears to be an emerging problem requiring more attention from the scientific community than the subject currently receives. Drug-resistant strains of Schistosoma mansoni have been isolated by various investigators as a result of laboratory experimentation or from a combination of field and laboratory studies. Review of this data appears to indicate that the lack of susceptibility observed for some of the isolated strains cannot be ascribed solely to previous administration of antischistosome drugs and thus further studies are required to elucidate this phenomena. Strains of S. mansoni have now been identified from Brazil which are resistant to oxamniquine, hycanthone and niridazole; from Puerto Rico which are resistant to hycanthone and oxamniquine; and from Kenya which are resistant to niridazole and probably oxamniquine. Strains derived by in vitro selection and resistant to oxamniquine and possibly to oltipraz are also available. All of these strains are currently maintained in the laboratory in snails and mice, thus providing for the first time an opportunity for indepth comparative studies. Preliminary data indicates that S. haematobium strains resistant to metrifonate may be occurring in Kenya. This problem could poise great difficulty in the eventual development of antischistosomal agents. Biomphalaria glabrata from Puerto Rico and Brazil were found to be susceptible to drug-resistant S. mansoni from each country.