Chemotherapeutic effects on larval stages of Schistosoma mansoni during infection and re-infection of mice Efeitos da quimioterapia nos estágios larvais do Schistosoma mansoni durante infecção e re-infecção de camundongos

The sensitivity of the larval stages of Schistosoma mansoni to chemotherapy with praziquantel and oxamniquine was tested in mice during primary and secondary infections and after different intervals from cercarial exposure. Worm recovery by perfusion of the porto-mesenteric system, followed by counting and a morphometric study of the parasite, allowed the conclusion that the relative resistance of the larval stages of S. mansoni to schistosomicide drugs, demonstrated in primary infections, also persists when the host is already infected. This indicates that a therapeutic failure may result when an infected host is treated some time after being re-infected, because of the presence of migrating, drug-resistant, immature forms of the parasite. Key-words: Schistosoma mansoni. Larval stages. Praziquantel. Oxamniquine. Resumo A susceptibilidade dos estágios larvais do Schistosoma mansoni aos esquistossomicidas praziquantel e oxamniquine foi testada em camundongos durante infecção primária ou secundária, e após diferentes intervalos de tempo após a exposição cercariana. A avaliação foi feita pela contagem dos vermes após recuperação destes por perfusão do sistema porto-mesentérico e pelo estudo morfométrico dos mesmos. O estudo revelou que a relativa resistência das formas larvais aos esquistossomicidas, já demonstrada em infecção primária, persiste no caso de hospedeiros já infectados. Este fato indica que uma falha terapêutica pode resultar quando o tratamento é feito em hospedeiros re-infectados recentemente, em virtude dos mesmos apresentarem formas migrantes e imaturas do parasita, as quais são particularmente resistentes aos esquistossomicidas. Palavras-chaves: Schistosoma mansoni. Estágio Larval. Praziquantel. Oxamniquine. 1. Laboratório de Patologia Experimental do Centro de Pesquisas Gonçalo Moniz da Fundação Oswaldo Cruz, Salvador, BA, Brazil. 2. Laboratório de Imunopatologia do Centro de Pesquisas Aggeu Magalhães da Fundação Oswaldo Cruz, Recife, PE, Brasil. Financial support: PRONEX Address to: Dr. Zilton Andrade. Rua Waldemar Falcão 121 Brotas, 40295-001 Salvador, BA, Brasil. e-mail:[email protected] Recebido para publicação em 27/7/2002 Aceito em 26/2/2003 Oxamniquine and praziquantel are the two drugs used in Brazil for the treatment of schistosomiasis. Large scale treatment programs using either drug have been carried out in several Brazilian endemic areas 11 . Treatment efficacy is considered satisfactory, but failures have been registered with variable frequency. Such therapeutic failures are often attributed to the development of drug resistance by the worms and to early post treatment re-infection 6 . However, in areas of high transmission, another possibility may occur. Treated individuals, even though apparently cured, may re-establish the infection in consequence of the existence of migrating larval forms of Schistosoma mansoni, which are usually resistant to chemotherapy, as experimentally demonstrated . Sabath et al16 have shown that schistosomula are far less susceptible than adult worms to six schistosomicides at curative doses, including praziquantel and oxamniquine. However, these studies were performed in mice with experimental primary infections treated at different points of time after cercarial exposure. Since the effect of chemotherapy is influenced by the immune state of the host3 4 15, the response of the larval stages of S. mansoni to schistosomicides should also be tested during reinfection. The present investigation studied the effects of oxamniquine or praziquantel on different larval stages of S. mansoni in mice with primary infection compared to mice submitted to re-infection.