Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes of Schistosoma mansoni.
There is a pressing need to develop novel anti-schistosomal drugs, as current treatment relies largely on praziquantel (PZQ). To further strengthen current evidence of the anti-schistosomal properties of mefloquine (MQ), we studied the temporal effect of this compound in vitro and in vivo, and examined alterations on the tegumental surface of schistosomula and adults of S. mansoni by means of scanning electron microscopy (SEM). Schistosomula and adults were each incubated in vitro using MQ over a wide concentration range (1-100 microg/ml). In addition, mice infected with adult S. mansoni were treated with a single oral dose of 400 mg/kg MQ, and worms were recovered 24, 48, 72, 96 and 120 h following treatment. MQ showed a rapid onset of action on schistosomula in vitro; 100 and 75 microg/ml of MQ killed schistosomula immediately; the minimal lethal and effective concentrations of MQ on schistosomula after 1 h were 25 and 5 microg/ml, respectively. Adult worms incubated with 100 and 10 microg/ml of MQ were dead after 1 h and 24 h of incubation, respectively. A hepatic shift of adult schistosomes was observed in mice already 24 h after treatment, and 120 h following treatment >98% of all worms had translocated to the liver. SEM observations revealed extensive tegumental destruction, including blebbing, shrinking and sloughing, particularly following in vitro incubation and on the tegument of female worms.
Manneck
T
T
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, CH-4002 Basel, Switzerland.
Haggenmüller
Y
Y
Keiser
J
J
D000825:Animal Structures / Q000187:drug effects; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects; D008109:Liver Diseases, Parasitic / Q000188:drug therapy / Q000469:parasitology; D015767:Mefloquine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008855:Microscopy, Electron, Scanning; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology
D000871:Anthelmintics; D015767:Mefloquine