title: First insight into the effect of single oral dose therapy with artemisinin-naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection.
abstract: Praziquantel is the current drug of choice against schistosomiasis. The dependency on praziquantel exclusively is problematic, given the spread of the disease and the threat of drug resistance. This study investigates an alternative antischistosomal drug using the compound naphthoquine phosphate tablet, which is a novel single oral dose antimalarial drug, containing a combination of naphthoquine phosphate and artemisinin. In the present study, the therapeutic efficacies of different artemisinin-naphthoquine phosphate combination-dosing protocols were evaluated in experimentally infected mice harbouring juvenile or adult stages of Schistosoma mansoni (Egyptian strain). The study shows that the oral administration of artemisinin-naphthoquine phosphate combination in a single dose of 400 mg/kg on day 7 p.i. resulted in a significant worm burden reduction of 95.07%. When used at a dose of 600 mg/kg on day 21 p.i., all female worms were killed before depositing eggs, resulting in complete absence of eggs in hepatic and intestinal tissues. The same dose given on day 42 p.i. reduced total and female worm burdens by 93.36% and 94.17%, respectively. In addition, artemisinin-naphthoquine phosphate combination induced significant reductions of 80.18% and 76.73% in the hepatic and intestinal tissue egg loads, respectively. Artemisinin-naphthoquine phosphate combination also induced significant alterations in the oogram pattern with elevated levels of dead eggs. Antipathological activities were evident in the amelioration of hepatic granulomata. Our findings hold promise for the development of a novel antischistosomal drug using an artemisinin-naphthoquine phosphate combination. Further in vitro and in vivo studies should be launched to elucidate the possible mechanism/s of action and to study the effect of artemisinin-naphthoquine phosphate combination on other human schistosomes.
authors.affiliation: Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. selbeshbishi@yahoo.com
authors.forename: Samar N
authors.initials: SN
authors.lastname: El-Beshbishi
authors.forename: Amira
authors.initials: A
authors.lastname: Taman
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Malky
authors.forename: Manar S
authors.initials: MS
authors.lastname: Azab
authors.forename: Amira K
authors.initials: AK
authors.lastname: El-Hawary
authors.forename: Dina A
authors.initials: DA
authors.lastname: El-Tantawy
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D007422:Intestines / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000008:administration & dosage*; D010270:Parasite Egg Count; D059208:Parasite Load; D012550:Schistosoma mansoni / Q000302:isolation & purification; D012555:Schistosomiasis mansoni / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000871:Anthelmintics; D037621:Artemisinins; D009285:Naphthoquinones; C543979:artemisinin-naphthoquine combination