TABLE 4.

Key studies and findings focused on experimentally induced PZQ resistance in different Schistosoma species

Strain(s)	Study design	Treatment	Findings/outcomes	Reference(s)
S. mansoni WW and LE	Miracidia from feces of infected patients were used to infect B. glabrata to obtain cercaria (strain WW), which were used to infect mice; infected mice were treated with antischistosomal drugs; sensitivities of strains WW and LE to drugs were compared	Hycanthone, 80 and 20 mg/kg; niridazole, 100 and 50 mg/kg/day for 5 days; oxamniquine, 100 and 50 mg/kg, 1 dose	Hycanthone altered oogram pattern of 100% of mice infected with strain LE; hycanthone did not affect oogram pattern of mice infected with strain WW; strain WW was more resistant to niridazole and oxamniquine	88, 89
S. mansoni Brazilian	Mice were infected with S. mansoni obtained from infected individual, they were treated with different antischistosomal drugs during the time of embryological development of genital organs of schistosomula of both sexes	Oxamniquine, 50 mg/kg, 1 dose; oltipraz, 60 mg/kg daily for 5 days; PZQ, 50 mg/kg for 5 days	All treated groups had larger percentages of worms in liver and portal vein and significantly lighter parasite loads than control group, high rates of worm reduction, low rates of surviving worms, and 100% had changed oogram pattern; failure to induce resistance in Brazilian strain	90
S. mansoni Egyptian	S. mansoni infected mice were treated with subcurative different doses of PZQ after 6 wk p.i.;a eggs produced by worms that survived to treatment were used to infect snails	PZQ, 3 × 300 mg/kg	S. mansoni subjected to drug pressure may develop resistance to schistosomicidal drugs after relatively few passages; first demonstration of resistance to PZQ	91
	Miracidia obtained from eggs from infected patient were used to infected mice; eggs produced by worms that survive to treatment 6 wk p.i. were used to infect snails and mice of the following generations	PZQ, 300 or 500 mg/kg	Subcurative dose of PZQ led to development of resistance to therapeutic dose of PZQ in following generations	92
S. mansoni LE	Infected B. glabrata snails were treated with PZQ; after treatment, cercariae obtained from these snails (LE-PZQ isolate) and susceptible LE strains were used to infect mice that were treated p.i.	B. glabrata, 3 × 100 mg/kg, 5 consecutive days; infected mice, 45 days p.i., 200, 400, 800 mg/kg	Experimental model of development of resistance to S. mansoni using infected snails; mean no. of worms recovered from group of mice infected with LE-PZQ isolate treated with 200 and 400 mg/kg was significantly higher than that from mice infected with LE strain with same treatment; in vitro, worms of LE-PZQ isolates were also less susceptible to PZQ	93
S. japonicum	Mice were infected with isolates from two distinct regions, PZQ-susceptible isolates and PZQ-induced isolates, and then treated with PZQ; cercariae and miracidia of different isolates were exposed to PZQ solution, and morphological alterations were observed	Infected mice, 35 days p.i., 0,37.5,75, 150, 300, and 600 mg/kg; cercariae and miracidia, 10−5, 5 × 10−6, 5 × 10−7, and 10− M	PZQ-resistant isolates of S. japonicum were established in mice with subcurative doses of PZQ by artificial selection in laboratory; drug resistance might be exhibited by different developmental stages (miracidia, cercaria, adult worms); established PZQ ED50s for different developmental stages	94

^ap.i., postinfection.