Effects of Praziquantel on Different Developmental Stages of Schistosoma mansoni in Vitro and in Vivo

Abstract

To discern whether stage-specific resistance of Schistosoma mansoni to praziquantel occurs in vitro, we determined minimal effective concentrations (MECs) of drug needed to increase motor activity, produce contraction and/or paralysis, and cause tegumental vesiculation of developmental stages from day 0 to day 42 of S. mansoni. Recovery of these stages from exposure to praziquantel in vitro was also evaluated. MECs of praziquantel inducing increased motor activity and muscular contraction or paralysis or both were 0.005-0.01 micrograms/ml, irrespective of the stage examined. However, day-3 lung forms were more resistant than other stages when either drug-induced tegumental vesiculation (MEC, 1 microgram/ml) or recovery from drug exposure was tested. Three-day infections with S. mansoni in CF1 mice were also less responsive to praziquantel treatment than were infections of shorter or longer duration. The concentrations of praziquantel and periods of drug exposure causing gross tegumental damage to S. mansoni in vitro correlated with the peak serum levels and time course of unchanged praziquantel associated with reduction of worm burden in vivo. Thus, stage-specific resistance of S. mansoni to praziquantel does occur in vitro and correlates better with the tegumental than the muscular action of the drug.

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

“…The slightly lower susceptibility of adult S. mansoni worms than NTS to artesunate might be due to the lack of hemin, a primary activator of the peroxide group, in the incubation medium (41). Overall, the findings on the individual parasite stages are consistent with previous in vitro studies with these drugs (2,10,24,27,40).…”

Efficacy and side effects of praziquantel in the treatment of Schistosomiasis mansoni in schoolchildren in Shesha Kekele Elementary School, Wondo Genet, Southern Ethiopia

“…In areas with heavy transmission of schistosomiasis, it has been suggested that people might have been infected in the previous 3-5 weeks. Hence, such patients would harbor immature schistosomes that are less susceptible to PZQ [7,[39][40][41] . These immature stages have the high chance to survive a single treatment and mature to deposit eggs in the subsequent weeks.…”

Use of Cell-Free Circulating Schistosome DNA in Serum, Urine, Semen, and Saliva To Monitor a Case of Refractory Imported Schistosomiasis Hematobia

“…One possible explanation for the lingering worm DNA detection may have been unsatisfactory treatment. Immature ova/ worms are refractory to PZQ treatment (11)(12)(13)(14). Multiple treatments with PZQ are needed with intervals between the treatments to allow maturation of immature worms/ova (2 to 4 weeks) (13)(14)(15).…”