Drug-Resistant Schistosomiasis: Resistance to Praziquantel and Oxamniquine Induced in Schistosoma Mansoni in Mice is Drug Specific

TLDR

Mice infected with *Schistosoma mansoni* were repeatedly treated with subcurative doses of praziquantel or oxamniquine, with surviving worms propagated through successive passages and increasing drug amounts, and eggs from these worms were used to infect snails to maintain the parasite line. After six to seven passages, praziquantel‑selected worms survived over 80 % of high‑dose treatments while oxamniquine‑selected worms survived over 90 % of oxamniquine doses but only about 25 % of praziquantel, showing rapid, drug‑specific resistance without cross‑resistance and constituting the first demonstration of praziquantel resistance in *S.

Abstract

Schistosoma mansoni infections in mice were treated with subcurative multiple doses of either praziquantel (PZQ) or oxamniquine (OX). With an early exception, the drug treatments commenced when the worms were adult, but before the infections had become fully patent, and the eggs subsequently produced by worms that had survived the drug treatments were used to infect snails. Six or seven drug-treated passages of S. mansoni in mice were completed for each of the drugs, with the amount of drug administered to the infected mice generally being increased with each passage. Eighty percent of the worms of the sixth passage selected for PZQ resistance survived three doses of 300 mg/kg of PZQ given between days 28 and 37 after infection, and 93% of those of the seventh passage survived the same drug dose. In contrast, only 13% of worms of the sixth PZQ-selected passage survived three doses of 200mg/kg of OX given during the same period after infection. Only 11% or fewer worms derived from S. mansoni infections that had not been subjected to any drug pressure survived the 3 x 300 mg/kg PZQ treatments. Worms selected for OX resistance over six passages were completely resistant to three doses of 200 mg/kg, but only 26% survived three doses of 300 mg/kg of PZQ. Therefore, the results indicate that S. mansoni subjected to drug pressure may develop resistance to schistosomicidal drugs over the course of relatively few passages, but that cross-resistance between PZQ and OX does not occur. This is the first demonstration of drug resistance to PZQ, the current drug of choice for human schistosomiasis.