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Praziquantel Resistance Among Parasitic Flatworms
(Left) The Nile River from downtown Cairo and (right) pyramids at Giza outside of Cairo. Lurking throughout Egypt, but not visible in these pictures, are schistosomes! For many years, schistosomiasis was the primary health threat for Egyptians. But, with the introduction of the antischistosomal praziquantel in the 1970's the situation has improved in Egypt, probably moreso than in any country in which schistosomiasis is endemic. Unfortunately, this improvement has come through extremely extensive, often indiscriminate use of praziquantel. This heavy use may be leading to praziquantel resistance.
Praziquantel (PZQ) is used for the treatment of schistosome infections. In a number of regions, including much of Egypt, PZQ has been copiously used, and the impact of the drug on schistosomiasis has been significant. Unfortunately, reports of resistance to PZQ have recently appeared. However, the reality of these reports is difficult to establish, because it is often difficult to distinguish between host factors and parasite factors when patients are not cured of schistosomiasis by normally effective doses. For example, since the host immune system plays an active role in the process of killing PZQ-damaged worms, normal parasites might survive treatment in immunocompromised hosts.
Through efforts in Egypt led by Dr. Magdi Ismail of Zagazig University, schistosomes have been isolated from Egyptian patients not cured by PZQ.
- Characterization of praziquantel-resistant schistosomes
Our lab, is collaborating with Dr. Ismail to characterize and understand these isolates. We have found that the worms are, in fact, less responsive to PZQ in vitro. We are using muscle tension recordings, since the classical PZQ response in vitro is contraction of the worm musculature.
(Left) Tim (the tall one) training Hany and Ashraf, two graduate students in the Department of Parasitology at Zagazig University in Egpyt. They are learning to measure the force of schistosome muscle responses to praziquantel. (Right) Ashraf, Hany, Mamoud and Ahmed taking a rare break from the intense trainng. - Development of field-amenable assays for resistance
We are also working with Dr. Sanaa Butros of Thedore Bilharz Research Institue in Cairo and Jim Bennett of Michigan State to develop new assays to detect PZQ resistance that could be applied in the field.
- Biological costs of the resistance traits
If the resistant worms have heritable genetic alterations as compared to their susceptible counterparts, it is likely that the resistant worms are less fit biologically. There is usually a cost associated with resistance traits. We are collaborating with the Egyptian laboratories to compare the biological fitness of the resistant and the susceptible schistosomes.
- Genetic variability of parasites in praziquantel-intensive and -naive populations
The effects of praziquantel pressure on the genetics of schistosome populations is not known. We are interested in the hypothesis that extreme chemotherapeutic pressure would decease the genetic variability of the schistosomes, producing a more uniform population.
