title: Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug.
abstract: Schistosomiasis is a neglected tropical disease caused by blood-dwelling flukes of the genus Schistosoma. While the disease may affect as many as 249 million people, treatment largely relies on a single drug, praziquantel. The near exclusive use of this drug for such a prevalent disease has led to concerns regarding the potential for drug resistance to arise and the effect this would have on affected populations. In this study, we use an in vitro assay of drug sensitivity to test the effect of praziquantel on miracidia hatched from eggs obtained from fecal samples of Kenyan adult car washers and sand harvesters as well as school children. Whereas in a previous study we found the car washers and sand harvesters to harbor Schistosoma mansoni with reduced praziquantel sensitivity, we found no evidence for the presence of such strains in any of the groups tested here. Using miracidia derived from seven car washers to infect snails, we used the shed cercariae to establish a strain of S. mansoni with significantly reduced praziquantel sensitivity in mice. This was achieved within 5 generations by administering increasing doses of praziquantel to the infected mice until the parasites could withstand a normally lethal dose. This result indicates that while the threat of praziquantel resistance may have diminished in the Kenyan populations tested here, there is a strong likelihood it could return if sufficient praziquantel pressure is applied.
authors.affiliation: Center for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Ibrahim N
authors.initials: IN
authors.lastname: Mwangi
authors.affiliation: Dept. of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Sanchez
authors.affiliation: Center for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Mkoji
authors.affiliation: Center for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Lelo E
authors.initials: LE
authors.lastname: Agola
authors.affiliation: Dept. of Biochemistry and Biotechnology, Kenyatta University, Nairobi, Kenya.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Runo
authors.affiliation: Dept. of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Cupit
authors.affiliation: Dept. of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Cunningham
keywords: Drug resistance; Helminths; Miracidia; Praziquantel; Schistosoma; Schistosomiasis