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Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug

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 c...

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Detalles Bibliográficos
Autores principales: Mwangi, Ibrahim N., Sanchez, Melissa C., Mkoji, Gerald M., Agola, Lelo E., Runo, Steven M., Cupit, Pauline M., Cunningham, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266778/
https://www.ncbi.nlm.nih.gov/pubmed/25516840
http://dx.doi.org/10.1016/j.ijpddr.2014.09.006
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author Mwangi, Ibrahim N.
Sanchez, Melissa C.
Mkoji, Gerald M.
Agola, Lelo E.
Runo, Steven M.
Cupit, Pauline M.
Cunningham, Charles
author_facet Mwangi, Ibrahim N.
Sanchez, Melissa C.
Mkoji, Gerald M.
Agola, Lelo E.
Runo, Steven M.
Cupit, Pauline M.
Cunningham, Charles
author_sort Mwangi, Ibrahim N.
collection PubMed
description 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.
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spelling pubmed-42667782014-12-16 Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug Mwangi, Ibrahim N. Sanchez, Melissa C. Mkoji, Gerald M. Agola, Lelo E. Runo, Steven M. Cupit, Pauline M. Cunningham, Charles Int J Parasitol Drugs Drug Resist Article 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. Elsevier 2014-09-26 /pmc/articles/PMC4266778/ /pubmed/25516840 http://dx.doi.org/10.1016/j.ijpddr.2014.09.006 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Mwangi, Ibrahim N.
Sanchez, Melissa C.
Mkoji, Gerald M.
Agola, Lelo E.
Runo, Steven M.
Cupit, Pauline M.
Cunningham, Charles
Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
title Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
title_full Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
title_fullStr Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
title_full_unstemmed Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
title_short Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
title_sort praziquantel sensitivity of kenyan schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266778/
https://www.ncbi.nlm.nih.gov/pubmed/25516840
http://dx.doi.org/10.1016/j.ijpddr.2014.09.006
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