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Development of DNA assays for the detection of single nucleotide polymorphism associated with benzimidazole resistance, in human soil-transmitted helminths

Authors: Diawara, Aïssatou;

Development of DNA assays for the detection of single nucleotide polymorphism associated with benzimidazole resistance, in human soil-transmitted helminths

Abstract

Les géo-helminthes sont des vers parasitant l'Homme et causant de nombreux handicaps dans les régions tropicales des pays en voie de développement. Des programmes de contrôles tels que le partenariat FRESH : ''Focussing Resources on Effective School Health'' ont été mis en place afin d'éliminer les géo-helminthes en administrant massivement en milieu scolaire des pays en voie de développement des medicaments anthelmintiques. L'albendazole et le mébendazole appartiennent au groupe des benzimidazoles et sont distribués dans les régions grandement infestées. Cependant, cette attribution massive de médicaments, aux enfants, pourrait entraîner une sélection de parasites résistants aux anthelmintiques. La substitution de l'acide aminé phénylalanine (Phe) par la tyrosine (Tyr) connue pour être associée à la résistance aux benzimidazoles chez les nématodes a été identifiée chez les filaires à la position 200 du gène de la ß-tubuline. Nous avons développés des tests pour les parasites Trichuris trichiura, Ascaris lumbricoides et Necator americanus en utilisant la méthode du pyroséquençage afin de détecter le polymorphisme d'un unique nucleotide (SNP) au niveau du codon 200 du gène de la ß-tubuline. Ce test a été appliqué sur des vers adultes provenant d'individus du Kenya n'ayant jamais été traités par des anthelmintiques. Puis ce même test a été appliqué à des vers adultes individuels, à des pools d'œufs et de larves provenant d'individus d'Afrique de l'est, des Caraïbes et d'Amérique centrale, où les programmes de contrôles de masse sont implantés. Le SNP fût détecté chez T. trichiura provenant d'individus non-traités aux benzimidazoles ainsi que chez T. trichiura et N. ameri

Soil-transmitted helminths are parasitic worms of humans, causing many disabilities in tropical parts of the developing world. Control programs such as "The Focussing Resources on Effective School Health” (FRESH) Partnership have been implemented to remove human soil transmitted nematodes through large-scale use of benzimidazole anthelmintic drugs for school-aged children in developing countries. The benzimidazole drugs, albendazole and mebendazole are used as a single annual dose in areas where the burden is high. Unfortunately, there is concern that increased use of anthelmintics in children could select for resistant populations of these human parasites. In filarial nematodes, a single amino acid substitution from phenylalanine (Phe) to tyrosine (Tyr), known to be associated with benzimidazole resistance in other nematodes, has been found in parasite ß-tubulin at position 200. We have developed pyrosequencer assays for the codon 200 in Trichuris trichiura, Ascaris lumbricoides, and the hookworm Necator americanus to screen for this single nucleotide polymorphism (SNP). Assays for this resistance-associated SNP could be useful for monitoring for anthelmintic resistance in control programs. These assays have been tested on adult worms from a benzimidazle-naïve population in Kenya. Following this, these assays have been applied on individual worms, pooled eggs and pooled larvae from people in East Africa, the Caribbean and Central America where mass drug anthelmintic programs have been implemented. The 200Tyr SNP was detected in T. trichiura from non-treated people and in T. trichiura and N. americanus from benzimidazole-treated people.

Prichard, Roger K. (Supervisor)

Country
Canada
Related Organizations
Keywords

Biology - Parasitology, 610, Parasitology

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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Average
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