Countrywide survey shows very high prevalence of Plasmodium falciparum multilocus resistance genotypes in Cambodia
| Autor: | Nimol Khim, Socheat Doung, Odile Puijalon, Christiane Bouchier, Sandra Incardona, Ronan Jambou, Eric Legrand, Pharath Lim, Marie-Thérèse Ekala, Thierry Fandeur |
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| Přispěvatelé: | Inconnu, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur [Paris] (IP), Immunologie moléculaire des parasites, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de la Guyane, Institut Pasteur de Dakar, National Malaria Center, Ministère de la santé, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Genes Protozoan Protozoan Proteins MESH: Tetrahydrofolate Dehydrogenase Drug resistance MESH: Parasitic Sensitivity Tests MESH: Genotype 0302 clinical medicine Parasitic Sensitivity Tests Genotype Prevalence MESH: Animals Pharmacology (medical) MESH: Dihydropteroate Synthase Malaria Falciparum MESH: Protozoan Proteins MESH: Plasmodium falciparum Genetics 0303 health sciences biology Mefloquine MESH: Malaria Falciparum Drug Resistance Multiple 3. Good health [SDV] Life Sciences [q-bio] Infectious Diseases MESH: Genes Protozoan MESH: ATP-Binding Cassette Transporters Cambodia medicine.drug MESH: Thymidylate Synthase MESH: Mutation 030231 tropical medicine Plasmodium falciparum Context (language use) MESH: Drug Resistance Multiple 03 medical and health sciences Antimalarials parasitic diseases medicine Animals Humans [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology Experimental Therapeutics MESH: Prevalence Pharmacology Dihydropteroate Synthase MESH: Humans 030306 microbiology MESH: Cambodia Haplotype Thymidylate Synthase medicine.disease biology.organism_classification MESH: Antimalarials Tetrahydrofolate Dehydrogenase Mutation ATP-Binding Cassette Transporters Dihydropteroate synthase Malaria |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2005, 49 (8), pp.3147-3152 Antimicrobial Agents and Chemotherapy, 2005, 49 (8), pp.3147-52. ⟨10.1128/AAC.49.8.3147-3152.2005⟩ Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2005, 49 (8), pp.3147-52. ⟨10.1128/AAC.49.8.3147-3152.2005⟩ |
| ISSN: | 0066-4804 1098-6596 |
| DOI: | 10.1128/AAC.49.8.3147-3152.2005⟩ |
| Popis: | Cambodia is located in an area of resistance to multiple antimalarials and has been the first country to implement the systematic use of an artesunate-mefloquine combination as first-line treatment for Plasmodium falciparum malaria. Little is known, however, about the prevalence of resistance mutations within the natural parasite populations, impeding rational drug policy in this context. Using direct sequencing of PCR products, we have analyzed sequence polymorphism of the dihydrofolate reductase-thymidylate synthase, dihydropteroate synthetase, and multidrug resistance 1 genes in a large number of clinical P. falciparum isolates collected in various areas of Cambodia. This highlighted a 100% prevalence of haplotypes with multiple mutations in the target genes of antifolates after more than a decade without use of antifolates for malaria therapy. A high prevalence of mutations in Pfmdr1 , including mutations associated with decreased in vitro susceptibility to mefloquine and quinine, was also observed. In addition, novel, low-frequency mutations were detected in Pfmdr1 . Our findings show an alarming rate of multilocus resistance genotypes in Cambodia, requiring diligent surveillance and imposing limitations on possible future drug combinations. |
| Databáze: | OpenAIRE |
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