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Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles
by
Shi, Ya Ping
, Ouma, Peter
, Bloland, Peter
, Zhou, Zhiyong
, Vulule, John
, Poe, Amanda C.
, McCollum, Andrea M.
, Slutsker, Laurence
, Huber, Curtis
, Hamel, Mary
, Barnwell, John W.
, Udhayakumar, Venkatachalam
, Escalante, Ananias A.
in
Alleles
/ Animals
/ Antimalarials - pharmacology
/ Codons
/ Drug Combinations
/ Drug Resistance - genetics
/ Folic acid antagonists
/ Folic Acid Antagonists - pharmacology
/ Genetic mutation
/ Genotype
/ Genotypes
/ Haplotypes
/ HIV Infections - complications
/ Humans
/ Malaria
/ Malaria, Falciparum - parasitology
/ Microsatellite Repeats - genetics
/ Microsatellites
/ Mutation
/ Parasites
/ Plasmodium falciparum
/ Plasmodium falciparum - drug effects
/ Plasmodium falciparum - enzymology
/ Plasmodium falciparum - genetics
/ Polymerase chain reaction
/ Pyrimethamine - pharmacology
/ Sequencing
/ Sulfadoxine - pharmacology
/ Tetrahydrofolate Dehydrogenase - genetics
2006
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Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles
by
Shi, Ya Ping
, Ouma, Peter
, Bloland, Peter
, Zhou, Zhiyong
, Vulule, John
, Poe, Amanda C.
, McCollum, Andrea M.
, Slutsker, Laurence
, Huber, Curtis
, Hamel, Mary
, Barnwell, John W.
, Udhayakumar, Venkatachalam
, Escalante, Ananias A.
in
Alleles
/ Animals
/ Antimalarials - pharmacology
/ Codons
/ Drug Combinations
/ Drug Resistance - genetics
/ Folic acid antagonists
/ Folic Acid Antagonists - pharmacology
/ Genetic mutation
/ Genotype
/ Genotypes
/ Haplotypes
/ HIV Infections - complications
/ Humans
/ Malaria
/ Malaria, Falciparum - parasitology
/ Microsatellite Repeats - genetics
/ Microsatellites
/ Mutation
/ Parasites
/ Plasmodium falciparum
/ Plasmodium falciparum - drug effects
/ Plasmodium falciparum - enzymology
/ Plasmodium falciparum - genetics
/ Polymerase chain reaction
/ Pyrimethamine - pharmacology
/ Sequencing
/ Sulfadoxine - pharmacology
/ Tetrahydrofolate Dehydrogenase - genetics
2006
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Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles
by
Shi, Ya Ping
, Ouma, Peter
, Bloland, Peter
, Zhou, Zhiyong
, Vulule, John
, Poe, Amanda C.
, McCollum, Andrea M.
, Slutsker, Laurence
, Huber, Curtis
, Hamel, Mary
, Barnwell, John W.
, Udhayakumar, Venkatachalam
, Escalante, Ananias A.
in
Alleles
/ Animals
/ Antimalarials - pharmacology
/ Codons
/ Drug Combinations
/ Drug Resistance - genetics
/ Folic acid antagonists
/ Folic Acid Antagonists - pharmacology
/ Genetic mutation
/ Genotype
/ Genotypes
/ Haplotypes
/ HIV Infections - complications
/ Humans
/ Malaria
/ Malaria, Falciparum - parasitology
/ Microsatellite Repeats - genetics
/ Microsatellites
/ Mutation
/ Parasites
/ Plasmodium falciparum
/ Plasmodium falciparum - drug effects
/ Plasmodium falciparum - enzymology
/ Plasmodium falciparum - genetics
/ Polymerase chain reaction
/ Pyrimethamine - pharmacology
/ Sequencing
/ Sulfadoxine - pharmacology
/ Tetrahydrofolate Dehydrogenase - genetics
2006
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Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles
Journal Article
Antifolate Resistance in Plasmodium falciparum: Multiple Origins and Identification of Novel dhfr Alleles
2006
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Overview
BackgroundSulfadoxine-pyrimethamine has been widely used as first-line therapy for uncomplicated malaria throughout sub-Saharan Africa. Recent studies conducted in Asia and Africa suggest the triple-mutant dhfr genotype (51I/59R/108N) may have been generated as a single event in Southeast Asia, with subsequent spread of the single lineage to the African continent, but this hypothesis needs further validation MethodsDirect sequencing of polymerase chain reaction (PCR) products, pyrosequencing, and cloning of PCR products were utilized to identify mutations in dhfr. To investigate the evolutionary history of dhfr alleles, we assayed microsatellite loci flanking dhfr along chromosome 4 ResultsA total of 15 of 479 samples from western Kenya showed the presence of I164L, in 5 different genotypes. We document C50R in 2 of our samples. Using microsatellite markers, we show 2 haplotypes for both the 51I/108N/164L and 51I/59R/108N/164L genotypes. Our results also show multiple lineages for the triple-mutant dhfr genotype in Africa ConclusionsThese findings highlight the importance of local characterization of alleles before molecular surveillance of drug-resistant alleles is considered in different endemic settings and populations
Publisher
The University of Chicago Press,University of Chicago Press,Oxford University Press
Subject
/ Animals
/ Antimalarials - pharmacology
/ Codons
/ Folic Acid Antagonists - pharmacology
/ Genotype
/ HIV Infections - complications
/ Humans
/ Malaria
/ Malaria, Falciparum - parasitology
/ Microsatellite Repeats - genetics
/ Mutation
/ Plasmodium falciparum - drug effects
/ Plasmodium falciparum - enzymology
/ Plasmodium falciparum - genetics
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