Antifolate resistance in Plasmodium falciparum: Multiple origins and identification of novel dhfr alleles

Andrea M. McCollum, Amanda C. Poe, Mary Hamel, Curtis Huber, Zhiyong Zhou, Ya Ping Shi, Peter Ouma, John Vulule, Peter Bloland, Laurence Slutsker, John W. Barnwell, Venkatachalam Udhayakumar, Ananias A. Escalante

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background. Sulfadoxine-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. Methods. Direct 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. Results. A 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. Conclusions. These findings highlight the importance of local characterization of alleles before molecular surveillance of drug-resistant alleles is considered in different endemic settings and populations.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalJournal of Infectious Diseases
Volume194
Issue number2
DOIs
StatePublished - Jul 15 2006

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Folic Acid Antagonists
Plasmodium falciparum
Alleles
Genotype
Microsatellite Repeats
Polymerase Chain Reaction
Southeastern Asia
Chromosomes, Human, Pair 4
Africa South of the Sahara
Kenya
Haplotypes
Malaria
Organism Cloning
History
Mutation
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

McCollum, A. M., Poe, A. C., Hamel, M., Huber, C., Zhou, Z., Shi, Y. P., ... Escalante, A. A. (2006). Antifolate resistance in Plasmodium falciparum: Multiple origins and identification of novel dhfr alleles. Journal of Infectious Diseases, 194(2), 189-197. https://doi.org/10.1086/504687

Antifolate resistance in Plasmodium falciparum : Multiple origins and identification of novel dhfr alleles. / McCollum, Andrea M.; Poe, Amanda C.; Hamel, Mary; Huber, Curtis; Zhou, Zhiyong; Shi, Ya Ping; Ouma, Peter; Vulule, John; Bloland, Peter; Slutsker, Laurence; Barnwell, John W.; Udhayakumar, Venkatachalam; Escalante, Ananias A.

In: Journal of Infectious Diseases, Vol. 194, No. 2, 15.07.2006, p. 189-197.

Research output: Contribution to journalArticle

McCollum, AM, Poe, AC, Hamel, M, Huber, C, Zhou, Z, Shi, YP, Ouma, P, Vulule, J, Bloland, P, Slutsker, L, Barnwell, JW, Udhayakumar, V & Escalante, AA 2006, 'Antifolate resistance in Plasmodium falciparum: Multiple origins and identification of novel dhfr alleles', Journal of Infectious Diseases, vol. 194, no. 2, pp. 189-197. https://doi.org/10.1086/504687
McCollum, Andrea M. ; Poe, Amanda C. ; Hamel, Mary ; Huber, Curtis ; Zhou, Zhiyong ; Shi, Ya Ping ; Ouma, Peter ; Vulule, John ; Bloland, Peter ; Slutsker, Laurence ; Barnwell, John W. ; Udhayakumar, Venkatachalam ; Escalante, Ananias A. / Antifolate resistance in Plasmodium falciparum : Multiple origins and identification of novel dhfr alleles. In: Journal of Infectious Diseases. 2006 ; Vol. 194, No. 2. pp. 189-197.
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