Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia

Michael Alifrangis; Sidsel Nag; Mette L Schousboe; Deus Ishengoma; John Lusingu; Hirva Pota; Reginald A Kavishe; Richard Pearce; Rosalynn Ord; Caroline Lynch; Seyoum Dejene; Jonathan Cox; John Rwakimari; Daniel T R Minja; Martha M Lemnge; Cally Roper

doi:10.3201/eid2008.131897

Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia

Michael Alifrangis, Sidsel Nag, Mette L Schousboe, Deus Ishengoma, John Lusingu, Hirva Pota, Reginald A Kavishe, Richard Pearce, Rosalynn Ord, Caroline Lynch, Seyoum Dejene, Jonathan Cox, John Rwakimari, Daniel T R Minja, Martha M Lemnge, Cally Roper

16 Citations (Scopus)

Abstract

Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.

Original language	English
Journal	Emerging Infectious Diseases (Print Edition)
Volume	20
Issue number	8
Pages (from-to)	1280-6
Number of pages	7
ISSN	1080-6040
DOIs	https://doi.org/10.3201/eid2008.131897
Publication status	Published - Aug 2014

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Alifrangis, M., Nag, S., Schousboe, M. L., Ishengoma, D., Lusingu, J., Pota, H., Kavishe, R. A., Pearce, R., Ord, R., Lynch, C., Dejene, S., Cox, J., Rwakimari, J., Minja, D. T. R., Lemnge, M. M., & Roper, C. (2014). Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia. Emerging Infectious Diseases (Print Edition), 20(8), 1280-6. https://doi.org/10.3201/eid2008.131897

Alifrangis, M , Nag, S, Schousboe, ML, Ishengoma, D, Lusingu, J, Pota, H, Kavishe, RA, Pearce, R, Ord, R, Lynch, C, Dejene, S, Cox, J, Rwakimari, J, Minja, DTR, Lemnge, MM & Roper, C 2014, 'Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia', Emerging Infectious Diseases (Print Edition), vol. 20, no. 8, pp. 1280-6. https://doi.org/10.3201/eid2008.131897

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title = "Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia",

abstract = "Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.",

author = "Michael Alifrangis and Sidsel Nag and Schousboe, {Mette L} and Deus Ishengoma and John Lusingu and Hirva Pota and Kavishe, {Reginald A} and Richard Pearce and Rosalynn Ord and Caroline Lynch and Seyoum Dejene and Jonathan Cox and John Rwakimari and Minja, {Daniel T R} and Lemnge, {Martha M} and Cally Roper",

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AU - Lusingu, John

AU - Pota, Hirva

AU - Kavishe, Reginald A

AU - Pearce, Richard

AU - Ord, Rosalynn

AU - Lynch, Caroline

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AU - Cox, Jonathan

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AU - Minja, Daniel T R

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AB - Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.

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DO - 10.3201/eid2008.131897

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JO - Emerging Infectious Diseases

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ER -

Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia

Abstract

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