Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations.

Abstract

BACKGROUND:

Plasmodium falciparum malaria resistant to chloroquine and pyrimethamine originated in limited foci and migrated to Africa. It remains unresolved whether P. falciparum resistance to sulfadoxine, which is conferred by mutations in dihydropteroate synthase (DHPS), evolved following a similar pattern.

METHODS:

The dhps locus of 893 P. falciparum isolates from 12 countries in Asia, the Pacific Islands, Africa, and South America was sequenced. Haplotypes of 6 microsatellite loci flanking the dhps locus were determined to define the genetic relationships among sulfadoxine-resistant lineages.

RESULTS:

Six distinct sulfadoxine-resistant lineages were identified. Highly resistant lineages appear to have originated only in Southeast Asia and South America. Two resistant lineages found throughout Southeast Asia have been introduced to East Africa, where they appear to have spread.

CONCLUSIONS:

The infrequent selection of parasites highly resistant to sulfadoxine and the subsequent migration of resistant lineages from Asia to Africa are similar to the patterns observed in chloroquine and pyrimethamine resistance. These findings strongly suggest that the global migration of resistant parasites has played a decisive role in the establishment of drug-resistant P. falciparum parasites, and that similar patterns may be anticipated for the spread of artemisinin resistance.

• Authors: Toshihiro Mita, Meera Venkatesan, Jun Ohashi, Richard Culleton, Nobuyuki Takahashi, Takahiro Tsukahara, Mathieu Ndounga, Lek Dysoley, Hiroyoshi Endo, Francis Hombhanje, Marcelo U Ferreira, Christopher V Plowe, Kazuyuki Tanabe
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 204 Issue 12 Pg. 1980-8 (Dec 15 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 22021623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Sulfadoxine
• Dihydropteroate Synthase

Topics

• Africa, Eastern
• Alleles
• Animals
• Antimalarials (pharmacology)
• Asia, Southeastern
• Dihydropteroate Synthase (genetics)
• Drug Resistance (genetics)
• Genes, Protozoan
• Haplotypes
• Malaria, Falciparum (drug therapy, parasitology)
• Plasmodium falciparum (drug effects, genetics)
• Sequence Analysis, DNA
• South America
• Sulfadoxine (pharmacology)