Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 87, Issue 5, Pages 813-821Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.2012.12-0094
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Funding
- National Institutes of Health [RO1 AI 075416, U19 AI089681]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2010/51835-7]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [10/51835-7] Funding Source: FAPESP
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Emerging resistance to chloroquine (CQ) poses a major challenge for Plasmodium vivax malaria control, and nucleotide substitutions and copy number variation in the P. vivax multidrug resistance 1 (pvmdr-1) locus, which encodes a digestive vacuole membrane transporter, may modulate this phenotype. We describe patterns of genetic variation in pvmdr-1 alleles from Acre and Amazonas in northwestern Brazil, and compare then with those reported in other malaria-endemic regions. The pvmdr-1 mutation Y976F, which is associated with CQ resistance in Southeast Asia and Oceania, remains rare in northwestern Brazil (1.8%) and its prevalence mirrors that of CO resistance worldwide. Gene amplification of pvmdr-1, which is associated with mefloquine resistance but increased susceptibility to CO, remains relatively rare in northwestern Brazil (0.9%) and globally (< 4%), but became common (> 10%) in Tak Province, Thailand, possibly because of drug-mediated selection. The global database we have assembled provides a baseline for further studies of genetic variation in pvmdr-1 and drug resistance in P. vivax malaria.
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