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GENETICS OF DRUG-RESISTANT PLASMODIUM FALCIPARUM MALARIA IN THE VENEZUELAN STATE OF BOLIVAR

By Carmen E. Contreras, Joseph F. Cortese, Alejandro Caraballo and Christopher V. Plowe

Abstract

Abstract. The state of Bolivar in Venezuela experiences episodic outbreaks of multidrug-resistant Plasmodium falciparum malaria. We obtained P. falciparum-infected blood samples in Bolivar in 1998−2000, and performed mo-lecular assays for mutations conferring resistance to the antifolate combination of sulfadoxine-pyrimethamine (SP) and to chloroquine. All infections carried the dihydrofolate reductase (dhfr) S108A and N51I mutations, and 45 % of the infections had the dhfr C50R mutation, which has been implicated in mid-level resistance to SP. Two dihydropteroate synthase (dhps) mutations also involved in SP resistance, A581G and K540E, were detected in 90 % and 67 % of the samples, respectively. The dhfr I164L mutation, which confers high-level resistance, was not identified. The P. falci-parum chloroquine resistance transporter (pfcrt) K76T mutation, which is critical for chloroquine resistance, was found in 167 of 168 infections. Six dhfr/dhps allelotypes and four pfcrt-resistant alleles were observed. Their interrelationships suggest a semi-clonal propagation of P. falciparum malaria in Bolivar, and an invasion of multi-resistant pathogens from Brazil. Despite national restrictions on the use of SP and chloroquine, genotypic resistance to these therapies remains widespread in Bolivar

Year: 2014
OAI identifier: oai:CiteSeerX.psu:10.1.1.507.6256
Provided by: CiteSeerX
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