Characterisation of pvmdr1 and pvdhfr genes associated with chemoresistance in Brazilian Plasmodium vivax isolates

Gama, Bianca Ervatti; Oliveira, Natália K Almeida de; Souza, José Maria de; Daniel-Ribeiro, Cláudio Tadeu; Ferreira-da-Cruz, Maria de Fátima

doi:10.1590/s0074-02762009000700012

Cited by 24 publications

(25 citation statements)

References 30 publications

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“…Most (82.9%) of 228 samples from the Western Amazon, but none of the 28 isolates from Paragominas, in Pará State (Eastern Brazilian Amazon), 26 had the YF haplotype. The distance between Paragominas and the other four sites in Brazil is 2,300 km.…”

Section: Resultsmentioning

confidence: 99%

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Single-Nucleotide Polymorphism and Copy Number Variation of the Multidrug Resistance-1 Locus of Plasmodium vivax: Local and Global Patterns

Vargas-Rodríguez

Bastos²,

Menezes³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. 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 CQ resistance worldwide. Gene amplification of pvmdr-1, which is associated with mefloquine resistance but increased susceptibility to CQ, 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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Section: Resultsmentioning

confidence: 99%

“…Sixty-five (7.4%) of the 883 P. vivax isolates analyzed worldwide had the FF haplotype, but they originated from only three countries: Brazil (Paragominas and Granada), 14,26 Honduras, 24 and Papua New Guinea. 9 More extensive genotyping at and surrounding the pvmdr-1 locus might indicate whether these haplotypes share a common ancestor.…”

Section: Resultsmentioning

confidence: 99%

Single-Nucleotide Polymorphism and Copy Number Variation of the Multidrug Resistance-1 Locus of Plasmodium vivax: Local and Global Patterns

Vargas-Rodríguez

Bastos²,

Menezes³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…The last survey examined the relationship between SPR and the pvmdr1 and pvdhfr genes in a set of 28 samples , Eldin de Pécoulas et al 1998). This identified a potential leader mutation in pvmdr1 in 100% of the examined isolates (Gama et al 2009a). This study contrasted with the reported 10% of in vivo CQ treatment failures (Santana Filho et al 2007).…”

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confidence: 99%

“…Molecular characterisation of P. vivax isolates was also carried out in Brazil (Sá et al 2005, Gama et al 2009a, OrjuelaSánchez et al 2009b. In these publications, the sequence of pvmdr1 in three Brazilian isolates was shown, without association between mutations and in vitro outcomes (Sá et al 2005).…”

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confidence: 99%

“…This study contrasted with the reported 10% of in vivo CQ treatment failures (Santana Filho et al 2007). Moreover, the presence of mutations in pvdhfr gene could reflect the selection of SP-resistant P. vivax parasites due to misdiagnosed, or even undiagnosed, P. falciparum and P. vivax co-infections (Gama et al 2009a). Evaluation of the therapeutic effectiveness of antimalarials is performed utilising in vivo as well as in vitro efficacy studies.…”

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confidence: 99%

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Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in Brazil: consequences on disease morbidity and control

Gama

Lacerda

Daniel-Ribeiro

et al. 2011

Mem. Inst. Oswaldo Cruz

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Molecular Markers of Plasmodium Resistance to Antimalarials

Ecker

Lehane

Fidock

2011

Treatment and Prevention of Malaria

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Investigations into the molecular basis of Plasmodium parasite resistance to antimalarial drugs have made strong progress in defining key determinants. Mutations in the digestive vacuole transmembrane proteins P. falciparum chloroquine resistance transporter (PfCRT) and P. falciparum multidrug resistance protein 1 (PfMDR1) are important drivers of parasite resistance to several quinolinebased drugs including chloroquine, amodiaquine, and to a lesser extent quinine. Amplification of pfmdr1 can also mediate resistance to mefloquine and impact lumefantrine efficacy. Parasite resistance to antifolates has been mapped to point mutations in the target enzymes dihydrofolate reductase and dihydropteroate synthase, and mutations in cytochrome b have been found to ablate atovaquone efficacy. Antibiotic resistance has been associated with mutations that preclude drug inhibition of protein translation in the parasite apicoplast. The study of resistance to artemisinin derivatives and several partner drugs used in artemisinin-based combination therapies is an area of active research that has yet to define clearly how in vitro resistance can translate into predictions of treatment failures. Research in this area is important not only for its ability to generate molecular markers of

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Characterisation of pvmdr1 and pvdhfr genes associated with chemoresistance in Brazilian Plasmodium vivax isolates

Cited by 24 publications

References 30 publications

Single-Nucleotide Polymorphism and Copy Number Variation of the Multidrug Resistance-1 Locus of Plasmodium vivax: Local and Global Patterns

Single-Nucleotide Polymorphism and Copy Number Variation of the Multidrug Resistance-1 Locus of Plasmodium vivax: Local and Global Patterns

Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in Brazil: consequences on disease morbidity and control

Molecular Markers of Plasmodium Resistance to Antimalarials

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