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In Vitro Sensitivity of Plasmodium falciparum from China-Myanmar Border Area to Major ACT Drugs and Polymorphisms in Potential Target Genes
- Source :
- PLoS ONE, PloS one, vol 7, iss 5, PLoS ONE, Vol 7, Iss 5, p e30927 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science, 2012.
-
Abstract
- Drug resistance has always been one of the most important impediments to global malaria control. Artemisinin resistance has recently been confirmed in the Greater Mekong Subregion (GMS) and efforts for surveillance and containment are intensified. To determine potential mechanisms of artemisinin resistance and monitor the emergence and spread of resistance in other regions of the GMS, we investigated the in vitro sensitivity of 51 culture-adapted parasite isolates from the China-Myanmar border area to four drugs. The 50% inhibitory concentrations (IC₅₀s) of dihydroartemisinin, mefloquine and lumefantrine were clustered in a relatively narrow, 3- to 6-fold range, whereas the IC₅₀ range of artesunate was 12-fold. We assessed the polymorphisms of candidate resistance genes pfcrt, pfmdr1, pfATP6, pfmdr6 and pfMT (a putative metabolite/drug transporter). The K76T mutation in pfcrt reached fixation in the study parasite population, whereas point mutations in pfmdr1 and pfATP6 had low levels of prevalence. In addition, pfmdr1 gene amplification was not detected. None of the mutations in pfmdr1 and pfATP6 was associated significantly with in vitro sensitivity to artemisinin derivatives. The ABC transporter gene pfmdr6 harbored two point mutations, two indels, and number variations in three simple repeats. Only the length variation in a microsatellite repeat appeared associated with altered sensitivity to dihydroartemisinin. The PfMT gene had two point mutations and one codon deletion; the I30N and N496- both reached high levels of prevalence. However, none of the SNPs or haplotypes in PfMT were correlated significantly with resistance to the four tested drugs. Compared with other parasite populations from the GMS, our studies revealed drastically different genotype and drug sensitivity profiles in parasites from the China-Myanmar border area, where artemisinins have been deployed extensively for over 30 years.
- Subjects :
- Heredity
medicine.medical_treatment
Drug Resistance
Protozoan Proteins
lcsh:Medicine
Artesunate
Myanmar
Drug resistance
Protozoology
chemistry.chemical_compound
0302 clinical medicine
Genotype
Artemisinin
lcsh:Science
Genetics
0303 health sciences
education.field_of_study
Multidisciplinary
Artemisinins
3. Good health
Plasmodium Falciparum
Infectious Diseases
5.1 Pharmaceuticals
Ethanolamines
Medicine
Development of treatments and therapeutic interventions
Multidrug Resistance-Associated Proteins
Infection
medicine.drug
Research Article
China
General Science & Technology
Plasmodium falciparum
030231 tropical medicine
Population
Genotypes
Dihydroartemisinin
Calcium-Transporting ATPases
Biology
Microbiology
Vaccine Related
Antimalarials
03 medical and health sciences
Rare Diseases
Genetic
Biodefense
parasitic diseases
medicine
Parasitic Diseases
Polymorphism
education
Fluorenes
Lumefantrine
Polymorphism, Genetic
Population Biology
030306 microbiology
Prevention
lcsh:R
Haplotype
Membrane Transport Proteins
Correction
Computational Biology
Tropical Diseases (Non-Neglected)
biology.organism_classification
Malaria
Vector-Borne Diseases
chemistry
Genetic Polymorphism
Parastic Protozoans
lcsh:Q
Antimicrobial Resistance
Population Genetics
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....2280ba27ef0a53cd489eb08232648db7