Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure.
The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria.
Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria. solagbotosho@yahoo.co.uk
Grace O
GO
Gbotosho
Onikepe A
OA
Folarin
Carolina
C
Bustamante
Luis Hildebrando Pereira
LH
da Silva
Elieth
E
Mesquita
Akintunde
A
Sowunmi
Mariano G
MG
Zalis
Ayoade M J
AM
Oduola
Christian T
CT
Happi
D000483:Alleles; D000655:Amodiaquine / Q000627:therapeutic use; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D001938:Brazil / Q000453:epidemiology; D056915:DNA Copy Number Variations; D004338:Drug Combinations; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009154:Mutation; D009549:Nigeria / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D000655:Amodiaquine; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C515299:amodiaquine, artesunate drug combination