Prevalence of the K76T mutation in the putative Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene and its relation to chloroquine resistance in Mozambique.
K76T, a mutation in the Plasmodium falciparum chloroquine (CQ) resistance transporter protein, has been implicated in resistance to CQ. A modified 14-day in vivo test to estimate the CQ resistance level was done in southern Mozambique: 21 (42%) of 50 subjects who completed the follow-up were CQ susceptible. Use of msa2-restriction fragment length polymorphism (RFLP) genotyping to differentiate new from recrudescent infections made little difference in the estimated prevalence of resistance. The K76T mutation prevalence was estimated by RFLP-polymerase chain reaction and sequencing, and its relation to parasitological CQ resistance was explored on day 0 samples: 51 of 56 pretreatment samples presented the T76 codon, and it was present in 100% of children with parasitological resistance. T76 also was present in 18 of 23 subjects in whom the infection resolved after CQ treatment. These findings show a high prevalence of the K76T mutation among wild isolates but also suggest additional factors responsible for CQ resistance.
Mayor
A G
AG
Centro de Investigaçao em Saúde da Manhiça, Dirección Nacional de Saúde, Ministerio de Saúde, Maputo, Mozambique. epidemia@medicina.ub.es
Gómez-Olivé
X
X
Aponte
J J
JJ
Casimiro
S
S
Mabunda
S
S
Dgedge
M
M
Barreto
A
A
Alonso
P L
PL
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D003062:Codon; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D026901:Membrane Transport Proteins; D009073:Mozambique / Q000453:epidemiology; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D015800:Protozoan Proteins
D000962:Antimalarials; D003062:Codon; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine