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Prevalence of the K76T Mutation in the PutativePlasmodium falciparumChloroquine Resistance Transporter(pfcrt)Gene and Its Relation to Chloroquine Resistance in Mozambique
Author(s) -
Alfredo Mayor,
F. Xavier GómezOlivé,
John J. Aponte,
Sónia Casimiro,
Samuel Mabunda,
Martinho Dgedge,
Avertino Barreto,
Pedro L. Alonso
Publication year - 2001
Publication title -
the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/319856
Subject(s) - chloroquine , biology , genotyping , plasmodium falciparum , restriction fragment length polymorphism , virology , apicomplexa , drug resistance , malaria , polymorphism (computer science) , mutation , polymerase chain reaction , genetics , immunology , genotype , gene
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.

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