Polymorphisms in Plasmodium Falciparum Chloroquine Resistance Transporter (Pfcrt) and Multidrug-Resistant Gene 1 (Pfmdr-1) in Nigerian children 10 years Post-Adoption Of Artemisinin-Based Combination Treatments
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Date
2020-12-24
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Elsevier: International Journal for Parasitology
Abstract
The emergence and spread of Plasmodium falciparum parasites resistant to artemisinin derivatives and
their partners in southeastern Asia threatens malaria control and elimination efforts, and heightens
the need for an alternative therapy. We have explored the distribution of P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr-1) haplotypes 10 years following adoption of artemisinin-based combination therapies in a bid to investigate the possible re-emergence of
Chloroquine-sensitive parasites in Nigeria, and investigated the effect of these P. falciparum haplotypes
on treatment outcomes of patients treated with artemisinin-based combination therapies. A total of
271 children aged <5 years with uncomplicated falciparum malaria were included in this study.
Polymorphisms on codons 72–76 of the Pfcrt gene and codon 86 and 184 of Pfmdr-1 were determined
using the high resolution melting assay. Of 240 (88.6%) samples successfully genotyped with HRM for
Pfcrt, wildtype C72M74N75K76 (42.9%) and mutant C72I74E75T76 (53.8%) were observed. Also, wildtype
N86Y184 (62.9%) and mutant N86F184 (21.1%), Y86Y184 (6.4%), and Y86F184 (0.4%) haplotypes of Pfmdr-1 were
observed. Measures of responsiveness to ACTs were similar in children infected with P. falciparum crt
haplotypes (C72I74E75T76 and C72M74N75K76) and major mdr-1 haplotypes (N86Y184, N86F184 and
Y86Y184). Despite a 10 year gap since the malaria treatment policy changed to ACTs, over 50% of the P. falciparum parasites investigated in this study harboured the Chloroquine-resistant C72I74E75T76 haplotype,
however this did not compromise the efficacy of artemisinin-based combination therapies. Should complete artemisinin resistance emerge from or spread to Nigeria, chloroquine might not be a good alternative therapy
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Keywords
Malaria, Plasmodium falciparum, HRM, Pfcrt, Pfmdr-1, Drug resistance Nigeria