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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
In vitro amodiaquine resistance and its association with mutations in pfcrt and pfmdr1 genes of Plasmodium falciparum isolates from Nigeria
Acta Tropica, Volume 120, No. 3, Year 2011
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Description
Amodiaquine (AQ) is currently being used as a partner drug in combination with artesunate for treatment of uncomplicated malaria in most endemic countries of Africa. In the absence of molecular markers of artemisinin resistance, molecular markers of resistance to AQ may be useful for monitoring the development and spread of parasites resistance to Artesunate-Amodiaquine combination. This study was designed to assess the potential role of polymorphisms on pfcrt and pfmdr1 genes and parasite in vitro susceptibility for epidemiological surveillance of amodiaquine resistance in Plasmodium falciparum. The modified schizont inhibition assay was used to determine in vitro susceptibility profiles of 98 patients' isolates of P. falciparum to amodiaquine. Polymorphisms on parasites pfcrt and pfmdr1 genes were determined with nested PCR followed by sequencing.The geometric mean (GM) of AQ 50% inhibitory concentration (IC-50) in the 97 P. falciparum isolates was 20.48. nM (95% CI 16.53-25.36. nM). Based on the cut-off value for AQ in vitro susceptibility, 87% (84) of the P. falciparum isolates were sensitive to AQ (GM IC-50. = 16.32. nM; 95%CI 13.3-20.04. nM) while 13% were resistant to AQ in vitro (GM IC-50. = 88.73. nM; 95%CI 69.67-113.0. nM). Molecular analysis showed presence of mutant CVIET pfcrt haplotype, mutant pfmdr1Tyr86 allele and the double mutant CVIET pfcrt haplotype. +. pfmdr1Tyr86 in 72%, 49% and 35%, respectively. The GM IC-50 of isolates harboring the wild-type pfcrt CVMNK haplotype. +. pfmdr1Asn86 allele (3.93. nM; 95%CI 1.82-8.46. nM) was significantly lower (p= 0.001) than those isolates harboring the double mutant pfcrt CVIET haplotype. +. pfmdr1Tyr86 allele (50.40. nM; 95%CI 40.17-63.24. nM).Results from this study suggest that polymorphisms in pfcrt and pfmdr1 genes are important for AQ resistance and therefore may be useful for epidemiological surveillance of P. falciparum resistance to AQ. © 2011 Elsevier B.V.
Authors & Co-Authors
Folarin, Onikepe Abiola
Nigeria, Ibadan
College of Medicine, University of Ibadan
Bustamante, Carolina
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Gbotosho, Grace Olusola
Nigeria, Ibadan
College of Medicine, University of Ibadan
Sowunmi, Akintunde
Nigeria, Ibadan
College of Medicine, University of Ibadan
Zalis, Mariano G.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Oduola, Ayoade M.J.
Switzerland, Geneva
Organisation Mondiale de la Santé
Happi, Christian Tientcha
Nigeria, Ibadan
College of Medicine, University of Ibadan
Statistics
Citations: 53
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1016/j.actatropica.2011.08.013
ISSN:
0001706X
e-ISSN:
18736254
Research Areas
Genetics And Genomics
Infectious Diseases
Study Locations
Nigeria