A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon

Autor: Ghyslain Mombo Ngoma, Matthias P. Dal-Bianco, Martin P. Grobusch, Nicola Lehners, Pembe Issamou Mayengue, Klaus Dietz, Julian J. Gabor, Francine Ntoumi, Peter G. Kremsner, David U Kombila, Bertrand Lell, Matthias Frank, Christian Supan
Přispěvatelé: Faculteit der Geneeskunde, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Infectious diseases
Jazyk: angličtina
Rok vydání: 2011
Předmět:
lcsh:Arctic medicine. Tropical medicine
microsatellite analysis
haplotype analysis
lcsh:RC955-962
Molecular Sequence Data
Plasmodium falciparum
Drug Resistance
Protozoan Proteins
Amodiaquine
Drug resistance
Biology
Polymerase Chain Reaction
lcsh:Infectious and parasitic diseases
chemistry.chemical_compound
Antimalarials
Chloroquine
parasitic diseases
medicine
Humans
lcsh:RC109-216
Gabon
Selection
Genetic
artesunate plus amodiaquine
chloroquine resistance
Research
Health Policy
Haplotype
Membrane Transport Proteins
Sequence Analysis
DNA
DNA
Protozoan
medicine.disease
biology.organism_classification
Virology
Artemisinins
Malaria
Drug Combinations
Infectious Diseases
chemistry
Parasitology
Haplotypes
Artesunate
chloroquine sensitivity
Polymorphism
Restriction Fragment Length
medicine.drug
Microsatellite Repeats
Zdroj: Malaria Journal, 10(1). BioMed Central
Malaria Journal, Vol 10, Iss 1, p 304 (2011)
Malaria Journal
Malaria journal, 10(1). BioMed Central
ISSN: 1475-2875
Popis: Background Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania. In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant pfcrt allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003. Methods The prevalence of the wild type pfcrt allele was assessed in 144 isolates from the years 2005 - 07 by PCR fragment restriction digest and direct sequencing. For haplotype analysis of the chromosomal regions flanking the pfcrt locus, microsatellite analysis was done on a total of 145 isolates obtained in 1995/96 (43 isolates), 2002 (47 isolates) and 2005 - 07 (55 isolates). Results The prevalence of the mutant pfcrt allele decreased from 100% in the years 1995/96 and 2002 to 97% in 2005 - 07. Haplotype analysis showed that in 1995/96 79% of the isolates carried the same microsatellite alleles in a chromosomal fragment spanning 39 kb surrounding the pfcrt locus. In 2002 and 2005 - 07 the prevalence of this haplotype was 62% and 58%, respectively. Pfcrt haplotype analysis showed that all wild type alleles were CVMNK. Conclusion Four years after the withdrawal of CQ from national treatment guidelines the prevalence of the mutant pfcrt allele remains at 97%. The data suggest that the combination of artesunate plus AQ may result in continued selection for the mutant pfcrt haplotype even after discontinuance of CQ usage.
Databáze: OpenAIRE
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