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

被引:37
作者
Frank, Matthias [1 ,2 ]
Lehners, Nicola [1 ]
Mayengue, Pembe I. [1 ,5 ]
Gabor, Julian [1 ,2 ]
Dal-Bianco, Matthias [1 ,2 ]
Kombila, David U. [1 ,2 ]
Ngoma, Ghyslain Mombo [1 ,2 ,6 ]
Supan, Christian [1 ,2 ]
Lell, Bertrand [1 ,2 ]
Ntoumi, Francine [1 ,2 ,5 ]
Grobusch, Martin P. [1 ,2 ,4 ]
Dietz, Klaus [3 ]
Kremsner, Peter G. [1 ,2 ]
机构
[1] Univ Tubingen, Inst Trop Med, Wilhelmstr 27, D-72074 Tubingen, Germany
[2] Albert Schweitzer Hosp, Med Res Unit, Lambarene, Gabon
[3] Univ Tubingen, Dept Med Biometry, D-72074 Tubingen, Germany
[4] Univ Amsterdam, Amsterdam Med Ctr, NL-1012 WX Amsterdam, Netherlands
[5] Univ Marien Ngouabi, Fac Hlth Sci, Congolese Fdn Med Res, Brazzaville, Rep Congo
[6] Univ Sci Sante, Dept Parasitol, Libreville, Gabon
来源
MALARIA JOURNAL | 2011年 / 10卷
关键词
chloroquine resistance; chloroquine sensitivity; microsatellite analysis; haplotype analysis; artesunate plus amodiaquine; RESISTANCE TRANSPORTER GENE; MOLECULAR MARKERS; DRUG-RESISTANCE; ANTIMALARIAL-DRUG; SELECTIVE SWEEPS; MALARIA; MALAWI; MUTATIONS; AMODIAQUINE; PREVALENCE;
D O I
10.1186/1475-2875-10-304
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.
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