Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study.

Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study.
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DOI:
10.1186/s40249-017-0350-y
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发表时间:
2017-11-06
影响因子:
8.1
通讯作者:
Amambua-Ngwa A
Amambua-Ngwa A
中科院分区:
医学1区
文献类型:
--
作者:
Apinjoh TO;Mugri RN;Miotto O;Chi HF;Tata RB;Anchang-Kimbi JK;Fon EM;Tangoh DA;Nyingchu RV;Jacob C;Amato R;Djimde A;Kwiatkowski D;Achidi EA;Amambua-Ngwa A

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抗药性是疟疾控制方案面临的最大挑战之一,监测寄生虫对青蒿素或青蒿素综合疗法伙伴药物的抗药性对消灭工作至关重要。在喀麦隆西南部的自然寄生虫种群中评估了对广泛的抗疟药物的抗性标记。通过2013年5月至2014年3月沿着喀麦隆山斜坡的横断面调查,招募了无症状寄生虫病或无并发症疟疾患者。使用CF 11纤维素柱去除通过光学显微镜筛选的恶性疟原虫疟疾寄生虫血中的白细胞,并通过在Illumina HiSeq平台上测序确定寄生虫基因型。共有259名来自三个不同海拔的参与者参加了这项研究。虽然pfdhfr、pfmdr 1和pfcrt中与耐药性相关的一些等位基因非常普遍,但所有样本中只有不到3%的pfkelch 13基因携带突变,这些突变都与东南亚青蒿素寄生虫清除率缓慢有关。最普遍的单倍型是三重突变体Pfdhfr I51 R59 N108 I164(99%)、pfcrt-C72 V73 I74 E75 T76(47.3%)和单突变体PfdhpsS 436 G437 K540 A581 A613(69%)和Pfmdr 1 N86 F184 D1246(53.2%).占主导地位的Pf pfcrt CVIET和Pf dhfr IRN三重突变体寄生虫和pfkelch 13抗性等位基因的情况下,阿莫地喹和乙胺嘧啶成分的AS-AQ和SP可能不再是有效的,而氯喹耐药性仍然存在于喀麦隆西南部。本文的在线版本(doi:10.1186/s40249-017-0350-y)包含补充材料,可供授权用户使用。
Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon. Plasmodium falciparum malaria parasitaemic blood, screened by light microscopy, was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform. A total of 259 participants were enrolled in this study from three different altitudes. While some alleles associated with drug resistance in pfdhfr, pfmdr1 and pfcrt were highly prevalent, less than 3% of all samples carried mutations in the pfkelch13 gene, none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia. The most prevalent haplotypes were triple mutants Pfdhfr I 51 R 59 N 108 I 164(99%), pfcrt- C72V73 I 74 E 75 T 76 (47.3%), and single mutants PfdhpsS436 G 437K540A581A613(69%) and Pfmdr1 N86 F 184D1246 (53.2%). The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon. The online version of this article (doi:10.1186/s40249-017-0350-y) contains supplementary material, which is available to authorized users.
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