Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.
Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.
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DOI：
10.1093/infdis/jiu358
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发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Sutherland CJ
中科院分区：
文献类型：
--
作者：
Henriques G;Hallett RL;Beshir KB;Gadalla NB;Johnson RE;Burrow R;van Schalkwyk DA;Sawa P;Omar SA;Clark TG;Bousema T;Sutherland CJ
基于青蒿素的联合疗法（ACT）治疗恶性疟原虫疟疾的疗效可能会受到对青蒿素反应性降低的寄生虫的威胁。在肯尼亚Mbita的298名接受青蒿素综合疗法治疗的儿童中，治疗后第3天亚显微镜下恶性疟原虫的持续存在与随后在第28或42天显微镜下检测到的寄生虫血症有关。在治疗前、治疗开始后第2天和第3天以及治疗失败当天，在Mbita队列中测定耐药相关寄生虫基因座pfcrt、pfmdr 1、pfubp 1和pfap 2 mu的DNA序列。在ACT治疗后第2天或第3天存活的寄生虫比基线人群更可能携带pfcrt（密码子72-76处的CVMNK; P <0.001）和pfmdr 1（密码子86、184、1246处的NFD; P <0.001）的野生型单倍型。相比之下，新候选抗性基因pfap 2 mu（S160 N/T; P = .006）和pfubp-1（E1528 D; P < .001）的变异等位基因在治疗后显著更普遍。没有发现与最近在柬埔寨描述的青蒿素耐受寄生虫的遗传相似性。在肯尼亚西部接受治疗的儿童中，pfcrt、pfmdr 1、pfap 2 mu和pfubp 1的某些恶性疟原虫基因型在亚显微镜水平上更容易在ACT中存活，并有助于向前传播和随后的复发。
The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42. DNA sequences of resistance-associated parasite loci pfcrt, pfmdr1, pfubp1, and pfap2mu were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment, and on the day of treatment failure. Parasites surviving ACT on day 2 or day 3 posttreatment were significantly more likely than the baseline population to carry the wild-type haplotypes of pfcrt (CVMNK at codons 72–76; P < .001) and pfmdr1 (NFD at codons 86, 184, 1246; P < .001). In contrast, variant alleles of the novel candidate resistance genes pfap2mu (S160N/T; P = .006) and pfubp-1 (E1528D; P < .001) were significantly more prevalent posttreatment. No genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia. Among treated children in western Kenya, certain P. falciparum genotypes defined at pfcrt, pfmdr1, pfap2mu, and pfubp1 more often survive ACT at the submicroscopic level, and contribute to onward transmission and subsequent patent recrudescence.
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影响因子：
6.4
作者：
Sawa, Patrick;Shekalaghe, Seif A.;Bousema, Teun
通讯作者：
Bousema, Teun
影响因子：
4.6
作者：
Borrmann S;Straimer J;Mwai L;Abdi A;Rippert A;Okombo J;Muriithi S;Sasi P;Kortok MM;Lowe B;Campino S;Assefa S;Auburn S;Manske M;Maslen G;Peshu N;Kwiatkowski DP;Marsh K;Nzila A;Clark TG
通讯作者：
Clark TG
影响因子：
4.9
作者：
Humphreys, G. S.;Merinopoulos, I.;Hallett, R. L.
通讯作者：
Hallett, R. L.
影响因子：
3
作者：
Henriques, Gisela;Martinelli, Axel;Cravo, Pedro
通讯作者：
Cravo, Pedro
影响因子：
6.4
作者：
Preston, Mark D.;Assefa, Samuel A.;Clark, Taane G.
通讯作者：
Clark, Taane G.