Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania.
Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania.
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DOI：
10.1186/s12936-015-0783-3
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发表时间：
2015-07-08
期刊：
影响因子：
3
通讯作者：
Swedberg G
中科院分区：
文献类型：
--
作者：
Golassa L;Kamugisha E;Ishengoma DS;Baraka V;Shayo A;Baliraine FN;Enweji N;Erko B;Aseffa A;Choy A;Swedberg G
恶性疟原虫对抗疟药物的抗药性是全球有效控制和消除疟疾的一个主要障碍。青蒿素联合疗法（ACT）目前是无并发症恶性疟疾的主要一线治疗方法。已知恶性疟原虫pfmdr-1、pfcrt和pfubp-1基因座的遗传特征可调节体内和体外寄生虫对ACT的反应。本研究的目的是评估这些耐药基因标记在埃塞俄比亚和坦桑尼亚不同疟疾传播强度的分离株中的分布。恶性疟原虫临床分离株收集自埃塞俄比亚和坦桑尼亚的不同地区。采用PCR和测序方法分析pfcrt、pfmdr-1和pfubp-1基因的遗传多态性。在这三个基因的不同等位基因的频率进行了比较内和地区之间，以及两国之间。来自埃塞俄比亚的大多数分离物是pfcrt 76的突变体和pfmdr-1 86的野生型。相比之下，大多数坦桑尼亚样本的pfcrt和pfmdr-1基因座均为野生型。在pfmdr-1的可变接头区的分析表明，从坦桑尼亚的分离株相比，埃塞俄比亚的分离株，有很小的变化有很大的变化。pfubp-1区的直接测序显示，92.8%（26/28）的埃塞俄比亚分离株与野生型参考恶性疟原虫菌株3D 7具有相同的基因组序列。在42个来自坦桑尼亚的分离株中，只有13个（30.9%）与3D 7具有相同的基因组序列。在坦桑尼亚样本中，鉴定了10种变异单倍型。大多数埃塞俄比亚分离株携带氯喹（CQ）抗性的主要标记，而来自坦桑尼亚的大多数样品携带CQ敏感性标记。多态性基因在坦桑尼亚分离株中表现出更多的变异。在埃塞俄比亚的pfmdr-1的多态性区域的低变异性可能是低传输强度相比，坦桑尼亚的高传输强度和大的变化的结果。
Plasmodium falciparum resistance to anti-malarials is a major drawback in effective malaria control and elimination globally. Artemisinin-combination therapy (ACT) is currently the key first-line treatment for uncomplicated falciparum malaria. Plasmodium falciparum genetic signatures at pfmdr-1, pfcrt, and pfubp-1 loci are known to modulate in vivo and in vitro parasite response to ACT. The objective of this study was to assess the distribution of these resistance gene markers in isolates collected from different malaria transmission intensity in Ethiopia and Tanzania. Plasmodium falciparum clinical isolates were collected from different regions of Ethiopia and Tanzania. Genetic polymorphisms in the genes pfcrt, pfmdr-1 and pfubp-1 were analysed by PCR and sequencing. Frequencies of the different alleles in the three genes were compared within and between regions, and between the two countries. The majority of the isolates from Ethiopia were mutant for the pfcrt 76 and wild-type for pfmdr-1 86. In contrast, the majority of the Tanzanian samples were wild-type for both pfcrt and pfmdr-1 loci. Analysis of a variable linker region in pfmdr-1 showed substantial variation in isolates from Tanzania as compared to Ethiopian isolates that had minimal variation. Direct sequencing of the pfubp-1 region showed that 92.8% (26/28) of the Ethiopian isolates had identical genome sequence with the wild type reference P. falciparum strain 3D7. Of 42 isolates from Tanzania, only 13 (30.9%) had identical genome sequences with 3D7. In the Tanzanian samples, 10 variant haplotypes were identified. The majority of Ethiopian isolates carried the main marker for chloroquine (CQ) resistance, while the majority of the samples from Tanzania carried markers for CQ susceptibility. Polymorphic genes showed substantially more variation in Tanzanian isolates. The low variability in the polymorphic region of pfmdr-1 in Ethiopia may be a consequence of low transmission intensity as compared to high transmission intensity and large variations in Tanzania.
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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.
DOI：
10.1093/infdis/jiu358
发表时间：
2014-12-15
期刊：
The Journal of infectious diseases
影响因子：
--
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
通讯作者：
Sutherland CJ
DOI：
10.1056/nejmp1108322
发表时间：
2011-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Dondorp AM;Fairhurst RM;Slutsker L;Macarthur JR;Breman JG;Guerin PJ;Wellems TE;Ringwald P;Newman RD;Plowe CV
通讯作者：
Plowe CV
影响因子：
16
作者：
Fidock, DA;Nomura, T;Wellems, TE
通讯作者：
Wellems, TE