Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V.
Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V.
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DOI：
10.1016/j.ijpddr.2016.08.004
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发表时间：
2016-12
影响因子：
4
通讯作者：
Roper, Cally
中科院分区：
文献类型：
--
作者：
Oguike, Mary C.;Falade, Catherine O.;Shu, Elvis;Enato, Izehiuwa G.;Watila, Ismaila;Baba, Ebenezer S.;Bruce, Jane;Webster, Jayne;Hamade, Prudence;Meek, Sylvia;Chandramohan, Daniel;Sutherland, Colin J.;Warhurst, David;Roper, Cally
在尼日利亚的恶性疟原虫种群中，很少有关于二氢蝶酸合成酶（dhps）和二氢叶酸还原酶（dhfr）基因突变的报道，但以前的一项研究记录了从尼日利亚输入英国的感染中密码子431处的新dhps突变。为了评估这种突变在该国不同地区寄生虫中的分布情况，从而填补尼日利亚磺胺嘧啶-乙胺嘧啶（SP）耐药数据的差距，我们回顾性分析了2003年至2015年期间从南部和北部四个地点对孕妇和儿童进行的调查中收集的1000个滤纸血点。从滤纸血斑和胎盘印迹中提取基因组DNA。通过巢式PCR扩增，然后直接测序来评估dhfr基因的密码子16、50、51、59、108、140和164以及dhps基因的密码子431、436、437、540、581和613处的点突变。dhps-431 V突变在整个尼日利亚分布广泛，在埃努古的患病率最高（46%）。在伊巴丹，我们进行了连续抽样，其患病率在2003年至2008年期间从0%增加到6.5%。虽然存在多种dhps突变与431 V的组合，但431 V +436 A +437 G +581 G +613 S的组合是最常见的。所有这些观察都支持dhps-431 V正在增加的观点。此外，恶性疟原虫DHPS晶体结构建模显示，从异亮氨酸到缬氨酸（dhps-431 V）的变化可以改变S436 A/F和A437 G两者的作用，其紧密跟随第二β链。因此，现在的研究重点是评估dhps-VAGKGS突变单倍型对继续使用SP进行季节性疟疾化学预防（SMC）和妊娠期间歇性预防治疗（IPTp）的影响。我们的数据还提供了2003年至2015年期间尼日利亚SP耐药标志物的监测数据。我们提供了尼日利亚恶性疟原虫群体中dhps和dhfr突变的数据。2003年至2015年期间，I431 V突变的患病率从0增加到36%。dhps-431 V突变以431 V +436 A +437 G +581 G +613 S最常见。Pf DHPS的晶体结构模拟表明，431 V可以改变S436 A和A437 G。
There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north. Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing. The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common. All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015. We present data on dhps and dhfr mutations in P. falciparum populations in Nigeria. Increased prevalence of I431V mutation was seen between 2003 and 2015 from 0 to 36%. The 431V + 436A + 437G + 581G + 613S was the most common with dhps-431V mutation. Crystal structure modelling of Pf DHPS shows that 431Vcould alter S436A and A437G.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.4269/ajtmh.1999.61.125
发表时间：
1999-07-01
影响因子：
3.3
作者：
Jelinek, T;Kilian, AHD;Warhurst, DC
通讯作者：
Warhurst, DC
影响因子：
5.2
作者：
Chauvin, Pamela;Menard, Sandie;Berry, Antoine
通讯作者：
Berry, Antoine
DOI：
10.1159/000360578
发表时间：
2014
期刊：
Medical principles and practice : international journal of the Kuwait University, Health Science Centre
影响因子：
--
作者：
Falade CO;Dada-Adegbola HO;Ogunkunle OO;Oguike MC;Nash O;Ademowo OG
通讯作者：
Ademowo OG
影响因子：
3.7
作者：
Gesase, Samwel;Gosling, Roly D.;Hashim, Ramadhan;Ord, Rosalynn;Naidoo, Inbarani;Madebe, Rashid;Mosha, Jacklin F.;Joho, Angel;Mandia, Victor;Mrema, Hedwiga;Mapunda, Ephraim;Savael, Zacharia;Mosha, Frank W.;Greenwood, Brian;Roper, Cally;Chandramohan, Daniel
通讯作者：
Chandramohan, Daniel