Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum.
Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum.
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DOI：
10.1186/1475-2875-12-249
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发表时间：
2013-07-17
期刊：
影响因子：
3
通讯作者：
Guerin PJ
中科院分区：
文献类型：
--
作者：
Flegg JA;Patil AP;Venkatesan M;Roper C;Naidoo I;Hay SI;Sibley CH;Guerin PJ
恶性疟原虫一再对一线抗疟疾药物产生抗药性，阻碍了控制和消灭这种疾病的努力，在一段时间内，这在很大程度上导致死亡率上升。在这里，一个数学模型被开发来映射的时空趋势的突变分布在恶性疟原虫二氢蝶酸合成酶（dhps）基因，赋予抗疟疾磺胺嘧啶的抗性，是一个有用的标志物组合的等位基因在dhfr和dhps是高度相关的磺胺嘧啶-乙胺嘧啶（SP）的抗性。这项研究的目的是提出一个概念证明，用于建立抗疟疾药物耐药性趋势的时空模型，可用于监测青蒿素综合疗法或其他抗疟疾药物耐药性出现或传播的趋势。在三个密码子位置的二氢蝶酸合成酶（dhps）基因的单核苷酸多态性的患病率测量从整个非洲的dhps突变的已发表的研究。采用基于模型的地质统计学方法来创建1990-2010年撒哈拉以南非洲空间域dhps 540 E突变的预测表面。统计模型是在贝叶斯框架内实施的，因此量化了撒哈拉以南非洲dhps 540 E突变患病率预测的相关不确定性。这些地图显示了撒哈拉以南非洲dhps 540 E突变流行率的变化。这些可以预测的空间-时间趋势的寄生虫耐药性SP，并提供概率分布的耐药流行的地方，没有数据，以及洞察力的传播的方式，数据本身不允许。这项工作的结果将被扩展到设计最佳的采样策略，为未来的耐药性分子监测，提供了一个概念证明类似的技术，设计最佳的策略，以监测耐药性ACT。
Plasmodium falciparum has repeatedly evolved resistance to first-line anti-malarial drugs, thwarting efforts to control and eliminate the disease and in some period of time this contributed largely to an increase in mortality. Here a mathematical model was developed to map the spatiotemporal trends in the distribution of mutations in the P. falciparum dihydropteroate synthetase (dhps) gene that confer resistance to the anti-malarial sulphadoxine, and are a useful marker for the combination of alleles in dhfr and dhps that is highly correlated with resistance to sulphadoxine-pyrimethamine (SP). The aim of this study was to present a proof of concept for spatiotemporal modelling of trends in anti-malarial drug resistance that can be applied to monitor trends in resistance to components of artemisinin combination therapy (ACT) or other anti-malarials, as they emerge or spread. Prevalence measurements of single nucleotide polymorphisms in three codon positions of the dihydropteroate synthetase (dhps) gene from published studies of dhps mutations across Africa were used. A model-based geostatistics approach was adopted to create predictive surfaces of the dhps540E mutation over the spatial domain of sub-Saharan Africa from 1990-2010. The statistical model was implemented within a Bayesian framework and hence quantified the associated uncertainty of the prediction of the prevalence of the dhps540E mutation in sub-Saharan Africa. The maps presented visualize the changing prevalence of the dhps540E mutation in sub-Saharan Africa. These allow prediction of space-time trends in the parasite resistance to SP, and provide probability distributions of resistance prevalence in places where no data are available as well as insight on the spread of resistance in a way that the data alone do not allow. The results of this work will be extended to design optimal sampling strategies for the future molecular surveillance of resistance, providing a proof of concept for similar techniques to design optimal strategies to monitor resistance to ACT.
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影响因子：
3
作者：
Enevold, Anders;Nkya, Watoky M. M. M.;Theisen, Michael;Vestergaard, Lasse S.;Jensen, Anja T. R.;Staalsoe, Trine;Theander, Thor G.;Bygbjerg, Ib C.;Alifrangis, Michael
通讯作者：
Alifrangis, Michael
DOI：
10.1086/596741
发表时间：
2009-03-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Greenhouse B;Slater M;Njama-Meya D;Nzarubara B;Maiteki-Sebuguzi C;Clark TD;Staedke SG;Kamya MR;Hubbard A;Rosenthal PJ;Dorsey G
通讯作者：
Dorsey G
DOI：
10.1073/pnas.0901415106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Harrington, W. E.;Mutabingwa, T. K.;Duffy, P. E.
通讯作者：
Duffy, P. E.
影响因子：
3
作者：
Gething PW;Patil AP;Smith DL;Guerra CA;Elyazar IR;Johnston GL;Tatem AJ;Hay SI
通讯作者：
Hay SI
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