Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa.
Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa.
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DOI：
10.1186/1475-2875-10-79
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发表时间：
2011-04-06
期刊：
影响因子：
3
通讯作者：
Mugittu K
中科院分区：
文献类型：
--
作者：
Mwingira F;Nkwengulila G;Schoepflin S;Sumari D;Beck HP;Snounou G;Felger I;Olliaro P;Mugittu K
在开始治疗后的28-63天（取决于药物的停留时间）内评估抗疟疾药物的疗效，以捕获晚期失败。然而，长期随访会增加新感染的可能性，这取决于传播强度。因此，恶性疟原虫msp 1，msp 2和glurp基因座的高度多态性区域的分子基因分型通常进行区分复发（真正的失败）从新的感染。这一工具现已被作为抗疟疾疗效研究和临床试验的一个组成部分。然而，有人担心它的效用和可靠性，因为从分子分型得出的结论取决于各自的寄生虫种群的遗传概况，但这一概况没有系统地记录在大多数流行地区。本研究介绍了在选定的撒哈拉以南非洲国家，即马拉维，坦桑尼亚，乌干达，布基纳法索和圣多美的恶性疟原虫msp 1，msp 2和glurp标记的遗传多样性。在1996年至2000年期间进行的随机对照临床试验中招募了780份来自7岁以下儿童的基线（第0天）血液样本进行基因分型。提取DNA;等位基因频率和多样性通过PCR随后毛细管电泳检测msp 2，并通过数字化凝胶成像仪检测msp 1和glurp的片段大小。恶性疟原虫msp 1、msp 2和glurp标记多态性高，等位基因频率低。共记录了17种msp 1基因型[8种MAD 20-，1种RO 33-和8种K1-型]; 116种msp 2基因型[83种3D 7和33种FC27-型]和14种glurp基因型。所有5个位点均记录了非常高的预期杂合性（HE）值（0.68 - 0.99）。msp 2位点HE最高（HE = 0.99），msp 1位点最低（HE = 0.68）（P < 0.0001）。遗传多样性和等位基因频率与传播强度无关（P = 0.84，P = 0.25）。少数基因型具有特别高的频率;然而，最丰富的基因型显示新感染与基线感染共享相同基因型的概率仅为4%。这不太可能混淆复发与新感染的区别，特别是如果使用一种以上的标记进行基因分型。因此，这项研究支持在撒哈拉以南非洲的疟疾临床试验中使用msp 1，msp 2和glurp来区分新的复发感染。
The efficacy of anti-malarial drugs is assessed over a period of 28-63 days (depending on the drugs' residence time) following initiation of treatment in order to capture late failures. However, prolonged follow-up increases the likelihood of new infections depending on transmission intensity. Therefore, molecular genotyping of highly polymorphic regions of Plasmodium falciparum msp1, msp2 and glurp loci is usually carried out to distinguish recrudescence (true failures) from new infections. This tool has now been adopted as an integral part of anti-malarial efficacy studies and clinical trials. However, there are concerns over its utility and reliability because conclusions drawn from molecular typing depend on the genetic profile of the respective parasite populations, but this profile is not systematically documented in most endemic areas. This study presents the genetic diversity of P. falciparum msp1, msp2 and glurp markers in selected sub-Saharan Africa countries with varying levels of endemicity namely Malawi, Tanzania, Uganda, Burkina Faso and São Tomé. A total 780 baseline (Day 0) blood samples from children less than seven years, recruited in a randomized controlled clinical trials done between 1996 and 2000 were genotyped. DNA was extracted; allelic frequency and diversity were investigated by PCR followed by capillary electrophoresis for msp2 and fragment sizing by a digitalized gel imager for msp1 and glurp. Plasmodium falciparum msp1, msp2 and glurp markers were highly polymorphic with low allele frequencies. A total of 17 msp1 genotypes [eight MAD20-, one RO33- and eight K1-types]; 116 msp2 genotypes [83 3D7 and 33 FC27- types] and 14 glurp genotypes were recorded. All five sites recorded very high expected heterozygosity (HE) values (0.68 - 0.99). HE was highest in msp2 locus (HE = 0.99), and lowest for msp1 (HE = 0.68) (P < 0.0001). The genetic diversity and allelic frequency recorded were independent of transmission intensity (P = 0.84, P = 0.25 respectively. A few genotypes had particularly high frequencies; however the most abundant showed only a 4% probability that a new infection would share the same genotype as the baseline infection. This is unlikely to confound the distinction of recrudescence from new infection, particularly if more than one marker is used for genotyping. Hence, this study supports the use of msp1, msp2 and glurp in malaria clinical trials in sub-Saharan Africa to discriminate new from recrudescent infections.
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影响因子：
3.3
作者：
Mugittu, Kefas;Priotto, Gerardo;Taylor, Walter R. J.
通讯作者：
Taylor, Walter R. J.
影响因子：
3
作者：
Soulama I;Nébié I;Ouédraogo A;Gansane A;Diarra A;Tiono AB;Bougouma EC;Konaté AT;Kabré GB;Taylor WR;Sirima SB
通讯作者：
Sirima SB
DOI：
10.1016/s0035-9203(99)90324-3
发表时间：
1999-02-01
影响因子：
2.2
作者：
Felger, I;Smith, T;Beck, HP
通讯作者：
Beck, HP
DOI：
10.1016/s0035-9203(99)90120-7
发表时间：
1999-07-01
影响因子：
2.2
作者：
Snounou, G;Zhu, XP;Viriyakosol, S
通讯作者：
Viriyakosol, S
影响因子：
168.9
作者：
Mutabingwa, TK;Anthony, D;Whitty, CJM
通讯作者：
Whitty, CJM