Antifolate antimalarial resistance in southeast Africa: a population-based analysis
Antifolate antimalarial resistance in southeast Africa: a population-based analysis
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DOI：
10.1016/s0140-6736(03)12951-0
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发表时间：
2003-04-05
期刊：
影响因子：
168.9
通讯作者：
Sharp, B
中科院分区：
文献类型：
--
作者：
Roper, C;Pearce, R;Sharp, B
20世纪80年代初，磺胺嘧啶-乙胺嘧啶首次在非洲用于治疗氯喹治疗失败的疟疾病例，此后成为许多国家的一线治疗方法。磺胺嘧啶，乙胺嘧啶的耐药性正在增加，特别是在东南African.Methods我们的特点在恶性疟原虫种群的夸祖鲁-纳塔尔，南非，在1995-99年期间，磺胺嘧啶，乙胺嘧啶的有效性迅速恶化的dhfr和dhps基因的遗传变化。我们通过分析dhfr和dhps基因侧翼区域的多态性微卫星重复序列来评估抗性的进化起源，这表明抗性等位基因是否起源于共享或独立的祖先突变事件。然后，我们通过对2001年坦桑尼亚北方基利曼哈罗地区社区采集的恶性疟原虫样本进行同样的分析，评估了dhfr和dhps抗性等位基因目前的扩散程度。结果在南非夸祖鲁-纳塔尔的卫生设施和更广泛的社区调查中，1995-99年期间的大遗传变化发生在dhps位点，显然是因为1995年以前就在达尔富尔难民营建立了抵抗力量。在这个省的抗性的等位基因决定因素有一个共同的进化起源与那些发现在基利曼哈罗，Tanzania，即使这两个网站是4000 km apart.Interpretation三个抗性dhfr等位基因，和一个抗性dhps等位基因，每个来自独立的祖先谱系，已被驱动通过非洲东南部。dhfr等位基因（乙胺嘧啶抗性）的移动先于dhps等位基因（磺胺嘧啶抗性）。我们的研究结果强调，基因流动而不是新的突变是非洲国家最常见的耐药性起源。
Background Sulfadoxine-pyrimethamine was first introduced for treatment of malaria in Africa during the early 1980s for cases when chloroquine treatment failed, and has since become the first-line treatment in many countries. Resistance to sulfadoxine-pyrimethamine is now increasing, especially in southeast Africa.Methods We characterised genetic change in dhfr and dhps genes in the Plasmodium falciparum population of KwaZulu-Natal, South Africa, during 1995-99, a period of rapid deterioration of the effectiveness of sulfadoxine-pyrimethamine. We assessed the evolutionary origin of the resistance by analysing polymorphic microsatellite repeats in the flanking region of the dhfr and dhps genes, which show whether resistance alleles originated through shared or independent ancestral mutation events. We then assessed the current extent of dispersal of dhfr and dhps resistance alleles by doing the same analysis in P falciparum sampled from communities in the Kilimanjaro region of northern Tanzania in 2001.Findings The large genetic change during 1995-99 in KwaZulu-Natal, South Africa, in both the health facility and the wider community surveys, was at the dhps locus, apparently because resistance at dhfr was established before 1995. The allelic determinants of resistance in this province share a common evolutionary origin with those found in Kilimanjaro, Tanzania, even though the two sites are 4000 km apart.Interpretation Three resistant dhfr alleles, and one resistant dhps allele, each derived from independent ancestral lineages, have been driven through through southeast Africa. The movement by the dhfr alleles (pyrimethamine resistance) preceded that of the dhps allele (sulfadoxine resistance). Our findings emphasise that gene flow rather than new mutations has been the most common originator of resistance in African countries.