Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
School of BioSciences, The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Australia.
J Infect Dis. 2020 Oct 13;222(10):1692-1701. doi: 10.1093/infdis/jiaa286.
The majority of Plasmodium falciparum infections, constituting the reservoir in all ages, are asymptomatic in high-transmission settings in Africa. The role of this reservoir in the evolution and spread of drug resistance was explored.
Population genetic analyses of the key drug resistance-mediating polymorphisms were analyzed in a cross-sectional survey of asymptomatic P. falciparum infections across all ages in Bongo District, Ghana.
Seven years after the policy change to artemisinin-based combination therapies in 2005, the pfcrt K76 and pfmdr1 N86 wild-type alleles have nearly reached fixation and have expanded via soft selective sweeps on multiple genetic backgrounds. By constructing the pfcrt-pfmdr1-pfdhfr-pfdhps multilocus haplotypes, we found that the alleles at these loci were in linkage equilibrium and that multidrug-resistant parasites have not expanded in this reservoir. For pfk13, 32 nonsynonymous mutations were identified; however, none were associated with artemisinin-based combination therapy resistance.
The prevalence and selection of alleles/haplotypes by antimalarials were similar to that observed among clinical cases in Ghana, indicating that they do not represent 2 subpopulations with respect to these markers. Thus, the P. falciparum reservoir in all ages can contribute to the maintenance and spread of antimalarial resistance.
在非洲高传播地区，大多数恶性疟原虫感染（构成所有年龄段的储存库）为无症状感染。本研究旨在探讨该储存库在耐药性演变和传播中的作用。
本研究在加纳邦戈区进行了一项横断面研究，对各年龄段的无症状恶性疟原虫感染进行了分析，采用了群体遗传学方法对关键耐药相关突变的多态性进行了分析。
在 2005 年抗疟药物政策改变为基于青蒿素的联合疗法后 7 年，pfcrt K76 和 pfmdr1 N86 野生型等位基因几乎已达到固定状态，并通过多种遗传背景的软选择而扩张。通过构建 pfcrt-pfmdr1-pfdhfr-pfdhps 多位点单倍型，我们发现这些基因座的等位基因处于连锁平衡状态，并且多药耐药寄生虫并未在该储存库中扩张。对于 pfk13，共鉴定出 32 个非同义突变，但均与基于青蒿素的联合疗法耐药无关。
抗疟药物对这些等位基因/单倍型的流行和选择与加纳临床病例中观察到的相似，这表明它们在这些标记物方面并不代表 2 个亚群。因此，各年龄段的恶性疟原虫储存库都可能有助于维持和传播抗疟药物耐药性。
