Parasitology and Mycology Laboratory, Université Cheikh Anta Diop, Dakar, Senegal.
Division of Vector Borne Diseases, ICMR-National Institute of Research in Tribal Health, Jabalpur, India.
Infect Genet Evol. 2018 Dec;66:222-228. doi: 10.1016/j.meegid.2018.10.007. Epub 2018 Oct 11.
Malaria is an age-old disease of human kind living in the tropical and sub-tropical regions of the globe, with Africa contributing the highest incidence of morbidity and mortality. Among many hurdles, evolution and spread of drug-resistant Plasmodium falciparum parasites constitute major challenges to malaria control and elimination. Information on molecular epidemiology and pattern of evolution of genes conferring resistance to different antimalarials are needed to track the route of the spread of resistant parasites and also to inform if the drug-resistant genes are adapted in the population following the Darwinian model of evolution. In the present study, we have followed molecular methods to detect both the known and emerging mutations in three genes (Pfcrt, Pfdhfr and Pfdhps) of P. falciparum conferring resistance to chloroquine and sulfadoxine-pyrimethamine from two different states (Edo: meso-endemic and Lagos: hypo-endemic) in southwestern Nigeria. High diversities in haplotypes and nucleotides in genes responsible for chloroquine (Pfcrt) and sulfadoxine (Pfdhps) resistance are recorded. About 96% of Pfdhfr and Pfdhps gene in both the meso- and hypo- endemic areas were mutant type, followed by 61% in Pfcrt gene. Many unique haplotypes of Pfdhps and Pfcrt were found to be segregated in these two populations. One particular mutant haplotype of Pfdhfr (AIRNI) was found to be in very high frequency in both Lagos and Edo. While the net haplotype diversity was highest in Pfdhps (0.81 in Lagos, 0.87 in Edo), followed by Pfcrt (0.69 in Lagos, 0.65 in Edo); highest number of haplotype was found in Pfdhps with 13 distinct haplotypes, followed by seven in Pfcrt and four in Pfdhfr gene. Moreover, detection of strong linkage among mutations of Pfcrt and Pfdhfr and feeble evidence for balancing selection in Pfdhps are indicative of evolutionary potential of mutation in genes responsible for drug resistance in Nigerian populations of P. falciparum.
疟疾是一种古老的疾病，影响着生活在全球热带和亚热带地区的人类。在众多挑战中，疟原虫对药物的抗药性的进化和传播是疟疾控制和消除的主要障碍。了解分子流行病学和导致不同抗疟药物耐药性的基因进化模式的信息，有助于追踪耐药寄生虫的传播途径，并确定耐药基因是否按照达尔文进化模式在人群中适应。在本研究中，我们采用分子方法检测了来自尼日利亚西南部两个不同州（埃多：中度流行区和拉各斯：低度流行区）的恶性疟原虫对氯喹和磺胺多辛-乙胺嘧啶耐药的三个基因（Pfcrt、Pfdhfr 和 Pfdhps）中的已知和新出现的突变。在负责氯喹（Pfcrt）和磺胺多辛（Pfdhps）耐药的基因中，记录到了高度的单倍型和核苷酸多样性。在中、低度流行区，约 96%的 Pfdhfr 和 Pfdhps 基因发生突变，其次是 Pfcrt 基因的 61%。在这两个人群中，发现了许多独特的 Pfdhps 和 Pfcrt 单倍型。在拉各斯和埃多，都发现了一种非常高频率的 Pfdhfr 特定突变体（AIRNI）。虽然在 Pfdhps 中的净单倍型多样性最高（拉各斯为 0.81，埃多为 0.87），其次是 Pfcrt（拉各斯为 0.69，埃多为 0.65）；但 Pfdhps 中发现的单倍型最多，有 13 个不同的单倍型，其次是 Pfcrt 有 7 个，Pfdhfr 有 4 个。此外，Pfcrt 和 Pfdhfr 突变之间的强连锁和 Pfdhps 中平衡选择的微弱证据表明，在尼日利亚恶性疟原虫人群中，耐药基因的突变具有进化潜力。
