Mbaye Aminata, Gaye Amy, Dieye Baba, Ndiaye Yaye D, Bei Amy K, Affara Muna, Deme Awa B, Yade Mamadou S, Diongue Khadim, Ndiaye Ibrahima M, Ndiaye Tolla, Sy Mouhamed, Sy Ngayo, Koita Ousmane, Krogstad Donald J, Volkman Sarah, Nwakanma Davis, Ndiaye Daouda
Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Malar J. 2017 Jun 14;16(1):250. doi: 10.1186/s12936-017-1897-6.
The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine-pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006. The purpose of this study is to assess the ex vivo sensitivity to different anti-malarial drugs of the P. falciparum population from Pikine.
Fifty-four samples were collected from patients with non-complicated malaria and aged between 2 and 20 years in the Deggo health centre in Pikine in 2014. An assay in which parasites are stained with 4', 6-di-amidino-2-phenylindole (DAPI), was used to study the ex vivo sensitivity of isolates to chloroquine, amodiaquine, piperaquine, pyrimethamine, and dihydroartemisinin. High resolution melting was used for genotyping of pfdhps, pfdhfr, pfmdr1, and pfcrt genes.
The mean ICs of chloroquine, amodiaquine, piperaquine, dihydroartemisinin, and pyrimethamine were, respectively, 39.44, 54.02, 15.28, 2.23, and 64.70 nM. Resistance mutations in pfdhfr gene, in codon 437 of pfdhps gene, and an absence of mutation at position 540 of pfdhps were observed. Mutations in codons K76T of pfcrt and N86Y of pfmdr1 were observed at 51 and 11% population prevalence, respectively. A relationship was found between the K76T and N86Y mutations and ex vivo resistance to chloroquine.
An increase in sensitivity of isolates to chloroquine was observed. A high sensitivity to dihydroartemisinin was observed; whereas, a decrease in sensitivity to pyrimethamine was observed in the parasite population from Pikine.
监测恶性疟原虫对抗疟药物的敏感性是有效管理疟疾病例的必要条件。该物种对抗疟药物具有很强的抗性。在塞内加尔，1988年在达喀尔地区报告了首例氯喹抗性病例，人群患病率近7%，到1990年达到47%。正是在这种背景下，2003年磺胺多辛-乙胺嘧啶暂时取代氯喹作为一线治疗药物，直到2006年引入以青蒿素为基础的联合疗法。本研究的目的是评估来自皮金的恶性疟原虫群体对不同抗疟药物的体外敏感性。
2014年在皮金的德戈健康中心从2至20岁患有非复杂性疟疾的患者中采集了54份样本。使用一种用4',6-二脒基-2-苯基吲哚（DAPI）对寄生虫进行染色的试验，来研究分离株对氯喹、阿莫地喹、哌喹、乙胺嘧啶和双氢青蒿素的体外敏感性。高分辨率熔解用于pfdhps、pfdhfr、pfmdr1和pfcrt基因的基因分型。
氯喹、阿莫地喹、哌喹、双氢青蒿素和乙胺嘧啶的平均半数抑制浓度分别为39.44、54.02、15.28、2.23和64.70 nM。观察到pfdhfr基因中的抗性突变、pfdhps基因第437密码子处的突变以及pfdhps第540位不存在突变。分别在51%和11%的人群患病率中观察到pfcrt基因K76T密码子和pfmdr1基因N86Y密码子的突变。发现K76T和N86Y突变与对氯喹的体外抗性之间存在关联。
观察到分离株对氯喹的敏感性增加。观察到对双氢青蒿素具有高敏感性；而在来自皮金的寄生虫群体中观察到对乙胺嘧啶的敏感性降低。
