Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda
Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda
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DOI：
10.1016/j.parint.2020.102277
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发表时间：
2021-04-01
影响因子：
1.9
通讯作者：
Mita，Toshihiro
中科院分区：
文献类型：
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作者：
Fukuda，Naoyuki;Tachibana，Shin-Ichiro;Mita，Toshihiro
在乌干达，蒿甲醚-苯芴醇于2006年作为一种青蒿素类复方疗法用于疟疾治疗。我们以前曾报道过在乌干达北方，本芴醇的体外疗效中度下降，在那里我们也检测到体外青蒿素耐药恶性疟原虫。因此，有必要为ACT寻找候选伙伴替代品。在这里，我们研究了2013年至2018年期间321例病例对四种ACT伴侣药物以及奎宁和氯喹的体外敏感性。pfcrt和pfmdr 1的耐药突变也被确定。阿莫地喹、奎宁和氯喹的体外敏感性保持良好，而甲氟喹耐药率为45.8%。多药耐药病例很少。与氯喹抗性和K76 T等位基因之间的关联相反，对甲氟喹和本芴醇的敏感性降低与pfcrt K76野生型等位基因显著相关。在所有病例中均未检测到Pfmdr 1重复。阿莫地喹是非洲国家广泛使用的ACT的伙伴药物，可能是出现本芴醇耐药性的第一个有希望的替代药物。甲氟喹的治疗用途可能不推荐在这方面。这项研究还强调，需要持续监测北方乌干达抗疟药的敏感性，以制定适当的治疗策略。
In Uganda, artemether-lumefantrine was introduced as an artemisinin-based combination therapy (ACT) for malaria in 2006. We have previously reported a moderate decrease in ex vivo efficacy of lumefantrine in Northern Uganda, where we also detected ex vivo artemisinin-resistant Plasmodium falciparum. Therefore, it is necessary to search for candidate partner alternatives for ACT. Here, we investigated ex vivo susceptibility to four ACT partner drugs as well as quinine and chloroquine, in 321 cases between 2013 and 2018. Drug-resistant mutations in pfcrt and pfmdr1 were also determined. Ex vivo susceptibility to amodiaquine, quinine, and chloroquine was well preserved, whereas resistance to mefloquine was found in 45.8%. There were few cases of multi-drug resistance. Reduced sensitivity to mefloquine and lumefantrine was significantly associated with the pfcrt K76 wild-type allele, in contrast to the association between chloroquine resistance and the K76T allele. Pfmdr1 duplication was not detected in any of the cases. Amodiaquine, a widely used partner drug for ACT in African countries, may be the first promising alternative in case lumefantrine resistance emerges. Therapeutic use of mefloquine may not be recommended in this area. This study also emphasizes the need for sustained monitoring of antimalarial susceptibility in Northern Uganda to develop proper treatment strategies.