Comparative Susceptibility of Plasmodium ovale and Plasmodium falciparum Field Isolates to Reference and Lead Candidate Antimalarial Drugs in Ghana.
Comparative Susceptibility of Plasmodium ovale and Plasmodium falciparum Field Isolates to Reference and Lead Candidate Antimalarial Drugs in Ghana.
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加纳卵形疟原虫和恶性疟原虫野外分离株对参考药物和主要候选抗疟药物的敏感性比较。
DOI：
10.1128/spectrum.04916-22
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发表时间：
2023-06-15
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
疟疾治疗导致全球最致命的恶性疟原虫数量下降，而在撒哈拉以南非洲地区，越来越多地发现了卵圆疟原虫等物种的感染。目前，没有实验性药物敏感性数据来指导卵形疟原虫感染的有效治疗和管理，这是有效消除疟疾所必需的。我们进行了一项为期1年的前瞻性研究，以评估卵形疟原虫的流行病学，并确定野外分离株对现有和最新发现的抗疟药物的体外敏感性。我们报告，虽然恶性疟原虫在有症状和无症状疟疾病例中占主导地位，但单感染或合并感染的卵形疟原虫导致7.16%的有症状疟疾。一线抗疟药物青蒿琥酯和甲苯胺对卵形疟原虫的抑制作用与恶性疟原虫一样强。氯喹对卵圆疟原虫和恶性疟原虫也有高度抑制作用，已在加纳被撤回。此外，卵形疟原虫和恶性疟原虫对奎宁表现出高度敏感性，与氯喹相当。乙胺嘧啶是疾病大规模预防的主要药物，对卵形疟原虫也有很好的抑制作用，与对恶性疟原虫的抑制作用相当。此外，我们发现GNF179对卵形疟原虫有很强的抑制作用，GNF179是一种类似于KAF156咪唑哌嗪（KAF156咪唑哌嗪是一种新型抗疟疾药物，目前正处于临床II期试验中）的药物。我们进一步证明了疟原虫磷脂酰肌醇-4- oh激酶（PI4K）特异性抑制剂KDU691对卵形疟原虫和恶性疟原虫具有高度抑制作用。我们的数据表明，现有的和领先的先进发现抗疟疾药物适合治疗加纳的卵形疟原虫感染。目前的疟疾控制和消除工具，如药物治疗并不是专门针对卵圆线虫的。卵形疟原虫可形成催眠子虫，引起复发性疟疾。卵形疟原虫是非洲第三大优势种，需要根治治疗，因为它可以形成肝脏休眠形式，称为催眠虫，逃脱所有安全治疗。对卵形疟原虫的不当治疗将使其在医疗需求最大的非洲继续传播。这是成功控制和消除疟疾的障碍。本研究为指导卵形疟治疗和疾病控制决策者使用参考抗疟药物提供了实验数据。我们还提供了2个临床候选药物的关键实验数据，可用于先导候选药物鉴定的优先选择，用于临床开发。
Malaria treatments resulted in the decline of the deadliest Plasmodium falciparum globally while species, such as P. ovale, infections have been increasingly detected across sub-Saharan Africa. Currently, no experimental drug sensitivity data are available to guide effective treatment and management of P. ovale infections, which is necessary for effective malaria elimination. We conducted a prospective study to evaluate P. ovale epidemiology over 1 year and determined ex vivo susceptibility of the field isolates to existing and lead advanced discovery antimalarial drugs. We report that while P. falciparum dominated both symptomatic and asymptomatic malaria cases, P. ovale in mono or co-infections caused 7.16% of symptomatic malaria. Frontline antimalarials artesunate and lumefantrine inhibited P. ovale as potently as P. falciparum. Chloroquine, which has been withdrawn in Ghana, was also highly inhibitory against both P. ovale and P. falciparum. In addition, P. ovale and P. falciparum displayed high susceptibility to quinine, comparable to levels observed with chloroquine. Pyrimethamine, which is a major drug for disease massive prevention, also showed great inhibition of P. ovale, comparable to effects on P. falciparum. Furthermore, we identified strong inhibition of P. ovale using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drugs currently in clinical phase II testing. We further demonstrated that the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor, KDU691, is highly inhibitory against P. ovale and P. falciparum field isolates. Our data indicated that existing and lead advanced discovery antimalarial drugs are suitable for the treatment of P. ovale infections in Ghana. IMPORTANCE Current malaria control and elimination tools such as drug treatments are not specifically targeting P.ovale. P. ovale can form hypnozoite and cause relapsing malaria. P. ovale is the third most dominant species in Africa and requires radical cure treatment given that it can form liver dormant forms called hypnozoites that escape all safe treatments. The inappropriate treatment of P. ovale would sustain its transmission in Africa where the medical need is the greatest. This is a hurdle for successful malaria control and elimination. Here, we provided experiment data that were lacking to guide P. ovale treatment and disease control policy makers using reference antimalarial drugs. We also provided key experimental data for 2 clinical candidate drugs that can be used for prioritization selection of lead candidate’s identification for clinical development.
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DOI：
10.1016/j.jmoldx.2021.07.022
发表时间：
2021-10
期刊：
The Journal of molecular diagnostics : JMD
影响因子：
--
作者：
Ansah F;Suurbaar J;Darko D;Anabire NG;Blankson SO;Domson BKS;Soulama A;Kpasra P;Chirawurah JD;Amenga-Etego L;Kanyong P;Awandare GA;Aniweh Y
通讯作者：
Aniweh Y
影响因子：
5.3
作者：
Dembele, Laurent;Diallo, Nouhoum;Sogore, Fanta;Diarra, Bintou;Ballo, Fatoumata, I;Daou, Amadou;Diakite, Ousmaila;Bare, Yacouba;Sangare, Cheick Papa Oumar;Haidara, Aboubecrin Sedhigh;Diakite, Seidina A. S.;Niangaly, Amadou;Diakite, Mahamadou;Campo, Brice;Awandare, Gordon A.;Aniweh, Yaw;Djimde, Abdoulaye A.
通讯作者：
Djimde, Abdoulaye A.
影响因子：
3.3
作者：
Win, TT;Lin, K;Kawamoto, F
通讯作者：
Kawamoto, F
影响因子：
3.8
作者：
Yman, Victor;Wandell, Grace;Farnert, Anna
通讯作者：
Farnert, Anna
DOI：
10.1016/s0140-6736(18)30291-5
发表时间：
2018-04-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
West African Network for Clinical Trials of Antimalarial Drugs (WANECAM)
通讯作者：
West African Network for Clinical Trials of Antimalarial Drugs (WANECAM)