Soulama Alamissa, Sogore Fanta, Ansah Felix, Diakite Ousmaila, Chirawurah Jersley D, Maiga Fatoumata O, Maiga Mohamed, Danwonno Harry A, Campo Brice, Djimde Abdoulaye A, Awandare Gordon A, Amenga-Etego Lucas N, Dembele Laurent, Aniweh Yaw
West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
Faculty of Pharmacy, Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Malaria Research and Training Centre (MRTC), Bamako, Mali.
Microbiol Spectr. 2025 Apr;13(4):e0217624. doi: 10.1128/spectrum.02176-24. Epub 2025 Mar 10.
Non-falciparum species causing malaria in humans are considered neglected in the fight toward malaria elimination. Recent data highlight the increasing contribution of to malaria morbidity and mortality. In this study, the susceptibility of and to current antimalarial drugs was compared to advanced lead candidate drugs using field isolates. The blood samples were collected from the Central region of Ghana and Faladje and Kati in Mali. Following this, an drug efficacy assay was conducted by screening mono-infected isolates against a panel of antimalarials. In Ghana, the susceptibility of the two species to most of the current antimalarial drugs was comparable, except for artemether, sulfadoxine, and atovaquone, for which the drugs were less potent against than (7.12 vs 2.15 nM, 25.72 vs 7.86 nM, and 10.38 vs 2.51 nM, respectively). In Mali, quinine was significantly more potent against than (18.35 and 26.84 nM), and tafenoquine was less potent against than (5.50 and 2.85 nM). Among the candidate drugs, except INE963, whose inhibitory potency was comparable between both species, the other compounds significantly inhibited more than . The data showed that current drugs investigated against the isolates from Ghana may be suitable for curing infections. However, in Mali, chloroquine resistance appeared to have affected the suitability of quinine-based compounds for non-falciparum malaria treatment. Therefore, additional studies are required to establish the efficacy of artemether-lumefantrine for the treatment of infections.
One major hurdle to research in the community is our inability to have continuous culture for parasites such as and . These two are common in the West African region and co-occur with in driving both clinical or asymptomatic infections as either mono-infections or mixed infections. This manuscript is a buildup of our efforts at using methods to study the susceptibility of and to conventional and lead compounds, comparing the isolates from Ghana and Mali. This is necessary to facilitate drug discovery efforts in combating malaria holistically. The community will greatly see this work as a step in the right direction, stimulating more research into these other parasites causing malaria.
在消除疟疾的斗争中，引起人类疟疾的非恶性疟原虫物种被视为被忽视的对象。最近的数据凸显了其对疟疾发病率和死亡率的贡献日益增加。在本研究中，使用野外分离株将 和 对当前抗疟药物的敏感性与先进的先导候选药物进行了比较。血样采集自加纳中部地区以及马里的法拉杰和卡蒂。在此之后，通过针对一组抗疟药筛选单感染分离株进行了药物疗效测定。在加纳，这两个物种对大多数当前抗疟药物的敏感性相当，但蒿甲醚、周效磺胺和阿托伐醌除外，这几种药物对 的效力低于对 的效力（分别为7.12对2.15纳摩尔、25.72对7.86纳摩尔以及10.38对2.51纳摩尔）。在马里，奎宁对 的效力显著高于对 的效力（分别为18.35和26.84纳摩尔），而tafenoquine对 的效力低于对 的效力（分别为5.50和2.85纳摩尔）。在候选药物中，除INE963对这两个物种的抑制效力相当外，其他化合物对 的抑制作用显著强于对 的抑制作用。数据表明，针对来自加纳的分离株所研究的当前药物可能适合治愈 感染。然而，在马里，氯喹耐药性似乎影响了基于奎宁的化合物用于非恶性疟原虫疟疾治疗的适用性。因此，需要开展更多研究来确定蒿甲醚 - 本芴醇治疗 感染的疗效。
该领域研究的一个主要障碍是我们无法对诸如 和 等寄生虫进行连续培养。这两种寄生虫在西非地区很常见，并且在导致临床或无症状感染方面，无论是单感染还是混合感染，都与 共同出现。本手稿是我们利用 方法研究 和 对传统化合物及先导化合物的敏感性、比较来自加纳和马里的分离株所做努力的成果。这对于全面推动抗疟药物研发工作是必要的。该领域将极大地视此工作为朝着正确方向迈出的一步，从而激励对这些其他引起疟疾的寄生虫开展更多研究。
