Burrows Jeremy N, Duparc Stephan, Gutteridge Winston E, Hooft van Huijsduijnen Rob, Kaszubska Wiweka, Macintyre Fiona, Mazzuri Sébastien, Möhrle Jörg J, Wells Timothy N C
Medicines for Malaria Venture, Route de Pré Bois 20, 1215, Geneva 15, Switzerland.
Neglected Infectious Diseases Consulting, Sevenoaks, Kent, UK.
Malar J. 2017 Jan 13;16(1):26. doi: 10.1186/s12936-016-1675-x.
A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.
十年来新型抗疟药物的发现与研发,使得人们重新聚焦于疟疾的消除与根除。新型抗疟药物研发方式的改变,导致目前处于临床前和早期临床开发阶段的新分子数量和种类急剧增加。面临的双重挑战可概括为来自大湄公河次区域的多重耐药疟疾,以及提供简化药物的需求。本综述列出了过去4年抗疟靶点候选物和目标产品概况的变化。除了用于治疗疾病和预防传播的新药外,人们越来越关注寻找具有化学预防作用的新药这一长期目标,这些新药可能采用长效分子或肠胃外制剂。本文还明确了疟疾药物储备中的其他缺口,如治疗重症疟疾的药物和内吸杀虫剂(杀死吸食服用该药物者血液的蚊子)。最终,消除疟疾需要在弱势群体中使用安全且耐受性良好的药物:孕妇,尤其是孕早期,以及营养不良或同时感染其他病原体的人群。这些更新反映了在生产下一代控制、消除并最终根除疟疾的药物方面,对关键挑战的认识正在不断成熟。