Towards the next generation of antimalaria combination therapies

In 2019, there were 229 million new malaria infections causing 409 000 deaths.1 Over the past 20 years, impressive progress has been made in the fight against malaria; however, parasites developed mutations in the K13 propeller gene that resulted in delayed clearance of parasites following artesunat...

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Bibliographic Details
Published in:The Lancet infectious diseases 2021-12, Vol.21 (12), p.1620-1621
Main Author: Möhrle, Jörg J
Format: Article
Language:English
Subjects:
Antimalarials - therapeutic use
Artesunate
Combined Modality Therapy
Comment
Drug development
Drug dosages
Drug resistance
Erythrocytes
Health services
Humans
Infections
Infectious diseases
Malaria
Mate selection
Mutation
Parasites
Severe acute respiratory syndrome coronavirus 2
Vector-borne diseases
Volunteers
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Summary:In 2019, there were 229 million new malaria infections causing 409 000 deaths.1 Over the past 20 years, impressive progress has been made in the fight against malaria; however, parasites developed mutations in the K13 propeller gene that resulted in delayed clearance of parasites following artesunate treatment.2,3 This emergence of partial resistance to artesunate treatment was swiftly followed by the acquisition of resistance to partner drugs, resulting in the reduced efficacy of artesunate combination treatments.4 Resistance to artesunate in southeast Asia was first reported in 2008, and this year reports from Africa indicated a similar development, with parasites harbouring mutations in the K13 gene, resulting in delayed clearance.5 To ensure that the gains in the fight against malaria can be extended to achieve eradication of this disease, new combination treatments and simplified treatment regimens are necessary to replace the existing treatments. In The Lancet Infectious Diseases, James McCarthy and colleagues report the results of a combined first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and a volunteer infection study with M5717.8 The study design was similar to previous first-in-human volunteer infection studies:9 in the single ascending dose part of the study, single doses of up to 2100 mg were tested in healthy adult volunteers, and in the volunteer infection study, participants were infected with Plasmodium falciparum-infected red blood cells and treated with 150, 400, or 800 mg M5717. To ensure that the selection of a suitable partner molecule to M5717 follows a data-driven process, Merck KGaA has joined a platform with other organisations that have antimalarial drug candidates in translational development, which is hosted by MMV.
ISSN:1473-3099
1474-4457
DOI:10.1016/S1473-3099(21)00270-X