Achan, J;
Barry, A;
Leroy, D;
Kamara, G;
Duparc, S;
Kaszubska, W;
Gandhi, P;
Buffet, B;
Tshilab, P;
Ogutu, B;
et al.
Achan, J; Barry, A; Leroy, D; Kamara, G; Duparc, S; Kaszubska, W; Gandhi, P; Buffet, B; Tshilab, P; Ogutu, B; Taylor, T; Krishna, S; Richardson, N; Ramachandruni, H; Rietveld, H
(2024)
Defining the next generation of severe malaria treatment: a target product profile.
Malar J, 23 (1).
p. 174.
ISSN 1475-2875
https://doi.org/10.1186/s12936-024-04986-z
SGUL Authors: Krishna, Sanjeev
Abstract
BACKGROUND: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. TARGET PRODUCT PROFILE: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. CONCLUSION: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.
Item Type: |
Article
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Additional Information: |
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
Keywords: |
Drug development, Severe malaria, Translational medicine, Antimalarials, Humans, Malaria, Artemisinins, Drug Resistance, Humans, Malaria, Artemisinins, Antimalarials, Drug Resistance, Severe malaria, Drug development, Translational medicine, 0605 Microbiology, 1108 Medical Microbiology, 1117 Public Health and Health Services, Tropical Medicine |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) Academic Structure > REF 2021 user group |
Journal or Publication Title: |
Malar J |
ISSN: |
1475-2875 |
Language: |
eng |
Dates: |
Date | Event |
---|
5 June 2024 | Published | 14 May 2024 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
38835069 |
Web of Science ID: |
WOS:001238674300001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116638 |
Publisher's version: |
https://doi.org/10.1186/s12936-024-04986-z |
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