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A discovery and development roadmap for new endectocidal transmission-blocking agents in malaria

Title: A discovery and development roadmap for new endectocidal transmission-blocking agents in malaria
Authors: Burrows, J
Slater, H
Macintyre, F
Rees, S
Thomas, A
Okumu, F
Van Huijsduijnen, RH
Duparc, S
Wells, TNC
Item Type: Journal Article
Abstract: Reaching the overall goal of eliminating malaria requires halting disease transmission. One approach to blocking transmission is to prevent passage of the parasite to a mosquito, by preventing formation or transmission of gametocytes. An alternative approach, pioneered in the veterinary field, is to use endectocides, which are molecules that render vertebrate blood meals toxic for the mosquito vector, also killing the parasite. Field studies and modelling suggest that reducing the lifespan of the mosquito may significantly reduce transmission, given the lengthy maturation process of the parasite. To guide the development of new endectocides, or the reformulation of existing molecules, it is important to construct a framework of the required attributes, commonly called the target candidate profile. Here, using a combination of insights from current endectocides, mathematical models of the malaria transmission dynamics, and known impacts of vector control, a target candidate profile (TCP-6) and a regulatory strategy are proposed for a transmission reducing agent. The parameters chosen can be used to assess the potential of a new medicine, independent of whether it has classical endectocide activity, reduces the insect and parasite lifespan or any combination of all three, thereby constituting an ‘endectocidal transmission blocking’ paradigm.
Issue Date: 10-Dec-2018
Date of Acceptance: 24-Nov-2018
URI: http://hdl.handle.net/10044/1/69896
DOI: https://dx.doi.org/10.1186/s12936-018-2598-5
ISSN: 1475-2875
Publisher: BioMed Central
Journal / Book Title: Malaria Journal
Volume: 17
Copyright Statement: © 2018 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
Keywords: Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Parasitology
Tropical Medicine
Malaria
Plasmodium
Transmission blocking
Endectocides
target candidate profile
Target product profile
Transmission reducing agent
PLASMODIUM-FALCIPARUM
IVERMECTIN
RESISTANCE
IMPACT
DRUG
MEDICINES
TICKS
Animals
Anopheles
Antiparasitic Agents
Humans
Insecticides
Mosquito Vectors
1108 Medical Microbiology
Publication Status: Published
Article Number: 462
Appears in Collections:Centre for Environmental Policy
Faculty of Medicine
Faculty of Natural Sciences
Epidemiology, Public Health and Primary Care



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