@article{fb9af825ec4b425492e35c1bdad876f1,
title = "Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study",
abstract = "BACKGROUND: Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use.METHODS: We validated an existing population-level mathematical model of the effect of ivermectin mass drug administration (MDA) on the mosquito population and malaria transmission against two datasets: clinical data from a cluster- randomised trial done in Burkina Faso in 2015 wherein ivermectin was given to individuals taller than 90 cm and entomological data from a study of mosquito outcomes after ivermectin MDA for onchocerciasis or lymphatic filariasis in Burkina Faso, Senegal, and Liberia between 2008 and 2013. We extended the existing model to include a range of complementary malaria interventions (seasonal malaria chemoprevention and MDA with dihydroartemisinin-piperaquine) and to incorporate new data on higher doses of ivermectin with a longer mosquitocidal effect. We consider two ivermectin regimens: a single dose of 400 μg/kg (1 × 400 μg/kg) and three consecutive daily doses of 300 μg/kg per day (3 × 300 μg/kg). We simulated the effect of these two doses in a range of usage scenarios in different transmission settings (highly seasonal, seasonal, and perennial). We report percentage reductions in clinical incidence and slide prevalence.FINDINGS: We estimate that MDA with ivermectin will reduce prevalence and incidence and is most effective in areas with highly seasonal transmission. In a highly seasonal moderate transmission setting, three rounds of ivermectin only MDA at 3 × 300 μg/kg (rounds spaced 1 month apart) and 70% coverage is predicted to reduce clinical incidence by 71% and prevalence by 34%. We predict that adding ivermectin MDA to seasonal malaria chemoprevention in this setting would reduce clinical incidence by an additional 77% in children younger than 5 years compared with seasonal malaria chemoprevention alone; adding ivermectin MDA to MDA with dihydroartemisinin-piperaquine in this setting would reduce incidence by an additional 75% and prevalence by an additional 64% (all ages) compared with MDA with dihydroartemisinin-piperaquine alone.INTERPRETATION: Our modelling predictions suggest that ivermectin could be a valuable addition to the malaria control toolbox, both in areas with persistently high transmission where existing interventions are insufficient and in areas approaching elimination to prevent resurgence.FUNDING: Imperial College Junior Research Fellowship.",
author = "Slater, {Hannah C} and Foy, {Brian D} and Kevin Kobylinski and Carlos Chaccour and Watson, {Oliver J} and Joel Hellewell and Ghaith Aljayyoussi and Teun Bousema and Jeremy Burrows and Umberto D'Alessandro and Haoues Alout and {Ter Kuile}, {Feiko O} and Walker, {Patrick G T} and Ghani, {Azra C} and Smit, {Menno R}",
note = "Funding Information: CC reports grants from UNITAID and the Bill and Melinda Gates Foundation during the conduct of the study. BDF has a US patent pending (16/275?172). TB reports grants from the Gates Foundation during the conduct of the study. UD'A reports grants from MRC Joint Global Health Trial Scheme during the conduct of the study. All other authors declare no competing interests.Material has been reviewed by the Walter Reed Army Institute of Research (Silver Spring, MD, USA). There is no objection to its presentation or publication. The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official, or as reflecting true views of the US Department of the Army or the US Department of Defense. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. This work was funded by an Imperial College Junior Research Fellowship to HCS, with additional financial support from the Gates Foundation. HCS and CC received additional financial support from the Gates Foundation under the Ivermectin development roadmap (OPPP1177135) and from UNITAID under the Project Preparation Facility of the BOHEMIA grant (2018-30-ISG). Funding Information: Material has been reviewed by the Walter Reed Army Institute of Research (Silver Spring, MD, USA). There is no objection to its presentation or publication. The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official, or as reflecting true views of the US Department of the Army or the US Department of Defense. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. This work was funded by an Imperial College Junior Research Fellowship to HCS, with additional financial support from the Gates Foundation. HCS and CC received additional financial support from the Gates Foundation under the Ivermectin development roadmap ( OPPP1177135 ) and from UNITAID under the Project Preparation Facility of the BOHEMIA grant (2018-30-ISG). Funding Information: CC reports grants from UNITAID and the Bill and Melinda Gates Foundation during the conduct of the study. BDF has a US patent pending (16/275 172). TB reports grants from the Gates Foundation during the conduct of the study. UD'A reports grants from MRC Joint Global Health Trial Scheme during the conduct of the study. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = apr,
doi = "https://doi.org/10.1016/S1473-3099(19)30633-4",
language = "English",
volume = "20",
pages = "498--508",
journal = "Lancet infectious diseases",
issn = "1473-3099",
publisher = "Lancet Publishing Group",
number = "4",
}