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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.

Authors+Show Affiliations

MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Electronic address: hslater@path.org.Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Instituto de Salud Tropical, Universidad de Navarra, Pamplona, Spain; Ifakara Health Institute, Ifakara, Tanzania.MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.Liverpool School of Tropical Medicine, Liverpool, UK.Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK; Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, Netherlands.Medicines for Malaria Venture, Geneva, Switzerland.MRC Unit The Gambia at LSHTM, Fajara, Banjul, Gambia.ASTRE unit (UMR117), INRA-CIRAD, Montpellier, France.Liverpool School of Tropical Medicine, Liverpool, UK.MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.Liverpool School of Tropical Medicine, Liverpool, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31948767

Citation

Slater, Hannah C., et al. "Ivermectin as a Novel Complementary Malaria Control Tool to Reduce Incidence and Prevalence: a Modelling Study." The Lancet. Infectious Diseases, 2020.
Slater HC, Foy BD, Kobylinski K, et al. Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study. Lancet Infect Dis. 2020.
Slater, H. C., Foy, B. D., Kobylinski, K., Chaccour, C., Watson, O. J., Hellewell, J., ... Smit, M. R. (2020). Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study. The Lancet. Infectious Diseases, doi:10.1016/S1473-3099(19)30633-4.
Slater HC, et al. Ivermectin as a Novel Complementary Malaria Control Tool to Reduce Incidence and Prevalence: a Modelling Study. Lancet Infect Dis. 2020 Jan 13; PubMed PMID: 31948767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study. AU - Slater,Hannah C, AU - Foy,Brian D, AU - Kobylinski,Kevin, AU - Chaccour,Carlos, AU - Watson,Oliver J, AU - Hellewell,Joel, AU - Aljayyoussi,Ghaith, AU - Bousema,Teun, AU - Burrows,Jeremy, AU - D'Alessandro,Umberto, AU - Alout,Haoues, AU - Ter Kuile,Feiko O, AU - Walker,Patrick G T, AU - Ghani,Azra C, AU - Smit,Menno R, Y1 - 2020/01/13/ PY - 2019/06/21/received PY - 2019/09/30/revised PY - 2019/10/21/accepted PY - 2020/1/18/entrez JF - The Lancet. Infectious diseases JO - Lancet Infect Dis N2 - 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. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/31948767/Ivermectin_as_a_novel_complementary_malaria_control_tool_to_reduce_incidence_and_prevalence:_a_modelling_study L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(19)30633-4 DB - PRIME DP - Unbound Medicine ER -