Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study

Hannah C. Slater; Brian D. Foy; Kevin Kobylinski; Carlos Chaccour; Oliver J. Watson; Joel Hellewell; Ghaith Aljayyoussi; Teun Bousema; Jeremy Burrows; Umberto D'Alessandro; Haoues Alout; Feiko Ter Kuile; Patrick G.T. Walker; Azra C. Ghani; Menno R. Smit

doi:10.1016/s1473-3099(19)30633-4

Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study

Hannah C. Slater, Brian D. Foy, Kevin Kobylinski, Carlos Chaccour, Oliver J. Watson, Joel Hellewell, Ghaith Aljayyoussi, Teun Bousema, Jeremy Burrows, Umberto D'Alessandro, Haoues Alout, Feiko Ter Kuile, Patrick G.T. Walker, Azra C. Ghani, Menno R. Smit

Research output: Contribution to journal › Article › peer-review

62 Citations (Scopus)

Abstract

Background: Ivermectin has been identified as a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have been shown to have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious.

Methods: In this study, we validate an existing population-level mathematical model of the impact of ivermectin on the mosquito population and malaria transmission to entomological and clinical data.

The model is extended to include a range of complementary malaria interventions and to incorporate new data on higher doses with a longer mosquitocidal effect. We then simulate the impact of these

doses in a range of usage scenarios in different transmission settings.

Findings: Mass drug administration (MDA) with ivermectin is predicted to reduce prevalence and incidence and is most effective in areas with a relatively short transmission season. In a highly seasonal moderate transmission setting, three rounds of ivermectin-only MDA spaced one month apart with a dose of 3x300μg/kg 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 will reduce clinical incidence by an additional 77% in under 5-year olds. Adding ivermectin MDA to MDA with antimalarials in this setting is predicted to reduce incidence by an additional 75%.

Interpretation: Ivermectin is a novel vector control tool that targets residual transmission, it has an excellent safety profile and has operationally synergistic distribution schedules with existing malaria

interventions. Based on modelling predictions in this study, we propose that this drug could be a valuable addition to the malaria control toolbox, both in areas with persistently high transmission where existing vector control is insufficient and in areas approaching elimination to prevent resurgence.

Original language	English
Pages (from-to)	498-508
Number of pages	11
Journal	The Lancet Infectious Diseases
Volume	20
Issue number	4
Early online date	13 Jan 2020
DOIs	https://doi.org/10.1016/s1473-3099(19)30633-4
Publication status	Published - 1 Apr 2020

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10.1016/s1473-3099(19)30633-4

Slater H-Modelling HD Ivermectin-Lancet ID 2019 (in press)Accepted author manuscript, 478 KB

Cite this

Slater, H. C., Foy, B. D., Kobylinski, K., Chaccour, C., Watson, O. J., Hellewell, J., Aljayyoussi, G., Bousema, T., Burrows, J., D'Alessandro, U., Alout, H., Ter Kuile, F., Walker, P. G. T., Ghani, A. C., & Smit, M. R. (2020). Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study. The Lancet Infectious Diseases, 20(4), 498-508. https://doi.org/10.1016/s1473-3099(19)30633-4

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abstract = "Background: Ivermectin has been identified as a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have been shown to have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious.Methods: In this study, we validate an existing population-level mathematical model of the impact of ivermectin on the mosquito population and malaria transmission to entomological and clinical data.The model is extended to include a range of complementary malaria interventions and to incorporate new data on higher doses with a longer mosquitocidal effect. We then simulate the impact of thesedoses in a range of usage scenarios in different transmission settings.Findings: Mass drug administration (MDA) with ivermectin is predicted to reduce prevalence and incidence and is most effective in areas with a relatively short transmission season. In a highly seasonal moderate transmission setting, three rounds of ivermectin-only MDA spaced one month apart with a dose of 3x300μg/kg 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 will reduce clinical incidence by an additional 77\% in under 5-year olds. Adding ivermectin MDA to MDA with antimalarials in this setting is predicted to reduce incidence by an additional 75\%.Interpretation: Ivermectin is a novel vector control tool that targets residual transmission, it has an excellent safety profile and has operationally synergistic distribution schedules with existing malariainterventions. Based on modelling predictions in this study, we propose that this drug could be a valuable addition to the malaria control toolbox, both in areas with persistently high transmission where existing vector control is insufficient and in areas approaching elimination to prevent resurgence.",

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 and Walker, \{Patrick G.T.\} and Ghani, \{Azra C.\} and Smit, \{Menno R.\}",

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Slater, HC, Foy, BD, Kobylinski, K, Chaccour, C, Watson, OJ, Hellewell, J, Aljayyoussi, G, Bousema, T, Burrows, J, D'Alessandro, U, Alout, H, Ter Kuile, F, Walker, PGT, Ghani, AC & Smit, MR 2020, 'Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study', The Lancet Infectious Diseases, vol. 20, no. 4, pp. 498-508. https://doi.org/10.1016/s1473-3099(19)30633-4

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

AU - Walker, Patrick G.T.

AU - Ghani, Azra C.

AU - Smit, Menno R.

PY - 2020/4/1

Y1 - 2020/4/1

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U2 - 10.1016/s1473-3099(19)30633-4

DO - 10.1016/s1473-3099(19)30633-4

M3 - Article

SN - 1473-3099

VL - 20

SP - 498

EP - 508

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

IS - 4

ER -

Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study

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