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. 2020 Feb;102(2s):3-24.
doi: 10.4269/ajtmh.19-0620.

A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool

The Ivermectin Roadmappers  1 ; Peter Billingsley  2 , Fred Binka  3 , Carlos Chaccour  4 , Brian Foy  5 , Silvia Gold  6 , Matiana Gonzalez-Silva  4 , Julie Jacobson  7 , George Jagoe  8 , Caroline Jones  9 , Patrick Kachur  10 , Kevin Kobylinski  11 , Anna Last  12 , James V Lavery  13 , David Mabey  12 , David Mboera  14 , Charles Mbogo  9 , Ana Mendez-Lopez  4 , N. Regina Rabinovich  4   15 , Sarah Rees  16 , Frank Richards  17 , Cassidy Rist  18 , Jessica Rockwood  19 , Paula Ruiz-Castillo  4 , Jetsumon Sattabongkot  20 , Francisco Saute  21 , Hannah Slater  22 , Andrew Steer  23 , Kang Xia  24 , Rose Zullinger  25
Affiliations

A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool

The Ivermectin Roadmappers et al. Am J Trop Med Hyg. 2020 Feb.

Abstract

In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.

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Conflict of interest statement

Disclosure: PB reports personal fees from Sanaria Inc., outside the submitted work BF has a patent 16/275,172 pending, and JJ advises the non-for-profit Foundation Mundo Sano on public health use of ivermectin-albendazole combination therapy. NRR, CCh, PRC, and MGS received funding from BMG for the development of this roadmap. NRR, CCh, and PRC are engaged in the BOHEMIA project (with funding from Unitaid) to evaluate ivermectin MDA to humans and livestock in Africa and, if results are positive, facilitate policy recommendation and national adoption. Part of their salary was funded by the BOHEMIA grant from Unitaid to ISGlobal. CCh was supported by a Ramón Areces fellowship. CJ reports part of her salary funded since February 2019 by a Unitaid grant through the University of Oxford for the BOHEMIA project. FR was a member of the Mectizan Expert Committee (MEC) at the Task Force for Global Health (TFGH) from May 2017–May 2019. Mectizan is the Merck & Co. brand name for their ivermectin tablet product that is donated to onchocerciasis and lymphatic filariasis programs. The MEC advises the TFGH Mectizan Donation Program that is involved in providing the Merck donation. SR works at IVCC, which is supported by the BMGF. RZ is supported by the President’s Malaria Initiative.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the President’s Malaria Initiative.

Figures

Figure 1.
Figure 1.
The theoretical efficacy of ivermectin mass drug administration based on three key parameters: (A) blood levels reached, (B) duration of blood levels, and (C) blood sources covered. This is a modified version of an original figure in by Chaccour and Rabinovich.
Figure 2.
Figure 2.
Modeled impact of the intervention across one transmission season in northern Mozambique. On the left, general population; on the right, children younger than five years (analysis by Hannah Slater).
Figure 3.
Figure 3.
Overlap between selected Loa loa, onchocerciasis, and malaria-endemic areas in Africa. (A) Estimated prevalence of L. loa eye worm, (B) estimated prevalence of palpable Onchocerca nodules in the 20 African Programme for Onchocerciasis Control countries in 2011, and (C) Plasmodium falciparum parasite rate in 2–10-years-old children in 2015.
Figure 4.
Figure 4.
Areas where high cattle density coincides with high malaria prevalence in 2–10-year-old children (Inbahale et al).
Figure 5.
Figure 5.
Malaria incidence per 1,000 population at risk in 20 selected countries during the 2018–2027 period and calculated additional impact attributable to the BOHEMIA intervention from 2023–2027.
Figure 6.
Figure 6.
Steps in the WHO evaluation system for new vector control tools.
Figure 7.
Figure 7.
General overview of the key milestones, as well as the factors involved in the potential inclusion of ivermectin into the malaria toolbox.
See this image and copyright information in PMC

References

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