Discovery to Development: Insecticides for Malaria Vector Control

Abstract

This report provides an outline of a program for the discovery of new public health insecticides for malaria vector control. The status of malaria vector control is first reviewed in terms of the chemical, physical chemical, and biochemical properties of the current WHOPES-recommended and approved vector control agents. This review provides a basis for a discussion on the critical need for discovery and development of multiple new chemical malaria vector control agents with novel and diverse modes of action. The Innovative Vector Control Consortium (IVCC) New Active Ingredient Ta rget Product Profile (TPP) describes the essential attributes for a successful new malaria vector control agent and then serves as the basis for development of a discovery cascade. The cascade addresses these attributes experimentally at each stage of the discovery process -from design and assembly of an appropriate collection of chemicals for screening, through development of testing protocols to sort candidates, and into the detailed profiling of advanced pre-development candidates against TPP requirements. In addition, this program defines a staged development system to provide intermediate guidance to the insecticide explorer regarding the progress of their discovery program against the ultimate product goal.

A testing cascade to identify repurposed insecticides for next-generation vector control tools: screening a panel of chemistries with novel modes of action against a malaria vector

“…High-throughput screening of existing compound libraries and chemical synthesis programmes provide an opportunity to identify novel insecticides, but are costly, risky and take a long time from initiation to delivery as a vector control tool to the market ( Turner et al , 2016). The cost of bringing a new crop protection product to market was estimated to be $286m in 2014 ( McDougall, 2016), and though the cost of developing a dedicated vector control insecticide would be lower, the total market for all public health insecticides may be only around $400m ( BMGF and BCG, 2007).…”

Experimental evolution supports the potential of neonicotinoid-pyrethroid combination for managing insecticide resistance in malaria vectors

“…Pyrethroid resistance is of major concern as these insecticides are mainly used for impregnating bednets 54 , 55 . In this context, the development of novel vector control products that can be used for controlling pyrethroid resistance has been encouraged by WHO 56 . Among them, IRS formulations combining two insecticides with different modes of action such as Fludora Fusion are of high interest.…”

Possibilities for rationally exploiting co-evolution in addressing resistance to insecticides, and beyond

“…This relates to the important fact that, although insecticide design is a process conducted as rationally as possible, and becoming ever more so in the industry, an ever increas-ingly large throughput of compounds, specialist formulation technolo-gies and high level testing (including on nontarget organisms) are re-quired for success. This process has been described in detail by members of ESAC1, J. Turner, C. Ruscoe and T. Perrior [14], and should be considered wherever rational design of insecticides is proposed, particularly when compound selection is based on in vitro bioassay.…”

“…According to Turner et al, [14], modifications to the physiochem-ical properties of the natural product lead may be essential for practical use, a frequent requirement also for all other toxins discussed above. Such modifications need also to be associated with the compound placed by GM into the rapidly evolving producer organism and with the caveat that this organism must essentially benefit by its presence.…”