Exploring the use of attractive sugar bait stations to deliver antiplasmodial compounds to Anopheles mosquitoes

Highton, Genevieve Anna

Abstract

Between 2000 and 2015, Sub-Saharan Africa made historic process against the scourge of malaria. Since this time there has been a plateau in the number of malaria cases and mortalities. The decreasing efficacy of the current methods used against this parasitic disease, such as IRS and bednets, is associated with a multitude of interspersed factors; such factors may be overcome with the incorporation of novel strategies. Furthermore, the re-emerging interest in attractive toxic sugar bait stations has been negatively impacted by the suggestion that the toxic compounds used could cause issues for non-target organisms. In this study the aim was to identify a series of methods through which the viability of anti-plasmodial compounds can be investigated for their application into a mosquito bait station. To do so, the potencies of two known sexual-stage active compounds were evaluated, alongside two control compounds, before and after their prolonged exposure to the environmental conditions of an attractive bait station in sub-Saharan Africa. The conditions used in this assessment included pH, temperature, time and light. The inhibition (%) of the compounds against the asexual and sexual stages of the P. falciparum (Dd2 strain) lifecycle were determined using luciferase assays and mosquito feeding assays respectively. Promisingly, the compounds maintained their stability within the relevant temperature cycles, however, they were unable to provide the necessary pan-activity against the oocyst and sporozoite stages of the plasmodia lifecycle. MMV011895 displayed some activity against the oocyst development, but not against sporozoite formation whereas MMV666060 displayed some activity against the sporozoite formation but not against oocyst development. Although a compound with the required characteristics has yet to be found, the in vitro methods used do provide a way in which the stability of candidate compounds can be screened without the use of more expensive, timely and labourintensive methods. With the identification of a suitable compound, the exposure of infected Anopheles to an anti-plasmodial using bait stations could be a climacteric strategy in the bid for malaria elimination.

Citation

Highton, G. A. (2022). Exploring the use of attractive sugar bait stations to deliver antiplasmodial compounds to Anopheles mosquitoes. (Thesis). Keele University

• Thesis Type: Thesis
• Publicly Available Date: May 30, 2023
• Award Date: 2022-06