Lead clinical and pre-clinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations

Upton, L.M., Brock, P.M. , Churcher, T.S., Ghani, A.C., Gething, P.W., Delves, M.J., Sala, K.A., Leroy, D., Sinden, R.E. and Blagborough, A.M. (2015) Lead clinical and pre-clinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations. Antimicrobial Agents and Chemotherapy, 59(1), pp. 490-497. (doi: 10.1128/AAC.03942-14) (PMID:25385107) (PMCID:PMC4291391)

Abstract

To achieve malarial elimination we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous anti-malarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention; namely impact on case incidence within a vertebrate population (reduction in Ro/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual anti-malarial drugs can impact the number of secondary P.berghei infections over a cycle of transmission. We examine the impact of multiple clinical and pre-clinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6mg/kg) and NITD609 (8.1mg/kg) have significant impact across multiple transmission settings, but artemether/lumefantrine (57/11.8mg/kg), OZ439 (6.5mg/kg) and primaquine (<1.25mg/kg) demonstrated potent efficacy only at lower transmission settings. While directly demonstrating the impact of drug treatment on anti-malarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Upton, Mrs Linda and Brock, Dr Patrick
• Authors: Upton, L.M., Brock, P.M., Churcher, T.S., Ghani, A.C., Gething, P.W., Delves, M.J., Sala, K.A., Leroy, D., Sinden, R.E., and Blagborough, A.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Antimicrobial Agents and Chemotherapy
• Journal Abbr.: Antimicrob Agents Chemother
• Publisher: American Society for Microbiology
• ISSN: 0066-4804
• ISSN (Online): 1098-6596
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Antimicrobial Agents and Chemotherapy 59(1):490-497
• Publisher Policy: Reproduced under a Creative Commons License