title: A high-throughput assay for the identification of malarial transmission-blocking drugs and vaccines.
abstract: Following the cessation of the global malaria eradication initiative in the 1970s, the prime objective of malarial intervention has been to reduce morbidity and mortality. This motivated the development of high throughput assays to determine the impact of interventions on asexual bloodstage parasites. In response to the new eradication agenda, interrupting parasite transmission from the human to the mosquito has been recognised as an important and additional target for intervention. Current assays for Plasmodium mosquito stage development are very low throughput and resource intensive, and are therefore inappropriate for high throughput screening. Using an ookinete-specific GFP reporter strain of the rodent parasite Plasmodium berghei, it has been possible to develop and validate a high biological complexity, high throughput bioassay that can rapidly, reproducibly and accurately evaluate the effect of transmission-blocking drugs or vaccines on the ability of host-derived gametocytes to undergo the essential onward steps of gamete formation, fertilisation and ookinete maturation. This assay may greatly accelerate the development of malaria transmission-blocking interventions.
authors.affiliation: Department of Life Sciences, Imperial College, London, UK. michael.delves@imperial.ac.uk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Delves
authors.forename: Chandra
authors.initials: C
authors.lastname: Ramakrishnan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blagborough
authors.forename: Didier
authors.initials: D
authors.lastname: Leroy
authors.forename: Timothy N C
authors.initials: TN
authors.lastname: Wells
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D001681:Biological Assay; D005260:Female; D005854:Germ Cells / Q000187:drug effects; D007303:Insect Vectors; D008163:Luminescent Measurements / Q000379:methods; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D021261:Parasitic Sensitivity Tests / Q000379:methods*; D010962:Plasmodium berghei / Q000502:physiology*; D010965:Plasmodium malariae; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000962:Antimalarials; D017780:Malaria Vaccines