Table 1 Summary of Key deliverables

Key deliverables to understand transmission dynamics

• Understanding of the low levels of natural transmission

• Clarification of the relationships between the different methods of measuring transmission to the mosquito

• Better definition of the infectious reservoir, and its role in control programmes

• Biomarkers to distinguish infectious from non-infectious hosts

• Improved integration of laboratory and field experimentation and data

Key deliverables to understand gametocyte biology

• New markers for commitment to gametocytogenesis

• Improved methods for the purification of the different stages of sexual and sporogonic development.

• Understanding of the pathways regulating sexual development (both gametocytogenesis and gametogenesis)

• Understanding of parasite metabolism during sexual and sporogonic development

• Improved understanding of the molecular basis of fertilization

• Understanding of the mechanisms controlling gametocyte distribution in the host bloodstream.

Key deliverables for translation

i) Vaccines

• Understand the biological relevance of membrane feeding assays

• Confirm structural and immunological fidelity of both current and new candidates

• New platforms to enhance and prolong antibody responses

• Designs for new field studies in a variety of endemic settings to evaluate TBVs alone and in combination

• Develop bifunctional vaccines to attack both population bottlenecks (e.g. ookinete and liver schizont)

ii) Drugs

• Phenotypic screens for novel entities against gametocytes and ookinetes

• New target-based screens

• Understanding of the mode of action of primaquine

• Identification of dual activity compounds from the known library of 25,000 compounds with schizonticidal activity

• Identification of novel transmission-blocking-specific compounds, to explore possible combinations with blood schizonticides

• Methods for sustained drug delivery

iii) 'Out-of-the-box'

• Reagents to modulate the mosquito innate immune system

• Understanding of the roles of natural-, or genetically modified- microflora in regulating malaria transmission in the mosquito.

Key research tools required

• Molecular markers for all stages of sexual development

• Widespread availability of reagents for all 'genes' (GM parasites expressing tagged proteins or knockouts; monoclonal antibodies)

• Improved access to high resolution, live imaging.

• Publicly available archives of numerical and microscopic data

• Wider access to transmission facilities

• GM rodent parasites expressing key proteins/gene-products from human malaria parasites

• Improved mathematical models of malaria transmission.