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Table 1 Summary of Key deliverables

From: The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies

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.