ReviewKinase signalling in Plasmodium sexual stages and interventions to stop malaria transmission

- Malaria sexual parasites are the only forms able to transmit the disease through mosquitoes.
- Asexual and sexual parasites differ in their sensitivity to drugs.
- The sexual developmental pathway requires protein kinase signalling.
- Protein kinase inhibitors could block transmission.
- Development of transmission-blocking pharmacological interventions will be challenging.

The symptoms of malaria, one of the infectious diseases with the highest mortality and morbidity world-wide, are caused by asexual parasites replicating inside red blood cells. Disease transmission, however, is effected by non-replicating cells which have differentiated into male or female gametocytes. These are the forms infectious to mosquito vectors and the insects are the only hosts where parasite sexual reproduction can take place. Malaria is thus a complex infection in which pharmacological treatment of symptoms may still allow transmission for long periods, while pharmacological blockage of infectivity may not cure symptoms. The process of parasite sexual differentiation and development is still being revealed but it is clear that kinase-mediated signalling mechanisms play a significant role. This review attempts to summarise our limited current knowledge on the signalling mechanisms involved in the transition from asexual replication to sexual differentiation and reproduction, with a brief mention to the effects of current treatments on the sexual stages and to some of the difficulties inherent in developing pharmacological interventions to curtail disease transmission.

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