Understanding the public health consequences of genetic variation in Plasmodium populations
The Plasmodium parasites that cause malaria have a remarkable talent for survival. They can evade the human immune system, develop resistance to antimalarial drugs, and cope with changes in the Anopheles vector and other environmental fluctuations. This biological tenacity stems from the continual accumulation of small variations in the parasite genome, which allows the parasite population to adapt to new circumstances by evolutionary selection.
The continual evolution of the parasite genome is a major obstacle to malaria control. MalariaGEN investigators are working on different aspects of this problem in three community projects:
- Plasmodium falciparum population genomics
- Plasmodium falciparum genetic crosses
- Plasmodium vivax genome variation
Five different species of Plasmodium can cause human malaria: P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. P. falciparum is more virulent than the other species and is responsible for most malaria deaths, and P. vivax is also a major global health problem.
The World Health Organisation and other international agencies are promoting a global effort to eliminate malaria. A pre-requisite of malaria elimination is effective surveillance of the parasite population for the emergence and spread of new genetic variants, and worldwide monitoring of parasite migration.
This requires characterisation of parasite genome variation in different geographical locations and recent evolutionary selection. It also requires a deep understanding of the factors that determine gene flow between locations, such as rates of inbreeding and population structure.
The rapid pace of progress in genome sequencing technology, coupled with advances in statistics and informatics, makes it possible to tackle this problem at a much higher level of resolution and on a greater scale than has hitherto been possible. MalariaGEN provides malaria researchers around the world with access to these new technologies, allowing them to investigate the biological consequences of genetic variation in Plasmodium populations at the level of the whole genome.
Our long-term goal is use this information to develop more effective methods of surveillance for the emergence and spread of drug resistance; and, when a malaria vaccine is introduced, to provide early warning of parasite mutations that might render it ineffective. Forewarned is forearmed: and we aim to improve the sustainability and efficacy of malaria control measures by providing doctors and public health agencies with real-time information about how parasite populations are evolving.