Genes indicate resistance to malaria

Five genes that play a role in conferring natural resistance or making people more susceptible to severe malaria have been identified.

The findings could lead to a better understanding of the process behind how and why people develop severe malaria and allow researchers to identify new therapeutics or vaccines to target the disease.

The genes were identified in an international project being led by Professor Dominic Kwiatkowski, who is principal investigator of the Malaria Genomic Epidemiology Network MalariaGEN. Researchers collected data on 11,890 cases of severe malaria across 12 locations in Africa, Asia and Oceania where access to health resources to treat the disease can be difficult.

Severe malaria comprises a number of life-threatening complications after infection with the malaria parasite, Plasmodium falciparum.

Of 27 malaria resistance genes analysed, five were found to significantly determine human susceptibility to severe malaria.

Dr Sarah Dunstan from The Nossal Institute of Global Health at the University of Melbourne led the Vietnamese investigation in the study.

“Our findings revealed that deficiency in G6PD, which causes a genetic blood disorder, can both reduce risk of cerebral malaria and increase risk of severe malarial anaemia, both of which are fatal complications of malaria,” Dunstan said in a statement.

The finding that G6PD deficiency has opposing effects on different fatal complications associated with P. falciparum infection shows that the evolutionary origins of this common human genetic disorder are more complex than previously thought.

Dunstan said the findings would contribute to a better understanding of the mechanisms and processes at work when progressing to severe disease.

“This consortium has allowed for investigation of genes that influence susceptibility to malaria on a scale that has previously not been achieved. It involved a large number of severe malaria patients from multiple countries, which allows us to identify genes that truly have an effect on whether or not you develop severe malaria,” she said, referring to the MalariaGEN consortium.

MalariaGEN is a global research consortium based at the Wellcome Trust Centre for Human Genetics, University of Oxford that uses a genetics approach to understand immunity to malaria.

The study has been published in Nature Genetics.