A large, international multi-center study – the largest of its kind to investigate the human genetics of malaria – has uncovered some new clues about susceptibility to severe malaria.

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Malaria is a disease that develops when a mosquito infected by the parasite Plasmodium bites a person. The parasite invades and lives in the new host’s red blood cells.

Writing in the journal Nature Genetics, the team, including Dr. Sarah Dunstan of The Nossal Institute of Global Health at the University of Melbourne in Australia, reports how it found five genes that have a complex role in either protecting or making people more susceptible to severe malaria.

Even with good hospital treatment, around 20% of patients who develop severe malaria die. The researchers hope their findings will lead to new drugs and vaccines to target the disease.

Malaria is a disease that develops when a mosquito infected by the parasite Plasmodium bites a person. The parasite invades and lives in the new host’s red blood cells.

There are several species of Plasmodium, of which P. falciparum is the one that most commonly causes severe disease in patients that are not immune.

Severe malaria can develop within a few days of infection. The condition affects many vital organs. If it affects the brain it can cause coma or cerebral malaria. If it affects the kidneys it can cause renal failure; in the lungs it can cause respiratory failure. It can also make the blood very acidic and lead to severe anemia and death.

For their study, Dr. Dunstan and colleagues analyzed data on nearly 12,000 cases of severe malaria collected from 12 sites across Africa, Asia and islands around the Pacific Ocean where access to treatment facilities can be difficult.

She says because of the international consortium behind it, the study was able to access a large amount of data to investigate genes that influence susceptibility to malaria on an unprecedented scale:

“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.”

Of the 27 malaria resistance genes that they analyzed, the team found five – HBB, ABO, ATP2B4, G6PD and CD40LG – that were significantly involved in determining human susceptibility to severe malaria.

The results also show the role of common human genetic disorders in severe malaria are more complex than previously thought, as Dr. Dunstan explains, in reference to one of the genes:

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 anemia, both of which are fatal complications of malaria.”

The consortium behind the study is the Malaria Genomic Epidemiology Network (MalariaGEN), a global research group that is trying to understand immunity to malaria from the point of view of genetics.

MalariaGEN is based at the Wellcome Trust Centre for Human Genetics, at the University of Oxford in the UK. Professor Dominic Kwiatkowski, senior author of the study, is the principal investigator of the MalariaGEN consortium.

One of the features of the malaria parasite that makes it difficult to study is the fact it takes less than 60 seconds to travel from one blood cell to infect another, and it quickly loses its infective ability within minutes of leaving a cell.

But the parasite’s journey from one cell to another should be much easier to study in detail, now that a group based at the Wellcome Trust Sanger Institute, near Cambridge in the UK, has developed laser optical tweezers to see how malaria invades red blood cells.