Irish researchers working in Dublin and Oxford have discovered a key gene that helps determine why some patients survive and others die of diseases such as malaria, tuberculosis, pneumonia and blood poisoning.
The finding should greatly improve treatments for at-risk patients and also lead to new drugs against these and other infectious diseases.
The series of discoveries was made while trying to answer the question why some patients die of malaria and others don't, explained the head of Trinity College Dublin's school of biotechnology and immunology and professor of molecular immunology, Prof Luke O'Neill.
Prof O'Neill and the University of Oxford's Irish-born professor of human genetics, Prof Adrian Hill, are joint lead authors of a paper explaining the research published this morning in the journal Nature Genetics.
A major implication of their findings is that a single gene, which produces a protein known as Mal, may be the key determinant whether a patient survives a dangerous infectious disease. The researchers hope to show this may be true for many infectious agents including the dangerous hospital bug, MRSA.
The two have already proven that Mal plays this role in malaria, TB, bacterial pneumonia and blood poisoning, said Prof O'Neill. "The fact that Mal is affected in all of these is significant. It could be implicated in most infectious diseases."
The researchers have also shown that the effect happens in diverse populations, given their study of more than 6,000 patients from Gambia, Vietnam, Turkey and the UK.
Malaria is a major killer worldwide and about a third of the world's population lives in areas where it is endemic, Prof O'Neill stated. Climate change is also pushing malaria into new areas, including the southern US.
Another million people die of blood poisoning in Europe and the US.
"About five million children a year are dying of malaria and it looks like Mal is a key factor of why they are dying," he stated.
"The discovery of Mal as a key determinant of death will help in discovering ways to allow more patients to survive."
We all have two copies of the gene that produces Mal, which is a very important switch that turns on our immune systems during infection. Both copies are underactive in about 2 to 3 per cent of the UK population and these patients are most likely to succumb to these diseases.
Another 26 per cent of people have what is known as the "Goldilocks phenomenon" where the two copies of Mal work "just right", Prof O'Neill said. But the majority, more than 70 per cent have copies that make Mal overactive.
Having the overactive Mal doubles the risk of succumbing to these diseases, with some populations facing a four-fold higher risk of getting malaria. "It turns out you are best off having the form that works just right," he said.
The findings have huge implications for the way these diseases are treated.
The great hope is that drugs could be developed either to dampen down or promote Mal activity to reach the "just right" level, Prof O'Neill said.
Equally, patients more at risk could be given higher doses of antibiotics early on or stronger antibiotics.
It may allow clinicians to predict a person's risk before they travel to areas where malaria is endemic.
