London: Scientists have for the first time revealed why malaria patients are at high risk of developing fatal bacterial infections, especially salmonella infections.
The finding opens the way to more effective treatments.
The vulnerability to salmonella infections is commonly believed to be due to generalised immuno suppression by malaria, whereby the entire immune system is weakened and compromised.
However, researchers at the London School of Hygiene and Tropical Medicine have discovered that the increased vulnerability to salmonella infections is a side effect of the body’s attempts to protect itself from the damaging effects of the malaria infection.
The researchers describe this defence mechanism as a trade-off, where the body fights one enemy but exposes itself to the other. This was demonstrated in their study exploring the connection between malaria and non-typhoid salmonella (NTS)- an infection that is particularly dangerous for children.
“It is a widespread belief that malaria is an immunosuppressive disease; that once the disease is contracted, the patient will be susceptible to several other infections because of a compromised immune system,” said Professor Eleanor Riley, one of the lead authors of the study.
“However, this study shows that increased susceptibility to salmonella infections is due to a very specific immunological effect which does not affect the immune system as a whole,” Riley explained.
The Medical Research Council (MRC) funded study found that in malaria-infected mice (which show exactly the same susceptibility to salmonella as is seen in humans) the body’s natural response to defend itself from the dangers of heme, an enzyme that degrades it (heme oxygenase-1 or HO-1), very selectively affects the immune system, crippling the production of white blood-cells (neutrophils) that are essential to fight NTS.
These crippled cells are unable to kill the bacteria, allowing them to spread freely.
The team identified Tin Protoporphyrin (SnPP) as a candidate for the prevention of salmonella infection. SnPP inhibits the activity of the heme oxygenase enzyme, reversing the susceptibility to salmonellosis in malaria infections.
But the authors say that careful testing will be needed before considering SnPP use in humans, as blocking the action of HO-1 may leave the heme free to cause tissue damage.
The Medical Research Council (MRC) funded study was published in Nature Medicine.