Malaria infection might cause children's immune systems to attack their own DNA, resulting in more severe disease than in adults, scientists report.
This could explain why existing DNA-based malaria vaccines haven't worked, they say.
Nigerian and US scientists took blood samples from 21 Nigerian children under the age of six infected with Plasmodium falciparum malaria and tested them for the presence of different immune components, such as cytokines — signalling chemicals released by the immune system — and antibodies.
They found that the samples contained modified white blood cells, called NETs, which capture the malaria parasite.
But they also found that NETs release copies of the body's own DNA. Samples also contained increased levels of antibodies specific to the children's DNA.
This has led the researchers to speculate that the DNA causes the immune system to attack its own cells — known as autoimmunity — which, in children, leads to a worse state of sickness.
They say this autoimmune-like response has a different effect in adults, particularly those repeatedly exposed to malaria. Adults have a more developed immune system, and the response actually helps strengthen protection against the parasite.
"This research sheds new light on how the children are responding to falciparum malaria. It appears that they are making antibodies that are not protective," Virginia Baker, from the US-based Chipola College and co-author of the study, told SciDev.Net.
Since some vaccines for malaria use DNA as an agent to increase immunity, the findings may help explain why these vaccines have failed to work.
Baker says that for any malaria DNA vaccine to work, it might require an immunosuppressive therapy before administration.
And protocols that treat the autoimmune-like response, as well the parasites, will be more effective in preventing severe malaria in young children, the researchers say.
Michael Oluseyi Obadofin, from Jos University Teaching Hospital in Nigeria and a co-author on the study, says the study offers a scientific explanation for a long-observed phenomenon.
"It is a groundbreaking study because, though much work has been done on malaria, we are not aware of any study that has so established the [immune] basis for malarial susceptibility in children."
He added that more research is still needed to help inform vaccine production.
The study was published in Malaria Journal.