Credit: Peter H. Seeberger
Two studies published in PLOS Pathogens provide new insight into the malaria-related complications that can occur in children.
One study revealed how the immune system manages to prevent malaria fever in children infected with Plasmodium falciparum.
And with the other study, researchers identified proteins that can help them distinguish children with complicated malaria syndromes from those with uncomplicated malaria.
Analyzing immune response
In the first study, Peter Crompton, MD, of the US National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues analyzed immune cells from healthy children before the malaria season and from the same children after their first bout of malaria fever during the ensuing malaria season.
The researchers exposed both sets of immune cells to parasite-infected red blood cells and found that their responses were different.
When confronted with parasites before the malaria season, the children’s immune cells produced large amounts of molecules that promote inflammation—such as IL-1b, IL-6, and IL-8—which results in fever and other malaria symptoms.
But after a malaria fever episode, the immune cells responded by producing more anti-inflammatory molecules—such as IL-10 and TGF-b—and showed evidence of an enhanced ability to recognize and destroy parasites.
The ability of the immune cells to mount this response—somewhat effective in controlling the parasites but avoiding systemic inflammation and fever—seems to depend on the continued exposure to parasites through bites of infected mosquitoes.
When the researchers took blood again from the same children after the subsequent dry season (when there are few or no new infections) and exposed the immune cells to parasite-infected red blood cells, the anti-inflammatory response had returned to baseline, leaving children susceptible again to malaria-induced inflammation and fever.
The researchers said these findings shed new light on the notion of premunition, an immune response that protects against illness and high numbers of parasites in the blood without completely eliminating the infection.
They suggested that it evolved as an appropriate immune response to at least partially protect young children from potentially life-threatening inflammation and unchecked parasite replication before they acquire antibodies that protect against the onset of malaria symptoms.
Proteins provide answers
In the second study, Peter Nilsson, PhD, of SciLifeLab in Stockholm, Sweden, and his colleagues used a systematic proteomics approach to distinguish children who develop malaria-related complications from those who do not.
The researchers compared proteins in the blood of uninfected children with proteins in malaria-infected children. And they compared proteins in children with severe malaria syndromes to proteins in uncomplicated cases.
The team analyzed 1015 proteins in blood samples from more than 719 children. They divided the samples into “discovery” and “verification” sets, and only associations found in both sets were reported.
The researchers identified 41 proteins that distinguished malaria patients from uninfected children from the same community. Most of these were components of the inflammatory response.
Thirteen proteins helped the team distinguish uncomplicated malaria from severe malaria syndromes. They identified proteins specific to the 2 most deadly complicated malaria syndromes in children—severe malarial anemia and cerebral malaria.
Markers of oxidative stress were related to severe malarial anemia. And markers of endothelial activation, platelet adhesion, and muscular damage were identified in children with cerebral malaria.
The researchers said their study could aid the discovery of distinct mechanisms in the human response to malaria infection between the 2 most fatal syndromes of childhood malaria.
