According to the World Health Organization, malaria caused approximately 627,000 deaths in 2012, the majority of which were among children. Most malaria-related deaths in children are a result of complications from the disease, but it has been unclear why some children are more susceptible to these complications than others. Now, two new studies could bring us a step closer to finding out.
Both studies, published in the journal PLOS Pathogens, investigated malaria caused by Plasmodium falciparum - one of the most common parasites that causes malaria infection in humans.
If not treated within 24 hours, P. falciparum malaria can rapidly progress to severe illness and even death. In children, this form of malaria can often lead to other complications, such as severe malaria anemia, respiratory problems and cerebral anemia - a condition in which parasite-filled blood cells block small blood vessels to the brain, causing swelling and even brain damage.
In the first study, a team of international researchers set out to identify human proteins in plasma that could be related to complications of childhood malaria.
The team analyzed 1,015 proteins from the plasma of 719 malaria-infected children from Ibadan in Nigeria.
Proteins specific to cerebral malaria and severe malaria anemia discovered
From this, the researchers identified several proteins that were present at higher levels in the blood of children with severe malaria, compared with children with a less severe form of the disease.
Some of these proteins in the children with severe malaria were specific to cerebral malaria and severe malaria anemia. The researchers say such proteins could be used as "signatures" to predict both conditions with high accuracy.
In addition, the investigators discovered a group of muscle-specific proteins in the blood of children with cerebral malaria, indicating that muscle cells are damaged. The team says some of this damage could be linked with coma - a condition that can occur in cerebral malaria among other conditions, such as meningitis.
Commenting on their research, the investigators say:
"These findings will hopefully lead to an increased understanding of the disease and may contribute to the development of clinical algorithms that could predict which children are more at risk to severe malaria."
How does the immune system fight malaria?
In the second study, a research team, led by Peter Crompton of the US National Institute of Allergy and Infectious Diseases, set out to understand how the immune system prevents malaria in the majority of cases.
In their background information, they note that in malaria-naïve individuals, P. falciparum infections cause high levels of parasite-infected red blood cells, known as iRBCs. This triggers systemic inflammation and fever.
Malaria caused around 627,000 deaths in 2012, the majority of which were among children. Could these latest studies better our understanding of the disease?
However, they point out that people who reside in areas with high malaria contagion - even young children - are often repeatedly infected but show no symptoms and have low iRBC levels.
To investigate why some individuals are able to stave off malaria symptoms, the team took immune cells from the blood of 34 healthy children prior to the malaria season in Mali in West Africa and 7 days after the children's first bout of malaria fever throughout this season.
The researchers exposed both sets of immune cells to malaria parasites in a test tube in order to simulate malaria infection.
The team found that the immune cells taken from the children prior to the malaria season produced an array of molecules that trigger inflammation and fever.
However, when the team re-exposed immune cells to malaria parasites following malaria fever, the molecules that caused the fever reduced in expression. Furthermore, the expression of molecules that kill parasites increased. Therefore, the immune cells were preventing the development of malaria-induced inflammation and fever.
But when the researchers took blood from the same 34 children outside of the malaria season and exposed their immune cells to malaria parasites, fever-causing molecules increased in expression, while expression of parasite-killing molecules reduced. This means the children were once again susceptible to inflammation and fever from malaria.
Commenting on their research, the study authors say:
"These findings suggest that in the face of P. falciparum re-exposure, children acquire exposure-dependent P. falciparum-specific immunoregulatory responses that dampen pathogenic inflammation while enhancing anti-parasite effector mechanisms.
These data provide mechanistic insight into the observation that P. falciparum-infected children in endemic areas are often afebrile and tend to control parasite replication."
The team adds that in order to better our understanding of the underlying mechanisms of malaria infection, further studies are warranted in symptomatic and asymptomatic individuals who are repeatedly exposed to P. falciparum infection.
They say such research "may help define the potential for interventions that safely prevent or mitigate Plasmodium-induced immunopathology without compromising control of parasite replication."
Earlier this year, Medical News Today reported on the discovery of a new protein that may lead to new treatments for toxoplasmosis and malaria.
Written by Honor Whiteman