New research at KTH Royal Institute of Technology offers hope to thousands of children who are stricken with malaria each year.
Malaria can be mild or deadly, especially for children under 5. But there is no way to tell which patients are at risk of developing more dangerous forms of the disease, such as cerebral malaria. Sometimes the seriousness of a malaria case isn't evident until it's too late.
New research from Sweden's KTH Royal Institute of Technology however could save lives and reduce suffering by enabling caregivers to distinguish patients with lethal variants of the parasitic illness from the ones with mild malaria, and therefore know early on whether a patient needs extra care.
The key was found in proteins that appear in the blood plasma of children with severe malaria syndromes.
In a study of more than 1,000 different proteins in blood samples from more than 700 children, 500 of whom were infected with malaria, the researchers found 13 individual proteins that distinguish patients with uncomplicated malaria from those with more serious variants of the disease, says Peter Nilsson, a proteomics professor at KTH.
"These proteins were greater in the blood of the children who developed severe malaria infection," Nilsson says.
The discovery of the biomarkers could enable early intervention for patients who have the more lethal variants of the parasitic illness.
"So, children at risk of dying will no longer be sent home," he says.
Malaria is a life-threatening disease that caused an estimated 627,000 deaths in 2012, according to the World Health Organization. In Nigeria, the researchers added, about a third of childhood deaths are attributable to Plasmodium falciparum, one of the parasites that causes malaria.
There are several major variants of malaria, of which cerebral malaria is the worst. "Our results indicate that there is muscle tissue that is broken down, particularly in patients who have cerebral malaria -- something that does not occur in patients who have lighter malaria variants," he says.
"This muscle decay occurs before patients lapse into the serious state of coma as a result," he says.
Nilsson says that malaria experts have expressed excitement over the findings, and that it is hoped the discovery of the biomarkers will reduce mortality from malaria.
"Until today, it has not been known which patients are likely to develop a dangerous type of malaria, which means you can quickly lapse into a coma and die," he says. "When taking blood samples from children with malaria fever, one can then see which of them you should keep under observation and advanced care.
"Today a great number of children are sent home directly. For many, that's fine, but obviously not for all, since many die."
Clinical tests of the findings could begin soon, since regulatory agencies such as the US Food and Drug Administration do not require approval for analysing additional proteins from blood samples.
"It may not be long before this can be tested in practice with children with malaria, which will also lead to an expansion of the knowledge about -- and the value of -- these proteins," he says. "We also have very good contact with clinics in Nigeria and we are planning to expand the study to include samples from other regions."
The study is the first to look at human proteins in large numbers of malaria cases. "Until now, research has mainly studied the malaria parasite's own proteins," Nilsson says.
- Julie Bachmann, Florence Burté, Setia Pramana, Ianina Conte, Biobele J. Brown, Adebola E. Orimadegun, Wasiu A. Ajetunmobi, Nathaniel K. Afolabi, Francis Akinkunmi, Samuel Omokhodion, Felix O. Akinbami, Wuraola A. Shokunbi, Caroline Kampf, Yudi Pawitan, Mathias Uhlén, Olugbemiro Sodeinde, Jochen M. Schwenk, Mats Wahlgren, Delmiro Fernandez-Reyes, Peter Nilsson. Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria. PLoS Pathogens, 2014; 10 (4): e1004038 DOI: 10.1371/journal.ppat.1004038
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