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Malaria-carrying mosquito
Photo by James Gathany

Changes in skin odor can reveal malaria infection in patients with no external symptoms, according to research published in PNAS.

Researchers examined chemical compounds released from the skin of Kenyan children and discovered characteristic patterns in these compounds that identified patients with acute and asymptomatic malaria infections.

“Our previous work in a mouse model found that malaria infection altered the odors of infected mice in ways that made them more attractive to mosquitoes, particularly at a stage of infection where the transmissible stage of the parasite was present at high levels,” said study author Consuelo De Moraes, PhD, of ETH Zurich in Switzerland.

“We also found long-term changes in the odor profiles of infected mice. [So] we had reason to hope that similar changes in human odors might provide biomarkers that could be used for diagnosis.”

To test this theory, Dr De Moraes and her colleagues studied more than 400 Kenyan school children. The researchers collected blood samples as well as samples of volatile substances released from the subjects’ skin.

The team used the blood samples to test for malaria, first via light microscopy and an SD Bioline Rapid Diagnostic Test, then using polymerase chain reaction (PCR) methods to confirm the initial results.

There were 330 subjects who were clearly positive or negative for malaria, and there were 66 subjects who were positive by PCR but negative by microscopy. The researchers compared these findings to results from the skin tests.

To assess the subjects’ skin, the researchers placed each child’s foot and arm into sealed Teflon bags and passed an air current over the skin for about 1 hour. The air was then channeled through special filters that collected the volatile compounds.

Using gas chromatography and mass spectrometry, the researchers then determined the identity and quantity of each compound to generate odor profiles for infected and uninfected children.

Further analysis of these profiles revealed volatile biomarkers that enabled the researchers to accurately identify whether a child was infected with the malaria parasite. Even for asymptomatic infections, the detection rate was close to 100%.

“This high detection rate was encouraging,” Dr De Moraes said. “Initially, we weren’t sure which chemical compounds we should be looking for.”

The researchers noted that malaria infection does not create new chemical compounds, but it alters the amounts of compounds that are already present in the odors of healthy people.

Odor profiles were different for malaria-infected and uninfected subjects, but profiles were also different for patients with acute and asymptomatic infections.

The researchers hope the biomarkers they identified could be used to develop a new tool for the early detection of malaria.

“These new volatile biomarkers are an important first step,” said Mark Mescher, of ETH Zurich. “Now, someone needs to develop an application that can be used cheaply and reliably in the field.”

“In the near-term, our goal is to refine the current findings to find the most reliable and effective biomarkers we can. There is still a lot more work to be done to develop a practical diagnostic assay.”

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