Why do some malaria patients exhibit only mild flu-like symptoms, while others go into a coma and die?

By examining malaria parasites taken straight from the blood of patients, researchers found three groups of the parasite, one of which was correlated with much more severe symptoms. Previous studies which examined the parasite in laboratory cultures had only found one group.

The study, published yesterday in the online edition of the journal Nature, was the result of an international collaboration between researchers at institutions including the Broad Institute—a joint Harvard-MIT venture—and the Harvard School of Public Health (HSPH).

To study the parasite in vivo, Johanna P. Daily—an assistant professor of medicine at Harvard Medical School and the first author of the study—collected blood samples from over 40 malaria patients in Senegal and worked with her collaborators to isolate the parasites’ genetic material.

By measuring the expression of every gene in the parasite, the authors found “completely novel states that are seen in patients that we never saw in the petri dish,” Daily said.

While one group of parasites had patterns of gene expression like those seen in lab culture, the second group had patterns that were the mirror image of what is seen in culture, and the third group had patterns that were entirely new compared to what had been observed, said Aviv Regev, a member of the Broad Institute and an assistant professor of biology at MIT.

“The parasite is doing a lot more in the host than in lab culture” Regev said.

The authors then took data from yeast, a model organism whose genome has been studied extensively, and looked for similar gene expression patterns.

They found that the first group of parasites corresponded to yeast flourishing in optimal conditions like those grown in culture, the second corresponded to the starvation-response group, and the third corresponded to the stress-response group.

In patients, there was no discernible clinical difference between those infected with the first and second parasite groups, but patients with the third type were more likely to have a severe case of malaria with high inflammation and fever.

Daily said that the experiment showed that “parasites can sense the environment and respond. Up to this study, it was not clear that this was the case.”

Dyann F. Wirth, co-director of the Infectious Disease Initiative at the Broad Institute and the chair of the HSPH department of immunology and infectious diseases, said that combining different research techniques was the key to the breakthrough.

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