Cerebral Malaria: A Wily Foe…8 Years Later

guest post by Kayt Sukel

With today’s headlines awash with tales of measles and the Ebola virus, it can be easy to forget that malaria, an infectious disease caused by the protozoan parasite Plasmodium falciparum, remains one of the most deadly diseases on the planet. According to the World Health Organization, more than 600,000 people died of malaria in 2012—the majority attributed to the most severe form of the disease, cerebral malaria. One of malaria’s biggest mysteries is why some people develop the cerebral form of the disease, in which the malarial parasites invade the blood vessels around the brain, and then recover, while others with this form, many of them young children, will die of the infection.

Dr. Terrie Taylor, Michigan State University, takes vitals on a child in the pediatric malaria ward at the Queen Elizabeth Hospital in Blantyre, Malawi, Africa. Photo by Jim Peck, MSU

Dr. Terrie Taylor, Michigan State University, takes vitals on a child in the pediatric malaria ward at the Queen Elizabeth Hospital in Blantyre, Malawi, Africa. Photo by Jim Peck, MSU

In 2008, I spoke with Terrie Taylor, DO, about her clinical work with cerebral malaria patients in Malawi. She explained how cerebral malaria is a “tricky disease,” but was optimistic that researchers would have a clearer picture of how Plasmodium falciparum occupy the brain’s blood vessels in five to ten years. One of her most important goals was to understand what might be different in the brains of those who died of the disease from those who survived. Now, eight years after my Cerebrum story “Cerebral Malaria:  A Wily Foe” was published, Taylor and colleagues have published a groundbreaking neuroimaging study in the New England Journal of Medicine highlighting one of those key differences.

In 2008, the researchers were finishing up two key studies:  an autopsy study of children who died from cerebral malaria and one linking malaria retinopathy to the cerebral form of the disease. The group learned that only children with malaria retinopathy, easily checked by someone with an ophthalmoscope, died from cerebral malaria and not some other disease.

“The Eureka moment for us was pairing these two studies. We were able to recognize that the children who had changes in their retinas were the same children that had sequestration of malaria parasites in the brain,” she says. “But we were frustrated by one thing: We thought that the cause of death in these children was massive brain swelling. Then we’d see herniation, or the brain being forced down and compressing the respiratory center in the brain stem. That would lead to what we kept seeing at the bedside:  respiratory arrest. But in the autopsy, we saw swollen brains but no textbook sign of that herniation. We were stymied, because we had all these interesting findings but we still didn’t know what was killing all these kids.”

To get a better idea of what was happening in the brain, Taylor and her colleagues convinced General Electric Healthcare to donate a magnetic resonance imaging (MRI) scanner to their hospital in Blantyre. Over the past six years, the group has scanned more than 150 children with the disease. They learned that their first instinct had been correct:  Raised intracranial pressure was found in those who died of the disease, pushing down the brain stem and leading to respiratory arrest.

The MRI brain scan on the left shows normal brain volumes in a 14-month old girl at the time of a one month follow-up image series. On the right, the scan shows increased brain volume in a 19-month old girl with retinopathy-positive cerebral malaria. [images courtesy of Kim Ward/MSU]

The MRI brain scan on the left shows normal brain volumes in a 14-month old girl at the time of a one month follow-up image series. On the right, the scan shows increased brain volume in a 19-month old girl with retinopathy-positive cerebral malaria. [images courtesy of Kim Ward/MSU]

“I remember looking at the first MRI we did and thinking, ‘A-ha, now we’ve caught this process!’” Taylor says. “We caught the parasite in the act—and if we had not had an MRI, we would have never figured it out.”

Taylor is careful to point out that they still don’t know exactly why these children’s brains swelled to this point. There could be a variety of different mechanisms by which the malaria parasites could cause such swelling. But in the meantime, this result offers the possibility of saving many children’s lives until they do figure it out.

“We are going to try to bring ventilators to Malawi and do a clinical trial of assisted ventilation,” she says. “The only thing these kids aren’t doing is taking a breath—everything is fine, they are just missing the impetus to inhale. So if we can do that for them with the ventilators, give the brain some time to settle down, then, in theory, we take them off the ventilator when the swelling goes down and they live happily ever after. It’s almost irresistible.”

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