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Malaria Puts Children at Risk for Future Diseases


A young girl with malaria in South Sudan rests.
A young girl with malaria in South Sudan rests.
Repeated bouts of malaria may leave children vulnerable to other deadly infections and even cardiovascular disease later in life. Now, a new study may explain why.

About 200 children in Blantyre, Malawi, took part in the study. It compared kids with mild and cerebral malaria with those who were healthy. Malaria is caused by a parasite that is transmitted to people by the bite of an infected mosquito. The parasite travels first to the liver and then to red blood cells.

Inflammation

In response to a parasitic invasion, the affected organs in the body become inflamed, or swollen. This inflammation is the body’s attempt to heal itself. Inflammation is the result of the body’s efforts to destroy and remove injured tissues. Many diseases, including malaria, are febrile diseases because they cause acute fevers, which trigger inflammation in the endothelium, the smooth, thin layer of cells lining blood vessels throughout the body.

According to the malaria study, the blood vessels of children with malaria, especially cerebral malaria, were different than blood vessels of children who were healthy. Dr. Chris Moxon, the lead author of the study and a clinical lecturer at Liverpool University in the UK (Dr. Moxon was a Ph.D. fellow at Wellcome Trust at the time of the study), said it appears that chronic inflammation of blood vessels makes the blood vessels much more vulnerable to other infections.

When healthy, the endothelium allows the blood to flow unrestricted, similar to Teflon coating on a non-stick cooking pan. The study, according to Dr. Moxon, was to look at whether the endothelium returns to normal after malaria treatment that stops fever and the resulting inflammation.

“We were just thinking that the burden of malaria is extremely high in Africa,” Dr. Moxon explained, “in the sort of level that’s very difficult for people who haven’t lived in a malaria endemic country to understand. Children are getting sometimes, in highly endemic areas, more than one infective bite a day and many repeated infections. And we just wondered what that might do to children and their endothelium in the long term.”


"Leaky" Endothelium

Moxon and his colleagues knew that mosquito control programs appeared to have effects beyond simply reducing malaria cases.

Moxon pointed to a number of studies that have shown that when malaria is reduced or eliminated in a small area, the reduction in mortality is higher than might be expected from simply a reduction in the number of acute febrile illnesses. “So we wondered whether there was another effect that malaria was having,” Dr. Moxon said. “Whether this might be that the endothelium remained [inflamed] for a longer period of time.”

The endothelial cells have proteins on their surface that are shed in healthy individuals, but when a person gets an illness and the endothelium changes, the proteins are shed in higher quantities. Blood tests can measure these proteins in the blood. Malaria changes the blood vessels, Moxon said, because it “hijacks” the endothelium to be able to stick to blood vessels. This is how the malaria parasite passes through the spleen and avoids being blocked by the body’s immune system.

So, if the endothelium is inflamed, it may predispose a child to other infections and possible future cardiovascular disease, because an inflamed endothelium is more permeable, or leaky.

“For example,” Moxon said, “that may allow viruses or bacteria to leak and invade areas, for example, in the gut. And then cardiovascular disease, those processes of inflammation make the endothelium more leaky to allow fat to accumulate inside the blood vessel wall.”

There’s been greater awareness in recent years of inflammation’s role in not only malaria, but a host of diseases. While more study is needed, Moxon said controlling inflammation may help prevent other infections following bouts of malaria, and in turn reduce child mortality. One option may be statins, drugs used to lower cholesterol, as they have been shown to reduce inflammation.
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