Fatal Forms of Malaria Identified by Protein Biomarkers

Canadian researchers have identified protein biomarkers that could facilitate easy diagnosis of two severe and debilitating forms of malaria.

With the findings, scientists have shed new light on the development two crippling malaria variations - one that develops in the placenta of pregnant women affecting countless unborn children, the other, cerebral malaria, that develops in the brain's blood vessels - malaria's most deadly form.

Since ages malaria has notoriously stalked pregnant women, said Tropical disease specialists affiliated with Toronto's McLaughlin-Rotman Centre for Global Health (MRC).

A decade ago, researchers showed malaria parasites could accumulate in the newly created placenta. But Dr. Kevin Kain, Director of the Sandra A. Rotman Laboratories at the MRC, said that it's still unclear how parasites hiding in the placenta actually result in placental and foetal injury.

And in the new research, the scientists claim to have unravelled part of this mystery, by finding that women with placental malaria carry a biomarker in their blood - a protein called C5a, which is an important part of the body's innate defence against infections but one that needs to be carefully controlled.

At the time of over-activation by malaria infection, C5a appears leads to an excessive inflammatory response and disrupts normal blood vessel growth in the placenta, raising the risk of spontaneous abortions or low birth weight infants.

The scientists conducted tests on pregnant women in Kenya, and found that those with placental malaria had elevated levels of C5a in their blood compared to expectant mothers without the disease.

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The discovery may help identify placental malaria carriers early enough to potentially prevent tragic consequences through better targeted treatment strategies.

"Children born with low birth weight from placental malaria have several strikes against them before they've drawn a breath. Any additional illness that comes along in early childhood is more likely to kill them. A test that helps detect placental malaria means women can be treated earlier pregnancy, reducing the risk of death or anemia for them, and perhaps saving their babies from malformation or miscarriage," said Kain.

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Meanwhile, the researchers in collaboration with scientists from Thailand have also found biomarkers that reveal potential victims of cerebral malaria, the disease's most fatal form.

Cerebral malaria is a scourge of people with little developed immunity, affecting particularly African children under five years old and other non-immune adults and travellers to developing countries. It kills 10 to 40% of its victims.

In the study, scientists compared the blood tests on patients with cerebral malaria were with samples from patients with uncomplicated malaria and from healthy test control subjects.

Cerebral malaria patients were found to have abnormal levels of proteins that regulate the activation of blood vessels known as angiopoietins. Angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2) must be in careful balance to maintain healthly endothelial cells that line blood vessels.

In cerebral malaria, the research showed ANG-1 and ANG-2 were deregulated, likely contributing to excessive activation of the endothelial cells and parasite obstruction of brain blood vessels, associated with cerebral malaria.

High levels of ANG-2 and low levels of ANG-1 were associated with the severity of disease; the levels recorded on admission to hospital predicted which children would subsequently die. The accuracy of ANG-1 and ANG-2 levels in identifying cerebral malaria was very high.

The results of the study could help doctors spot at-risk individuals early in the course of the disease, with profound implications for triaging critically ill children in developing countries and effectively allocating scarce health care resources.

Furthermore, drugs or agents that block ANG-2 or enhance ANG-1 may have a therapeutic role in preventing or treating cerebral malaria.

"While there is still much work ahead related to this finding, we believe it could soon help improve priority setting by doctors as they decide which patients need the most intensive anti-malaria therapy and supportive care once symptoms are detected," said Liles.

The findings will be described at annual meetings of the American Society of Tropical Medicine and Hygiene in New Orleans, Louisiana, USA.

Source-ANI
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