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Biomarkers in blood could aid diagnosis of two severe and debilitating forms of malaria

Published on December 8, 2008 at 1:02 PM · No Comments

Canadian researchers have identified protein biomarkers that shed new light on the development of two severe and debilitating forms of malaria.

The findings may let doctors detect earlier 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.

The double breakthrough will be described at annual meetings of the American Society of Tropical Medicine and Hygiene in New Orleans, Louisiana, USA, Dec. 7-11, 2008.

Over-activation of body's natural defences implicated in placental malaria

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

Many women growing up in areas such as sub-Saharan Africa gradually develop partial immunity to malaria and become relatively impervious to it until their first pregnancy. Often, the expectant mother with placental malaria appears relatively well and the disease is detected only after the child is delivered.

Some 10,000 women die annually from placental malaria, while up to 400,000 develop severe anemia. The disease also causes up to 200,000 infant deaths and countless cases of babies born with low birth weight - a major risk factor for early childhood death.

A decade ago, researchers showed malaria parasites can accumulate in the newly created placenta. But how parasites hiding in the placenta actually result in placental and fetal injury was unclear, says lead researcher and Dr. Kevin Kain, Director of the Sandra A. Rotman Laboratories at the MRC.

Dr. Kain, in collaboration with W. Conrad Liles and colleagues Andrea Conroy, Lena Serghides, Constance Finney, Simon O. Owino, Sanjeev Kumar, D. Channe Gowda, and Julie M. Moore say their work unravels part of this mystery.

They found 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.

When overactived by malaria infection, C5a appears to contribute to an excessive inflammatory response and dysrupts normal blood vessel growth in the placenta, raising the risk of spontaneous abortions or low birth weight infants.

Tests on pregnant women in Kenya revealed that those with placental malaria had elevated levels of C5a in their blood compared to expectant mothers without the disease. 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," says Dr. Kain, who is also Director of the Center for Travel and Tropical Medicine at Toronto General Hospital. "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."

Protein "biomarker" linked to cerebral malaria, predicts survival

Meanwhile, Drs. Kain and Liles, with colleagues Fiona E. Lovegrove, Erin I. Lafferty, Nimerta Rajwans, and Michael Hawkes, together with collaborators from Thailand, Noppadon Tangpukdee Srivicha Krudsood, Sornchai Looareesuwan, and Uganda, Robert O. Opoka and Chandy C. John, will report in New Orleans on a similar breakthrough: biomarkers that reveal potential victims of cerebral malaria, the disease's most fatal form.

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