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HEALTH: New Diagnostic Tool Could Slash Malaria Deaths

Stephen Leahy

UXBRIDGE, Canada, Dec 8 2008 (IPS) - Malaria kills a child every 30 seconds, but a new diagnostic breakthrough may cut that devastating death toll, Canadian scientists announced Sunday.

The discovery of "biomarkers" – a telltale biological signature in children's blood – that identify two of the most lethal forms of malaria was revealed at the annual meetings of the American Society of Tropical Medicine and Hygiene in New Orleans, Louisiana last week.

"A child with a fever may be treated in a clinic with anti-malarial drugs, but that won't be enough to treat cerebral malaria," said Conrad Liles, a tropical disease specialist affiliated with Toronto's McLaughlin-Rotman Centre for Global Health (MRC).

Cerebral malaria, which develops in the brain's blood vessels, is malaria's most deadly form. Some 2 to 5 percent of children with malaria develop the cerebral form and 40 percent will die, Liles told IPS.

Liles and colleagues at MRC discovered a correlation between cerebral malaria and an abnormal ratio between two forms of proteins that regulate the activation of blood vessels known as angiopoietins. When an abnormal ratio is detected in a blood sample, a child could then be treated much more intensively.

Field tests done with collaborators from Thailand, Noppadon Tangpukdee Srivicha Krudsood and Sornchai Looareesuwan, and Uganda, Robert Opoka and Chandy John, showed that success rates in identifying cerebral malaria were very high – 80 to 100 percent.

"Just killing the parasite is not enough because the disease can still develop," said Liles.

Malaria is a disease of the blood caused by a parasite found inside certain species of mosquitoes. Malaria symptoms, such as fever, headache and vomiting, appear about nine to 14 days after an infectious mosquito bite. If drugs are not available for treatment or if the parasites are resistant to them, the infection can lead to coma, severe life-threatening anemia, and death.

Worldwide, malaria causes around 350 to 500 million illnesses and more than one million deaths annually.

Pregnant women who exhibit no malarial symptoms can have high levels of parasites in their placentas, which is a major cause of miscarriage, low birth weight and maternal anemia. 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.

"Children born with low birth weight from placental malaria have several strikes against them before they've drawn a breath," said Kevin Kain of the MRC and director of the Centre for Travel and Tropical Medicine at Toronto General Hospital.

"Any additional illness that comes along in early childhood is more likely to kill them," said Kain.

Tests on pregnant women in Kenya revealed that those with placental malaria had elevated levels of another biomarker in their blood – a protein called C5a. This protein is an important part of the body's innate defence against infections.

"A test that helps detect placental malaria means women can be treated earlier in pregnancy, reducing the risk of death or anemia for them, and perhaps saving their babies from malformation or miscarriage," Kain said.

Such tests are not yet available. The MRC and others are developing a "point-of-care diagnostics test" which would test for a number of things, including the two biomarkers. The hope is that such diagnostic tools will be inexpensive, easy to use, not require refrigeration and be available in three to five years, said Liles.

These discoveries come from a new ability to detect the pathogenesis of a disease at the molecular level. By understanding the progress of the disease, researchers hope to not only detect it sooner but to interrupt the disease pathway. These biomarkers offer new targets for potential new drugs or even existing drugs used for other conditions that could disrupt the progress of malarial infection, he said.

Angiopoietins were only discovered 10 years ago, in the context of cancerous tumor growth. Thinking that the process of cerebral malaria involved sepsis (inflammation) similar in some ways to blood vessel growth in tumours, it was "an educated guess" to see if there was a relationship, Liles recalled.

Developing such biomarkers and diagnostic tools can dramatically improve treatment while reducing overall costs by a more effecient use of limited resources, he said.

"I think the discovery has significant implications," he concluded.

Meanwhile, the New England Journal of Medicine reported Monday that the world's most clinically advanced malaria vaccine candidate has successfully provided both infants and young children with significant protection against malaria.

"Today’s study results strongly show that our investments in developing malaria vaccines are beginning to pay dividends," said Christian Loucq, director of the Malaria Vaccine Initiative. "We are closer than ever before to developing a malaria vaccine for children in Africa."

In infants, the vaccine candidate can be administered as part of existing African national immunisation programmes for diseases like diphtheria, tetanus and polio. In children aged 5 to 17 months, the candidate RTS,S/AS01 reduced the risk of malaria by 53 percent over an eight-month follow-up period. The studies were conducted in Kenya and Tanzania.

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