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Conquering a Killer

There is no vaccine and half the world's population is at risk from this mosquito-borne viral infection. But papaya could offer a solution, say researchers at the University of Nottingham Malaysia.

Dengue fever infects millions of people worldwide and claims thousands of lives every year. Incidences have risen dramatically in recent decades, particularly in tropical countries such as Malaysia where weather patterns and urbanisation are leading to an increase in the mosquito population.

But now researchers are studying the properties of a traditional herbal remedy with the aim of developing new treatments. Papaya leaf juice is a traditional treatment for dengue in India and South East Asia. Carpaine, a bioactive compound in the juice, helps with blood clotting and can restrict the internal bleeding caused by the disease, which is carried by the Aedes mosquito.

More infections

With funding from the Malaysian Ministry of Higher Education, a team of researchers are tackling the challenge of extracting the carpaine for use in a pill for dengue.

Leading the research is Associate Professor Ching Lik Hii at the University of Nottingham Malaysia.

He said: “Dengue has been a big issue in Malaysia and other countries with similar climates for more than 20 years. People are dying and more people are being infected as the Aedes mosquito population grows and becomes more active. This global problem inspired me to look for something that is a well-known traditional plant-based remedy and make it make it into products that can be available to consumers.

Internal bleeding

“We are targeting carpaine as we know it can increase blood platelets and therefore help to reduce internal bleeding. We are also looking at whether the younger leaves or the older leaves contain more carpaine, and whether the stems of the papaya plant could also be useful.”

"It has the potential to reduce fatality globally, so it’s an exciting time to be involved in this research."
Dr Ching Lik Hii

The carpaine compound is extracted by using alcohol. An acid-base extraction procedure is then used to yield crude carpaine material. Further purification using chromatography produces solid carpaine that is at least 95% pure.

By the end of the three-year project, Dr Ching Lik Hii said cross-disciplinary strengths in biosciences, pharmacy and other fields would allow the team to discover the best processing method to achieve the highest yield of carpaine, and to find out how the carpaine degrades during storage and which parts of the papaya plant were best to use.

Freeze-drying

He added: “Traditionally, the leaf if used in dried form is dried under the sun or using a hot air oven, but this has limitations. We are investigating a combined pre-treatment and freeze-drying technique to process the leaf at low temperatures in a bid to prevent degradation during processing. We are also investigating how storage over prolonged periods affects the potency and stability of carpaine.”

One challenge will be to find adequate sources of papaya leaf because there are not many large papaya farms in Malaysia – and existing farms do not harvest the leaves as their priority is to grow papaya fruit.

Ultimately the researchers aim to work with industry partners in Malaysia and beyond to produce a carpaine medication.

“If the combined pre-treatment and freeze-drying technique can successfully preserve high amount of extractable carpaine, it will mark a big milestone in the treatment of dengue,” said Dr Ching Lik Hii. “We can then collaborate with pharmaceutical companies to develop a targeted medication. Time is of the essence to save a dengue sufferer’s life, so we hope that the carpaine extracted from the leaf can be manufactured as either a fast-acting pill or a medicated syrup.

“It has the potential to reduce fatality globally, so it’s an exciting time to be involved in this research.”

Half the world’s population at risk

Dengue is a mosquito-borne viral infection. It causes flu-like illness and occasionally develops into a potentially lethal complication, severe dengue (also known as Dengue Haemorrhagic Fever).

The global incidence of dengue has grown dramatically in recent decades. About half of the world’s population is now at risk and severe dengue is a leading cause of serious illness and death among children in some Asian and Latin American countries.

Dengue cases are underreported and many cases are misclassified. One recent estimate indicates 390 million dengue infections per year, of which 96 million manifest clinically.

Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas.

There is no specific treatment for dengue/severe dengue, but early detection and access to proper medical care lowers fatality rates below 1%.

Source: World Health Organisation

Ching Lik Hii

Dr Ching Lik Hii is Director of the Food and Pharmaceutical Engineering Research Group, in the Faculty of Engineering, University of Nottingham Malaysia.

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