2003 WINNER

The mystery of a very sleepy Sultan

By Claire Bithell
Winner of the 20-28 category

A sigh of relief must have echoed through the kingdom of Melli the day Sultan Dja a died of a mysterious lethargy that had plagued him for months. A corrupt and tyrannical leader, the Sultan was succeeded by his son Musa, who was everything his father was not.

Now, five centuries later, Sultan Djata’s death is thought to be the first documented case of African sleeping sickness. This disease seems relatively innocuous in its early stages, where symptoms include fever, joint pain and itching. Meanwhile, the sleeping sickness parasite is busy inside the body, dividing and changing until it is ready to invade the nervous system. Once this attack is under way, the victim suffers brain swelling and he characteristic unresponsiveness or "sleepiness ” which eventually leads to death.

An estimated 50,000 people died of African sleeping sickness in 2001, according to World Health Organisation records, but the total number affected is probably closer to half a million.

In 1901, English physicians working in the Gambia identified microscopic parasites, known as trypanosomes, as the cause of the illness.

The following year, the tsetse fly was found to spread the disease. Despite 100 years of study, the disease remains a threat to more han 60 million Africans. In some areas, sleeping sickness is a bigger killer than Aids.

So how has the parasite avoided eradication for all his time? Quite simply, the trypanosome has some good tricks up its sleeve when it comes to evading detection by the human immune system - puting on the micro-organism equivalent of a big coat and sunglasses. In trypanosome terms, this means changing the proteins on its surface.

Dr Keith Matthews, a research fellow at the University of Manchester, says:"By constantly changing its disguise, the parasite avoids recognition by the host. ” This process (known as antigenic variation) means effective vaccination is almost impossible to produce. Current treatment is either ineffectual or so toxic that it can prove fatal.

But hope is at hand. "Much of the genome sequence of these parasites has been determined and this is already starting to tell us how trypanosomes differ from the mammalian host,” says Dr Mathews. "These differences are key to attacking the parasite. ”One of these differences is already being exploited by Prof Kiyoshi Kita and his colleagues at the University of Tokyo, who hope to find a drug which can starve the parasite of energy. Whereas humans get energy by directing the carbohydrate from their diet and the oxygen they breathe in to a complex metabolic pathway (respiration), for the trypanosome this is not an option.

The trypanosome has to use carbohydrate and oxygen from the host blood system. The unwelcome guest is no shy atttaking the goodies on offer. In fact, the trypanosome guzzles its own dry weight in glucose every hour.

Unsurprisingly, given its voracious appetite and lack of social graces, the trypanosome respiration pathway is very different to that of humans. It is this which may prove its ultimate downfall. Trypanosome Alternative Oxidase (TAO) an enzyme specific to the trypanosome respiration pathway is of particular interest to Prof Kita and his colleagues in Japan. Prof Kita ’s group know that if they can prevent TAO doing its job then they can kill the trypanosome without any collateral damage to the patient.

In the most recent step towards this goal Prof Kita and his group have purified TAO made in bacteria. Prof Kita explains: "The inability to purify stable TAO has severely hampered biochemical studies. ”The group can now use purified TAO to carry out intensive research on drugs that migh stop it working.

One hope is a compound called Ascofuranone. Made from a fungus notorious for causing disease in lentil and chickpea crops, the Ascochy a fungus has a chance to leave its delinquent past behind and make a contribution to medical science.

Ascofuranone can kill tyrpanosomes in mice, and Prof Kita and his colleagues can now study how the drug is working.

"The most important thing in his field is the development of a new drug for real practical and clinical use,” says Prof Kita.

"In this regard, Ascofuranone is a promising drug for trypanosome infection. ’’

The challenges ahead remain formidable. "It is hugely expensive to develop drug therapies," says Dr Mathews.

"These costs are unlikely to be recovered given the dismal health funding in Africa."

Thus, while Sultan Djatat’s sleeping sickness may be the first recorded case, it is unlikely that we shall see the last case for some time.