IMAGINE a disease that always kills all who are infected. Imagine a disease, the most commonly used treatment for which is fatal in one-in-20 of those treated. Imagine a disease that puts 60 million people throughout sub-Saharan Africa at risk, and kills up to 50,000 every year. Surely such a disease must be one of the most talked about, analysed and understood conditions on the planet? It must be ranked as one of the major threats to worldwide health. Well, think again.
In the information age one disease ravages on a biblical scale away from the glare of worldwide publicity – human African trypanosomiasis, more commonly known as sleeping sickness. What does it say about our world when a disease, first identified mor
e than 1,000 years ago, is still killing at such a ferocious rate, and for which the only effective treatment is so toxic? What does it say about our world that, in the 21st century, a drug containing arsenic is still the main treatment?
Sleeping sickness is truly one of the "neglected diseases" that affect vast numbers of people throughout sub-Saharan Africa. Yet the drug used to treat it is ludicrously out-of-date, highly toxic, and sometimes ineffective. Since there are no financial incentives for the large drug companies to invest in drug development, the disease has been largely neglected by the Western world.
These are some of the points that were first put to me 20 years ago by my friend and colleague Professor Max Murray of the University of Glasgow's renowned Veterinary School, at a meeting that fired my interest in researching this killer disease. I was horrified at the sheer scale of the disease, and also at the way in which animals such as domestic cattle are affected by trypanosomiasis. So as well as having a direct effect in causing massive human suffering, it also disrupts livestock production with profound economic effects.
The disease is caused by a single-celled parasite called a trypanosome, a particularly wily and effective little predator that causes a degree of human and animal havoc out of all proportion to its size. The parasite is transmitted from an infected human or animal host to other humans by the bite of the blood-sucking tsetse fly.
Once infected, the fly is infectious for life. The area that is affected, indeed held captive by the tsetse fly, is about a third of the entire landmass of Africa, an area that is slightly larger than the USA. In these areas effective farming is just not viable.
Unfortunately, despite efforts for over a century, it has not been possible to achieve large scale control of the tsetse fly, although local infested regions have sometimes been cleared. Because of the extraordinary ability of the parasite to rapidly change the pattern of proteins on its surface – a trick called antigenic variation – it has not been possible to develop a vaccine against the disease. Nor is a vaccine likely in the future.
Once it gets inside the body the trypanosome starts to wreak havoc, first infecting the blood, lymph nodes, liver and spleen. Then, in the later stages, the parasite crosses the physical barrier between the blood and the brain to enter the central nervous system. Here it produces many different symptoms including limb paralysis, psychiatric symptoms, confusion, excruciating pains in the limbs, seizures and the typical sleep disturbance that gives the disease its name. For the patient it is as if day and night are reversed, with a constant and irresistible desire to fall asleep. Untreated the stricken patient will go into a deep coma and die, always.
What about treatment? There is no available drug that can be taken by mouth, so the patient has to be hospitalised for injection therapy, something that is not easy in the African bush. Most of the drugs currently in use were developed in the first half of the 20th century and would not have passed modern day safety standards if they were introduced today.
The most commonly used drug for the late stage of the disease is the arsenic-based melarsoprol. Not only is melarsoprol painful and unpleasant for the patient, but it also kills one in 20 of those receiving it as it can cause deadly brain inflammation. That figure is difficult to take in. It is a fascinating, but revealing fact that the first person to use arsenic to treat trypanosomiasis was David Livingstone, who used it on a horse in 1847. So nothing much has changed.
What is urgently required is a safe drug that can be taken by mouth which is effective for both the early and the late stages of trypanosomiasis. There has been some modest success with combination therapy, where mixtures of drugs are used to try to reduce the toxicity of existing drugs. Because drug treatment is so toxic, it is vital to be able to tell when the patient does actually have the late stage brain infection. But here again, there are formidable problems.
It is essential to carry out a lumbar puncture – a prick in the base of the spine – to obtain a small amount of cerebrospinal fluid – the fluid that circulates within the brain cavities and covering layers – so that one can look for the parasites and evidence of brain inflammation. But there is no universal agreement as to what findings definitely prove that the brain is infected. So the patient and the doctor lose either way – if you treat someone who hasn't got brain disease, then there is an unnecessary risk of drug toxicity. But if you don't treat someone who is infected, then they will die.
This is one of the greatest dilemmas of the disease. What is urgently required is a cheap, easy-to-perform, and reliable test to prove one way or another whether the patient has the brain disease.
Yet right now there is still no oral drug available or any new drug on the horizon. We in Glasgow, and others, are actively investigating the possible mechanisms of the brain infection, and new drug possibilities for sleeping sickness, but it still receives a tiny fraction of the funding available for the diseases of Western civilisation.
• Professor Peter Kennedy is Burton Chair of Neurology, Head of the Division of Clinical Neuroscience, Faculty of Medicine, University of Glasgow
• The Fatal Sleep by Peter Kennedy is published by Luath Press (50 per cent of the authors royalties are being donated to Médecins Sans Frontières and the Drugs For Neglected Diseases Initiative).
The full article contains 1101 words and appears in The Scotsman newspaper.
