Melarsoprol

THE African tsetse belt covers 36 countries and is home to one of the world's most under-reported epidemics. The several species of tsetse fly after which it is named are host to parasites called trypanosomes and they expose a tenth of the African population to the risk of sleeping sickness. The World Health Organization (WHO) estimates that each year 600,000 Africans will become infected. Because the majority live in rural, remote areas, most will die without being diagnosed--45,000 deaths each year. The parasites can also kill livestock, so the flies pose an enormous risk to food security, too.

Since 1970 a sleeping sickness epidemic has been raging in the tsetse belt. But because generally it does not pass from person to person (although it's possible for mothers to pass it to unborn babies) and perhaps because it affects mainly rural communities, not much is heard of it.

The disease gets its name from the end-stage coma the parasites that cause it inflict. Many of the early symptoms--fever, headache and a rapid heartbeat--are mistaken for malaria. Other symptoms, like the rash and the painless swelling of the lymph nodes at the base of the neck, hardly ever warrant a visit to the doctor. If sleeping sickness is caught in time, it can be cured. But that requires active and constant surveillance which is both difficult and expensive.

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Most often it is diagnosed late. By then the parasites have crossed the blood/brain barrier and the victim is suffering acutely. Every patient whose disease has entered the second phase will suffer permanent nerve damage. Late-stage sleeping sickness causes constant headaches, appetite loss and wasting. The skin becomes so sensitive that the slightest touch causes extreme pain. It disrupts the sleep cycle so that sufferers sleep during the day and are wide awake at night. They suffer from vivid, often paranoid hallucinations, speech disorders, seizures and severe, sometimes manic behavioural changes. Towards the end, patients fall into a coma. Without treatment, they will die.

A cure that kills

There are only two drugs used to treat late-stage sleeping sickness. One is melarsoprol. It corrodes just about everything with which it comes into contact, including human veins. It must be delivered in glass syringes, because it eats through every other kind. It is the only drug available in much of the tsetse belt. A third of patients fail to respond to it, but often that's not clear until it and the disease have caused damage to the patient's body. Another one in ten will die from treatment with the drug.

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Melarsoprol, invented in 1949, is arsenic dissolved in antifreeze--the last arsenical drug in the world. It isn't available in the West and it wouldn't pass a single modern ethical or drug-safety test. But it is being used in Africa because there isn't much choice.

Diagnosing second-stage sleeping sickness is also fraught with risk. In Uganda, tests may take place on a bench in a hospital laboratory; in Chad they will likely be carried out on mats under trees, outside the district hospital. Many patients will have travelled for days on foot from their villages. Exhausted and hungry, they will receive a lumbar puncture (or spinal tap)--an injection into the lower spine to extract fluid for testing. If the needle slips or the patient moves, the needle can damage nerves and cause paralysis. Even in the most sterile conditions patients can be exposed to bacterial infections that will rapidly progress to the brain from the spinal cord. In the West, lumbar punctures are always performed with anaesthetic and still cause 'moderate pain'. In Africa, anaesthetic is usually unavailable. Patients, many of them children, have to lie still on their stomachs for four hours after the test, despite the pain. A Ugandan nurse recounted how a boy of eight who needed to be brought in for treatment had jumped out of a school window and run away when they went to fetch him. The image would be funny if it weren't such a clear illustration of his terror.

The course of treatment with melarsoprol is 21 days. Every day for three days patients receive one slow, intensely painful, intravenous injection. It is like a slow shot of hot chilli sauce through the veins. Small children are tied or held down. The nurses apologize constantly as they deliver the drug and feel terrible doing it. The first series of injections is followed by a rest period of eight to ten days. Then the procedure is conducted twice more.

An allergic reaction to melarsoprol is an often fatal swelling of the brain. Any patients who survive this side effect will likely have irreparable nerve damage. Patients who fail melarsoprol treatment are usually given the other drug, eflornithine.

Tangled web

Eflornithine is much safer than melarsoprol. It is being made available in a number of countries in the tsetse belt through an agreement between Aventis (which owns the patent for the drug) and the WHO and is delivered by Medecins Sans Frontieres (MSF). But the only reason eflornithine is available at all is because it's the active ingredient in a cosmetic drug called Vaniqa, made by Bristol Myers Squibb (BMS) and Gillette under license from Aventis. Vaniqa is used in Europe and North America by women who are concerned about 'excessive facial hair'.

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Eflornithine was first tested in the early 1970s as a drug for cancer, but was not found to be particularly effective. In 1979, it was discovered to be effective in killing trypanosomes. In 1990, it was produced as an alternative to melarsoprol by Hoechst Marion Roussel. In 1995, Hoechst Marion Roussel merged with Aventis. The merger brought both melarsoprol and eflornithine into Aventis' portfolio of drugs. Examining its portfolio, Aventis decided to discontinue production of eflornithine which it claimed was unprofitable. By 1999 the drug was almost completely gone.

This was a spur to action for MSF doctors, who had quickly embraced eflornithine and were faced with returning their patients to melarsoprol therapy. MSF began a campaign to protect the supply of eflornithine, and three other drugs for sleeping sickness, negotiating with WHO, Aventis and Bayer (who own the drug most used in early-stage treatment--pentamidine) to continue production. The negotiations were not going well, when by chance an MSF pharmacist saw a tube of Vaniqa and recognized the active ingredient as the very one whose supply for the treatment of sleeping sickness was under threat. BMS was invited to join discussions with WHO, Aventis, Bayer and MSF. The issue was clear: the companies were willing to make eflornithine as an ingredient in a medication to remove facial hair hair but not for use to treat a deadly disease. When MSF threatened to go public with the scandal a deal was worked out. BMS will produce a limited amount of eflornithine for the WHO with permission from Aventis. The WHO will find manufacturers to turn the eflornithine into the injectable solution needed for sleeping sickness. MSF will deliver the drug to the places that need it and will help governments to understand the procedure needed to procure the drugs. All this is guaranteed for five years after which Aventis and BMS will review the programme.

Eflornithine is much safer than melarsoprol, particularly in reviving patients from coma. But it has to be delivered for fourteen consecutive days, four times a day, through intravenous injections that last two hours each. It has many side effects--and the WHO warns it can be deadly. Patients have to be closely observed throughout its delivery, so it can only be administered in centres where there are enough staff to follow the strict system. That means many centres in the tsetse belt must continue to use melarsoprol, despite its dangers.

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No-one working with sleeping sickness would want the production of eflornithine to end. But most decry having to give drugs that kill to patients--simply because they are too poor to matter to the pharmaceutical industry.

The modern pharmaceutical industry emphasises the development of 'blockbuster drugs'--drugs that will bring in revenues of at least a billion dollars a year. So while there are three new competitors for Viagra ready to hit the stores, with more on the way, there are no new drugs in the pipeline of the major drug companies for sleeping sickness.

Once research and development in the drug industry was driven by a motive to improve human health. Jonas Salk refused to patent the polio vaccine. He thought the severity of the disease made it imperative that the drug should be widely available. He realized polio could only be brought under control if everybody had equal access to his vaccine. Now it seems, R&D in the proprietary pharmaceutical industry is driven by profit alone.

This emphasis on money before all has led to the crass commodification of health. There are women who suffer from debilitatingly excessive facial hair. But the rest of us don't. Hair on a human face is normal. Yet selling it as a disease through women's magazines as UFH (or unwanted facial hair, ask your dermatologist) yields $48 per 30mg tube.

If that's where the market lies, the pharmaceutical industry will become a glorified cosmetic industry. And it seems that sleeping sickness, for the most part a deadly disease of the poor, just doesn't cut it.

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Sources:

WHO Fact Sheet 259, March 2001, www.Who.int/inf-fs/en/fact259.html

www.aventis.com/future/futo201/defeating_sleeping_ sickness.html

Donald McNeil, Jr, 'Profits on cosmetic save a cure for sleeping sickness', New York Times, 9 February 2001.

www.accessmed-msf.org/campaign/slpo1.shtm

Donald G McNeil Jr, 'Let 'em die: US policy towards disease in Africa', speech at Une Fete Africaine, 31 January 2003.

Price of Vaniqa from www.vaniqa.com accessed on 2 September 2003

Spring Gombe is Global Access Liaison for three NGOs working on access to medicines--Health Action International, OXFAM and MSF. She lobbies European policy makers to improve access to essential medicines in Africa.

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