Anti-fungal fight shows its teeth

July 19, 1996

A little-known group of opportunistic invaders is on the rampage in the UK, preying on the weak and sick and killing an unknown number of them every year. The victims are the immunocompromised - Aids patients, cancer patients and transplantees. Their killers are sinister cousins of the fungi that cause athlete's foot, ringworm and thrush.

Fungi seldom trouble a healthy immune system, but a weakened immune system opens the door to a variety of fungal infections. Fungal pneumonia is a classic symptom of full-blown Aids, affecting 50-60 per cent of sufferers. The disease-causing agent, pneumocystis, was originally thought to be a protozoan but has recently been reclassified as a fungus. Meningitis caused by another fungus, Cryptococcus, infects a further 5-10 per cent. Oral thrush is the single most common infectious complication of Aids. Some estimates suggest that 80 per cent of Aids fatalities are related to fungal infections.

Fungi are also a threat to cancer patients, either because the cancer itself suppresses the immune system or because therapy does. Transplant patients are at risk for life because their immune systems have to be permanently suppressed to prevent organ rejection.

Despite anecdotal evidence that the death toll is rising, there are no exact mortality figures. "They are not notifiable diseases so there are no firm records," explains Glyn Evans, head of the Public Health Laboratory Service Medical Mycobiology lab at the University of Leeds. "We're trying to set up a reporting system in the UK at the moment."

Professor Evans expects mortality to rise as the number of Aids cases escalates and transplant surgery becomes more common. The current supply of transplantable livers, lungs and hearts cannot satisfy demand but if genetically engineered pig organs becomes widely available transplants will become much more common. "The more transplants we do in a blunderbuss, non-specific way, the more we are opening ourselves to fungal infection," says Professor Evans.

Current anti-fungal drugs do not offer much relief. Most are fungistatic rather than fungicidal: they stop fungi from growing but do not kill them. The best that can be achieved in many immuno-compromised patients is to keep the infection under control. Clearing up fungal infections in Aids patients is all but impossible. The drug of last resort, Amphotericin B, is poisonous and causes kidney failure if used for long periods. A less toxic form has been developed by combining the drug with microscopic fatty spheres called liposomes but its cost - around Pounds 200 per patient per day - prohibits long-term use.

New drugs are available but they too are imperfect. Yeast infections are starting to show signs of resistance to a new drug called fluconazole. There is a huge clinical need for safe and effective anti-fungal drugs but many researchers despair of finding one. Biochemically, fungi are so similar to mammals that what is toxic to fungi is usually toxic to man too.

But a new chemical has been discovered that could confound the pessimists. The chemical is produced by the soil-dwelling fungus Streptoverticillium fervens, and contains a long chain of carbon triangles resembling sharks' teeth. This has earned it the nickname "jawsamycin". Tests indicate that jawsamycin kills fungi without harming mammals. The leading jawsamycin research group is run by Tony Barrett at Imperial College, London who won the international race to elucidate its strucure and synthesise the chemical in the lab. Aids has turned anti-fungals into a very big pot of gold. Professor Barrett estimates a good drug would be worth $1 billion a year.

Meanwhile, says Professor Evans, high-risk groups could benefit from preventative advice. "They shouldn't be keeping pigeons or digging around in compost. Both are a rich source of fungal spores."

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