Whether a genuine attempt to end life, or a cry for help and attention, hundreds of thousands of people attempt suicide every year. Take any country in the world, and such people will tend to be young men or, more often, young women who have thought about it for less than half an hour – and most will not be intending actually to kill themselves.

Yet the outcomes of such impulsive acts can vary markedly depending on the country. In the UK, for example, the death rate per overdose is low. But in many countries in South-East Asia and the Western Pacific, the death rates for deliberate self-poisoning can be 40 per cent. The huge disparity lies not with differences in healthcare systems, although these do play a part, but with the extreme toxicity of the poisons most commonly taken in South-East Asia – pesticides such as organophosphates and herbicides such as paraquat. Even small doses can be lethal within hours.

“The Asia Pacific region is the suicide belt of the world,” says toxicologist Professor Nick Buckley at the Australia National University, Canberra, Australia. “The region has much higher rates of suicide than the rest of the world, and this is largely due to pesticide poisoning; WHO estimates suggest that up to half-a-million people a year die this way.”

The problems of deliberate self-poisoning are particularly acute in Sri Lanka, which has the highest total and youth suicide rates in the world. The importance of the issue has been recognised by the Sri Lankan government, which has established a National Poisons Information Centre, and implemented a programme to restrict the most toxic pesticides.

Yet any national approach is hampered by a lack of evidence on what is the best treatment for patients with pesticide poisoning and, in contrast to communicable diseases such as malaria, there are no comprehensive programmes to test out new methods of prevention and treatment.

To tackle this problem, Sri Lankan and Australian researchers have joined forces to establish a new toxicology research centre in Sri Lanka. Backed by £1.25 million funding from the Wellcome Trust and the National Health and Medical Research Council of Australia, the collaboration, led by Professor Buckley and Professor Nimal Senanayake (Peradeniya University) aims to halve deaths from pesticide poisoning within five years.

Tackling the poisons

For people contemplating suicide in the rural, farming areas of Sri Lanka, pesticides are the poison of choice because they are so readily available. But the effects on the body can be horrific, as pesticides generally act in the same way as chemical warfare nerve agents. They knock out the ‘circuit breakers’ of the nervous system (by inhibiting the enzyme acetylcholinesterase, which breaks down neurotransmitters in the synapse), allowing nerves to fire again and again. This leads to frothing at the mouth, uncontrollable sweating, swings in blood pressure, difficulties with breathing and unconsciousness.

“For organophosphate pesticides, there are two powerful antidotes available, atropine and pralidoxime, so if the patient gets to the hospital in time, there is hope and many lives are saved,” says Professor Senanayake. “But we have nothing that can directly counter the effects of organochlorines or paraquat.”

Although other antidotes have been developed, in many cases they have been studied only in animals. Some countries therefore do not use them at all, while other countries use them in small or large doses – which may be ineffective or a waste of money. “Without testing and clear protocols, we don’t know if the antidotes are effective,” says Professor Buckley. “Antidotes are expensive, so we need to work out the most efficient, evidence-based and cost-effective ways of treatment. We need to get the right antidotes to the right people at the right doses at a price they can afford.”

A new centre

Bringing together expertise from Sri Lanka and Australia, the new project builds on clinical trials led by Michael Eddleston – a Wellcome Trust-funded fellow who worked in Sri Lanka. The new, longer-term centre aims to tackle all aspects of pesticide poisoning: the basic science of poisoning, therapeutic trials, epidemiological studies, and pharmacoeconomics (see box below). It will also act as a training centre for doctors, and for PhD students from both Sri Lanka and Australia.

“The scope of the project is very wide,” says Professor Senanayake. “At one end will be studies of treatments that can be directly translated to practice, such as testing new drugs for the treatment of paraquat poisoning. If we have some recoveries, that will be quite a breakthrough. At the other end is research to help us understand the poisoning process. We will investigate the areas of the body affected by organophosphates, such as the neuromuscular junctions, to see what changes are taking place. That will help us, and scientists anywhere in the world, to come up with new approaches to antidotes.”

By gathering such evidence, the researchers aim to help inform the government’s national policy. “Sri Lanka is the leader in the region, as it has been restricting pesticides over the last 15 years,” says Professor Buckley. “This hasn’t made the impact expected, probably because it’s been difficult to tell which pesticides to restrict. We hope to be able to help inform these decisions, so we’ll be working closely with the Department of Agriculture, who have been very interested and helpful.”

The work should have a big impact: “The overall goal is to reduce death rates by half,” says Professor Buckley. “It’s an ambitious goal, but it has happened already in Anuradhapura hospital. Just with new protocols and specific teams who look after people, the average mortality dropped from 23–24 per cent to 13 per cent. This shows that it can be done – and this is without using any new antidotes. We aim to do this across the country.”