Tag Archives: drugs

The town that breeds resistance to Malaria drugs

Pailin is a small settlement nestling in tropical rainforest near Cambodia’s border with Thailand. It is an unassuming town that lies at the centre of one of the country’s main logging areas. Pailin harbours secrets, however. It was in this town, in the late 1970s, that the Khmer Rouge set up one of its main strongholds and ruled Cambodia with a ferocity that caused at least two million deaths. It is a grim legacy, by any standards.

But Pailin has another unwanted claim to fame, one that is also associated with widespread death. The town, it transpires, lies at the heart of a region that has seen successive waves of resistance to malaria drugs arise in local people and then spread across the globe. The resulting death tolls can be measured in millions of lives, say scientists.

Just why malarial drug resistance has arisen here is not clear. Nevertheless scientists are emphatic: the region has seen the creation of several mutations in malaria parasites that have allowed them to shrug off medicines that once protected humans. Even worse, they have discovered that a new wave of malarial drug resistance has recently appeared in this tiny area and has already spread into Thailand, Laos, and Vietnam, and begun to move into Myanmar and travel towards India and Bangladesh.

The prospect has so alarmed scientists and politicians that the issue is to be raised as an emergency topic to be debated at the heads of Commonwealth meeting in London next week (16-20 April). There are 19 Commonwealth member states in Africa, the continent that is the most vulnerable to malaria. According to World Health Organisation statistics, about 90% of all malaria deaths occur in Africa. Hence the concern of many Commonwealth heads of state who believe their homelands are most at risk of a spreading malarial resistance.

“The problem is that we are pussyfooting around,” said Professor Sir Nicholas White, of the Mahidol Oxford Tropical Medicine Research Unit. “The World Health Organisation has not provided the necessary leadership. We need very firm direct action and at present we are not getting that.”

Resistance to major malaria drugs first appeared in the late 1950s when chloroquine -– then a highly effective successful treatment for the disease -– began to lose its efficacy. Crucially, this resistance first appeared in Pailin on the Cambodian-Thai border and then spread to Africa by the early 1980s. Several million deaths were added to the already grim toll of lives lost to the disease as a result.

A new set of drugs, known as sulfadoxine-pyrimethamines, was then developed and used to treat malaria. But once more resistance to the drugs appeared and again it first manifested itself around Pailin before spreading westwards. Again the disease’s death toll soared.

malaria map

Then, at beginning of this century, a new set of malarial medicines was developed. Known as artemisinins, they were discovered in 1972 by Tu Youyou, a Chinese scientist who was awarded the 2015 Nobel prize in medicine for her work. Administered with a slower-acting second drug, artemisinins have become the medicine of choice for dealing with malaria across the globe, leading to improvements in malarial statistics with deaths and case numbers declining globally.

But now scientists have recently discovered once more that resistance to key malarial drugs has evolved -– and in exactly the same place as before: the farms and village that surround around Pailin. “That resistance has emerged in exactly the same place that resistance to chloroquine and then pyrimethamines emerged. The same very place. Around Pailin,” said White.

Just why this tiny region of south-east Asia has proved to be such a fertile zone for the emergence of deadly resistance to malarial medicine is not clear, a point stressed by Dominic Kwiatkowski, director of the centre for genomics and global health at Oxford University.

“We would love to know the answer, but it is not obvious,” Kwiatkowski told the Observer.

The Observer

The Observer is the world’s oldest Sunday newspaper, founded in 1791. It is published by Guardian News & Media and is editorially independent.

“One idea is that resistance keeps arising here for historical reasons. Maybe it has something to do with the way that malarial medicines are administered here. But how exactly?” In fact, the This theory is just one of a great many other suggestions that have been put forward to explain why this resistance is appearing here first.

The local strain of malaria parasites may have some special properties, or the ecology of the region may have features that boost the rise of resistance. “The crucial point is that we need to do something about it and once we have, we need to monitor the situation very, very carefully,” said Kwiatkowski.

One factor that has recently become clear is that malarial drug resistance appeared very quickly in the region. Writing in Lancet Infectious Diseasescorrect in February, researchers from the Wellcome Sanger Institut and collaborators reported that resistance to combination therapies that included artemisinins arose almost as soon as the treatment was introduced as a first-line malarial drug. However, that this loss of efficacy was not spotted, for a variety of reasons, until several years had passed.

The implications of this failure were stressed by Ben Rolfe, head of the Asia Pacific Leaders Malaria Alliance. “On our watch, drug resistant strains have spread almost unnoticed,” he told the BMJ recently (pdf). “As a result, we now risk a global resurgence of the disease.”

Khmer families are screened for malaria in Pailin province in 2010.


Khmer families are screened for malaria in Pailin province in 2010. Photograph: Paula Bronstein/Getty Images

The question facing scientists -– and heads of state and health leaders -– is straightforward: what can be done? White -– who is scheduled to speak at the Commonwealth heads of state meeting -– is emphatic. “We have a window of opportunity but it is closing rapidly,” he told the Observer.

What is needed is a campaign, run with military efficiency, to use current drugs -– while they still have some efficacy -– not only on people who already have malaria but on those individuals who have been infected but who have not succumbed or shown symptoms of the disease.

“These individuals carry small numbers of parasites and although they don’t get ill they are sources of new infections,” said White. “Mosquitos bite them, take their blood and spread it to others. They are the source of new infections.”

The plan, proposed by White and other scientists, is that everyone in a village in a malaria hotspot should be treated with anti-malarial drugs -– regardless of their symptoms. “It is called mass drug administration. It is very controversial but it works -– if it is done as part of a concerted strategy. If you do it badly you will only make the problem of resistance worse. So this has to be done right. But if we don’t do it we won’t be able to eliminate malaria quickly enough, and if resistance worsens it may become untreatable,” says White.

In addition, it is proposed that a third anti-malarial drug be added to the combination therapy currently used to treat those who have actually succumbed to malaria: a triple whammy instead of a double. Next week, Britain’s Department for International Development is expected to announce support for trials using triple combination drugs.

For its part, WHO officials say that the dangers posed by the new malaria superbug are exaggerated and that better prevention efforts, monitoring and treatments will limit its spread from the Mekong region. Others are not so sure, however. The Malaria summit -– organised by the Ready to Beat Malaria campaign is to be held in London on 18 April at next week’s Commonwealth summit and will be attended by scientists and business leaders, including Bill and Melinda Gates. They are pressing for urgent commitments from all world leaders to battle the disease.

“We are currently on a cliff edge,” said a spokesman for Ready to Beat Malaria. “We can continue to battle the disease or risk an acute and deadly resurgence.”

This view is backed by White. “We are running out of time and unless we act rapidly, people will suffer and the people who will suffer most will be the children of Africa.”

The town that breeds resistance to Malaria drugs

Pailin is a small settlement nestling in tropical rainforest near Cambodia’s border with Thailand. It is an unassuming town that lies at the centre of one of the country’s main logging areas. Pailin harbours secrets, however. It was in this town, in the late 1970s, that the Khmer Rouge set up one of its main strongholds and ruled Cambodia with a ferocity that caused at least two million deaths. It is a grim legacy, by any standards.

But Pailin has another unwanted claim to fame, one that is also associated with widespread death. The town, it transpires, lies at the heart of a region that has seen successive waves of resistance to malaria drugs arise in local people and then spread across the globe. The resulting death tolls can be measured in millions of lives, say scientists.

Just why malarial drug resistance has arisen here is not clear. Nevertheless scientists are emphatic: the region has seen the creation of several mutations in malaria parasites that have allowed them to shrug off medicines that once protected humans. Even worse, they have discovered that a new wave of malarial drug resistance has recently appeared in this tiny area and has already spread into Thailand, Laos, and Vietnam, and begun to move into Myanmar and travel towards India and Bangladesh.

The prospect has so alarmed scientists and politicians that the issue is to be raised as an emergency topic to be debated at the heads of Commonwealth meeting in London next week (16-20 April). There are 19 Commonwealth member states in Africa, the continent that is the most vulnerable to malaria. According to World Health Organisation statistics, about 90% of all malaria deaths occur in Africa. Hence the concern of many Commonwealth heads of state who believe their homelands are most at risk of a spreading malarial resistance.

“The problem is that we are pussyfooting around,” said Professor Sir Nicholas White, of the Mahidol Oxford Tropical Medicine Research Unit. “The World Health Organisation has not provided the necessary leadership. We need very firm direct action and at present we are not getting that.”

Resistance to major malaria drugs first appeared in the late 1950s when chloroquine -– then a highly effective successful treatment for the disease -– began to lose its efficacy. Crucially, this resistance first appeared in Pailin on the Cambodian-Thai border and then spread to Africa by the early 1980s. Several million deaths were added to the already grim toll of lives lost to the disease as a result.

A new set of drugs, known as sulfadoxine-pyrimethamines, was then developed and used to treat malaria. But once more resistance to the drugs appeared and again it first manifested itself around Pailin before spreading westwards. Again the disease’s death toll soared.

malaria map

Then, at beginning of this century, a new set of malarial medicines was developed. Known as artemisinins, they were discovered in 1972 by Tu Youyou, a Chinese scientist who was awarded the 2015 Nobel prize in medicine for her work. Administered with a slower-acting second drug, artemisinins have become the medicine of choice for dealing with malaria across the globe, leading to improvements in malarial statistics with deaths and case numbers declining globally.

But now scientists have recently discovered once more that resistance to key malarial drugs has evolved -– and in exactly the same place as before: the farms and village that surround around Pailin. “That resistance has emerged in exactly the same place that resistance to chloroquine and then pyrimethamines emerged. The same very place. Around Pailin,” said White.

Just why this tiny region of south-east Asia has proved to be such a fertile zone for the emergence of deadly resistance to malarial medicine is not clear, a point stressed by Dominic Kwiatkowski, director of the centre for genomics and global health at Oxford University.

“We would love to know the answer, but it is not obvious,” Kwiatkowski told the Observer.

The Observer

The Observer is the world’s oldest Sunday newspaper, founded in 1791. It is published by Guardian News & Media and is editorially independent.

“One idea is that resistance keeps arising here for historical reasons. Maybe it has something to do with the way that malarial medicines are administered here. But how exactly?” In fact, the This theory is just one of a great many other suggestions that have been put forward to explain why this resistance is appearing here first.

The local strain of malaria parasites may have some special properties, or the ecology of the region may have features that boost the rise of resistance. “The crucial point is that we need to do something about it and once we have, we need to monitor the situation very, very carefully,” said Kwiatkowski.

One factor that has recently become clear is that malarial drug resistance appeared very quickly in the region. Writing in Lancet Infectious Diseasescorrect in February, researchers from the Wellcome Sanger Institut and collaborators reported that resistance to combination therapies that included artemisinins arose almost as soon as the treatment was introduced as a first-line malarial drug. However, that this loss of efficacy was not spotted, for a variety of reasons, until several years had passed.

The implications of this failure were stressed by Ben Rolfe, head of the Asia Pacific Leaders Malaria Alliance. “On our watch, drug resistant strains have spread almost unnoticed,” he told the BMJ recently (pdf). “As a result, we now risk a global resurgence of the disease.”

Khmer families are screened for malaria in Pailin province in 2010.


Khmer families are screened for malaria in Pailin province in 2010. Photograph: Paula Bronstein/Getty Images

The question facing scientists -– and heads of state and health leaders -– is straightforward: what can be done? White -– who is scheduled to speak at the Commonwealth heads of state meeting -– is emphatic. “We have a window of opportunity but it is closing rapidly,” he told the Observer.

What is needed is a campaign, run with military efficiency, to use current drugs -– while they still have some efficacy -– not only on people who already have malaria but on those individuals who have been infected but who have not succumbed or shown symptoms of the disease.

“These individuals carry small numbers of parasites and although they don’t get ill they are sources of new infections,” said White. “Mosquitos bite them, take their blood and spread it to others. They are the source of new infections.”

The plan, proposed by White and other scientists, is that everyone in a village in a malaria hotspot should be treated with anti-malarial drugs -– regardless of their symptoms. “It is called mass drug administration. It is very controversial but it works -– if it is done as part of a concerted strategy. If you do it badly you will only make the problem of resistance worse. So this has to be done right. But if we don’t do it we won’t be able to eliminate malaria quickly enough, and if resistance worsens it may become untreatable,” says White.

In addition, it is proposed that a third anti-malarial drug be added to the combination therapy currently used to treat those who have actually succumbed to malaria: a triple whammy instead of a double. Next week, Britain’s Department for International Development is expected to announce support for trials using triple combination drugs.

For its part, WHO officials say that the dangers posed by the new malaria superbug are exaggerated and that better prevention efforts, monitoring and treatments will limit its spread from the Mekong region. Others are not so sure, however. The Malaria summit -– organised by the Ready to Beat Malaria campaign is to be held in London on 18 April at next week’s Commonwealth summit and will be attended by scientists and business leaders, including Bill and Melinda Gates. They are pressing for urgent commitments from all world leaders to battle the disease.

“We are currently on a cliff edge,” said a spokesman for Ready to Beat Malaria. “We can continue to battle the disease or risk an acute and deadly resurgence.”

This view is backed by White. “We are running out of time and unless we act rapidly, people will suffer and the people who will suffer most will be the children of Africa.”

The town that breeds resistance to Malaria drugs

Pailin is a small settlement nestling in tropical rainforest near Cambodia’s border with Thailand. It is an unassuming town that lies at the centre of one of the country’s main logging areas. Pailin harbours secrets, however. It was in this town, in the late 1970s, that the Khmer Rouge set up one of its main strongholds and ruled Cambodia with a ferocity that caused at least two million deaths. It is a grim legacy, by any standards.

But Pailin has another unwanted claim to fame, one that is also associated with widespread death. The town, it transpires, lies at the heart of a region that has seen successive waves of resistance to malaria drugs arise in local people and then spread across the globe. The resulting death tolls can be measured in millions of lives, say scientists.

Just why malarial drug resistance has arisen here is not clear. Nevertheless scientists are emphatic: the region has seen the creation of several mutations in malaria parasites that have allowed them to shrug off medicines that once protected humans. Even worse, they have discovered that a new wave of malarial drug resistance has recently appeared in this tiny area and has already spread into Thailand, Laos, and Vietnam, and begun to move into Myanmar and travel towards India and Bangladesh.

The prospect has so alarmed scientists and politicians that the issue is to be raised as an emergency topic to be debated at the heads of Commonwealth meeting in London next week (16-20 April). There are 19 Commonwealth member states in Africa, the continent that is the most vulnerable to malaria. According to World Health Organisation statistics, about 90% of all malaria deaths occur in Africa. Hence the concern of many Commonwealth heads of state who believe their homelands are most at risk of a spreading malarial resistance.

“The problem is that we are pussyfooting around,” said Professor Sir Nicholas White, of the Mahidol Oxford Tropical Medicine Research Unit. “The World Health Organisation has not provided the necessary leadership. We need very firm direct action and at present we are not getting that.”

Resistance to major malaria drugs first appeared in the late 1950s when chloroquine -– then a highly effective successful treatment for the disease -– began to lose its efficacy. Crucially, this resistance first appeared in Pailin on the Cambodian-Thai border and then spread to Africa by the early 1980s. Several million deaths were added to the already grim toll of lives lost to the disease as a result.

A new set of drugs, known as sulfadoxine-pyrimethamines, was then developed and used to treat malaria. But once more resistance to the drugs appeared and again it first manifested itself around Pailin before spreading westwards. Again the disease’s death toll soared.

malaria map

Then, at beginning of this century, a new set of malarial medicines was developed. Known as artemisinins, they were discovered in 1972 by Tu Youyou, a Chinese scientist who was awarded the 2015 Nobel prize in medicine for her work. Administered with a slower-acting second drug, artemisinins have become the medicine of choice for dealing with malaria across the globe, leading to improvements in malarial statistics with deaths and case numbers declining globally.

But now scientists have recently discovered once more that resistance to key malarial drugs has evolved -– and in exactly the same place as before: the farms and village that surround around Pailin. “That resistance has emerged in exactly the same place that resistance to chloroquine and then pyrimethamines emerged. The same very place. Around Pailin,” said White.

Just why this tiny region of south-east Asia has proved to be such a fertile zone for the emergence of deadly resistance to malarial medicine is not clear, a point stressed by Dominic Kwiatkowski, director of the centre for genomics and global health at Oxford University.

“We would love to know the answer, but it is not obvious,” Kwiatkowski told the Observer.

The Observer

The Observer is the world’s oldest Sunday newspaper, founded in 1791. It is published by Guardian News & Media and is editorially independent.

“One idea is that resistance keeps arising here for historical reasons. Maybe it has something to do with the way that malarial medicines are administered here. But how exactly?” In fact, the This theory is just one of a great many other suggestions that have been put forward to explain why this resistance is appearing here first.

The local strain of malaria parasites may have some special properties, or the ecology of the region may have features that boost the rise of resistance. “The crucial point is that we need to do something about it and once we have, we need to monitor the situation very, very carefully,” said Kwiatkowski.

One factor that has recently become clear is that malarial drug resistance appeared very quickly in the region. Writing in Lancet Infectious Diseasescorrect in February, researchers from the Wellcome Sanger Institut and collaborators reported that resistance to combination therapies that included artemisinins arose almost as soon as the treatment was introduced as a first-line malarial drug. However, that this loss of efficacy was not spotted, for a variety of reasons, until several years had passed.

The implications of this failure were stressed by Ben Rolfe, head of the Asia Pacific Leaders Malaria Alliance. “On our watch, drug resistant strains have spread almost unnoticed,” he told the BMJ recently (pdf). “As a result, we now risk a global resurgence of the disease.”

Khmer families are screened for malaria in Pailin province in 2010.


Khmer families are screened for malaria in Pailin province in 2010. Photograph: Paula Bronstein/Getty Images

The question facing scientists -– and heads of state and health leaders -– is straightforward: what can be done? White -– who is scheduled to speak at the Commonwealth heads of state meeting -– is emphatic. “We have a window of opportunity but it is closing rapidly,” he told the Observer.

What is needed is a campaign, run with military efficiency, to use current drugs -– while they still have some efficacy -– not only on people who already have malaria but on those individuals who have been infected but who have not succumbed or shown symptoms of the disease.

“These individuals carry small numbers of parasites and although they don’t get ill they are sources of new infections,” said White. “Mosquitos bite them, take their blood and spread it to others. They are the source of new infections.”

The plan, proposed by White and other scientists, is that everyone in a village in a malaria hotspot should be treated with anti-malarial drugs -– regardless of their symptoms. “It is called mass drug administration. It is very controversial but it works -– if it is done as part of a concerted strategy. If you do it badly you will only make the problem of resistance worse. So this has to be done right. But if we don’t do it we won’t be able to eliminate malaria quickly enough, and if resistance worsens it may become untreatable,” says White.

In addition, it is proposed that a third anti-malarial drug be added to the combination therapy currently used to treat those who have actually succumbed to malaria: a triple whammy instead of a double. Next week, Britain’s Department for International Development is expected to announce support for trials using triple combination drugs.

For its part, WHO officials say that the dangers posed by the new malaria superbug are exaggerated and that better prevention efforts, monitoring and treatments will limit its spread from the Mekong region. Others are not so sure, however. The Malaria summit -– organised by the Ready to Beat Malaria campaign is to be held in London on 18 April at next week’s Commonwealth summit and will be attended by scientists and business leaders, including Bill and Melinda Gates. They are pressing for urgent commitments from all world leaders to battle the disease.

“We are currently on a cliff edge,” said a spokesman for Ready to Beat Malaria. “We can continue to battle the disease or risk an acute and deadly resurgence.”

This view is backed by White. “We are running out of time and unless we act rapidly, people will suffer and the people who will suffer most will be the children of Africa.”

The town that breeds resistance to Malaria drugs

Pailin is a small settlement nestling in tropical rainforest near Cambodia’s border with Thailand. It is an unassuming town that lies at the centre of one of the country’s main logging areas. Pailin harbours secrets, however. It was in this town, in the late 1970s, that the Khmer Rouge set up one of its main strongholds and ruled Cambodia with a ferocity that caused at least two million deaths. It is a grim legacy, by any standards.

But Pailin has another unwanted claim to fame, one that is also associated with widespread death. The town, it transpires, lies at the heart of a region that has seen successive waves of resistance to malaria drugs arise in local people and then spread across the globe. The resulting death tolls can be measured in millions of lives, say scientists.

Just why malarial drug resistance has arisen here is not clear. Nevertheless scientists are emphatic: the region has seen the creation of several mutations in malaria parasites that have allowed them to shrug off medicines that once protected humans. Even worse, they have discovered that a new wave of malarial drug resistance has recently appeared in this tiny area and has already spread into Thailand, Laos, and Vietnam, and begun to move into Myanmar and travel towards India and Bangladesh.

The prospect has so alarmed scientists and politicians that the issue is to be raised as an emergency topic to be debated at the heads of Commonwealth meeting in London next week (16-20 April). There are 19 Commonwealth member states in Africa, the continent that is the most vulnerable to malaria. According to World Health Organisation statistics, about 90% of all malaria deaths occur in Africa. Hence the concern of many Commonwealth heads of state who believe their homelands are most at risk of a spreading malarial resistance.

“The problem is that we are pussyfooting around,” said Professor Sir Nicholas White, of the Mahidol Oxford Tropical Medicine Research Unit. “The World Health Organisation has not provided the necessary leadership. We need very firm direct action and at present we are not getting that.”

Resistance to major malaria drugs first appeared in the late 1950s when chloroquine -– then a highly effective successful treatment for the disease -– began to lose its efficacy. Crucially, this resistance first appeared in Pailin on the Cambodian-Thai border and then spread to Africa by the early 1980s. Several million deaths were added to the already grim toll of lives lost to the disease as a result.

A new set of drugs, known as sulfadoxine-pyrimethamines, was then developed and used to treat malaria. But once more resistance to the drugs appeared and again it first manifested itself around Pailin before spreading westwards. Again the disease’s death toll soared.

malaria map

Then, at beginning of this century, a new set of malarial medicines was developed. Known as artemisinins, they were discovered in 1972 by Tu Youyou, a Chinese scientist who was awarded the 2015 Nobel prize in medicine for her work. Administered with a slower-acting second drug, artemisinins have become the medicine of choice for dealing with malaria across the globe, leading to improvements in malarial statistics with deaths and case numbers declining globally.

But now scientists have recently discovered once more that resistance to key malarial drugs has evolved -– and in exactly the same place as before: the farms and village that surround around Pailin. “That resistance has emerged in exactly the same place that resistance to chloroquine and then pyrimethamines emerged. The same very place. Around Pailin,” said White.

Just why this tiny region of south-east Asia has proved to be such a fertile zone for the emergence of deadly resistance to malarial medicine is not clear, a point stressed by Dominic Kwiatkowski, director of the centre for genomics and global health at Oxford University.

“We would love to know the answer, but it is not obvious,” Kwiatkowski told the Observer.

The Observer

The Observer is the world’s oldest Sunday newspaper, founded in 1791. It is published by Guardian News & Media and is editorially independent.

“One idea is that resistance keeps arising here for historical reasons. Maybe it has something to do with the way that malarial medicines are administered here. But how exactly?” In fact, the This theory is just one of a great many other suggestions that have been put forward to explain why this resistance is appearing here first.

The local strain of malaria parasites may have some special properties, or the ecology of the region may have features that boost the rise of resistance. “The crucial point is that we need to do something about it and once we have, we need to monitor the situation very, very carefully,” said Kwiatkowski.

One factor that has recently become clear is that malarial drug resistance appeared very quickly in the region. Writing in Lancet Infectious Diseasescorrect in February, researchers from the Wellcome Sanger Institut and collaborators reported that resistance to combination therapies that included artemisinins arose almost as soon as the treatment was introduced as a first-line malarial drug. However, that this loss of efficacy was not spotted, for a variety of reasons, until several years had passed.

The implications of this failure were stressed by Ben Rolfe, head of the Asia Pacific Leaders Malaria Alliance. “On our watch, drug resistant strains have spread almost unnoticed,” he told the BMJ recently (pdf). “As a result, we now risk a global resurgence of the disease.”

Khmer families are screened for malaria in Pailin province in 2010.


Khmer families are screened for malaria in Pailin province in 2010. Photograph: Paula Bronstein/Getty Images

The question facing scientists -– and heads of state and health leaders -– is straightforward: what can be done? White -– who is scheduled to speak at the Commonwealth heads of state meeting -– is emphatic. “We have a window of opportunity but it is closing rapidly,” he told the Observer.

What is needed is a campaign, run with military efficiency, to use current drugs -– while they still have some efficacy -– not only on people who already have malaria but on those individuals who have been infected but who have not succumbed or shown symptoms of the disease.

“These individuals carry small numbers of parasites and although they don’t get ill they are sources of new infections,” said White. “Mosquitos bite them, take their blood and spread it to others. They are the source of new infections.”

The plan, proposed by White and other scientists, is that everyone in a village in a malaria hotspot should be treated with anti-malarial drugs -– regardless of their symptoms. “It is called mass drug administration. It is very controversial but it works -– if it is done as part of a concerted strategy. If you do it badly you will only make the problem of resistance worse. So this has to be done right. But if we don’t do it we won’t be able to eliminate malaria quickly enough, and if resistance worsens it may become untreatable,” says White.

In addition, it is proposed that a third anti-malarial drug be added to the combination therapy currently used to treat those who have actually succumbed to malaria: a triple whammy instead of a double. Next week, Britain’s Department for International Development is expected to announce support for trials using triple combination drugs.

For its part, WHO officials say that the dangers posed by the new malaria superbug are exaggerated and that better prevention efforts, monitoring and treatments will limit its spread from the Mekong region. Others are not so sure, however. The Malaria summit -– organised by the Ready to Beat Malaria campaign is to be held in London on 18 April at next week’s Commonwealth summit and will be attended by scientists and business leaders, including Bill and Melinda Gates. They are pressing for urgent commitments from all world leaders to battle the disease.

“We are currently on a cliff edge,” said a spokesman for Ready to Beat Malaria. “We can continue to battle the disease or risk an acute and deadly resurgence.”

This view is backed by White. “We are running out of time and unless we act rapidly, people will suffer and the people who will suffer most will be the children of Africa.”

The town that breeds resistance to Malaria drugs

Pailin is a small settlement nestling in tropical rainforest near Cambodia’s border with Thailand. It is an unassuming town that lies at the centre of one of the country’s main logging areas. Pailin harbours secrets, however. It was in this town, in the late 1970s, that the Khmer Rouge set up one of its main strongholds and ruled Cambodia with a ferocity that caused at least two million deaths. It is a grim legacy, by any standards.

But Pailin has another unwanted claim to fame, one that is also associated with widespread death. The town, it transpires, lies at the heart of a region that has seen successive waves of resistance to malaria drugs arise in local people and then spread across the globe. The resulting death tolls can be measured in millions of lives, say scientists.

Just why malarial drug resistance has arisen here is not clear. Nevertheless scientists are emphatic: the region has seen the creation of several mutations in malaria parasites that have allowed them to shrug off medicines that once protected humans. Even worse, they have discovered that a new wave of malarial drug resistance has recently appeared in this tiny area and has already spread into Thailand, Laos, and Vietnam, and begun to move into Myanmar and travel towards India and Bangladesh.

The prospect has so alarmed scientists and politicians that the issue is to be raised as an emergency topic to be debated at the heads of Commonwealth meeting in London next week (16-20 April). There are 19 Commonwealth member states in Africa, the continent that is the most vulnerable to malaria. According to World Health Organisation statistics, about 90% of all malaria deaths occur in Africa. Hence the concern of many Commonwealth heads of state who believe their homelands are most at risk of a spreading malarial resistance.

“The problem is that we are pussyfooting around,” said Professor Sir Nicholas White, of the Mahidol Oxford Tropical Medicine Research Unit. “The World Health Organisation has not provided the necessary leadership. We need very firm direct action and at present we are not getting that.”

Resistance to major malaria drugs first appeared in the late 1950s when chloroquine -– then a highly effective successful treatment for the disease -– began to lose its efficacy. Crucially, this resistance first appeared in Pailin on the Cambodian-Thai border and then spread to Africa by the early 1980s. Several million deaths were added to the already grim toll of lives lost to the disease as a result.

A new set of drugs, known as sulfadoxine-pyrimethamines, was then developed and used to treat malaria. But once more resistance to the drugs appeared and again it first manifested itself around Pailin before spreading westwards. Again the disease’s death toll soared.

malaria map

Then, at beginning of this century, a new set of malarial medicines was developed. Known as artemisinins, they were discovered in 1972 by Tu Youyou, a Chinese scientist who was awarded the 2015 Nobel prize in medicine for her work. Administered with a slower-acting second drug, artemisinins have become the medicine of choice for dealing with malaria across the globe, leading to improvements in malarial statistics with deaths and case numbers declining globally.

But now scientists have recently discovered once more that resistance to key malarial drugs has evolved -– and in exactly the same place as before: the farms and village that surround around Pailin. “That resistance has emerged in exactly the same place that resistance to chloroquine and then pyrimethamines emerged. The same very place. Around Pailin,” said White.

Just why this tiny region of south-east Asia has proved to be such a fertile zone for the emergence of deadly resistance to malarial medicine is not clear, a point stressed by Dominic Kwiatkowski, director of the centre for genomics and global health at Oxford University.

“We would love to know the answer, but it is not obvious,” Kwiatkowski told the Observer.

The Observer

The Observer is the world’s oldest Sunday newspaper, founded in 1791. It is published by Guardian News & Media and is editorially independent.

“One idea is that resistance keeps arising here for historical reasons. Maybe it has something to do with the way that malarial medicines are administered here. But how exactly?” In fact, the This theory is just one of a great many other suggestions that have been put forward to explain why this resistance is appearing here first.

The local strain of malaria parasites may have some special properties, or the ecology of the region may have features that boost the rise of resistance. “The crucial point is that we need to do something about it and once we have, we need to monitor the situation very, very carefully,” said Kwiatkowski.

One factor that has recently become clear is that malarial drug resistance appeared very quickly in the region. Writing in Lancet Infectious Diseasescorrect in February, researchers from the Wellcome Sanger Institut and collaborators reported that resistance to combination therapies that included artemisinins arose almost as soon as the treatment was introduced as a first-line malarial drug. However, that this loss of efficacy was not spotted, for a variety of reasons, until several years had passed.

The implications of this failure were stressed by Ben Rolfe, head of the Asia Pacific Leaders Malaria Alliance. “On our watch, drug resistant strains have spread almost unnoticed,” he told the BMJ recently (pdf). “As a result, we now risk a global resurgence of the disease.”

Khmer families are screened for malaria in Pailin province in 2010.


Khmer families are screened for malaria in Pailin province in 2010. Photograph: Paula Bronstein/Getty Images

The question facing scientists -– and heads of state and health leaders -– is straightforward: what can be done? White -– who is scheduled to speak at the Commonwealth heads of state meeting -– is emphatic. “We have a window of opportunity but it is closing rapidly,” he told the Observer.

What is needed is a campaign, run with military efficiency, to use current drugs -– while they still have some efficacy -– not only on people who already have malaria but on those individuals who have been infected but who have not succumbed or shown symptoms of the disease.

“These individuals carry small numbers of parasites and although they don’t get ill they are sources of new infections,” said White. “Mosquitos bite them, take their blood and spread it to others. They are the source of new infections.”

The plan, proposed by White and other scientists, is that everyone in a village in a malaria hotspot should be treated with anti-malarial drugs -– regardless of their symptoms. “It is called mass drug administration. It is very controversial but it works -– if it is done as part of a concerted strategy. If you do it badly you will only make the problem of resistance worse. So this has to be done right. But if we don’t do it we won’t be able to eliminate malaria quickly enough, and if resistance worsens it may become untreatable,” says White.

In addition, it is proposed that a third anti-malarial drug be added to the combination therapy currently used to treat those who have actually succumbed to malaria: a triple whammy instead of a double. Next week, Britain’s Department for International Development is expected to announce support for trials using triple combination drugs.

For its part, WHO officials say that the dangers posed by the new malaria superbug are exaggerated and that better prevention efforts, monitoring and treatments will limit its spread from the Mekong region. Others are not so sure, however. The Malaria summit -– organised by the Ready to Beat Malaria campaign is to be held in London on 18 April at next week’s Commonwealth summit and will be attended by scientists and business leaders, including Bill and Melinda Gates. They are pressing for urgent commitments from all world leaders to battle the disease.

“We are currently on a cliff edge,” said a spokesman for Ready to Beat Malaria. “We can continue to battle the disease or risk an acute and deadly resurgence.”

This view is backed by White. “We are running out of time and unless we act rapidly, people will suffer and the people who will suffer most will be the children of Africa.”

The town that breeds resistance to Malaria drugs

Pailin is a small settlement nestling in tropical rainforest near Cambodia’s border with Thailand. It is an unassuming town that lies at the centre of one of the country’s main logging areas. Pailin harbours secrets, however. It was in this town, in the late 1970s, that the Khmer Rouge set up one of its main strongholds and ruled Cambodia with a ferocity that caused at least two million deaths. It is a grim legacy, by any standards.

But Pailin has another unwanted claim to fame, one that is also associated with widespread death. The town, it transpires, lies at the heart of a region that has seen successive waves of resistance to malaria drugs arise in local people and then spread across the globe. The resulting death tolls can be measured in millions of lives, say scientists.

Just why malarial drug resistance has arisen here is not clear. Nevertheless scientists are emphatic: the region has seen the creation of several mutations in malaria parasites that have allowed them to shrug off medicines that once protected humans. Even worse, they have discovered that a new wave of malarial drug resistance has recently appeared in this tiny area and has already spread into Thailand, Laos, and Vietnam, and begun to move into Myanmar and travel towards India and Bangladesh.

The prospect has so alarmed scientists and politicians that the issue is to be raised as an emergency topic to be debated at the heads of Commonwealth meeting in London next week (16-20 April). There are 19 Commonwealth member states in Africa, the continent that is the most vulnerable to malaria. According to World Health Organisation statistics, about 90% of all malaria deaths occur in Africa. Hence the concern of many Commonwealth heads of state who believe their homelands are most at risk of a spreading malarial resistance.

“The problem is that we are pussyfooting around,” said Professor Sir Nicholas White, of the Mahidol Oxford Tropical Medicine Research Unit. “The World Health Organisation has not provided the necessary leadership. We need very firm direct action and at present we are not getting that.”

Resistance to major malaria drugs first appeared in the late 1950s when chloroquine -– then a highly effective successful treatment for the disease -– began to lose its efficacy. Crucially, this resistance first appeared in Pailin on the Cambodian-Thai border and then spread to Africa by the early 1980s. Several million deaths were added to the already grim toll of lives lost to the disease as a result.

A new set of drugs, known as sulfadoxine-pyrimethamines, was then developed and used to treat malaria. But once more resistance to the drugs appeared and again it first manifested itself around Pailin before spreading westwards. Again the disease’s death toll soared.

malaria map

Then, at beginning of this century, a new set of malarial medicines was developed. Known as artemisinins, they were discovered in 1972 by Tu Youyou, a Chinese scientist who was awarded the 2015 Nobel prize in medicine for her work. Administered with a slower-acting second drug, artemisinins have become the medicine of choice for dealing with malaria across the globe, leading to improvements in malarial statistics with deaths and case numbers declining globally.

But now scientists have recently discovered once more that resistance to key malarial drugs has evolved -– and in exactly the same place as before: the farms and village that surround around Pailin. “That resistance has emerged in exactly the same place that resistance to chloroquine and then pyrimethamines emerged. The same very place. Around Pailin,” said White.

Just why this tiny region of south-east Asia has proved to be such a fertile zone for the emergence of deadly resistance to malarial medicine is not clear, a point stressed by Dominic Kwiatkowski, director of the centre for genomics and global health at Oxford University.

“We would love to know the answer, but it is not obvious,” Kwiatkowski told the Observer.

The Observer

The Observer is the world’s oldest Sunday newspaper, founded in 1791. It is published by Guardian News & Media and is editorially independent.

“One idea is that resistance keeps arising here for historical reasons. Maybe it has something to do with the way that malarial medicines are administered here. But how exactly?” In fact, the This theory is just one of a great many other suggestions that have been put forward to explain why this resistance is appearing here first.

The local strain of malaria parasites may have some special properties, or the ecology of the region may have features that boost the rise of resistance. “The crucial point is that we need to do something about it and once we have, we need to monitor the situation very, very carefully,” said Kwiatkowski.

One factor that has recently become clear is that malarial drug resistance appeared very quickly in the region. Writing in Lancet Infectious Diseasescorrect in February, researchers from the Wellcome Sanger Institut and collaborators reported that resistance to combination therapies that included artemisinins arose almost as soon as the treatment was introduced as a first-line malarial drug. However, that this loss of efficacy was not spotted, for a variety of reasons, until several years had passed.

The implications of this failure were stressed by Ben Rolfe, head of the Asia Pacific Leaders Malaria Alliance. “On our watch, drug resistant strains have spread almost unnoticed,” he told the BMJ recently (pdf). “As a result, we now risk a global resurgence of the disease.”

Khmer families are screened for malaria in Pailin province in 2010.


Khmer families are screened for malaria in Pailin province in 2010. Photograph: Paula Bronstein/Getty Images

The question facing scientists -– and heads of state and health leaders -– is straightforward: what can be done? White -– who is scheduled to speak at the Commonwealth heads of state meeting -– is emphatic. “We have a window of opportunity but it is closing rapidly,” he told the Observer.

What is needed is a campaign, run with military efficiency, to use current drugs -– while they still have some efficacy -– not only on people who already have malaria but on those individuals who have been infected but who have not succumbed or shown symptoms of the disease.

“These individuals carry small numbers of parasites and although they don’t get ill they are sources of new infections,” said White. “Mosquitos bite them, take their blood and spread it to others. They are the source of new infections.”

The plan, proposed by White and other scientists, is that everyone in a village in a malaria hotspot should be treated with anti-malarial drugs -– regardless of their symptoms. “It is called mass drug administration. It is very controversial but it works -– if it is done as part of a concerted strategy. If you do it badly you will only make the problem of resistance worse. So this has to be done right. But if we don’t do it we won’t be able to eliminate malaria quickly enough, and if resistance worsens it may become untreatable,” says White.

In addition, it is proposed that a third anti-malarial drug be added to the combination therapy currently used to treat those who have actually succumbed to malaria: a triple whammy instead of a double. Next week, Britain’s Department for International Development is expected to announce support for trials using triple combination drugs.

For its part, WHO officials say that the dangers posed by the new malaria superbug are exaggerated and that better prevention efforts, monitoring and treatments will limit its spread from the Mekong region. Others are not so sure, however. The Malaria summit -– organised by the Ready to Beat Malaria campaign is to be held in London on 18 April at next week’s Commonwealth summit and will be attended by scientists and business leaders, including Bill and Melinda Gates. They are pressing for urgent commitments from all world leaders to battle the disease.

“We are currently on a cliff edge,” said a spokesman for Ready to Beat Malaria. “We can continue to battle the disease or risk an acute and deadly resurgence.”

This view is backed by White. “We are running out of time and unless we act rapidly, people will suffer and the people who will suffer most will be the children of Africa.”

Prescription of opioid drugs continues to rise in England

Doctors give patients drugs such as tramadol despite risks of addiction and ineffectiveness when treating chronic pain

Tramadol packet


Tramadol was the most commonly prescribed opioid in England from August 2010 to February 2014. Photograph: Jeremy Durkin/Rex Features

The prescription of opioid drugs by GPs in England is steadily rising, especially in more deprived communities, even though they are potentially dangerous and do not work for chronic pain, a new study reveals.

The study shines an alarming new light on the legal use of opioids in England; potentially inappropriate yet sanctioned by doctors. It also reveals a north-south divide. Nine out of 10 of the highest-prescribing regions were in the north. Prescriptions of painkillers were higher in areas of socio-economic deprivation.

Opioids have hit the headlines mainly because of their abuse in the United States. The authors of the study in the British Journal of General Practice, which uses official government data, say opioids are rightly given to people to cope with cancer pain and short-lived acute pain. But as the authors also point out, the widespread prescribing of opioids for people with long-term pain is controversial because “opioids are ineffective in much chronic pain beyond modest effects in the short term”.

Q&A

Why is there an opioid crisis in America?

Almost 100 people are dying every day across America from opioid overdoses – more than car crashes and shootings combined. The majority of these fatalities reveal widespread addiction to powerful prescription painkillers. The crisis unfolded in the mid-90s when the US pharmaceutical industry began marketing legal narcotics, particularly OxyContin, to treat everyday pain. This slow-release opioid was vigorously promoted to doctors and, amid lax regulation and slick sales tactics, people were assured it was safe. But the drug was akin to luxury morphine, doled out like super aspirin, and highly addictive. What resulted was a commercial triumph and a public health tragedy. Belated efforts to rein in distribution fueled a resurgence of heroin and the emergence of a deadly, black market version of the synthetic opioid fentanyl. The crisis is so deep because it affects all races, regions and incomes

They are also potentially dangerous. Luke Mordecai, a pain research fellow at University College London Hospital and the lead author of the study, is calling for a register of all those who are taking the equivalent of more than 120mg of morphine a day. “There should be a national database to keep track of these people,” he said. “There is very high morbidity and mortality [among them], a lot of it avoidable.”

The gold standard, he said, was treatment by a multi-disciplinary team of pain experts, including a specialist consultant, nurse, psychologist and physiotherapist. Yet that is rare: only 40% of pain consultants provide it. Many people could come off opioids altogether with the best care.

Chronic pain is very common. As many as one in seven people have complained of moderate to severely disabling pain and the numbers rise with age. Opioids do not work, but, says the study, many GPs prescribe them because they think it is unethical to refuse their patients painkillers.

The study looks at the total amount prescribed in grams of each of eight common opioid drugs and finds a rise in six of them. Mordecai talked of “a steady increase” but declined to quantify it in percentage terms because of the relatively short time period.

The most prescribed opioid drug in England over the 43 months of the study, from August 2010 to February 2014, was tramadol. It is stronger than over-the-counter codeine but does not have the stigma of the powerful morphine.

“It is not seen as a strong opiate although actually I think it really is,” said Mordecai. “It is the first port of call for troublesome pain but it can become quite addictive.”

Tramadol is implicated in a rising number of deaths due to drug misuse – in Northern Ireland up from 9% to 40% in 2011. In England it was found responsible for 132 deaths in 2010 but 240 in 2014. In that year, it was reclassified as schedule 3 and prescription was limited to one month’s supply at a time. But, the study’s authors note, that failed to work with codeine in Australia. Prescriptions of buprenorphine, oxycodone, codeine and morphine also rose, the study finds. There was a small rise in fentanyl prescription, while prescribing of methadone and dihydrocodeine dropped.

Mordecai said more studies would be needed to find out why prescriptions were highest in more deprived areas and in the north. “We know that chronic pain affects more people of low socio-economic status,” he said. The paper notes that an association has also been found between unemployment and poor outcomes in chronic pain.

“It is something that needs a great deal more work. People of higher socio-economic status might have access to better facilities and ask more questions or want the best treatment possible,” he said.

“This study exposes increasing rates of prescription of a class of drugs whose use for chronic pain is controversial, with potential for abuse, and an association with serious adverse effects and premature death,” concludes the paper. “The authors call on policymakers to identify the reasons for this variation to enable avoidable harm to be addressed.”

Prescription of opioid drugs continues to rise in England

Doctors give patients drugs such as tramadol despite risks of addiction and ineffectiveness when treating chronic pain

Tramadol packet


Tramadol was the most commonly prescribed opioid in England from August 2010 to February 2014. Photograph: Jeremy Durkin/Rex Features

The prescription of opioid drugs by GPs in England is steadily rising, especially in more deprived communities, even though they are potentially dangerous and do not work for chronic pain, a new study reveals.

The study shines an alarming new light on the legal use of opioids in England; potentially inappropriate yet sanctioned by doctors. It also reveals a north-south divide. Nine out of 10 of the highest-prescribing regions were in the north. Prescriptions of painkillers were higher in areas of socio-economic deprivation.

Opioids have hit the headlines mainly because of their abuse in the United States. The authors of the study in the British Journal of General Practice, which uses official government data, say opioids are rightly given to people to cope with cancer pain and short-lived acute pain. But as the authors also point out, the widespread prescribing of opioids for people with long-term pain is controversial because “opioids are ineffective in much chronic pain beyond modest effects in the short term”.

Q&A

Why is there an opioid crisis in America?

Almost 100 people are dying every day across America from opioid overdoses – more than car crashes and shootings combined. The majority of these fatalities reveal widespread addiction to powerful prescription painkillers. The crisis unfolded in the mid-90s when the US pharmaceutical industry began marketing legal narcotics, particularly OxyContin, to treat everyday pain. This slow-release opioid was vigorously promoted to doctors and, amid lax regulation and slick sales tactics, people were assured it was safe. But the drug was akin to luxury morphine, doled out like super aspirin, and highly addictive. What resulted was a commercial triumph and a public health tragedy. Belated efforts to rein in distribution fueled a resurgence of heroin and the emergence of a deadly, black market version of the synthetic opioid fentanyl. The crisis is so deep because it affects all races, regions and incomes

They are also potentially dangerous. Luke Mordecai, a pain research fellow at University College London Hospital and the lead author of the study, is calling for a register of all those who are taking the equivalent of more than 120mg of morphine a day. “There should be a national database to keep track of these people,” he said. “There is very high morbidity and mortality [among them], a lot of it avoidable.”

The gold standard, he said, was treatment by a multi-disciplinary team of pain experts, including a specialist consultant, nurse, psychologist and physiotherapist. Yet that is rare: only 40% of pain consultants provide it. Many people could come off opioids altogether with the best care.

Chronic pain is very common. As many as one in seven people have complained of moderate to severely disabling pain and the numbers rise with age. Opioids do not work, but, says the study, many GPs prescribe them because they think it is unethical to refuse their patients painkillers.

The study looks at the total amount prescribed in grams of each of eight common opioid drugs and finds a rise in six of them. Mordecai talked of “a steady increase” but declined to quantify it in percentage terms because of the relatively short time period.

The most prescribed opioid drug in England over the 43 months of the study, from August 2010 to February 2014, was tramadol. It is stronger than over-the-counter codeine but does not have the stigma of the powerful morphine.

“It is not seen as a strong opiate although actually I think it really is,” said Mordecai. “It is the first port of call for troublesome pain but it can become quite addictive.”

Tramadol is implicated in a rising number of deaths due to drug misuse – in Northern Ireland up from 9% to 40% in 2011. In England it was found responsible for 132 deaths in 2010 but 240 in 2014. In that year, it was reclassified as schedule 3 and prescription was limited to one month’s supply at a time. But, the study’s authors note, that failed to work with codeine in Australia. Prescriptions of buprenorphine, oxycodone, codeine and morphine also rose, the study finds. There was a small rise in fentanyl prescription, while prescribing of methadone and dihydrocodeine dropped.

Mordecai said more studies would be needed to find out why prescriptions were highest in more deprived areas and in the north. “We know that chronic pain affects more people of low socio-economic status,” he said. The paper notes that an association has also been found between unemployment and poor outcomes in chronic pain.

“It is something that needs a great deal more work. People of higher socio-economic status might have access to better facilities and ask more questions or want the best treatment possible,” he said.

“This study exposes increasing rates of prescription of a class of drugs whose use for chronic pain is controversial, with potential for abuse, and an association with serious adverse effects and premature death,” concludes the paper. “The authors call on policymakers to identify the reasons for this variation to enable avoidable harm to be addressed.”

Prescription of opioid drugs continues to rise in England

Doctors give patients drugs such as tramadol despite risks of addiction and ineffectiveness when treating chronic pain

Tramadol packet


Tramadol was the most commonly prescribed opioid in England from August 2010 to February 2014. Photograph: Jeremy Durkin/Rex Features

The prescription of opioid drugs by GPs in England is steadily rising, especially in more deprived communities, even though they are potentially dangerous and do not work for chronic pain, a new study reveals.

The study shines an alarming new light on the legal use of opioids in England; potentially inappropriate yet sanctioned by doctors. It also reveals a north-south divide. Nine out of 10 of the highest-prescribing regions were in the north. Prescriptions of painkillers were higher in areas of socio-economic deprivation.

Opioids have hit the headlines mainly because of their abuse in the United States. The authors of the study in the British Journal of General Practice, which uses official government data, say opioids are rightly given to people to cope with cancer pain and short-lived acute pain. But as the authors also point out, the widespread prescribing of opioids for people with long-term pain is controversial because “opioids are ineffective in much chronic pain beyond modest effects in the short term”.

Q&A

Why is there an opioid crisis in America?

Almost 100 people are dying every day across America from opioid overdoses – more than car crashes and shootings combined. The majority of these fatalities reveal widespread addiction to powerful prescription painkillers. The crisis unfolded in the mid-90s when the US pharmaceutical industry began marketing legal narcotics, particularly OxyContin, to treat everyday pain. This slow-release opioid was vigorously promoted to doctors and, amid lax regulation and slick sales tactics, people were assured it was safe. But the drug was akin to luxury morphine, doled out like super aspirin, and highly addictive. What resulted was a commercial triumph and a public health tragedy. Belated efforts to rein in distribution fueled a resurgence of heroin and the emergence of a deadly, black market version of the synthetic opioid fentanyl. The crisis is so deep because it affects all races, regions and incomes

They are also potentially dangerous. Luke Mordecai, a pain research fellow at University College London Hospital and the lead author of the study, is calling for a register of all those who are taking the equivalent of more than 120mg of morphine a day. “There should be a national database to keep track of these people,” he said. “There is very high morbidity and mortality [among them], a lot of it avoidable.”

The gold standard, he said, was treatment by a multi-disciplinary team of pain experts, including a specialist consultant, nurse, psychologist and physiotherapist. Yet that is rare: only 40% of pain consultants provide it. Many people could come off opioids altogether with the best care.

Chronic pain is very common. As many as one in seven people have complained of moderate to severely disabling pain and the numbers rise with age. Opioids do not work, but, says the study, many GPs prescribe them because they think it is unethical to refuse their patients painkillers.

The study looks at the total amount prescribed in grams of each of eight common opioid drugs and finds a rise in six of them. Mordecai talked of “a steady increase” but declined to quantify it in percentage terms because of the relatively short time period.

The most prescribed opioid drug in England over the 43 months of the study, from August 2010 to February 2014, was tramadol. It is stronger than over-the-counter codeine but does not have the stigma of the powerful morphine.

“It is not seen as a strong opiate although actually I think it really is,” said Mordecai. “It is the first port of call for troublesome pain but it can become quite addictive.”

Tramadol is implicated in a rising number of deaths due to drug misuse – in Northern Ireland up from 9% to 40% in 2011. In England it was found responsible for 132 deaths in 2010 but 240 in 2014. In that year, it was reclassified as schedule 3 and prescription was limited to one month’s supply at a time. But, the study’s authors note, that failed to work with codeine in Australia. Prescriptions of buprenorphine, oxycodone, codeine and morphine also rose, the study finds. There was a small rise in fentanyl prescription, while prescribing of methadone and dihydrocodeine dropped.

Mordecai said more studies would be needed to find out why prescriptions were highest in more deprived areas and in the north. “We know that chronic pain affects more people of low socio-economic status,” he said. The paper notes that an association has also been found between unemployment and poor outcomes in chronic pain.

“It is something that needs a great deal more work. People of higher socio-economic status might have access to better facilities and ask more questions or want the best treatment possible,” he said.

“This study exposes increasing rates of prescription of a class of drugs whose use for chronic pain is controversial, with potential for abuse, and an association with serious adverse effects and premature death,” concludes the paper. “The authors call on policymakers to identify the reasons for this variation to enable avoidable harm to be addressed.”

Prescription of opioid drugs continues to rise in England

Doctors give patients drugs such as tramadol despite risks of addiction and ineffectiveness when treating chronic pain

Tramadol packet


Tramadol was the most commonly prescribed opioid in England from August 2010 to February 2014. Photograph: Jeremy Durkin/Rex Features

The prescription of opioid drugs by GPs in England is steadily rising, especially in more deprived communities, even though they are potentially dangerous and do not work for chronic pain, a new study reveals.

The study shines an alarming new light on the legal use of opioids in England; potentially inappropriate yet sanctioned by doctors. It also reveals a north-south divide. Nine out of 10 of the highest-prescribing regions were in the north. Prescriptions of painkillers were higher in areas of socio-economic deprivation.

Opioids have hit the headlines mainly because of their abuse in the United States. The authors of the study in the British Journal of General Practice, which uses official government data, say opioids are rightly given to people to cope with cancer pain and short-lived acute pain. But as the authors also point out, the widespread prescribing of opioids for people with long-term pain is controversial because “opioids are ineffective in much chronic pain beyond modest effects in the short term”.

Q&A

Why is there an opioid crisis in America?

Almost 100 people are dying every day across America from opioid overdoses – more than car crashes and shootings combined. The majority of these fatalities reveal widespread addiction to powerful prescription painkillers. The crisis unfolded in the mid-90s when the US pharmaceutical industry began marketing legal narcotics, particularly OxyContin, to treat everyday pain. This slow-release opioid was vigorously promoted to doctors and, amid lax regulation and slick sales tactics, people were assured it was safe. But the drug was akin to luxury morphine, doled out like super aspirin, and highly addictive. What resulted was a commercial triumph and a public health tragedy. Belated efforts to rein in distribution fueled a resurgence of heroin and the emergence of a deadly, black market version of the synthetic opioid fentanyl. The crisis is so deep because it affects all races, regions and incomes

They are also potentially dangerous. Luke Mordecai, a pain research fellow at University College London Hospital and the lead author of the study, is calling for a register of all those who are taking the equivalent of more than 120mg of morphine a day. “There should be a national database to keep track of these people,” he said. “There is very high morbidity and mortality [among them], a lot of it avoidable.”

The gold standard, he said, was treatment by a multi-disciplinary team of pain experts, including a specialist consultant, nurse, psychologist and physiotherapist. Yet that is rare: only 40% of pain consultants provide it. Many people could come off opioids altogether with the best care.

Chronic pain is very common. As many as one in seven people have complained of moderate to severely disabling pain and the numbers rise with age. Opioids do not work, but, says the study, many GPs prescribe them because they think it is unethical to refuse their patients painkillers.

The study looks at the total amount prescribed in grams of each of eight common opioid drugs and finds a rise in six of them. Mordecai talked of “a steady increase” but declined to quantify it in percentage terms because of the relatively short time period.

The most prescribed opioid drug in England over the 43 months of the study, from August 2010 to February 2014, was tramadol. It is stronger than over-the-counter codeine but does not have the stigma of the powerful morphine.

“It is not seen as a strong opiate although actually I think it really is,” said Mordecai. “It is the first port of call for troublesome pain but it can become quite addictive.”

Tramadol is implicated in a rising number of deaths due to drug misuse – in Northern Ireland up from 9% to 40% in 2011. In England it was found responsible for 132 deaths in 2010 but 240 in 2014. In that year, it was reclassified as schedule 3 and prescription was limited to one month’s supply at a time. But, the study’s authors note, that failed to work with codeine in Australia. Prescriptions of buprenorphine, oxycodone, codeine and morphine also rose, the study finds. There was a small rise in fentanyl prescription, while prescribing of methadone and dihydrocodeine dropped.

Mordecai said more studies would be needed to find out why prescriptions were highest in more deprived areas and in the north. “We know that chronic pain affects more people of low socio-economic status,” he said. The paper notes that an association has also been found between unemployment and poor outcomes in chronic pain.

“It is something that needs a great deal more work. People of higher socio-economic status might have access to better facilities and ask more questions or want the best treatment possible,” he said.

“This study exposes increasing rates of prescription of a class of drugs whose use for chronic pain is controversial, with potential for abuse, and an association with serious adverse effects and premature death,” concludes the paper. “The authors call on policymakers to identify the reasons for this variation to enable avoidable harm to be addressed.”