Malaria: A slow-burning global emergency

BANGKOK - Thailand is playing a key role in countering a major threat to public health - growing resistance to the most effective drug to counter malaria News that resistance to the anti-malaria drug artemisinin has spread across mainland Southeast Asia is a slow-burning global emergency, according to Bangkok-based malaria expert Nick White.

Professor White is the chairman of the Worldwide Anti-Malarial Resistance Network and Professor of Tropical Medicine at the Mahidol Oxford Tropical Medicine Research Unit (MORU), part of Mahidol University in Bangkok, which has just released a new study.

The study, which analysed blood samples from 1,241 malaria patients in 10 countries across Asia and Africa, found that artemisinin resistance in Plasmodium falciparum - the most deadly parasite that causes malaria - is now firmly established in western Cambodia, Thailand, Vietnam, eastern Myanmar and northern Cambodia. There are also signs of emerging resistance in central Myanmar, southern Laos and northeast Cambodia.

This essentially confirms what White and malaria experts have feared ever since resistance to artemisinin was observed in western Cambodia seven years ago, before "jumping" to the Thai-Myanmar border in recent years. The news has reared like a cloud over the substantial gains made in the worldwide fight against the disease over the past decade and a half.

"We see the potential for our main tool [to fight malaria] being lost … artemisinin resistance is clearly established across most of mainland Southeast Asia, and knocking on the door of India," Prof White said, in an interview after the findings of the survey were announced at the start of the month.

"The drugs are still working but beginning to fail. And a new drug is at least five years away."

A British doctor with an interest in tropical diseases, who first arrived in Thailand back in 1980, White - and a handful of local and foreign scientists based in Bangkok and Mae Sot - is now at the forefront of international efforts to track resistance to artemisinin and develop strategies to contain the spread of a disease that is re-emerging as a major health concern.

Billions of dollars have been spent under multinational campaigns led by the Global Fund for HIV, TB and Malaria and backed by the World Health Organisation to reduce malaria deaths through the distribution of insecticide-treated bed nets, and the use of artemisinin combination therapies. These are estimated to have saved about three million lives - mainly because of a big drop in the death rate among children in Africa - since the turn of the century, White said.

But the malaria parasite is fighting back, as it did against chloroquine, the world's main anti-malarial drug from the 1950s to the 1970s. Indeed resistance to chloroquine in malaria parasites also arose near the Thailand-Cambodia border, and spread across Asia and Africa at a cost of millions of lives. Resistance to SP, the drug which followed chloroquine, also arose in the same place, and also spread to Africa. So there are deadly precedents to the current problem of artemisinin resistance.

Three sites in Africa were included in the latest survey - in Kenya, Nigeria and the Democratic Republic of the Congo - and artemisinin resistance was not detected in these locations. However, White was quick to concede this was a "minuscule" sampling on a large continent, and that artemisinin resistance "could be there".

But mosquitoes differ around the world and there is some hope, he said, that African mosquitoes may be less accommodating to artemisinin-resistant malaria parasites - and that resistance may not spread as quickly as it has in Southeast Asia.

White is concerned that the global response to the emergence of artemisinin resistance has been muted, partly because those who get malaria are often "disenfranchised rural people". He also fears that world leaders are notoriously difficult to prod into radical action for "slow-burning emergencies".

"The only time we've taken pre-emptive action is for nuclear bombs - to try to stop the spread of nuclear weapons. ... Our response to slow-burning emergencies is profoundly disappointing."

Climate change comes to mind, but White gave a brief history of penicillin, the development of antibiotics and the Chinese discovery of artemisinin.

"Some say resistance to anti-microbials [medicines] is the single greatest threat to human beings," he said. "Antibiotics and anti-malarials are miracles. But we're these using these incredibly precious medicines like [chocolate] Smarties, and we're not discovering new antibiotics quick enough to keep up with the development of resistance."

In the year 2000, roughly 3,000 people were dying from malaria every day. That figure has since dropped to about 2,000 a day (approximately 600,000 deaths a year worldwide), thanks largely to the availability of artemisinin and scaled-up activities by national health ministries.

Thailand has less than 20,000 cases a year, mainly in areas adjacent to forests and provinces such as Tak where many people who may carry the parasite pass through. But the annual death toll is small, in the dozens, he said, unlike in neighbouring countries. In Myanmar, malaria probably kills thousands every year, many of them unreported.

Thailand could eliminate malaria if it wanted, but Myanmar, he said, had enormous needs and after 40 years of weak government funding - among the lowest health investment per capita worldwide - was only really beginning to confront a disease that flourished during decades of civil war and internal strife. There has been substantial recent improvement, but Nay Pyi Taw has also been swamped by the arrival of dozens of non-government groups, all with their own agendas.

White said the MORU survey of artemisinin resistance was conducted over three years and cost about Bt300 million. Funding was provided by Britain's Department of International Development, the Wellcome Trust, and the Bill & Melinda Gates Foundation. It will be followed by a second three-year study, funding for which has already been approved.

"In tropical diseases Thailand has a very good reputation for research. We see our role as a regional or international research hub. The latest international survey was coordinated from Bangkok - science shouldn't have any borders - and Thailand is well regarded. It has good scientists and leads the world in clinical research on malaria and its treatment.

"Having two papers in the latest issue of the top international medical journal [The New England Journal of Medicine], Thailand should be proud that it's playing on the world stage, as a leading contributor to global health and a major player in top medical research. These health benefits will be greatest in other countries, in Africa, or Asia."

After 30 years of work in Thailand, White fears that the clock is counting down and millions of lives are at risk. It would take a major effort - a big ramp-up in national spending and commitment by all states in ASEAN plus international lending bodies - but attempting to kill the spread of the disease before it jumps to other continents is "surely worth a shot", he says.

"We haven't got time to slowly build evidence and consensus. The fire is already burning, and threatening to get out of control. We've got to take risks. I think it's an emergency. We're looking for a leader to lead this - what we need to do is eliminate falciparum malaria in this area."