Malaria is a seasonal disease; with tropical rains come the fevers. In the news media, malaria is also seasonal. Every spring around World Malaria Day we hear about its devastating effects, including deaths in the hundreds of thousands. This year the reports were encouraging: Infections have been reduced and many lives saved. In May, researchers reported in Science that yet another potential malaria vaccine may be around the corner. Malaria seems to be on the retreat.
But is it really?
Malaria is caused by a tiny parasite, transported by a particular type of mosquito from person to person. Preventing mosquito bites by using insect repellents or nets and clothing treated with insecticides can reduce malaria in some areas. And if people are infected, drugs can be used to kill the parasites in their blood.
But the mosquitoes are constantly adapting and becoming resistant to the chemicals, while at the same time the parasites are adapting and becoming resistant to the drugs. So the fight against malaria is really a race against time in which we try to develop new treatments before they become ineffective, causing millions to die.
I have been working on the Thai-Myanmar border for 30 years. Once, in the early ’90s, we faced the prospect of untreatable malaria. The number of people infected with the parasite (Plasmodium falciparum in this case) had been in decline, but the drug we were using — mefloquine, brand name Lariam — was becoming less effective and more patients were dying.
I remember a young Buddhist monk who was carried to our bamboo clinic two weeks after taking Lariam. His blood was still full of parasites. Lying in his saffron robe, he was unconscious, burning up and agitated by frequent convulsions. We tried in vain to save his life.
Then we heard about artesunate, a drug that comes from the Artemisia annua plant in China and was just becoming available. Preliminary studies indicated that it was very safe and was killing the malaria parasite extremely rapidly. But it was also quickly eliminated from the body, requiring too many days of treatment to be practical. We reasoned that combining this new drug with the more long-lasting mefloquine could be the answer.
Indeed it was. In 1994, after large studies confirmed the safety and the efficacy of this new treatment, this first artemisinin-based combination therapy, or ACT, was deployed in all the refugee camps. The number of new cases, and lives lost, declined sharply.
By the end of the 1990s, there was strong evidence that ACTs worked, but the World Health Organization was slow to recommend the treatments in other parts of the world, particularly in Africa, where malaria was on the rampage. Thousands of people died in the 2000-01 malaria epidemic in Burundi largely because they received ineffective drugs. Despite this, in 2002 an adviser for U.S.A.I.D. declared that ACTs were “not ready for prime time.” Only after The Lancet published a virulent attack in 2004 accusing the W.H.O. of medical malpractice did it effectively make ACTs the standard worldwide.
But history repeats itself. While malaria rates went down again as a result of insecticide-treated mosquito nets and widespread deployment of ACTs, the parasite adapted its genetic machinery to resist these powerful medicines and is now preparing for a devastating return.
Today, the artemisinins in ACTs are taking longer to kill parasites in Cambodia, Vietnam, Thailand and Myanmar. Recently, a young patient in our clinic tested positive for malaria for more than seven days after starting treatment (instead of the usual two), and when we sampled her blood after six days of treatment, the parasite was still healthy. If P. falciparum becomes totally resistant, then the ACTs would become ineffective and all investments in their development and distribution would be lost, with dire consequences.
Over the years, millions of dollars have been spent on fighting malaria. Late last year, the Global Fund to Fight AIDS, Tuberculosis and Malaria allocated $100 million to tackle artemisinin resistance in the Mekong region where I work. But all this well-intentioned money keeps us only a step ahead of the parasites. We have to keep coming up with new combinations of drugs before our patients taking the old ones start dying. And bed nets, on which at least $20 million will be spent, aren’t always effective here in Southeast Asia, where many mosquitoes that carry the parasite bite outside and early in the evening. Of course, an effective vaccine could save us but, despite the frequent announcements that we’re close to developing one, it has never materialized because we do not fully understand the underlying biology.
We have to accept that these strategies of control are failing and instead start figuring out how to eliminate the parasite altogether, as we have in Europe, Russia and North America.
In pilot studies in Cambodia, Vietnam and here on the Thai-Myanmar border, we have begun testing one approach to rapid elimination. Doing surveys of the population, we discovered that in some communities, many villagers — sometimes more than half — carry malaria parasites in their blood but are not ill and therefore are not treated. Because these “healthy” carriers have only a small number of parasites in their blood, they are difficult to detect with conventional tests. So eliminating the parasites may require treating everybody in the village, an approach that is used for other parasitic diseases, like river blindness and filariasis. Because P. falciparum infects only humans, if we can treat entire populations, we should be able to eliminate this parasite from certain regions.
Giving medicines to large numbers of villagers in remote areas who are not ill is not an easy task. It cannot work without the trust and participation of the local population. And we would need to hit whole regions at once. Even then we don’t know that it would work; the effectiveness, feasibility and economics of mass treatment are still being studied. But what else can we do to stop the seemingly inevitable spread of drug-resistant malaria across Asia to Africa, and the enormous consequent death toll?
Some funding bodies — like the Bill & Melinda Gates Foundation, the Wellcome Trust and Britain’s Department for International Development, which also support our research unit — are moving in this direction already. But for now, governments and medical organizations need more evidence, and they need leadership from the W.H.O.
For years, the fight against malaria in tropical countries has been compromised by politics. Here on the front line, our work is more difficult because of the bureaucracy, the inertia and sometimes the incompetence of the people in control. Money and its corruptive power are flying around. And the more money we throw at malaria, the bigger the problems get. We have the science to defeat malaria. We just have to act, before it defeats us.
François H. Nosten is a professor of tropical medicine at the University of Oxford and the director of the Shoklo Malaria Research Unit.