Battling malaria drug resistance along the Thai-Cambodian border
Background
Source of resistance
Since the 1970s the border area between Cambodia and Thailand has become noteworthy for an unusual scientific phenomena – malaria parasites in this particular area uniquely have developed resistance to a succession of malaria drugs. Resistance to key anti-malarials like chloroquine and sulfadoxine-pyrimethamine (brand name Fansidar) subsequently spread to other parts of Asia and Africa, rendering these drugs virtually useless against the disease in many parts of the world. In turn, this caused a surge in malaria deaths globally as the resistance spread.
So why have parasites in this particular area proved so adaptable and such a source of resistance? Scientists are still trying to find answers to that question. But there are many factors which scientists believe have contributed to the emergence of anti-malarial drug resistance in this region. These factors include the following.
- Natural selection. The effect of drugs on different patients will vary depending on their individual body chemistry (eg. differing metabolisms). Eventually a mutant parasite will arise and become tolerant to the formerly effective drug. These mutant parasites will survive and eventually multiply and tolerance to the drug will become evident.
- Substandard drugs. Counterfeit and substandard drugs have been widely available in South-East Asia. In Cambodia they have been a huge problem, particularly as most people have sought treatment from the private sector – pharmacies, clinics, drug shops and markets stalls - rather than through government clinics. Fake drugs with inadequate amounts of active ingredient may kill off some more susceptible parasites, but leave stronger ones – those more likely to develop tolerance - to multiply. Use of these drugs also extends the period of infectiousness, and can lead to the patient’s death.
- Single-drug treatments. Treatments comprising just one drug – known as monotherapies – are believed to be a major cause of resistance. It is easier for a parasite to develop resistance to a single drug treatment as it only needs to adapt to the characteristics of one drug. If a treatment involving two or more drugs is used, it is likely to kill the parasite even if it has developed tolerance, or resistance, to one of the drugs. It is far more complicated for a parasite to develop resistance to effective ingredients in both drugs. Until a ban against the use of monotherapies for treatment of malaria was introduced in Cambodia in 2009, they were widely available through the private sector in Cambodia to treat malaria. The monotherapies were perceived as having fewer side effects and often cheaper than the artemisinin-based treatments involving a number of drugs.
- Lack of compliance. The recommended treatment for malaria – artemisinin combination therapy (ACT) - requires drugs to be taken over a three-day period. Some patients do not finish the full course of treatment, sometimes stopping medication after they start to feel better. Failure to take the full course means that while some more susceptible parasites are killed, more resilient ones live on, leading to tolerance, or resistance, to the drugs to which they were initially exposed. This has been particularly a problem when drugs are obtained through the private sector and are often dispensed without proper information to the patient regarding use of the drugs.
- Mobile and migrant populations. This region has a highly mobile population with people moving both internally and across the Thai-Cambodian border. In the border area, it is mostly seasonal agricultural workers, but there are also construction workers, woodcutters, army troops and their families, and miners. Mobile people often do not know how to access appropriate treatment and are often unaware of the dangers of malaria and the need to sleep under a mosquito net. They are more likely to seek drugs in the market which may be substandard. The situation is complicated by the fact that many Cambodian seasonal workers in Thailand are working illegally and do not wish to be readily visible. There are fears these people will take resistant parasites to other areas, contributing to the spread of the drug resistance.
Artemisinin-based treatments
Since the 1990s new treatments – based on the Chinese herb, artemisinin, (or the Chinese name qinqhaosu) – have been increasingly introduced across the globe and have proved highly effective. Artemisinin, used in combination with other drugs, is now considered the world’s best treatment against malaria – and it is one of the few effective treatments against the most serious and life-threatening strain, Plasmodium falciparum malaria. As use of artemisinin-based treatments has been dramatically stepped up over recent years and extended to more parts of Africa – where 90 per cent of malaria deaths occur - the death rate from malaria globally has been falling. Artemisinin-based treatments have been a major factor in the huge strides that have been made in combating malaria worldwide over the past decade.
Resistance reemerges
But, once again, malarial parasites resistant to a key malaria drug – this time artemisinin - have emerged in western Cambodia, along the border with Thailand. Studies in 2007-2008 found a significant delay in the time taken to clear falciparum malaria parasites from some patients in this area. This alarmed health specialists across the globe, who feared that if earlier trends reoccur - and the resistant parasites reached Africa - millions of lives would be at risk as there are currently no recommended alternative treatments. And consequently, the huge gains made in combating malaria over the past decade, could be reversed. In response to this potentially catastrophic situation, WHO, working closely with the health ministries of Cambodia and Thailand, and many other partners, developed an ambitious strategy to combat the resistance, known as the containment project.