Wellcome to the jungle

6 June 2011
 avloclor/paludrine

avloclor/paludrine by hockadilly, on Flickr

Drug resistance to malaria is a huge deal. The battle to stay ahead of the parasite has been fought for decades. But how does drug resistance arise? What can be done to prevent it? We sent Benjamin Thompson to find out…

Each time a new drug has been introduced to combat malaria, the parasite that causes the disease has quickly become resistant. Fun fact: the drug resistant strains of the parasites all came from the same place – the Cambodia/Thailand border. What is it about the environment there that aids the evolution of drug resistance? What can be done about it?

The first Packed Lunch event of May saw Dr Shunmay Yeung, Clinical Senior Lecturer at the London School of Hygiene and Tropical Medicine, discuss this topic and explain the challenges of undertaking malaria research in Cambodia.

The talk began with Dr Yeung describing her travels by boat, foot and ox-cart through the jungles of Cambodia, visiting remote villages to find out what people did when they caught malaria. What treatment did they seek? What drugs did they buy? How much did they cost?

This work was undertaken to get a snapshot of what is actually occurring in Cambodia. We learnt that anti-malarial drugs are freely available in local shops. Current research is trying to find out what these drugs contain, very important to stem the tide of resistance.

Dr Yeung’s study used a ‘mystery shopper’ approach, where research staff went into shops and clinics pretending to have malaria, to discover whether they were offered a diagnosis and what drugs they were given. Generally shopkeepers and medical professionals all claim to offer the correct treatment, although the reality is often very different.

The talk moved onto the biology of malaria (helpfully illustrated in this Wellcome Trust animation). This disease remains one of the world’s biggest killers and is in the top three causes of death for children in sub-Saharan Africa.

It turns out that malaria can be caused by four separate parasites. Plasmodium falciparum causes the most severe form of the disease and is the most common strain found in Africa. In Asia both P. falciparum and P. vivax are prevalent. P. vivax has an extra developmental stage that allows it to lie dormant in the liver for months before going on to infect red blood cells.

But why study malaria in Cambodia specifically? Dr Yeung explained that the P. falciparum strain of malaria found in the region of the Cambodian/Thai border has always been quick to develop drug resistance, while African P. falciparum is still relatively drug sensitive.

By studying the way people take anti-malarial drugs we can better understand what causes resistance to develop. Often in Cambodia people only take a single anti-malarial drug when they become ill – not finishing the course of treatment. This can easily lead to drug resistance occurring. To combat this, people need to take a decent dose of a drug for long enough – ideally in combination with other drugs.

Malaria is not a health priority in Cambodia: it doesn’t really affect those that live in cities, only those that live in remote areas – disproportionately affecting the poorest people. Globally, however, Cambodian malaria is a huge problem. Already strains of the disease have been discovered with tolerance to artemisinins, fantastic drugs that have only been used for a decade or so.

Artemisinin combination therapy (ACT) should be the weapon of choice against the malaria for the foreseeable future – if resistance develops and spreads, there are very few new compounds in the drug development pipeline, and those do exist are years away from clinical use.

The reasons for this enhanced ability for Asian P. falciparum drug resistance are being intensely studied. Some believe that resistance occurs in this region first is a self-fulfilling prophecy. In the 1950s, the drug chloroquine was added to salt in an early example of a mass drug administration (MDA).

People eating the salt consumed a low-level of the drug with the aim of killing all the parasites and breaking the human-parasite-mosquito cycle. Sadly all this did was create an evolutionary pressure that selected for parasites resistant to chloroquine. New drugs had to be used to kill the chloroquine resistant strain, which of course had more time to develop resistance to the new drugs, meaning that yet again they were the first to develop resistance to the new drugs.

Benjamin Thompson is a writer at the Wellcome Trust.