Strategies to combat future emergence and spread of antimalarial drug resistance

Drug resistance has been a major problem in the treatment of malaria, with poor drugs leading to an increase in the number of people dying from the disease across the developing world.

Understanding how drug resistance develops and spreads, and preventing it, is essential to protect current drugs and prevent deaths and disease in the future.

Cally Roper, senior lecturer at the School, has led research into the origins of drug resistance mutations in African Plasmodium falciparum malaria, identifying mutations with a common ancestral origin though DNA matches.

She applied this in population surveys in South and East Africa in partnership with the Tanzanian National Institute of Medical Research and the South African Medical Research Council. These surveys showed that point mutations in a gene conferring pyrimethamine resistance and another conferring sulphadoxine resistance were derived from the same few ancestral lineages. These findings overturned the widely held view that such mutations arise at the individual level.

Comparisons of African and South East Asian parasites, undertaken in collaboration with research groups in Thailand and the United States, showed that the highly pyrimethamine-resistant strain of the disease in Africa was derived from an Asian ancestor.

The earlier work on gene mutations in Tanzania and South Africa was expanded to include 20 African countries and maps of the pattern of resistance showed that there was infrequent emergence of new resistant mutations and a large-scale pattern of regional dispersal.

Roper was asked to the serve on a World Health Organization (WHO) committee monitoring sulphadoxine-pyrimethamine resistance which produced recommendations informing WHO policy on the use of the drug in preventive therapy for infants.

Roper’s work on the spread of resistance has underpinned the urgent response to the rise in drug resistance on the Thai-Cambodia border. In 2008, Shunmay Yeung, clinical senior lecturer in health economics and policy at the School, served as temporary adviser at a WHO meeting to formulate a response and served as a co-ordinator of a two-year programme to confirm, characterise and contain the threat of resistance.

Yeung championed the introduction of fixed dose Artemisinin based combination therapy and a ban on the sale of oral artemisinin based monotherapies, which are thought to have contributed to the emergence of drug resistance, in the epicentre of resistance in Cambodia.

This intervention proved effective, and as a consequence, less than 5% of private outlets stocked monotherapies in 2011 compared to around 40% in 2008. There has also been a large reduction in severe malaria in the containment zone, and subsequently, a similar containment programme has also been implemented in Myanmar.