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Eradicating malaria: the evolution problem

Posted by on October 1, 2014

TonyHolderDr Tony Holder is Head of the Division of Parasitology at the MRC-National Institute for Medical Research, and has worked on malaria for nearly 35 years. He will be speaking at the Biology Week Debate: ‘Malaria eradication – Can we do it? Should we do it?’ at the Royal Institution on Thursday 16th October.

There are many ways to try and combat malaria, and passionate arguments still rage around the pros and cons of targeting the mosquitoes that spread the malaria parasite, providing widespread and rapid access to drugs to treat the disease, or developing vaccines.

Better housing and environmental improvements would also contribute to improving the lot of millions living in some of the poorest parts of the world where malaria is endemic. Indeed many of the arguments around control, as well as elimination and eventual eradication of malaria have a large political and economic component and will be shaped by human resourcefulness and frailty.

Malaria eradication requires a shift beyond efforts to control the disease. However we don’t currently have an effective vaccine, and the development of parasite resistance to antimalarial drugs and of mosquito resistance to insecticides will challenge both control programmes and further elimination efforts.

Insecticides provide selection on the mosquito. Therapeutic intervention, whether by drug treatment or vaccination provides selection on the parasite; and from a biological perspective one key issue is evolution.

If we focus our attention on the parasite, mutations in genes that are beneficial may rapidly accumulate in the population. The accumulation of beneficial mutations under selection will depend on the mutation rate, the number of parasites in the world, transmission efficiency and geographic isolation.

As we develop vaccines or deploy new drugs we apply selection on the parasites in our bodies.  Vaccines aim to pre-arm the immune system to give an advantage to the human host over the parasite; but as the host’s immune system has evolved sophisticated ways to combat the pathogen so the parasite has evolved sophisticated ways to evade these systems.

Successful vaccines will introduce a strong selection and new mutations or epigenetic mechanisms in the parasite will result. It is well known, both experimentally and in the field that some drugs will very rapidly select resistant parasites, and this is a real danger with monotherapy – the use of a single drug.

Selection of resistant parasites can be mitigated against by combinations of drugs that work through different mechanisms because, simplistically, the evolution of two beneficial mutations at once has a much lower probability.

Successful intervention will reduce the number of parasites, reducing the opportunity for parasite evolution to occur, but at the same time will provide a powerful selection on the parasite genome.

As we develop vaccines or new drugs, strategies to deploy them and maintain their effectiveness over long periods will have to recognise the confounding impact of parasite evolution.

Places are still available for the Biology Week Debate: ‘Malaria eradication – Can we do it? Should we do it?’ at the Royal Institution on Thursday 16th October.
Read what fellow speaker Professor Robert Sinden has to say: Malaria control drains financial and human resources.

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