Running to stand still

SagradaWhat is a picture of Barcelona’s La Sagrada Familia doing on the BUG blog? I recently joined a BBSRC funded workshop in Barcelona organised by Silvie Huijben (Institute for Global Health, Barcelona) and Paul Neve (Rothamsted Research Institute). The workshop was entitled ‘Running to stand still: evolution and management of drug and pesticide resistance in healthcare and agriculture’ and brought together a range of clinical, experimental and theoretical scientists all working on drug resistance in diverse systems, including malaria, bacteria, fungi, crop pests, mosquitoes, herbicides, cancer and, of course, helminths. Our aim was to discuss common principles and approaches to tackling drug resistance from a more evolutionary standpoint. It was a fantastic opportunity to explore the topic in a relaxed environment.

The meeting began with a number of overview talks that summarized the state of play in the different disciplines. The similarity in the questions we all ask was striking; however, as the meeting progressed it was clear that while the questions may be similar, the approaches that are possible are different. Some fields are much more advanced than others, but in many cases the data do not exist to establish directly whether a high dose or low dose of drug gives the best outcome for the patient/animal/crop or field. Similarly, while combination therapies are the ‘norm’ in some areas, for the helminths, the small range of drug classes available for use imposes limitations on this approach. For an experimental scientist, it was very interesting to listen to talks on theoretical approaches to drug resistance and it reinforced the importance of having mathematical modellers involved in our more experimental projects.

For BUG, it was a useful experience to interact with such a diverse range of scientists and to think about the problem of anthelmintic resistance from a more evolutionary standpoint. Major questions remain like how to apply evolutionary principles to new drug design, what can we learn from scenarios where resistance has not evolved despite the use of a specific drug over an extended period of time? There are some good examples of this, e.g. Plasmodium vivax malaria and chloroquine in India, Candida albicans and amphotericin B. Other important topics discussed were the exploitation of fitness costs and the design of treatments using ‘evolutionary traps’. Several speakers highlighted the ecological impact of resistance; e.g. in anti-microbial resistance what is the effect on the microbiome of treatment, and, on a larger scale, the effect on the ecosystem? This is an important area in anthelmintic research where livestock frequently harbour multiple species with varying resistance profiles to any one drug. Application of novel approaches such as the ‘Nemabiome’ based on analysis of ITS-2 sequences or multiplexing PCR methods will help inform the outcome of differential responsiveness to drugs. Another area of interest that is often overlooked in discussions of drug resistance is the impact of the immune response; an effective immune response is often critical for removal of an infectious agent, how is that integrated with drug treatment and how does resistance impact the ability to clear infection? Is there a role for suboptimal vaccines in combination with drug therapy?

The meeting reinforced my view that while we know a lot about some aspects of anthelmintic resistance, there is still much to be learned and that there are overlaps with other fields that could be better exploited. Meetings such as this are incredibly valuable for breaking down the taxonomic partitioning that inevitably happen, where we each know a lot about our own areas, but not so much about other areas. On this basis, we are organising a ‘Resistance Day’ here in Glasgow, to bring together researchers working on drug resistance in helminths, protozoa, bacteria, fungi, viruses, and arthropods.

I will shortly leave for India where I will be attending another drug resistance discussion meeting in Bangalore and then off to Lucknow for a meeting at the Central Drug Research Institute on Current Trends in Drug Discovery and Research. Look out for more information!


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