Evolutionary responses to medicines

We use experiments and collaborations with theoreticians to investigate evolutionary responses to treatments designed to prevent parasite proliferation in the host or block transmission to the vector. Interventions change the environment for parasites and can affect optimal life-history strategies. This selects for an evolutionary (genetic change) or facultative (plastic adjustment of behvaviours during infection) response.

Gametocyte investment

Adjusting reproductive effort is another way that parasites can use safety in numbers to protect themselves from drugs. By reducing investment into sexual stages (gametocytes), parasites maximise the benefits of “safety in numbers”. 

P. chabaudi gametocytes and asexuals. (Photo credit: Sarah Reece) 

Gametocyte sex ratio

We have also investigated parasite responses to interventions designed to block transmission by interfering with parasite mating in a sex-specific way. In this case, parasites can adjust their investment in male versus female sexual stages (sex ratio) to partially restore fertility. However, damaging male or female stages in such a way as to allow mating, but preventing offspring development, is possible and “evolution proof” with respect to parasite reproductive strategies. 

Virulence evolution

When drug treatment fails to clear all parasites from infections (suboptimal treatment), parasite fitness is maximised at higher levels of harm to the host and more virulent parasites are favoured by natural selection. Thus, more virulent parasites are favoured by natural selection.

 


  (credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

(credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

What next?

Current work focuses on how plasticity in sexual stage investment interacts with the evolution of other forms of drug resistance and its epidemiological consequences. Understanding how virulence and ultimately, transmission success of parasites is shaped by human-induced selection pressures is important for the development of disease control policies.