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How does genetic diversity within infections impact on disease severity and infectiousness?
In our rodent model, aggregate (total) virulence is a function of the virulence of constituent clones. In mixed infections of clones with similar or with very different virulence, total virulence was maximal when genetic diversity in the inoculum was highest. This may reflect the costs of fighting a more diverse infection. However, at some inoculum frequencies, avirulent clones in an infection can reduce the virulence of virulent clones. Thus, depending on how mixed infections arise, host health can be enhanced or reduced. Intervention measures that reduce rates of superinfection could thus impact on virulence evolution in a manner analogous to vaccination. Using quantitative PCR, we are tracking clones differing in virulence to determine how their frequencies in mixed infections act to generate aggregate virulence.
Are genetically diverse infections more infectious? They could be more infectious, if more diverse infections produce more transmission stages. Clones can transmit as well or better from mixed-clone infections than from single infections (Taylor et al. 1997, Read and Taylor 2001). Thus, in-host competition can have no effect on parasite fitness or, paradoxically, enhance it. This unexpected finding is opposite to that assumed by virulence theory. However, these data concern two clones of similar virulence, and while we have seen the same phenomenon in other two-clone infections, we failed to find it in a single experiment with three clones. We need to see how general the phenomenon is and, importantly, how the in-host competitive ability of individual clones relates to their (i) virulence, and (ii) transmission (between host fitness). These relationships are central for understanding how in-host diversity affects virulence evolution, yet the few data we have on them in any disease system often contradict existing theory
Group members involved: Andy Bell
Collaborators: Richard
Carter, Joanne Thompson, Hamza
Babiker