Achievements

Most important

Evolutionary Vaccinology

  • Hypothesis that vaccination can prompt virulence evolution, so as to degrade the public health benefits of vaccines seen in clinical trials and put the unvaccinated at greater risk (Gandon et al. 2001, 2002, 2003,  Mackinnon et al. 2008, Read and Mackinnon 2008).
  • Hypothesis that more virulent strains will be less readily controlled by vaccine-generated immunity, another selective force by which vaccines could drive the evolution of more virulent strains (Mackinnon and Read 2004, Read and Mackinnon 2008)
  • Experimental demonstration that immunity promotes the evolution of more virulent malaria parasites (Mackinnon and Read 2004).
  • Experimental demonstration that bivalent malaria vaccines need not generate better protection than monovalent vaccines (Barclay et al. 2008).

Virulence evolution

  • Characterisation of clonal variation of virulence in a rodent malaria (Mackinnon and Read 1999).
  • Experimental demonstration that virulent malaria strains are more transmissible (Mackinnon and Read 1999, Ferguson et al. 2003).
  • Experimental demonstration that P. chabaudi virulence-transmission relationship are qualitatively similar in immunised and naïve mice (Mackinnon and Read 2003).
  • Demonstration that virulent malaria strains are less rapidly cleared by mice (Mackinnon and Read 2003, 2004)
  • Experimental demonstration that serial passage increases virulence – even when there is extremely strong selection for avirulence (Mackinnon and Read 1999). Thus, there is evidence of factors thought to drive virulence up (within-host competition) but not of factors thought to counter this selection (host death).
  • Experimental demonstration that malaria parasite strains differ in their virulence to mosquitoes (Ferguson and Read 2002, Ferguson et al. 2003).
  • Experimental demonstration that virulence in the vertebrate host is unrelated to virulence in the vector (Ferguson et al. 2003).
  • Experimental demonstration that inoculating dose has an effect on rodent malaria virulence, but that the effect is small compared to intrinsic clone differences in virulence (Timms et al. 2001).
  • Experimental demonstration that more virulent malaria clones outcompete less virulent strains within rodent malaria infections (de Roode et al. 2005, Bell et al. 2006).  This provides a potent selective force favoring more virulent parasites.
  • Demonstration of host*parasite interactions for virulence in the P. chabaudi system, but that these are small enough that main effects selection on virulence can be analysed (Grech et al. 2006)
  • Putting together all the P. chabaudi experimental work gives one of the most complete analyses of the selective tensions that act on the evolution of virulence in any host parasite system (Mackinnon and Read 2004, Mackinnon et al. 2008).

Drug resistance evolution

  • Demonstration that prophylatic chemotherapy leads to competitive release of resistant parasites (de Roode et al. 2004).
  • Demonstration that theraputic chemotherapy leads to competitive release of resistant parasites (Wargo et al. 2007, Huijben et al. 2010).
  • Demonstration that this competitive release is not dependent on genetic diversity in an infection (multiplicity of infection) (Huijben et al. 2011)
  • Evidence that virulent malaria parasites are less sensitive to drugs (Schneider et al. 2008).  This raises the prospect that chemotherapy could select for more resistant parasites.
  • Review of evolutionary fallacies about malaria drug resistance and problems that need evolutionary insight (Read and Huijben 2009).
  • Argument that aggressive chemotherapy is a double-edge sword for resistance management: it reduces the chance that de novo resistance mutations will occur (dead bugs don’t mutate) but maximises the selective advantage of any that are present (Read et al. 2011).
  • Argument (and demonstration) that resistance management should be evidence-based, with contrasting strategies being empirically evaluated for their capacity to improve patient health, reduce infectiousness and reduce transmission of resistant parasites (Read et al. 2011).

Within-host dynamics

  • Demonstration that there is intense competition between clonal lineages of malaria parasites proliferating within a host (Taylor et al. 1997, de Roode et al 2003)
  • Demonstration that competitive ability within a host need not translate in to transmission success: numerically suppressed clones can transmit better than they would have in the absence of competition (Taylor et al. 1997, Taylor and Read 1998).
  • Demonstration that mixed clone infections could be more infectious (Taylor et al. 1997) – though not always (de Roode et al. 2003).
  • Experimental demonstration that mixed clone infections can be virulent (Taylor et al. 1998) – but not always (de Roode et al. 2003).
  • Development of Quantitative PCR methods to determine clone dynamics in mixed clone infections (Cheesman et al. 2003).
  • Experimental demonstration that more virulent malaria clones outcompete less virulent strains within rodent malaria infections (de Roode et al. 2005, Bell et al. 2006).
  • Experimental demonstration that host genotype influences the outcome of within host competition (de Roode et al. 2004).
  • Demonstration that prior residency and initial frequencies affect the outcome of within host competition (de Roode et al. 2005)
  • Hypothesis that competition plays a key role in ensuring that antigenic diversity results in chronic trypanosome infections (Lythgoe et al. 2007)
  • First experimental evidence of immune-mediated competition (Raberg et al. 2006)
  • Demonstration that immune-mediated competition is not CD4+ T cell dependent (Barclay et al. 2008).
  • Demonstration that competition is neither intensified nor weakened in immunized hosts (Grech et al. 2008).
  • Various attempts to build explicit within-host models of rodent malaria dynamics tested against data (Mideo et al. 2008, 2011, Miller et al. 2010)
  • Direct estimation of magnitude of top-down (immune) and bottom-up (resource) regulation of malaria population dynamics in rodent infections (Metcalf et al. 2011).

Public health insecticides

  • Demonstration that entomopathogenic fungi can eliminated 99.9% of malaria transmission – in the lab (Blanford et al. 2005)
  • Hypothesis that late-life acting insecticides could provide evolution-proof malaria control (Read et al. 2009).
  • Question of whether insecticide resistant mosquitoes really are a problem for malaria control (Rivero et al. 2010).
  • Discovery that fungal-infected mosquitoes loose the ability to detect human odors (George et al. 2011) and fail to regain appetite (Blanford et al. 2011). This means fungal biopesticides can block malaria transmission as effectively as a chemical insecticide.

Phenotypic effects of chemotherapy and vaccination on malaria parasites

  • Experimental demonstration that subcurative doses of antimalarial drugs can induce surviving parasites to produce more transmission stages. In our hands, this had the effect of negating any transmission-blocking advantages of chemotherapy
    (Buckling et al. 1997, 1999, Buckling and Read 1999)
  • Experimental demonstration of strain-specific transmission blocking immunity in rodent malaria (Buckling and Read 2001)

Effects of external environment on host-parasite interactions

  • Demonstration that female Daphnia raised in poor condition produce offspring with enhanced resistance (Mitchell and Read 2005). Stressed mothers evidently produce fewer but better provisioned offspring.
  • Demonstration that the virulence of a Daphnia pathogen is hugely temperature-sensitive (Mitchell et al. 2005).
  • Hypothesis that daily temperature fluctuations will greatly impact vectorial capacity of mosquitoes (Paaijmans et al. 2009)
  • Demonstration that daily temperature fluctuations impact capacity of mosquitoes to transmit malaria (Paaijmans et al. 2010)

Worm life histories

  • An adaptive explanation (yet to be falsified) of the apparently pointless and very hazardous migrations under taken through host tissues by nematode worms (Read and Skorping 1995).
  • Hypothesis that chemotherapy could promote life history evolution in parasites, in clinically-beneficial and -harmful ways (Skorping and Read 1998).
  • Experimental demonstration that host immunity affects sexuality in parasitic nematodes (Gemmill et al. 1997, West et al. 2001)
  • Development of optimality models of age to maturity in gastrointestinal nematodes that made successfully predicted the quantitative relationship between life expectancy and prepatent period in gastrointestinal worms (Gemmill et al. 1999, Read et al. 2000). This relationship explains more than half the variance in prepatent period in the GI worms of mammals (which range from a few days to many months), and is one of only a very few quantitatively successful life history models.
  • Experimental demonstration that age to maturity in gastrointestinal worms is determined by host immune status [although to be fair, not in the way we expected it to be!] (Guinnee et al. 2003)
  • Experimental demonstration that host-specificity in a gastrointestinal worm is not mediated by thymus-dependent immunity (Gemmill et al. 2000).
  • Demonstration, using cross species data, that as predicted by population dynamical models, hosts living at higher densities have more macroparasites (Arneberg et al. 1998)
  • Mathematical analyses showing that the direction of selection on nematode age to maturity depends on how mortality rates vary as a function of worm size and developmental status (Lynch et al. 2008).  This means that optimism that health interventions will always prompt the evolution of less clinically damaging worms is premature.
  • Demonstration, that as predicted by our earlier models, nematodes (here filarial worms) detect the presence of host immune effectors which predict life expectancy in a host and modified their age to maturity accordingly (Babayan et al. 2010).

Pathogen sex allocation

  • Quantitative verification of sex allocation theory as applied to pathogens – so far as we know, the first quantitative demonstration that optimality models can make successful predictions in the infectious disease context (Read et al. 1995, West et al. 2000).
  • Extension of sex allocation theory in the malaria context to incorporate wide range of population genetic structures and fertility insurance (Shutler and Read 1998, Nee et al. 2002, West et al. 2002)
  • Extension of sex allocation theory in the malaria context to incorporate wide range of population genetic structures and fertility insurance (Shutler and Read 1998, Nee et al. 2002, West et al. 2002)
  • Determination of the halve lives of male and female gametocytes in P. chabaudi (Reece et al. 2003).

Host defenses

  • Experimental demonstration of strain-specific immunity in invertebrates (Little et al. 2003)
  • Experimental demonstration of genetic variation in tolerance in vertebrates (Råberg et al. 2007).  This paper brought tolerance, a concept long ago developed by plant biologists, to the attention of the much larger animal immunology community.
  • Analysis of the evolutionary paradox that is immunopathology (Graham et al. 2005).
  • Argument that the increasingly mechanistic focus of immunology is blinkering the science to new immune phenomena (Little et al. 2005).
  • Hypothesis that majority of host defenses might be tolerance mechanisms rather than the classical resistance mechanisms studied by immunologists (Read et al. 2008)

Sex

  • The idea of reproductive restraint in malaria parasites (Taylor and Read 1997)
  • The argument that the evolution of sex may well have multiple causes (West, Lively & Read 1999).

Page last updated: Dec 23, 2011