The effect of parasite dose on disease severity in the rodent malaria Plasmodium chabaudi

Experiments were designed to look at the relationship between infective
dose and disease severity using two clones of Plasmodium chabaudi
that differ in virulence. We asked whether there were dose–severity
relationships, whether clone differences in virulence were maintained over
a range of doses, and whether disease severity could be accounted for by
parasite dynamics. Groups of mice were infected with parasite doses
differing by an order of magnitude, ranging from 100 to 1×108 parasites.
Infective dose affected the probability of death, but only with the more
virulent clone. Dose also affected morbidity. For both clones, higher
doses induced greater anaemia. Larger doses caused greater weight loss,
but only for infections with the more virulent clone. Here, for a given
dose, mice lost a fixed amount of weight, irrespective of their initial
weight. Larger doses induced earlier mortality and morbidity than did
lower dose treatments. Finally, dose affected parasite dynamics, with
earlier and higher peak parasite densities in larger dose infections. All
these effects were small relative to clone differences in disease
severity, which were apparent across the range of doses. Dose effects were
manifested through the timing and/or magnitude of peak parasite densities,
broadly supporting the idea that dose affects disease severity by altering
the time the host has to control parasite densities and ameliorate the
effects of parasites. We discuss the possible efficacy of intervention
strategies aimed at reducing human disease severity by reducing infective
parasite dose.