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Regular subculture on a similar kind of medium at 3- to 4-week intervals, coupled with this approach, increased the multiplication rate by 8- to 10-fold (Fig. 1D).
When hyperparasitaemia is created by an increase in the parasite multiplication rate, the probability of resistance emergence does not differ from nonhyperparasitaemia (Pb = 9.60 × 10−7) as increasing the multiplication rate causes an increase in both the sensitive and resistant parasites equally.
Hyperparasitaemia in the blood-stage model is established through either an increase in the per-generation multiplication rate from 10to1313 or an increase in the initial number of parasites entering the blood stage from 10 to 10. Figure 3 shows the effect of hyperparasitaemia on the probability of resistance emerging when the resistance to the partner drug is present (Pb = 4.84 × 10−6).
While the herder is doing worse, on the scale of population multiplication rate, the herd still increases and performance is better on the scale of absolute herd size.
The reduction in multiplication rate leads to a slow increase or even a decrease in the parasite population, equally for sensitive and resistant parasites.
We also modelled two possible alternative causes: (i) a large number of parasites released from the liver or (ii) more rapid increase of parasites over the erythrocytic cycles (high multiplication rate).
In the avalanche mechanism, this would need an avalanche path of 7L, corresponding to a multiplication rate of exp 7) ≈ 103.
For instance, using two strains that differ in virulence and multiplication rate.
The results of the evolution experiments with mixed infections indicate a rapid switch in population composition where the genotype with higher multiplication rate and hypovirulent outcompetes the hypervirulent one but with lower multiplication rate.
Total cell numbers were divided by the total cell number 24 hours earlier to give the multiplication rate.
The morphology of the parasites as well as the multiplication rate were determined by light microscopy after Giemsa staining.
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