Abstract
Disease tolerance is a defense strategy against infections that aims at maintaining host health even at high pathogen replication or load. Tolerance mechanisms are currently intensively studied with the long-term goal of exploiting them therapeutically. Because tolerance-based treatment imposes less selective pressure on the pathogen it has been hypothesised to be “evolution-proof”. However, the primary public health goal is to reduce the incidence and mortality associated with a disease. From this perspective, tolerance-based treatment bears the risk of increasing the prevalence of the disease, which may lead to increased mortality. We assessed the promise of tolerance-based treatment strategies using mathematical models. Conventional treatment was implemented as an increased recovery rate, while tolerance-based treatment was assumed to reduce the disease-related mortality of infected hosts without affecting recovery. We investigated the endemic phase of two types of infections: acute and chronic. Additionally, we considered the effect of pathogen resistance against conventional treatment. We show that, for low coverage of tolerance-based treatment, chronic infections can cause even more deaths than without treatment. Overall, we found that conventional treatment always outperforms tolerance-based treatment, even when we allow the emergence of pathogen resistance. Our results cast doubt on the potential benefit of tolerance-based over conventional treatment. Any clinical application of tolerance-based treatment of infectious diseases has to consider the associated detrimental epidemiological feedback.
Highlights
Hosts can respond to infections in various ways
Alternative therapies that exploit host tolerance mechanisms have received attention from the medical community as a promising strategy. These treatments aim at reducing the level of illness due to the infection, rather than eliminating the pathogen directly. We show that these treatments are beneficial at the individual level, they can have undesired public health consequences
Disease tolerance has received attention as a host strategy that has an impact on the evolutionary dynamics of host-pathogen systems very different to that of host resistance [1,2,3]
Summary
The host can reduce the pathogen replication or load and improve its health. In evolutionary ecology, such a response is called “host resistance”. Another possible host response is “disease tolerance”, that induces a state, in which the host, at a given pathogen load, suffers less from the negative consequences of being infected. In a first scenario, when resistance is cost-free, resistance genes are predicted to fix in the population [4, 5] Another possibility, if the pathogen population is not cleared fast enough, or if there is cost of resistance, is that resistance and susceptible genes will coexist in the host population [6,7,8]
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