Paper Info
Title
Assessing the public health impact of tolerance-based therapies with mathematical models.
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.
Year
DOI
Venue
2018
10.1371/journal.pcbi.1006119
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Public health,Population,Disease,Biology,Plant disease resistance,Epidemiology,Conventional treatment,Bioinformatics,Pathogen
Journal
14
Issue
ISSN
Citations 
5
1553-734X
0
PageRank 
References 
Authors
0.34
1
3
Name
Order
Citations
PageRank
N. Hoze100.68
Sebastian Bonhoeffer22911.99
Roland R. Regoes3197.11