Unveiling Time in Dose-Response Models to Infer Host Susceptibility to Pathogens

Abstract

The biological effects of interventions to control infectious diseases typically depend on the intensity of pathogen challenge. As much as the levels of natural pathogen circulation vary over time and geographical location, the development of invariant efficacy measures is of major importance, even if only indirectly inferrable. Here a method is introduced to assess host susceptibility to pathogens, and applied to a detailed dataset generated by challenging groups of insect hosts (Drosophila melanogaster) with a range of pathogen (Drosophila C Virus) doses and recording survival over time. The experiment was replicated for flies carrying the Wolbachia symbiont, which is known to reduce host susceptibility to viral infections. The entire dataset is fitted by a novel quantitative framework that significantly extends classical methods for microbial risk assessment and provides accurate distributions of symbiont-induced protection. More generally, our data-driven modeling procedure provides novel insights for study design and analyses to assess interventions.

Host Responses to Pathogen Priming in a Natural Songbird Host

“…Exposure level to a pathogen has been shown to alter infectivity, disease progression, and an individual's susceptibility to reinfection across systems (e.g., McElroy et al 1997; Timms et al 2001; Spekreijse et al 2010; Banyard et al 2014; Song et al 2015). Thus, understanding how exposure level mediates host responses can be critical for predicting population-level disease dynamics (Ben-Ami et al 2010; Tidbury et al 2012; Best et al 2012; Pessoa et al 2014). …”

Reticulate Evolution

“…Despite the vast theoretical work developed around a single symbiont, and most notably one particular reproduction manipulation phenotype out of the many observed, obtaining estimates for all known relevant parameters is not trivial, and more elaborate frameworks may be necessary to estimate some of them (Pessoa et al 2014), or quantify environmental effects such as pathogen burden, which is likely to depend on a multitude of microbial species (Calzolari et al 2012). Furthermore, the models discussed so far concern only evolution of the host insofar as there is selection to carry or not carry the symbiont-i.e., the symbiont is a fixed set of genes inherited separately from host nuclear genes, and it may be or not be advantageous to have those genes.…”

“…This could also be achieved with a DENV-blocking strain with high protection (measuring absolute protection is tricky, but see Gomes et al 2014;Pessoa et al 2014). This could also be achieved with a DENV-blocking strain with high protection (measuring absolute protection is tricky, but see Gomes et al 2014;Pessoa et al 2014).…”

Host–Symbiont–Pathogen–Host Interactions: Wolbachia, Vector-Transmitted Human Pathogens, and the Importance of Quantitative Models of Multipartite Coevolution

“…This could also be achieved with a DENV-blocking strain with high protection (measuring absolute protection is tricky, but see Gomes et al 2014;Pessoa et al 2014). If no evolution was expected, continuous DENV transmission could be eliminated in areas where A. aegypti is the only or main vector, which is the case in urban areas; because the wMel-Aedes association is not a natural, and therefore unlikely to be an evolutionary stable one, there is a reason to expect immediate response of the host, if it is evolutionarily perceived as an aggression and if there is variation in the population that can be selected to counter these effects.…”

“…Therefore, unlike some early results suggested, not all costs affect invasion in the same way; ecology and age structure affect establishment of Wolbachia; and spatial spread does not follow trivially from local invasion. Despite the vast theoretical work developed around a single symbiont, and most notably one particular reproduction manipulation phenotype out of the many observed, obtaining estimates for all known relevant parameters is not trivial, and more elaborate frameworks may be necessary to estimate some of them (Pessoa et al 2014), or quantify environmental effects such as pathogen burden, which is likely to depend on a multitude of microbial species (Calzolari et al 2012). Furthermore, the models discussed so far concern only evolution of the host insofar as there is selection to carry or not carry the symbiont-i.e., the symbiont is a fixed set of genes inherited separately from host nuclear genes, and it may be or not be advantageous to have those genes.…”