Biology subjects

Alizon, S.

Publications and source records attributed to Alizon, S..

6 recordsLinked to original sources

bioRxiv2018

Modelling coinfections to detect within-host interactions from genotype combination prevalences

Parasite genetic diversity can provide information on disease transmission dynamics but most methods ignore the exact combinations of genotypes in infections. We introduce and validate a new method that combines explicit epidemiological modelling of coinfections and regression Approximate Bayesian Computing (ABC) to detect within-host interactions. Using genital infections by different types of Human Papillomaviruses (HPVs) as a test case, we show that, if sufficiently strong, within-host parasite interactions can be detected from epidemiological data and that this detection is robust even in the face of host heterogeneity in behaviour. These results suggest that the combination of mathematical modelling and sophisticated inference techniques is promising to extract additional epidemiological information from existing datasets.

epidemiology↗

bioRxiv2018

Why multiple infections favour virulent parasites

It is now a fact that several strains/species (hereafter types) of parasites circulate in natural host populations. Parasite polymorphism can even occur within the same host, where distinct parasite types can interact in various ways. This can affect their transmission and, therefore, their evolution. We still lack general predictions regarding the evolution, in such multiple infection contexts, of virulence - the infection-induced host mortality, essentially because its emanation from within-host growth was often ignored so far. Here, we explicitly investigate within-host interactions, within-host competition outcomes, epidemiological dynamics and evolutionary invasibility using a formalism as general as possible. Focusing on chronic dimorphic infections caused by horizontally-transmitted microparasites, we apply both dynamical systems and probabilistic approaches to this bottom-up sequence of dynamics to explore the evolutionary outcomes. We show that within-host growth traits are under strong selective pressure and when small mutations affect them, most of the surviving mutants are more virulent than their resident. We thus identify a robust and unavoidable selection bias towards higher virulence.

evolutionary biology↗

bioRxiv2017

Epithelial stratification shapes infection dynamics

Infections of stratified epithelia collectively represent a large burden on global health. Experimental models provide a means to understand how the cell dynamics themselves influence the outcomes of these infections. Mathematical approaches are needed to improve quantification and theoretical advancement of these complex systems. Here, we develop a general ecology-inspired model for stratified epithelial dynamics, which allows us to simulate infections and to estimate parameters that are difficult to measure with organotypic cell cultures. To explore how epithelial cell dynamics affect infection dynamics, we focus on two contrasting pathogens of the cervicovaginal epithelium: Chlamydia trachomatis and Human papillomaviruses. We find that key infection symptoms stem from differential interactions with the layers, while clearance and pathogen burden are bottom-up processes. Cell protective responses to infections (e.g. increased cell proliferation) generally lowered pathogen load but there were specific effects based on infection strategies. These generic responses by the epithelium, then, will have varying results depending on the pathogens infection strategy. Our modeling approach opens new perspectives for 3D tissue culture experimental systems of infections and, more generally, for developing and testing hypotheses related to infections of stratified epithelia.

systems biology↗

bioRxiv2017

Co-evolution of virulence and immunosuppression through multiple infections

Many components of host-parasite interactions have been shown to affect the way virulence (i.e., parasite-induced harm to the host) evolves. However, coevolution of multiple parasite traits is often neglected. We explore how an immunosuppressive mechanism of parasites affects and co-evolves with virulence through multiple infections. Applying the adaptive dynamics framework to epidemiological models with coinfection, we show that immunosuppression is a double-edged-sword for the evolution of virulence. On one hand, it amplifies the adaptive benefit of virulence by increasing the abundance of coinfections through epidemiological feedbacks. On the other hand, immunosuppression hinders host recovery, prolonging the duration of infection and elevating the cost of killing the host. The balance between the cost and benefit of immunosuppression varies across different background mortality rates of hosts. In addition, we find that immunosuppression evolution is influenced considerably by the precise trade-off shape determining the effect of immunosuppression on host recovery and susceptibility to further infection. These results demonstrate that the evolution of virulence is shaped by immunosuppression while highlighting that the evolution of immune evasion mechanisms deserves further research attention.

evolutionary biology↗

bioRxiv2017

The underestimated importance of acute infections by human papillomaviruses

Most infections by human papillomaviruses (HPVs) are acute, that is non-persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms. From a dynamical perspective, adopting concepts from spatial ecology, such as meta-populations or meta-communities, can help explain why HPV acute infections sometimes last for years. Furthermore, cervical cancer screening and vaccines impose novel iatrogenic pressures on HPVs, implying that anticipating any viral evolutionary response remain essential. Finally, hints at the associations between HPV acute infections and fertility deserve further investigation given their high worldwide prevalence. Overall, understanding asymptomatic and benign infections may be instrumental in reducing HPV virulence.

epidemiology↗

bioRxiv2017

Can Ebola Virus evolve to be less virulent in humans?

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology ( ). Understanding Ebola Virus (EBOV) virulence evolution is not only timely but also raises specific questions because it causes one of the most virulent human infections and it is capable of transmission after the death of its host. Using a compartmental epidemiological model that captures three transmission routes (by regular contact, via dead bodies and by sexual contact), we infer the evolutionary dynamics of case fatality ratio (CFR) on the scale of an outbreak and on the long term. Our major finding is that the viruss specific life cycle imposes selection for high levels of virulence and that this pattern is robust to parameter variations in biological ranges. In addition to shedding a new light on the ultimate causes of EBOVs high virulence, these results generate testable predictions and contribute to informing public health policies. In particular, burial management stands out as the most appropriate intervention since it decreases the R0 of the epidemics, while imposing selection for less virulent strains.\n\nImpact SummaryThe severe haemorrhagic fever caused by Ebola Virus (EBOV) usually kills more than one infected individual out of two in the absence of treatment, which makes this pathogen one of the most virulent known to humans. The recent outbreak in West Africa (2013-2016) revealed that the virus is able to spread and persist for months across countries. It is often thought that virulence could be due to the fact that the virus is adapted to its reservoir host. Given that microbes evolve rapidly, it is important to determine whether EBOV virulence is likely to decrease as the virus adapts to its human host. To address this problem, we developed a novel mathematical model tailored to EBOVs life cycle, notably by capturing its three main transmission routes (by regular contact, sexual contact and via dead bodies). We investigated the evolutionary trends of EBOVs virulence on different time scales (outbreak initiation, short term and long term). Our results reveal that the virulence of EBOV might not be due to the maladaptation of the virus, but could rather originate from its unique life cycle. These results are robust to the parameter values chosen. From a public health perspective, burial management stands out as the main leverage to fight the virulence of EBOV, both on the short and long terms.

evolutionary biology↗