Biology subjects

Hernandez-Vargas, E. A.

Publications and source records attributed to Hernandez-Vargas, E. A..

3 recordsLinked to original sources

bioRxiv2018

The trichotomy of pneumococcal infection outcomes

The successful elimination of bacteria such as Streptococcus pneumoniae from a host involves the coordination between different parts of the immune system. Previous studies have explored the effects of the initial pneumococcal load (bacterial dose) on different representations of innate immunity, finding that pathogenic outcomes can vary with the size of the bacterial dose. However, others yield support to the notion of dose-independent factors contributing to bacterial clearance. In this paper, we seek to provide a deeper understanding of the immune responses associated to the pneumococcus. To this end, we formulate a model that realizes an abstraction of the innate-regulatory immune host response. Stability and bifurcation analyses of the model reveal the following trichotomy of pneumococcal outcomes determined by the bifurcation parameters: (i) dose-independent clearance; (ii) dose-independent persistence; and (iii) dose-limited clearance. Bistability, where the bacteria-free equilibrium co-stabilizes with the most substantial steady-state bacterial load is the specific result behind dose-limited clearance. The trichotomy of pneumococcal outcomes here described integrates all previously observed bacterial fates into a unified framework.

microbiology↗

bioRxiv2017

Multiscale Model Within-host and Between-host for Viral Infectious Diseases

Multiscale models possess the potential to uncover new insights into infectious diseases. Here, a rigorous stability analysis of a multiscale model within-host and between-host is presented. The within-host model describes virus replication and the respective immune response while disease transmission is represented by a simple susceptible-infected (SI) model.\n\nThe bridge of within-to between-host is by considering transmission as a function of the viral load of the within-host level. Consequently, stability and bifurcation analyses were developed coupling the two basic reproduction numbers [Formula] and [Formula]for the within- and the between-host subsystems, respectively. Local stability results for each subsystem, such as a unique stable equilibrium point, recapitulate classical approaches to infection and epidemic control.\n\nUsing a Lyapunov function, global stability of the between-host system was obtained. A main result was the derivation of the [Formula] as a general increasing function of [Formula]. Numerical analyses reveal that a Michaelis-Menten form based on the virus is more likely to recapitulate the behavior between the scales than a form directly proportional to the virus. Our work contributes basic understandings of the two models and casts light on the potential effects of the coupling function on linking the two scales.

epidemiology↗

bioRxiv2017

Multiscale Modeling To Explore Ebola Vaccination Strategies

BackgroundTransmission in epidemics of infectious diseases is characterized by a high level of subject-specific elements. These include heterogeneous infection conditions, time-dependent transmission potential, and age-dependent contact structure. These insights are often lost in epidemic models using population data. Here we submit an approach that can capture these details, paving the way for studying epidemics in a more mechanistic and realistic way.\n\nMethodsUsing experimental data, we formulated mathematical models of a pathogen infection dynamics from which we can simulate its transmission potential mechanistically. The models were then embedded in our implement of an age-specific contact network structure that allows to express all elements relevant to the transmission process. This approach is illustrated here with an example of Ebola virus (EBOV).\n\nResultsThe results showed that within-host infection dynamics can capture EBOVs transmission parameters as good as approaches using population data. Population age-structure, contact distribution and patterns can also be captured with our network generating algorithm. This framework opens vast opportunities for the investigations of each element involved in the epidemic process. Here, estimating EBOVs reproduction number revealed a heterogeneous pattern among age-groups, prompting questions on current estimates which are not adjusted for this factor. Assessments of mass vaccination strategies showed that a time window from five months before to one week after the start of an epidemic appeared to be effective. Noticeably, compared to a non-intervention scenario, a low vaccination coverage of 33% could reduce number of cases by ten to hundred times as well as lessen the case-fatality rate.\n\nConclusionsThis is the first effort coupling directly within-host infection model into an age-structured epidemic network model, adding more realistic elements in simulating epidemic processes. Experimental data at the within-host infection are shown able to capture upfront key parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. Population of interest in epidemic assessments could be modeled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios are underway to explore multilevel aspects in infectious diseases epidemics.

epidemiology↗