Biology subjects

Dukic, V.

Publications and source records attributed to Dukic, V..

3 recordsLinked to original sources

bioRxiv2018

Using biological control data to understand host-pathogen dynamics

A key assumption of models of infectious disease is that population-scale spread is driven by transmission between host individuals at small scales. This assumption, however, is rarely tested, likely because observing disease transmission between host individuals is non-trivial in many infectious diseases. Quantifying the transmission of insect baculoviruses at a small scale is in contrast straightforward. We fit a disease model to data from baculovirus epizootics (= epidemics in animals) at the scale of whole forests, while using prior parameter distributions constructed from branch-scale experiments. Our experimentally-constrained model fits the large-scale data very well, supporting the role of small-scale transmission mechanisms in baculovirus epizootics. We further compared our experimentally-based model to an unconstrained model that ignores our experimental data, serving as a proxy for models that include large-scale mechanisms. This analysis supports our hypothesis that small-scale mechanisms are important, especially individual variability in host susceptibility to the virus. Comparison of transmission rates in the two models, however, suggests that large-scale mechanisms increase transmission compared to our experimental estimates. Our study shows that small-scale and large-scale mechanisms drive forest-wide epizootics of baculoviruses, and that synthesizing mathematical models with data collected across scales is key to understanding the spread of infectious disease.

ecology↗

bioRxiv2017

Recurring infection with ecologically distinct human papillomavirus (HPV) types explains high prevalence and diversity

The high prevalence of human papillomavirus (HPV), the most common sexually transmitted infection, arises from the coexistence of over 200 genetically distinct types. Accurately predicting the impact of vaccines that target multiple types requires understanding the factors that determine HPV diversity. The diversity of many pathogens is driven by type-specific or \"homologous\" immunity, which promotes the spread of variants to which hosts have little immunity. To test for homologous immunity and to identify mechanisms determining HPV transmission, we fitted nonlinear mechanistic models to longitudinal data on genital infections in unvaccinated men. Our results provide no evidence for homologous immunity, instead showing that infection with one HPV type strongly increases the risk of infection with that type for years afterwards. For HPV16, the type responsible for most HPV-related cancers, an initial infection increases the one-year probability of reinfection by 20-fold, and the probability of reinfection remains 14-fold higher two years later. This increased risk occurs in both sexually active and celibate men, suggesting that it arises from auto-inoculation, episodic reactivation of latent virus, or both. Overall our results show that high HPV prevalence and diversity can be explained by a combination of a lack of homologous immunity, frequent reinfections, weak competition between types, and variation in type fitness between host subpopulations. Due to the high risk of reinfection, vaccinating boys that have not yet been exposed may be crucial to reduce prevalence, but our results suggest that there may also be large benefits from vaccinating previously infected individuals.

epidemiology↗

bioRxiv2016

Eco-evolutionary theory and insect outbreaks

Eco-evolutionary theory argues that population cycles in consumer-resource interactions are partly driven by natural selection, such that changes in densities and changes in trait values are mutually reinforcing. Evidence that this theory explains cycles in nature, however, is almost nonexistent. Experimental tests of model predictions are almost always impossible because of the long time scales over which cycles occur, but for most organisms, even tests of model assumptions are logistically impractical. For insect baculoviruses in contrast, tests of model assumptions are straightforward, and baculoviruses often drive outbreaks of forest-defoliating insects, as in the gypsy moth that we study here. We therefore used field experiments with the gypsy moth baculovirus to test two key assumptions of eco-evolutionary models of host-pathogen population cycles, that reduced host infection risk is heritable and costly. Our experiments confirm the two assumptions, and inserting parameters estimated from our data into the models gives cycles closely resembling gypsy moth outbreak cycles in North America, whereas standard models predict unrealistic stable equilibria. Our work shows that eco-evolutionary models are useful for explaining outbreaks of forest insect defoliators, while widespread observations of intense selection imposed by natural enemies on defoliators, and frequent laboratory observations of heritable and costly resistance in defoliators, suggest that eco-evolutionary dynamics may play a general role in defoliator outbreaks.

ecology↗