Epidemics

Journal: Epidemics

Publisher

Elsevier

ISSN

1878-0067
1755-4365

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Publications1 - 10 of 23

Erratum to “Virus-induced target cell activation reconciles set-point viral load heritability and within-host evolution” [Epidemics (2013) 174–180]
Hool, Anna; Leventhal, Gabriel E.; Bonhoeffer, Sebastian (2014)
Epidemics
Virus-induced target cell activation reconciles set-point viral load heritability and within-host evolution
Hool, Anna; Leventhal, Gabriel E.; Bonhoeffer, Sebastian (2013)
Epidemics
The asymptomatic phase of HIV-1 infections is characterised by a stable set-point viral load (SPVL) within patients. The SPVL is a strong predictor of disease progression and shows considerable variation of multiple orders of magnitude between patients. Recent studies have found that the SPVL in donor and recipient pairs is strongly correlated indicating that the virus genotype strongly influences viral load. Viral genetic factors that increase both viral load and the replicative capacity of the virus would result in rapid within-host evolution to higher viral loads. Reconciling a stable SPVL over time with high SPVL heritability requires viral genetic factors that strongly influence SPVL but only weakly influence the competitive ability of the virus within hosts. We propose a virus trait that affects the activation of target cells, and therefore viral load, but does not confer a competitive advantage to the virus. We incorporate this virus-induced target cell activation into within- and between-host models and determine its effect on the competitive ability of virus strains and on the variation in SPVL in the host population. On the within-host level, our results show that higher rates of virus-induced target cell activation increase the SPVL and confer no selective advantage to the virus. This leads to a build up of diversity in target cell activation rates in the virus population during within-host evolution. On the between-host level, higher rates of target cell activation and therefore higher SPVL affect the transmission potential of the virus. Random selection of a new founder strain from the diverse virus population within a donor results in a standing variation in SPVL in the host population. Therefore, virus-induced target cell activation can explain the heritability of SPVL, the absence of evolution to higher viral loads during infection and a large standing variation in SPVL between hosts.
Eight challenges in phylodynamic inference
Frost, Simon D.W.; Pybus, Oliver G.; Gog, Julia R.; et al. (2015)
Epidemics
The field of phylodynamics, which attempts to enhance our understanding of infectious disease dynamics using pathogen phylogenies, has made great strides in the past decade. Basic epidemiological and evolutionary models are now well characterized with inferential frameworks in place. However, significant challenges remain in extending phylodynamic inference to more complex systems. These challenges include accounting for evolutionary complexities such as changing mutation rates, selection, reassortment, and recombination, as well as epidemiological complexities such as stochastic population dynamics, host population structure, and different patterns at the within-host and between-host scales. An additional challenge exists in making efficient inferences from an ever increasing corpus of sequence data.
Highly pathogenic avian influenza H5N8 in south-west France 2016–2017: A modeling study of control strategies
Andronico, Alessio; Courcoul, Aurélie; Bronner, Anne; et al. (2019)
Epidemics
In the winter 2016–2017 the largest epidemic of highly pathogenic avian influenza (HPAI) ever recorded in the European Union spread to all 28 member states. France was hit particularly hard and reported a total of 484 infected premises (IPs) by March 2017. We developed a mathematical model to analyze the spatiotemporal evolution of the epidemic and evaluate the impact of control strategies. We estimated that farms rearing ducks were on average 2.5 times more infectious and 5.0 times more susceptible to HPAI than farms rearing other avian species. The implementation of surveillance zones around IPs reduced transmission by a factor of 1.8 on average. Compared to the strengthening of pre-emptive culling measures enforced by French authorities in February 2017, we found that a faster depopulation of diagnosed IPs would have had a larger impact on the total number of infections. For example, halving the time delay from detection to slaughter of infected animals would have reduced the total number of IPs by 52% and total cull numbers by 50% on average. This study showcases the possible contribution of modeling to inform and optimize control strategies during an outbreak.
Virus-induced target cell activation reconciles set-point viral load heritability and within-host evolution
Hool, Anna; Leventhal, Gabriel E.; Bonhoeffer, Sebastian (2014)
Epidemics
The asymptomatic phase of HIV-1 infections is characterised by a stable set-point viral load (SPVL) within patients. The SPVL is a strong predictor of disease progression and shows considerable variation of multiple orders of magnitude between patients. Recent studies have found that the SPVL in donor and recipient pairs is strongly correlated indicating that the virus genotype strongly influences viral load. Viral genetic factors that increase both viral load and the replicative capacity of the virus would result in rapid within-host evolution to higher viral loads. Reconciling a stable SPVL over time with high SPVL heritability requires viral genetic factors that strongly influence SPVL but only weakly influence the competitive ability of the virus within hosts. We propose a virus trait that affects the activation of target cells, and therefore viral load, but does not confer a competitive advantage to the virus. We incorporate this virus-induced target cell activation into within- and between-host models and determine its effect on the competitive ability of virus strains and on the variation in SPVL in the host population. On the within-host level, our results show that higher rates of virus-induced target cell activation increase the SPVL and confer no selective advantage to the virus. This leads to a build up of diversity in target cell activation rates in the virus population during within-host evolution. On the between-host level, higher rates of target cell activation and therefore higher SPVL affect the transmission potential of the virus. Random selection of a new founder strain from the diverse virus population within a donor results in a standing variation in SPVL in the host population. Therefore, virus-induced target cell activation can explain the heritability of SPVL, the absence of evolution to higher viral loads during infection and a large standing variation in SPVL between hosts.
Applying mixture model methods to SARS-CoV-2 serosurvey data from Geneva
Bouman, Judith Aveline; Kadelka, Sarah; Stringhini, Silvia; et al. (2022)
Epidemics
Serosurveys are an important tool to estimate the true extent of the current SARS-CoV-2 pandemic. So far, most serosurvey data have been analyzed with cutoff-based methods, which dichotomize individual measurements into sero-positives or negatives based on a predefined cutoff. However, mixture model methods can gain additional information from the same serosurvey data. Such methods refrain from dichotomizing individual values and instead use the full distribution of the serological measurements from pre-pandemic and COVID-19 controls to estimate the cumulative incidence. This study presents an application of mixture model methods to SARS-CoV-2 serosurvey data from the SEROCoV-POP study from April and May 2020 in Geneva (2766 individuals). Besides estimating the total cumulative incidence in these data (8.1% (95% CI: 6.8%–9.9%)), we applied extended mixture model methods to estimate an indirect indicator of disease severity, which is the fraction of cases with a distribution of antibody levels similar to hospitalized COVID-19 patients. This fraction is 51.2% (95% CI: 15.2%–79.5%) across the full serosurvey, but differs between three age classes: 21.4% (95% CI: 0%–59.6%) for individuals between 5 and 40 years old, 60.2% (95% CI: 21.5%–100%) for individuals between 41 and 65 years old and 100% (95% CI: 20.1%–100%) for individuals between 66 and 90 years old. Additionally, we find a mismatch between the inferred negative distribution of the serosurvey and the validation data of pre-pandemic controls. Overall, this study illustrates that mixture model methods can provide additional insights from serosurvey data.
Advancing genomic epidemiology by addressing the bioinformatics bottleneck: Challenges, design principles, and a Swiss example
Chen, Chaoran; Nadeau, Sarah Ann; Topolsky, Ivan; et al. (2022)
Epidemics
The SARS-CoV-2 pandemic led to a huge increase in global pathogen genome sequencing efforts, and the resulting data are becoming increasingly important to detect variants of concern, monitor outbreaks, and quantify transmission dynamics. However, this rapid up-scaling in data generation brought with it many IT infrastructure challenges. In this paper, we report about developing an improved system for genomic epidemiology. We (i) highlight key challenges that were exacerbated by the pandemic situation, (ii) provide data infrastructure design principles to address them, and (iii) give an implementation example developed by the Swiss SARS-CoV-2 Sequencing Consortium (S3C) in response to the COVID-19 pandemic. Finally, we discuss remaining challenges to data infrastructure for genomic epidemiology. Improving these infrastructures will help better detect, monitor, and respond to future public health threats.
Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland
Chen, Chaoran; Nadeau, Sarah Ann; Topolsky, Ivan; et al. (2021)
Epidemics
Background: In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now named B.1.1.7. Based on initial data from the UK and later data from other countries, this variant was estimated to have a transmission fitness advantage of around 40–80 % (Volz et al., 2021; Leung et al., 2021; Davies et al., 2021). Aim: This study aims to estimate the transmission fitness advantage and the effective reproductive number of B.1.1.7 through time based on data from Switzerland. Methods: We generated whole genome sequences from 11.8 % of all confirmed SARS-CoV-2 cases in Switzerland between 14 December 2020 and 11 March 2021. Based on these data, we determine the daily frequency of the B.1.1.7 variant and quantify the variant's transmission fitness advantage on a national and a regional scale. Results: We estimate B.1.1.7 had a transmission fitness advantage of 43–52 % compared to the other variants circulating in Switzerland during the study period. Further, we estimate B.1.1.7 had a reproductive number above 1 from 01 January 2021 until the end of the study period, compared to below 1 for the other variants. Specifically, we estimate the reproductive number for B.1.1.7 was 1.24 [1.07–1.41] from 01 January until 17 January 2021 and 1.18 [1.06–1.30] from 18 January until 01 March 2021 based on the whole genome sequencing data. From 10 March to 16 March 2021, once B.1.1.7 was dominant, we estimate the reproductive number was 1.14 [1.00–1.26] based on all confirmed cases. For reference, Switzerland applied more non-pharmaceutical interventions to combat SARS-CoV-2 on 18 January 2021 and lifted some measures again on 01 March 2021. Conclusion: The observed increase in B.1.1.7 frequency in Switzerland during the study period is as expected based on observations in the UK. In absolute numbers, B.1.1.7 increased exponentially with an estimated doubling time of around 2–3.5 weeks. To monitor the ongoing spread of B.1.1.7, our plots are available online.
Pre-existence and emergence of drug resistance in a generalized model of intra-host viral dynamics
Alexander, Helen K.; Bonhoeffer, Sebastian (2012)
Epidemics
Understanding the source of drug resistance emerging within a treated patient is an important problem, from both clinical and basic evolutionary perspectives. Resistant mutants may arise de novo either before or after treatment is initiated, with different implications for prevention. Here we investigate this problem in the context of chronic viral diseases, such as human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV and HCV). We present a unified model of viral population dynamics within a host, which can capture a variety of viral life cycles. This allows us to identify which results generalize across various viral diseases, and which are sensitive to the particular virus's life cycle. Accurate analytical approximations are derived that allow for a solid understanding of the parameter dependencies in the system. We find that the mutation-selection balance attained prior to treatment depends on the step at which mutations occur and the viral trait that incurs the cost of resistance. Life cycle effects and key parameters, including mutation rate, infected cell death rate, cost of resistance, and drug efficacy, play a role in determining when mutations arising during treatment are important relative to those pre-existing.
Estimating pathogen spread using structured coalescent and birth–death models: A quantitative comparison
Seidel, Sophie; Stadler, Tanja; Vaughan, Timothy G. (2024)
Epidemics
Elucidating disease spread between subpopulations is crucial in guiding effective disease control efforts. Genomic epidemiology and phylodynamics have emerged as key principles to estimate such spread from pathogen phylogenies derived from molecular data. Two well-established structured phylodynamic methodologies – based on the coalescent and the birth–death model – are frequently employed to estimate viral spread between populations. Nonetheless, these methodologies operate under distinct assumptions whose impact on the accuracy of migration rate inference is yet to be thoroughly investigated. In this manuscript, we present a simulation study, contrasting the inferential outcomes of the structured coalescent model with constant population size and the multitype birth–death model with a constant rate. We explore this comparison across a range of migration rates in endemic diseases and epidemic outbreaks. The results of the epidemic outbreak analysis revealed that the birth–death model exhibits a superior ability to retrieve accurate migration rates compared to the coalescent model, regardless of the actual migration rate. Thus, to estimate accurate migration rates, the population dynamics have to be accounted for. On the other hand, for the endemic disease scenario, our investigation demonstrates that both models produce comparable coverage and accuracy of the migration rates, with the coalescent model generating more precise estimates. Regardless of the specific scenario, both models similarly estimated the source location of the disease. This research offers tangible modelling advice for infectious disease analysts, suggesting the use of either model for endemic diseases. For epidemic outbreaks, or scenarios with varying population size, structured phylodynamic models relying on the Kingman coalescent with constant population size should be avoided as they can lead to inaccurate estimates of the migration rate. Instead, coalescent models accounting for varying population size or birth–death models should be favoured. Importantly, our study emphasises the value of directly capturing exponential growth dynamics which could be a useful enhancement for structured coalescent models.

Publications1 - 10 of 23

Journal: Epidemics

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