Publications by authors named "Christiaan H van Dorp"

7 Publications

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Estimating the strength of selection for new SARS-CoV-2 variants.

medRxiv 2021 Apr 1. Epub 2021 Apr 1.

A challenge to controlling the SARS-CoV-2 pandemic is the ability of the virus to adapt to its new human hosts, with novel and more transmissible strains of the virus being continually identified. Yet there are no generally accepted methods to consistently estimate the relative magnitude of the change in transmissiblity of newly emerging variants. In this paper we consider three methods for examining and quantifying positive selection of new and emerging strains of SARS-CoV-2 over an existing wild-type strain. We consider replication at the level of countries and allow for the action of other processes that can change variants' frequencies, specifically migration and drift. We apply these methods to the D614G spike mutation and the variant designated B.1.1.7, in every country where there is sufficient sequence data. For each of D614G and B.1.1.7, we find evidence for strong selection (greater than 25% increased contagiousness) in more than half of countries analyzed. Our results also shows that the selective advantages of these strains are highly heterogeneous at the country level, suggesting the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.
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http://dx.doi.org/10.1101/2021.03.29.21254233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020992PMC
April 2021

Model-based evaluation of school- and non-school-related measures to control the COVID-19 pandemic.

Nat Commun 2021 03 12;12(1):1614. Epub 2021 Mar 12.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

The role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures at different time points during the COVID-19 pandemic in the Netherlands. Our analyses suggest that the impact of measures reducing school-based contacts depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce the effective reproduction number (R) with non-school-based measures are exhausted or undesired and R is still close to 1, the additional benefit of school-based measures may be considerable, particularly among older school children. As two examples, we demonstrate that keeping schools closed after the summer holidays in 2020, in the absence of other measures, would not have prevented the second pandemic wave in autumn 2020 but closing schools in November 2020 could have reduced R below 1, with unchanged non-school-based contacts.
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http://dx.doi.org/10.1038/s41467-021-21899-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955041PMC
March 2021

Models of SIV rebound after treatment interruption that involve multiple reactivation events.

PLoS Comput Biol 2020 10 1;16(10):e1008241. Epub 2020 Oct 1.

Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.

In order to assess the efficacy of novel HIV-1 treatments leading to a functional cure, the time to viral rebound is frequently used as a surrogate endpoint. The longer the time to viral rebound, the more efficacious the therapy. In support of such an approach, mathematical models serve as a connection between the size of the latent reservoir and the time to HIV-1 rebound after treatment interruption. The simplest of such models assumes that a single successful latent cell reactivation event leads to observable viremia after a period of exponential viral growth. Here we consider a generalization developed by Pinkevych et al. and Hill et al. of this simple model in which multiple reactivation events can occur, each contributing to the exponential growth of the viral load. We formalize and improve the previous derivation of the dynamics predicted by this model, and use the model to estimate relevant biological parameters from SIV rebound data. We confirm a previously described effect of very early antiretroviral therapy (ART) initiation on the rate of recrudescence and the viral load growth rate after treatment interruption. We find that every day ART initiation is delayed results in a 39% increase in the recrudescence rate (95% credible interval: [18%, 62%]), and a 11% decrease of the viral growth rate (95% credible interval: [4%, 20%]). We show that when viral rebound occurs early relative to the viral load doubling time, a model with multiple successful reactivation events fits the data better than a model with only a single successful reactivation event.
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http://dx.doi.org/10.1371/journal.pcbi.1008241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529301PMC
October 2020

Estimating Transmission Parameters for Respiratory Syncytial Virus and Predicting the Impact of Maternal and Pediatric Vaccination.

J Infect Dis 2020 10;222(Suppl 7):S688-S694

Centre for Infectious Disease Control, National institute for Public Health and the Environment, Bilthoven, the Netherlands.

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally.

Methods: Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012-2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination.

Results: Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20-64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children.

Conclusions: Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0-5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits.
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http://dx.doi.org/10.1093/infdis/jiaa424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751153PMC
October 2020

Infectious reactivation of cytomegalovirus explaining age- and sex-specific patterns of seroprevalence.

PLoS Comput Biol 2017 Sep 26;13(9):e1005719. Epub 2017 Sep 26.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

Human cytomegalovirus (CMV) is a herpes virus with poorly understood transmission dynamics. Person-to-person transmission is thought to occur primarily through transfer of saliva or urine, but no quantitative estimates are available for the contribution of different infection routes. Using data from a large population-based serological study (n = 5,179), we provide quantitative estimates of key epidemiological parameters, including the transmissibility of primary infection, reactivation, and re-infection. Mixture models are fitted to age- and sex-specific antibody response data from the Netherlands, showing that the data can be described by a model with three distributions of antibody measurements, i.e. uninfected, infected, and infected with increased antibody concentration. Estimates of seroprevalence increase gradually with age, such that at 80 years 73% (95%CrI: 64%-78%) of females and 62% (95%CrI: 55%-68%) of males are infected, while 57% (95%CrI: 47%-67%) of females and 37% (95%CrI: 28%-46%) of males have increased antibody concentration. Merging the statistical analyses with transmission models, we find that models with infectious reactivation (i.e. reactivation that can lead to the virus being transmitted to a novel host) fit the data significantly better than models without infectious reactivation. Estimated reactivation rates increase from low values in children to 2%-4% per year in women older than 50 years. The results advance a hypothesis in which transmission from adults after infectious reactivation is a key driver of transmission. We discuss the implications for control strategies aimed at reducing CMV infection in vulnerable groups.
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http://dx.doi.org/10.1371/journal.pcbi.1005719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630159PMC
September 2017

Long-term adaptation of the influenza A virus by escaping cytotoxic T-cell recognition.

Sci Rep 2016 09 15;6:33334. Epub 2016 Sep 15.

National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

The evolutionary adaptation of the influenza A virus (IAV) to human antibodies is well characterised. Much less is known about the long-term evolution of cytotoxic T lymphocyte (CTL) epitopes, which are important antigens for clearance of infection. We construct an antigenic map of IAVs of all human subtypes using a compendium of 142 confirmed CTL epitopes, and show that IAV evolved gradually in the period 1932-2015, with infrequent antigenic jumps in the H3N2 subtype. Intriguingly, the number of CTL epitopes per virus decreases with more than one epitope per three years in the H3N2 subtype (from 84 epitopes per virus in 1968 to 64 in 2015), mostly attributed to the loss of HLA-B epitopes. We confirm these observations with epitope predictions. Our findings indicate that selection pressures imposed by CTL immunity shape the long-term evolution of IAV.
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http://dx.doi.org/10.1038/srep33334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024124PMC
September 2016

Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution.

PLoS Comput Biol 2014 Dec 18;10(12):e1003899. Epub 2014 Dec 18.

Theoretical Biology and Bioinformatics, Universiteit Utrecht, Utrecht, The Netherlands.

It has been suggested that HIV-1 has evolved its set-point virus load to be optimized for transmission. Previous epidemiological models and studies into the heritability of set-point virus load confirm that this mode of adaptation within the human population is feasible. However, during the many cycles of replication between infection of a host and transmission to the next host, HIV-1 is under selection for escape from immune responses, and not transmission. Here we investigate with computational and mathematical models how these two levels of selection, within-host and between-host, are intertwined. We find that when the rate of immune escape is comparable to what has been observed in patients, immune selection within hosts is dominant over selection for transmission. Surprisingly, we do find high values for set-point virus load heritability, and argue that high heritability estimates can be caused by the 'footprints' left by differing hosts' immune systems on the virus.
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http://dx.doi.org/10.1371/journal.pcbi.1003899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270429PMC
December 2014