ORCID Profile
0000-0003-3227-5909
Current Organisations
Trends in Microbiology
,
Princeton University
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Publications
Vaccine nationalism and the dynamics and control of SARS-CoV-2
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-09-2021
Abstract: A triumph that has emerged from the catastrophe of the severe acute respiratory syndrome coronavirus 2 pandemic has been the rapid development of several potent vaccines. However, 18 months into the pandemic and more than 6 months after vaccine approval, wealthy countries remain the major beneficiaries. Wagner et al . model the consequences of vaccine stockpiling in affluent countries on disease rates in lower- and middle-income countries and the consequences for the eruption of new variants that could jeopardize the early success of vaccines. For countries that can readily access vaccines, it would be better to share vaccines equitably to lower disease burdens in countries with less access, reduce the cost of having to be constantly vigilant for case imports, and minimize virus evolution. —CA
Discovering the Phylodynamics of RNA Viruses
Publisher: Public Library of Science (PLoS)
Date: 26-10-2009
Population viability analyses on a cycling population: a cautionary tale
Publisher: Elsevier BV
Date: 2001
Modelling equine influenza 1: A stochastic model of within-yard epidemics
Publisher: Cambridge University Press (CUP)
Date: 06-2002
DOI: 10.1017/S0950268802006829
Abstract: This paper demonstrates that a simple stochastic model can capture the features of an epidemic of equine influenza in unvaccinated horses. When the model is modified to consider vaccinated horses, we find that vaccination dramatically reduces the incidence and size of epidemics. Although occasional larger outbreaks can still occur, these are exceptional. We then look at the effects of vaccination on a yard of horses, and in particular at the relationship between pre-challenge antibody level and quantity of virus shed when challenged with the virus. While on average, a high antibody level implies that less virus will be shed during the infectious period, we identify a high degree of heterogeneity in the response of horses with similar pre-challenge antibody levels. We develop a modified model that incorporates some heterogeneity in levels of infectivity, and compare this with the simpler model.
Balpara: A Practical Approach to Working With Ontological Difference in Indigenous Land & Sea Management
Publisher: Informa UK Limited
Date: 20-04-2023
Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-04-2021
Abstract: For two-dose vaccines against severe acute respiratory syndrome coronavirus 2, some jurisdictions have decided to delay the second dose to rapidly get the vaccine into more people. The consequences of deviating from manufacturer-prescribed dosing regimens are unknown but will depend on the strength of immune responses to the vaccines. Saad-Roy et al. took a modeling approach to tackling the inevitable uncertainties facing vaccine rollout. The authors found that although one-dose strategies generally reduce infections in the short term, in the long term, the outcome depends on immune robustness. A one-dose strategy may increase the potential for antigenic evolution if immune responses are suboptimal and the virus continues to replicate in some vaccinated people, potentially leading to immune-escape mutations. It is critical to gather serological data from vaccinated people and, to avoid negative outcomes, to r up vaccination efforts worldwide. Science , this issue p. 363
The impact of environmental and climatic variation on the spatiotemporal trends of hospitalized pediatric diarrhea in Ho Chi Minh City, Vietnam
Publisher: Elsevier BV
Date: 09-2015
Stochastic Processes Are Key Determinants of Short-Term Evolution in Influenza A Virus
Publisher: Public Library of Science (PLoS)
Date: 2006
Evolution of Equine Influenza Virus in Vaccinated Horses
Publisher: American Society for Microbiology
Date: 15-04-2013
DOI: 10.1128/JVI.03379-12
Abstract: Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated in iduals. To determine how prior immunity shapes viral ersity in vivo , we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic ersity were similar to those in naïve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites.
Unifying the Epidemiological and Evolutionary Dynamics of Pathogens
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-01-2004
Abstract: A key priority for infectious disease research is to clarify how pathogen genetic variation, modulated by host immunity, transmission bottlenecks, and epidemic dynamics, determines the wide variety of pathogen phylogenies observed at scales that range from in idual host to population. We call the melding of immunodynamics, epidemiology, and evolutionary biology required to achieve this synthesis pathogen “phylodynamics.” We introduce a phylodynamic framework for the dissection of dynamic forces that determine the ersity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of this model is the Evolutionary Infectivity Profile, which captures the relationship between immune selection and pathogen transmission.
Inferring the inter-host transmission of influenza A virus using patterns of intra-host genetic variation
Publisher: The Royal Society
Date: 07-01-2013
Abstract: Influenza A viruses (IAVs) cause acute, highly transmissible infections in a wide range of animal species. Understanding how these viruses are transmitted within and between susceptible host populations is critical to the development of effective control strategies. While viral gene sequences have been used to make inferences about IAV transmission dynamics at the epidemiological scale, their utility in accurately determining patterns of inter-host transmission in the short-term—i.e. who infected whom—has not been strongly established. Herein, we use intra-host sequence data from the viral HA1 (hemagglutinin) gene domain from two transmission studies employing different IAV subtypes in their natural hosts—H3N8 in horses and H1N1 in pigs—to determine how well these data recapitulate the known pattern of inter-host transmission. Although no mutations were fixed over the course of either experimental transmission chain, we show that some minor, transient alleles can provide evidence of host-to-host transmission and, importantly, can be distinguished from those that cannot.
Antibody Dynamics in Childhood Diseases: Waning and Boosting of Immunity and the Impact of Vaccination
Publisher: Elsevier BV
Date: 03-2003
Abstract: The introduction of vaccination against acute diseases such as measles induced a dramatic decline in the prevalence of the disease, and a more gradual rise in the proportion of the population whose immunity is derived solely from vaccination. These two factors combine to constitute an important shift in the dynamics of immunity, especially in highly vaccinated populations. We develop a general model to describe both loss of immunity in the absence of disease, and boosting of immunity corresponding to subclinical infection in in iduals whose immunity has waned. We consider the interaction between infection and immunity and identify the key parameters that determine the eradication threshold. We explore the dynamics in the years following the introduction of vaccination using a stochastic version of the model, and consider the effect of different assumptions concerning the nature of immunity. A comparison of the model results with recently published data suggests that heterogeneity in host immune response is an important feature of the antibody dynamics.
OVERCOMPENSATION AND POPULATION-CYCLES IN AN UNGULATE
Publisher: Springer Science and Business Media LLC
Date: 02-1992
DOI: 10.1038/355823A0
Abstract: Although theoretical studies show that overcompensatory density-dependent mechanisms can potentially generate regular or chaotic fluctuations in animal numbers, the majority of realistic single-species models of invertebrate populations are not overcompensatory enough to cause sustained population cycles. The possibility that overcompensation may generate cycles or chaos in vertebrate populations has seldom been considered. Here we show that highly overcompensatng density-dependent mortality can generate recurrent population crashes consistent with those observed in a naturally limited population of Soay sheep. The observed interval of three or more years between crashes points to sharp 'focusing' of mortality over a narrow range of population density.
Fogarty International Center collaborative networks in infectious disease modeling: Lessons learnt in research and capacity building
Publisher: Elsevier BV
Date: 03-2019
Age specific patterns of change in the dynamics of Wuchereria bancrofti infection in Papau New Guinea
Publisher: American Society of Tropical Medicine and Hygiene
Date: 05-1991
DOI: 10.4269/AJTMH.1991.44.518
Abstract: Results of a longitudinal study of the age-specific dynamics of Wuchereria bancrofti infection in a community of East Sepik Province, Papua New Guinea (PNG) are described. Microfilarial (mf) density and serum levels of W. bancrofti phosphorylcholine-containing antigen (PC-Ag) in in iduals were used as indirect measures of adult worm burden. These parasitological data were collected from 126 subjects greater than 4 years of age at two time points, 12 months apart, prior to the administration of the antifilarial drug diethylcambamazine (DEC). No significant changes in levels of mf density were observed for the study population between these two time points. However, significant changes in the levels of circulating PC-Ag were noted in subjects less than or equal to 20 years of age, but not in subjects greater than 20 years of age, between these two time points. The apparent shorter half life of circulating PC-Ag compared to that of mf makes antigenemia a more sensitive measure of the dynamics of adult worm populations. These data are discussed in terms of a basic mathematical model describing the dynamics of adult worm populations in relation to their life expectancy and attrition of larvae during establishment. Consideration of these data in the context of this simple immigration/death model suggests that the differences observed in patterns of change in intensity of infection between subjects less than or equal to 20 years old and those greater than 20 years old may be consistent with the acquisition of resistance to superinfection with increasing age.
Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes
Publisher: Cold Spring Harbor Laboratory
Date: 03-02-2021
DOI: 10.1101/2021.02.01.21250944
Abstract: As the threat of Covid-19 continues and in the face of vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels. How timing of delivery of the second dose affects infection burden but also prospects for the evolution of viral immune escape are critical questions. Both hinge on the strength and duration (i.e. robustness) of the immune response elicited by a single dose, compared to natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short-term, focusing on one dose generally decreases infections, but longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection, evaluating how different second dose delays might drive immune escape via a build-up of partially immune in iduals. Under certain scenarios, we find that a one-dose policy may increase the potential for antigenic evolution. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose, and to r up vaccination efforts throughout the world.
Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus
Publisher: Public Library of Science (PLoS)
Date: 23-10-2014
Host Species Barriers to Influenza Virus Infections
Publisher: American Association for the Advancement of Science (AAAS)
Date: 21-04-2006
Abstract: Most emerging infectious diseases in humans originate from animal reservoirs to contain and eradicate these diseases we need to understand how and why some pathogens become capable of crossing host species barriers. Influenza virus illustrates the interaction of factors that limit the transmission and subsequent establishment of an infection in a novel host species. Influenza species barriers can be categorized into virus-host interactions occurring within in iduals and host-host interactions, either within or between species, that affect transmission between in iduals. Viral evolution can help surmount species barriers, principally by affecting virus-host interactions however, evolving the capability for sustained transmission in a new host species represents a major adaptive challenge because the number of mutations required is often large.
Evolution of an Eurasian Avian-like Influenza Virus in Naive and Vaccinated Pigs
Publisher: Public Library of Science (PLoS)
Date: 31-05-2012
Waning immunity and subclinical measles infections in England
Publisher: Elsevier BV
Date: 09-2004
Pareto rules for malaria super-spreaders and super-spreading
Publisher: Springer Science and Business Media LLC
Date: 02-09-2019
DOI: 10.1038/S41467-019-11861-Y
Abstract: Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 “Pareto” rule has been proposed to describe this heterogeneity whereby 80% of transmission is accounted for by 20% of in iduals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain in iduals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders.
Partial immunity and SARS-CoV-2 mutations—Response
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-04-2021
Whole-Genome Analysis of Human Influenza A Virus Reveals Multiple Persistent Lineages and Reassortment among Recent H3N2 Viruses
Publisher: Public Library of Science (PLoS)
Date: 26-07-2005
Multiannual forecasting of seasonal influenza dynamics reveals climatic and evolutionary drivers
Publisher: Proceedings of the National Academy of Sciences
Date: 16-06-2014
Abstract: Seasonality in disease incidence is ubiquitous among infectious diseases. Seasonal drivers include weather variables, such as temperature and humidity, and social factors (e.g., contact patterns). Attempts to make long-term predictions of infectious diseases are h ered by the inability to understand the complex interplay of these factors. Here, we model the dynamics of seasonal influenza based on a high-quality 12-year Israeli dataset. The dynamics are completely explainable by the time evolution of the model equations, the antigenic jumps of the virus, and the climatic forcing, yielding high-correlation fits to the data ( r = 0.94). The forecasting ability is greatly increased through the predictability of the system’s transient dynamics, resulting in accurate predictions ( r = 0.93) that have not yet been found elsewhere.
Interpreting time-series analyses for continuous-time biological models - Measles as a case study
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S0022-5193(03)00031-6
Abstract: An increasing number of recent studies involve the fitting of mechanistic models to ecological time-series. In some cases, it is necessary for these models to be discrete-time approximations of continuous-time processes. We test the validity of discretization in the case of measles, where time-series models have recently been developed to estimate ecological parameters directly from data. We find that a non-homogeneous contact function is necessary to capture the host-parasite interaction in a discrete-time model, even in the absence of heterogeneities due to spatial or age structure. We derive a mathematical relationship describing the expected departure from mass-action transmission in terms of the epidemiological parameters in the model, and identify conditions under which the discretization process may fail.
The effect of heterogeneity in measles vaccination on population immunity
Publisher: Cambridge University Press (CUP)
Date: 09-07-2004
DOI: 10.1017/S0950268804002080
Abstract: High overall vaccination levels sometimes hide pockets of poor coverage. We adopted a meta-population framework to model local aggregation of populations, and used this to investigate the effects of vaccination heterogeneity. A recent survey of antibody levels in a community with low vaccination levels in The Netherlands enabled us to assess the relative importance of local and long-range infective contacts, and thus identify feasible levels of aggregation in the meta-population model. In the aggregated model, we found that heterogeneity in vaccination coverage can lead to a much increased rate of infection among unvaccinated in iduals, with a simultaneous drop in the average age at infection.
Changes in Rodent Abundance and Weather Conditions Potentially Drive Hemorrhagic Fever with Renal Syndrome Outbreaks in Xi’an, China, 2005–2012
Publisher: Public Library of Science (PLoS)
Date: 30-03-2015
Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study
Publisher: Elsevier BV
Date: 10-2020
Intra- and Interhost Evolutionary Dynamics of Equine Influenza Virus
Publisher: American Society for Microbiology
Date: 15-07-2010
DOI: 10.1128/JVI.00112-10
Abstract: Determining the evolutionary basis of cross-species transmission and immune evasion is key to understanding the mechanisms that control the emergence of either new viruses or novel antigenic variants with pandemic potential. The hemagglutinin glycoprotein of influenza A viruses is a critical host range determinant and a major target of neutralizing antibodies. Equine influenza virus (EIV) is a significant pathogen of the horse that causes periodical outbreaks of disease even in populations with high vaccination coverage. EIV has also jumped the species barrier and emerged as a novel respiratory pathogen in dogs, canine influenza virus. We studied the dynamics of equine influenza virus evolution in horses at the intrahost level and how this evolutionary process is affected by interhost transmission in a natural setting. To this end, we performed clonal sequencing of the hemagglutinin 1 gene derived from in idual animals at different times postinfection. Our results show that despite the population consensus sequence remaining invariant, genetically distinct subpopulations persist during the course of infection and are also transmitted, with some variants likely to change antigenicity. We also detected a natural case of mixed infection in an animal infected during an outbreak of equine influenza, raising the possibility of reassortment between different strains of virus. In sum, our data suggest that transmission bottlenecks may not be as narrow as originally perceived and that the genetic ersity required to adapt to new host species may be partially present in the donor host and potentially transmitted to the recipient host.
The Genesis and Spread of Reassortment Human Influenza A/H3N2 Viruses Conferring Adamantane Resistance
Publisher: Oxford University Press (OUP)
Date: 18-04-2007
Abstract: A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years -- from approximately 2% to approximately 90% in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently s led complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N-lineage") characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness-enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens.
The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population
Publisher: The Royal Society
Date: 07-08-2004
Heading Off an Influenza Pandemic
Publisher: American Association for the Advancement of Science (AAAS)
Date: 12-08-2005
Related Organisations
UK Governement
Location: United Kingdom of Great Britain and Northern Ireland
University Of Cambridge
Location: United Kingdom of Great Britain and Northern Ireland
RAPIDD (Research And Policy In Infectious Disease Dynamics) Program Of The US NIH And DH
Location: United States of America
National Center For Statistical Ecology
Location: United Kingdom of Great Britain and Northern Ireland
Independent Scientific Group On Bovine Tuberculosis
Location: United Kingdom of Great Britain and Northern Ireland
Isaac Newton Institute For Mathematical Sciences
Location: United Kingdom of Great Britain and Northern Ireland
Journal Of Animal Ecology
Location: United Kingdom of Great Britain and Northern Ireland
University Of Oxford
Location: United Kingdom of Great Britain and Northern Ireland
University Of Sheffield
Location: United Kingdom of Great Britain and Northern Ireland
University Of York
Location: United Kingdom of Great Britain and Northern Ireland
Wellcome Trust
Location: United Kingdom of Great Britain and Northern Ireland
Cambridge Infectious Disease Consortium
Location: United Kingdom of Great Britain and Northern Ireland
Centre For Immunity, Infection And Evolution
Location: United Kingdom of Great Britain and Northern Ireland
Imperial College London
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Bryan Grenfell.