About the Institute for Emerging Infections
The mission of the Institute for Emerging Infections is to understand the underlying processes that drive the emergence and spread of novel human infectious diseases. A multi-disciplinary team of biologists, mathematicians and clinicians are studying recently emerged infections and using the knowledge thus gained to anticipate challenges that will be posed by novel emergent infections in the 21st century.
There is no safe dose of prions
Helen Fryer and Angela McLean from of the Institute for Emerging Infections have published important new findings on the risk from prions, the infectious agent responsible for ‘mad cow disease’ and variant Creutzfeldt-Jakob disease (vCJD). Based on ideas from toxicology and radiology, it is often assumed that exposure to harmful agents, including prions, is completely safe at low enough doses. The study, published in the journal PLoS One, is the first to investigate the existence of a threshold dose of prions, below which the probability of infection is zero. Using mathematical tools to analyse data from over 4000 prion experiments, the pair have revealed that there is no evidence for the existence of such a threshold dose. The implications are profound for managing risks such as the potential transfer of vCJD via surgical instruments. The findings suggest that although very small quantities of prions may pose a very small risk of infection, that risk does not disappear as the dose becomes smaller.
Royal Society Committee
Professor Angela McLean, Co-Director of the Institute for Emerging Infections, has joined the Royal Society’s Scientific Aspects of International Security (SAIS) Committee
SAIS was established in 1988 and considers a range of security issues, including: arms control and non-proliferation; governance of ‘dual-use’ scientific research; security impacts of developing science and technology; and counter-terrorism.
Its principal role is to advise the Royal Society’s Science Policy Centre (SPC), and the SPC Advisory Group that oversees the Centre, on international security issues. The expertise on the committee covers a wide range of disciplines and the current membership includes Royal Society Fellows and other scientists, as well as science and security policy experts.
Dr Stephen Hicklilng, former Oxford Martin School Fellow, has been awarded an Oxford DPhil. Stephen's thesis was entitled "T-cell quality in HIV Infection". Stephen used state-of-the-art molecular methods to measure how strongly T-cells of HIV patients could bind viral proteins. His results were published in the Journal of Virology October 2010, p. 10543-10557, Vol. 84, No. 20.
Dr Jenny Smith, former Oxford Martin School Fellow, has been awarded an Oxford DPhil for her work on the viral diversity and dynamics of hepatitis C. Jenny continues to work as a Mathematical Biologist at Imperial College London, and we wish her every success for the future.
Jenny's thesis combined observational and modelling work to explore the causes and consequences of within-host competition between different strains of Hepatitis C Virus. In her first paper http://jid.oxfordjournals.org/content/202/12/1770.full she published these beautiful descriptions of the dynamics of HCV quasispecies clades within subjects through acute infection.
Lectureship in evolutionary genomics
Aris Katzourakis, former Martin-funded Fellow in the Institute for Emerging Infections has been elected to a lectureship in evolutionary genomics in the department of Zoology. Aris will also be tutorial fellow in biological sciences at St. Hilda's College. Aris will conduct a research program in evolutionary biology, focussing on genome evolution and virus evolution. He will teach evolution and quantitative methods for the undergraduate degree in biological sciences. He is currently running a departmental discussion group on genomics and bioinfrormatics.
Angela McLean Co-Director of the Institute for Emerging Infections said "This appointment of a Martin School Fellow to a faculty position in the University is a ringing endorsement of his creativity and the importance of his work. We are delighted to see a former Fellow from our Institute join the University Faculty and look forward to continue to work with Aris."
Competition between strains of influenza
The Institute for Emerging Infections has published an important new finding on competition between strains of influenza. In a new collaboration with virologists and biomathematicians in Melbourne . Angela McLean and Nim Pathy studied how well two different strains of influenza could transmit between individuals. Lead author of the study Dr James McCaw was a visitor at the Institute for Emerging Infections in the winter of 2010. The study has direct relevance to emerging infections because when an influenza pandemic occurs the new strain of influenza has to compete with the circulating strain. The study is published in the open access journal PLoS Computational Biology. The methods used were developed for analysing data, but are broadly applicable across a range of infectious agents.
How the human settlement distribution affects the emergence of novel infectious disease
Emerging infections are a continuing global public health issue, such as SARS or last year’s influenza A(H1N1) pandemic. Previous work, partly undertaken by researcher at the Institute for Emerging Infections, has explored the relationship between the evolutionary biology of an adapting pathogen, and the epidemiology of cases that may arise before such a pathogen becomes pandemic-capable.
Ruben Kubiak, Nim Arinaminpathy and Angela McLean extended this work to incorporate what is often an important host ecological feature, the spatial distribution of the host population. Many incidents occur away from large population centres. For example, HIV is thought to have entered the human population through bushmeat hunters in the sparsely populated jungles of Central Africa. We ask: when a pathogen is evolving to adapt for human transmission, under what circumstances does the spatial structure underlying the human population become important? Our results suggest that most communities are sufficiently interconnected to show no effect on the emergence process. As shown in the figure above, a small number of commuters is sufficient to successfully transmit the novel pathogen between settlements. Therefore, our research has important implications for Public Health and possible containment procedures.
Kubiak R.J., Arinaminpathy N. & McLean A.R. (2010). Insights into the Evolution and Emergence of a Novel Infectious Disease. PLoS Computational Biology, 6(9): e10000947. Available at: http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000947
The Royal Society Summer Science Exhibition
From 25 June to 4 July 2010, The Institute for Emerging Infections took part in the Royal Society’s Summer Science Exhibition at the Royal Festival Hall. During the 10 days of the Exhibition over 49,000 visitors were recorded. Our stand “Emerging infections: viruses that come in from the wild” attracted around 5,000 visitors.
The stand was staffed by 25 volunteers from across the University and offered visitors the opportunity to take part in a swine flu genetics game, a series of tuneable computer games on the control of infectious disease, a wet lab, where over 3,000 DNA extractions took place, and to watch a video on the plight of the Ethiopian Wolves, for whom rabies is a serious threat to the survival of their species.
The Evolutionary Biology of Retroviruses
Dr Aris Katzourakis has won a prestigious Royal Society University Fellowship. This will allow him 5 years’ independent research funding. Dr Katzourakis’ work combines evolutionary biology, mathematical modelling, in vitro experimental tests and sequencing, in order to answer fundamental questions regarding retroviral biology. Retroviruses are a group of viruses that infect the genomes of their hosts, and are responsible for a wide range of diseases, most notably HIV/AIDS. In common with other RNA viruses, retroviral evolution occurs very rapidly, obscuring their distant history due to the erosion of the evolutionary signal in viral genomes of events that have occurred millions of years ago. However, retroviruses are unusual among mico-organisms in possessing a rich ‘fossil record’, somewhat analogous to the palaeontological fossil record, resulting from an obligate step in the retroviral life cycle – the integration of the viral genome into the DNA of the host. Occasionally, this integration will occur in the reproductive tissue of the host, and when this occurs, the virus will be transmitted to the offspring. These inherited viruses are known as endogenous retroviruses (ERVs), and can yield unique information about the evolution of retroviruses.
Evolution and emergence of novel human pathogens
The ongoing 'swine flu' pandemic is a reminder of how humans continue to be afflicted by the prospect of new, emerging infectious diseases. Some pathogens infect sporadic cases, but do not transmit efficiently. However, where they adapt towards human transmission, they may signal their adaptation by causing large outbreaks. In a recent paper published in the Proceedings of the Royal Society B, Nim Arinaminpathy and Angela McLean present work that studies this process, using mathematical models to ask under what conditions we may expect a pandemic to be 'heralded' by large but self-limiting outbreaks. The work highlights close connections between the evolutionary biology of an adapting pathogen, and the outbreaks it causes on its course to emergence. Addressing the question of how such connections could be exploited for public health,
this work also discusses how ongoing outbreaks may be monitored, for early signs that a novel human pathogen is about to emerge.
HIV's ancestors plagued first mammals
A team led by Oxford University scientists, including Dr Aris Katzourakis, Research Fellow at the Institute for Emerging Infections, has found evidence that the retroviruses which gave rise to HIV have been battling it out with mammal immune systems since mammals first evolved around 100 million years ago.
The remains of an ancient HIV-like virus were discovered in the genome of the two-toed sloth, suggesting that these retroviruses existed about 85 million years earlier than previously thought. Because this sloth is so geographically and genetically isolated its genome gives us a window into the ancient past of mammals, their immune systems, and the types of viruses they had to contend with. This new research suggests that the ancestors of complex retroviruses, such as HIV, may have been with us from the very beginnings of mammal evolution.
Understanding the historical conflict between complex viruses and mammal immune systems could lead to new approaches to combating existing retroviruses, such as HIV. It can also help scientists to decide which viruses that cross species are likely to cause dangerous pandemics – such as swine flu – and which, like bird flu and foamy viruses, cross this species barrier but then never cause pandemics in new mammal populations.
The paper: "Macroevolution of Complex Retroviruses" is published in Science (2009) 325, no. 5947, p.1512 http://www.sciencemag.org/cgi/content/full/325/5947/1512
House of Lords
Pandemic Influenza preparedness is one of the major areas of interest for the Science and Technology select committee of the House of Lords. On Wednesday, 4th February 2009 the select committee invited six pandemic influenza experts to advise on various elements of preparedness, ranging from the possibility of a vaccine to the state of planning for critical care. Amongst those invited was Nim Pathy from the James Martin 21st Century School, to present work being done in the Institute of Emerging Infections. The work concerns evolution of a pandemic strain, and the ‘warning signs’, or patterns of infection, that may arise in the weeks or months before a pandemic.
Dr.Nim Pathy and Lord Robert May outside the House of Lords
Lemur virus reveals HIV's evolution
Aris Katzourakis (James Martin Fellow at the Institute of Emergent Infections) together with co-authors at Oxford, Stanford and Imperial College has published A transitional endogenous lentivirus from a basal primate and implications for lentivirus evolution in PNAS. This paper reports the discovery and analysis of a new member of the primate lentivirus group, the group of viruses that includes HIV and its counterparts in other primates, the SIVs (simian retroviruses). This virus has been identified in the grey mouse lemur (Microcebus murinus), a Madagascan primate that has evolved in isolation from the African primates in which all other known SIVs are found, shedding new light on the evolution of the primate lentiviruses.
pSIVgml (prosimian immunodeficiency virus-grey mouse lemur) is an endogenous lentivirus, demonstrating that primate lentiviruses can invade the germ line of their hosts. Furthermore, it is the first unambiguous example of a viral transitional form, intermediate between the SIV/HIV viruses with their complex genomes, and the more simple lentiviruses infecting other animals. Since the Madagascan lemurs that pSIVgml has infected have been isolated from their African cousins for >14 million years, it is likely that lentiviruses have been infecting primates for at least this period of time, and possibly for much longer. Furthermore, primate lentiviruses appear to be considerably more widespread than has previously been thought, highlighting the need for surveillance to locate potential zoonotic reservoirs of lentiviruses that could be transmissible to humans.For more information please see http://www.ox.ac.uk/media/news_stories/2008/081203.html
Nim Pathy and Mario Recker (James Martin Fellows in the Institute of Emergent Infections of Humans - IEIH) have recently returned from a fact-finding mission to Ho Chi Minh City - find out more
Oxford University Press has published a new edition of “Theoretical Ecology. Principles and Applications.” edited by Robert May and Angela McLean. This book is an entirely rewritten update of an established advanced level text book in this topic.
Mario Recker, Sunetra Gupta and their co-authors have published “The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types” in PNAS. This paper suggests that rather than virus mutation driving the epidemiology of influenza, the changing landscape of host population immunity governs whether and when epidemics emerge. This is an important suggestion because a proper understanding of the emergence of novel influenza strains would greatly enhance our ability to forsee the timing and nature of an influenza pandemic.
View this open access article