Christophe Fraser

Fraser and colleagues were among the first to hypothesise that the large variability in virulence observed between individuals living with HIV could be partly due to genetic variation in the virus.{{cite journal |doi=10.1073/pnas.0708559104 |title=Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis |date=2007 |pmc=2077275 |last1=Fraser |first1=Christophe |last2=Hollingsworth |first2=T. Déirdre |last3=Chapman |first3=Ruth |last4=De Wolf |first4=Frank |last5=Hanage |first5=William P. |journal=Proceedings of the National Academy of Sciences |volume=104 |issue=44 |pages=17441–17446 |pmid=17954909 |doi-access=free }}

In other words they hypothesised that virulence, considered as a phenotype of the virus, has appreciable heritability.

They{{cite journal |doi=10.1371/journal.ppat.1000876|title=HIV-1 Transmitting Couples Have Similar Viral Load Set-Points in Rakai, Uganda|date=2010|doi-access=free|pmc=2865511}}{{cite journal |doi=10.1126/science.1243727|title=Virulence and pathogenesis of HIV-1 infection: an evolutionary perspective|date=2014 |pmc=5034889 |last1=Fraser |first1=Christophe |last2=Lythgoe |first2=Katrina |last3=Leventhal |first3=Gabriel E. |last4=Shirreff |first4=George |last5=Hollingsworth |first5=T. Déirdre |last6=Alizon |first6=Samuel |last7=Bonhoeffer |first7=Sebastian |journal=Science |volume=343 |issue=6177 |pmid=24653038 }}{{cite journal |doi=10.1371/journal.pbio.2001855|title=Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe|date=2017|doi-access=free|hdl=10044/1/56788|hdl-access=free}} and others{{cite journal |doi=10.1093/molbev/msx246|title=Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity|date=2018 |pmc=5850767 |last1=Bertels |first1=Frederic |last2=Marzel |first2=Alex |last3=Leventhal |first3=Gabriel |last4=Mitov |first4=Venelin |last5=Fellay |first5=Jacques |last6=Günthard |first6=Huldrych F. |last7=Böni |first7=Jürg |last8=Yerly |first8=Sabine |last9=Klimkait |first9=Thomas |last10=Aubert |first10=Vincent |last11=Battegay |first11=Manuel |last12=Rauch |first12=Andri |last13=Cavassini |first13=Matthias |last14=Calmy |first14=Alexandra |last15=Bernasconi |first15=Enos |last16=Schmid |first16=Patrick |last17=Scherrer |first17=Alexandra U. |last18=Müller |first18=Viktor |last19=Bonhoeffer |first19=Sebastian |last20=Kouyos |first20=Roger |last21=Regoes |first21=Roland R. |author22=the Swiss HIV Cohort Study |journal=Molecular Biology and Evolution |volume=35 |pages=27–37 |pmid=29029206 }}{{cite journal |doi=10.1093/molbev/msx328|title=A Practical Guide to Estimating the Heritability of Pathogen Traits |date=2018 |pmc=5850476 |last1=Mitov |first1=Venelin |last2=Stadler |first2=Tanja |journal=Molecular Biology and Evolution |volume=35 |issue=3 |pages=756–772 |pmid=29329426 }}{{cite journal |doi=10.1016/j.tim.2016.04.008|title=Potential Pitfalls in Estimating Viral Load Heritability|date=2016}}{{cite journal |doi=10.1371/journal.pcbi.1005339|title=Estimating the Respective Contributions of Human and Viral Genetic Variation to HIV Control|date=2017|doi-access=free|pmc=5300119}} later provided evidence for this.

Fraser was principal investigator of the BEEHIVE project to investigate the mechanism of this heritability,{{Cite web|url=https://cordis.europa.eu/article/id/418109-hiv-analysis-shines-light-on-viral-process

|title=BEEHIVE}} which discovered the 'VB variant': a highly virulent strain within the B subtype of HIV found in 107 individuals living with HIV in the Netherlands.{{cite news |author=AP |date=February 3, 2022 |title=Study identifies virulent HIV variant unrecognized for years|url=https://apnews.com/article/science-health-europe-netherlands-western-europe-176156e8d785f10b53224c856c671aba|work= |location= |access-date=}}{{cite journal |doi=10.1126/science.abk1688|title=A highly virulent variant of HIV-1 circulating in the Netherlands|date=2022 |doi-access=free |last1=Wymant |first1=Chris |last2=Bezemer |first2=Daniela |last3=Blanquart |first3=François |last4=Ferretti |first4=Luca |last5=Gall |first5=Astrid |last6=Hall |first6=Matthew |last7=Golubchik |first7=Tanya |last8=Bakker |first8=Margreet |last9=Ong |first9=Swee Hoe |last10=Zhao |first10=Lele |last11=Bonsall |first11=David |last12=De Cesare |first12=Mariateresa |last13=Macintyre-Cockett |first13=George |last14=Abeler-Dörner |first14=Lucie |last15=Albert |first15=Jan |last16=Bannert |first16=Norbert |last17=Fellay |first17=Jacques |last18=Grabowski |first18=M. Kate |last19=Gunsenheimer-Bartmeyer |first19=Barbara |last20=Günthard |first20=Huldrych F. |last21=Kivelä |first21=Pia |last22=Kouyos |first22=Roger D. |last23=Laeyendecker |first23=Oliver |last24=Meyer |first24=Laurence |last25=Porter |first25=Kholoud |last26=Ristola |first26=Matti |last27=Van Sighem |first27=Ard |last28=Berkhout |first28=Ben |last29=Kellam |first29=Paul |last30=Cornelissen |first30=Marion |journal=Science |volume=375 |issue=6580 |pages=540–545 |pmid=35113714 |bibcode=2022Sci...375..540T |display-authors=1 |hdl=1887/3502598 |hdl-access=free }} UNAIDS stated that the discovery "provides evidence of urgency to halt the pandemic and reach all with testing and treatment".{{cite news |author=UNAIDS |date=7 February 2022 |title=Identification of fast-spreading HIV variant provides evidence of urgency to halt the pandemic and reach all with testing and treatment|url=https://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2022/february/20220207_hiv-variant}}

In March 2020 Fraser and his research group published epidemiological modelling supporting 'digital contact tracing' using COVID-19 apps to reduce the spread of SARS-CoV-2.{{Cite journal|doi=10.1126/science.abb6936|title=Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing|date=March 31, 2020|pmc=7164555 |last1=Ferretti |first1=Luca |last2=Wymant |first2=Chris |last3=Kendall |first3=Michelle |last4=Zhao |first4=Lele |last5=Nurtay |first5=Anel |last6=Abeler-Dörner |first6=Lucie |last7=Parker |first7=Michael |last8=Bonsall |first8=David |last9=Fraser |first9=Christophe |journal=Science |volume=368 |issue=6491 |pages=eabb6936 |pmid=32234805 }}

Fraser provided advice to the British government{{Cite news|url=https://www.bbc.co.uk/news/technology-52294896|title=Coronavirus: NHS contact tracing app to target 80% of smartphone users|work=BBC News|date=April 16, 2020}} and more broadly{{Cite web|url=https://results2021.ref.ac.uk/impact/d3d20ce5-b625-4da5-9e0e-8e4bf87ef238?page=1

|title=REF 2021 Impact Case Study}} about implementing such apps, including designing a risk evaluation algorithm with Anthony Finkelstein and others.{{Cite web|title=Defining an epidemiologically meaningful contact from phone proximity events: uses for digital contact tracing|url=https://github.com/BDI-pathogens/covid-19_instant_tracing/blob/master/Epidemiologically%20meaningful%20contact%20from%20phone%20proximity%20events%20-%20uses%20for%20digital%20contact%20tracing.pdf}}

Fraser's team developed the OpenABM-Covid-19 agent-based model,{{cite journal |doi=10.1371/journal.pcbi.1009146|title=OpenABM-Covid19—An agent-based model for non-pharmaceutical interventions against COVID-19 including contact tracing|date=2021 |doi-access=free |last1=Hinch |first1=Robert |last2=Probert |first2=William J. M. |last3=Nurtay |first3=Anel |last4=Kendall |first4=Michelle |last5=Wymant |first5=Chris |last6=Hall |first6=Matthew |last7=Lythgoe |first7=Katrina |last8=Bulas Cruz |first8=Ana |last9=Zhao |first9=Lele |last10=Stewart |first10=Andrea |last11=Ferretti |first11=Luca |last12=Montero |first12=Daniel |last13=Warren |first13=James |last14=Mather |first14=Nicole |last15=Abueg |first15=Matthew |last16=Wu |first16=Neo |last17=Legat |first17=Olivier |last18=Bentley |first18=Katie |last19=Mead |first19=Thomas |last20=Van-Vuuren |first20=Kelvin |last21=Feldner-Busztin |first21=Dylan |last22=Ristori |first22=Tommaso |last23=Finkelstein |first23=Anthony |last24=Bonsall |first24=David G. |last25=Abeler-Dörner |first25=Lucie |last26=Fraser |first26=Christophe |journal=PLOS Computational Biology |volume=17 |issue=7 |pages=e1009146 |pmid=34252083 |pmc=8328312 |bibcode=2021PLSCB..17E9146H }} used by the NHS to model the pandemic, winning the 2021 Analysis in Government award for Innovative methods.{{Cite web|url=https://www.gov.uk/government/news/analysis-in-government-award-winners-2021|title=2021 Analysis in Government awards}}

Fraser worked on

the 2002–2004 SARS outbreak,{{cite journal |doi=10.1126/science.1086478|title=Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions|date=2003 |last1=Riley |first1=Steven |last2=Fraser |first2=Christophe |last3=Donnelly |first3=Christl A. |last4=Ghani |first4=Azra C. |last5=Abu-Raddad |first5=Laith J. |last6=Hedley |first6=Anthony J. |last7=Leung |first7=Gabriel M. |last8=Ho |first8=Lai-Ming |last9=Lam |first9=Tai-Hing |last10=Thach |first10=Thuan Q. |last11=Chau |first11=Patsy |last12=Chan |first12=King-Pan |last13=Lo |first13=Su-Vui |last14=Leung |first14=Pak-Yin |last15=Tsang |first15=Thomas |last16=Ho |first16=William |last17=Lee |first17=Koon-Hung |last18=Lau |first18=Edith M. C. |last19=Ferguson |first19=Neil M. |last20=Anderson |first20=Roy M. |journal=Science |volume=300 |issue=5627 |pages=1961–1966 |pmid=12766206 |bibcode=2003Sci...300.1961R |s2cid=6429913 }}

the 2009 swine flu pandemic,{{cite journal |doi=10.1126/science.1176062|title=Pandemic potential of a strain of influenza A (H1N1): early findings|date=2009 |pmc=3735127 |last1=Fraser |first1=Christophe |last2=Donnelly |first2=Christl A. |last3=Cauchemez |first3=Simon |last4=Hanage |first4=William P. |last5=Van Kerkhove |first5=Maria D. |last6=Hollingsworth |first6=T. Déirdre |last7=Griffin |first7=Jamie |last8=Baggaley |first8=Rebecca F. |last9=Jenkins |first9=Helen E. |last10=Lyons |first10=Emily J. |last11=Jombart |first11=Thibaut |last12=Hinsley |first12=Wes R. |last13=Grassly |first13=Nicholas C. |last14=Balloux |first14=Francois |last15=Ghani |first15=Azra C. |last16=Ferguson |first16=Neil M. |last17=Rambaut |first17=Andrew |last18=Pybus |first18=Oliver G. |last19=Lopez-Gatell |first19=Hugo |last20=Alpuche-Aranda |first20=Celia M. |last21=Chapela |first21=Ietza Bojorquez |last22=Zavala |first22=Ethel Palacios |last23=Guevara |first23=Dulce Ma. Espejo |last24=Checchi |first24=Francesco |last25=Garcia |first25=Erika |last26=Hugonnet |first26=Stephane |last27=Roth |first27=Cathy |author28=The WHO Rapid Pandemic Assessment Collaboration |journal=Science |volume=324 |issue=5934 |pages=1557–1561 |pmid=19433588 |bibcode=2009Sci...324.1557F }}

the 2012 MERS outbreak{{cite journal |doi=10.1016/S1473-3099(13)70304-9|title=Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility|date=2014 |pmc=3895322 |last1=Cauchemez |first1=Simon |last2=Fraser |first2=Christophe |last3=Van Kerkhove |first3=Maria D. |last4=Donnelly |first4=Christl A. |last5=Riley |first5=Steven |last6=Rambaut |first6=Andrew |last7=Enouf |first7=Vincent |last8=Van Der Werf |first8=Sylvie |last9=Ferguson |first9=Neil M. |journal=The Lancet Infectious Diseases |volume=14 |issue=1 |pages=50–56 |pmid=24239323 }}

and the Western African Ebola virus epidemic.{{cite journal |doi=10.1371/journal.pmed.1002170|title=Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study|date=2016 |pmc=5112802 |doi-access=free |last1=Agua-Agum |first1=Junerlyn |last2=Ariyarajah |first2=Archchun |last3=Aylward |first3=Bruce |last4=Bawo |first4=Luke |last5=Bilivogui |first5=Pepe |last6=Blake |first6=Isobel M. |last7=Brennan |first7=Richard J. |last8=Cawthorne |first8=Amy |last9=Cleary |first9=Eilish |last10=Clement |first10=Peter |last11=Conteh |first11=Roland |last12=Cori |first12=Anne |last13=Dafae |first13=Foday |last14=Dahl |first14=Benjamin |last15=Dangou |first15=Jean-Marie |last16=Diallo |first16=Boubacar |last17=Donnelly |first17=Christl A. |last18=Dorigatti |first18=Ilaria |last19=Dye |first19=Christopher |last20=Eckmanns |first20=Tim |last21=Fallah |first21=Mosoka |last22=Ferguson |first22=Neil M. |last23=Fiebig |first23=Lena |last24=Fraser |first24=Christophe |last25=Garske |first25=Tini |last26=Gonzalez |first26=Lice |last27=Hamblion |first27=Esther |last28=Hamid |first28=Nuha |last29=Hersey |first29=Sara |last30=Hinsley |first30=Wes |journal=PLOS Medicine |volume=13 |issue=11 |pages=e1002170 |pmid=27846234 |display-authors=1 }}

Fraser's publications{{Google scholar id}} include "Factors that make an infectious disease outbreak controllable",{{cite journal |doi=10.1073/pnas.0307506101|title=Factors that make an infectious disease outbreak controllable|date=2004 |pmc=395937 |last1=Fraser |first1=Christophe |last2=Riley |first2=Steven |last3=Anderson |first3=Roy M. |last4=Ferguson |first4=Neil M. |journal=Proceedings of the National Academy of Sciences |volume=101 |issue=16 |pages=6146–6151 |pmid=15071187 |bibcode=2004PNAS..101.6146F |doi-access=free }} 2004, which argued that in addition to the basic reproduction number $R\_0$ a second key parameter of an infectious disease is the proportion of transmission that occurs before the onset of symptoms.

This proportion being large for SARS-CoV-2 was a key difficulty in infection control for the COVID-19 pandemic.

Fraser's 2007 analysis "Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic"{{cite journal|doi=10.1371/journal.pone.0000758|title=Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic|date=2007 |pmc=1950082 |doi-access=free |last1=Fraser |first1=Christophe |journal=PLOS ONE |volume=2 |issue=8 |pages=e758 |pmid=17712406 |bibcode=2007PLoSO...2..758F }} first defined an estimator for the instantaneous (time-varying) reproduction number $R(t)$ that was subsequently widely used.{{cite journal|doi=10.1093/aje/kwt133|title=A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics|date=2013 |pmc=3816335 |last1=Cori |first1=Anne |last2=Ferguson |first2=Neil M. |last3=Fraser |first3=Christophe |last4=Cauchemez |first4=Simon |journal=American Journal of Epidemiology |volume=178 |issue=9 |pages=1505–1512 |pmid=24043437 }} The definition was obtained by inverting the standard relationship between the reproduction number, the generation time distribution and the parameter $r$ of the Malthusian growth model that is implied by the renewal equation for epidemic dynamics{{cite journal|doi=10.1098/rspb.2006.3754|title=How generation intervals shape the relationship between growth rates and reproductive numbers|date=2007 |pmc=1766383 |last1=Wallinga |first1=J. |last2=Lipsitch |first2=M. |journal=Proceedings of the Royal Society B: Biological Sciences |volume=274 |issue=1609 |pages=599–604 |pmid=17476782 }} (or the Euler-Lotka equation as it is known in demography; the two are equivalent due to actual births being analogous to infectious disease transmissions as 'epidemiological births', giving rise to a new infected individual{{cite journal|doi=10.1016/0025-5564(95)00053-4|title=The intrinsic rate of increase of HIV/AIDS: Epidemiological and evolutionary implications|date=1996 | last1=Levin | first1=B.R | first2=J.J. | last2=Bull | first3 = F.M. | last3 = Stewart |journal=Mathematical Biosciences |volume=132 |pages=69-96}}{{cite journal|doi=10.1016/j.mbs.2009.10.004|title=Some model based considerations on observing generation times for communicable diseases|date=2010 | first1 = Gianpaolo | last1 = Scalia Tomba | first2=Åke | last2=Svensson | first3=Tommi | last3=Asikainen | first4=Johan | last4=Giesecke | journal=Mathematical Biosciences}}).

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Category:Living people

Category:Academics of the University of Oxford

Category:Academics of Imperial College London

Category:Alumni of the University of Edinburgh

Category:British epidemiologists

Category:Mathematical and theoretical biology

Category:COVID-19 pandemic in England

Category:1973 births