Molecular Epidemiology and Transmission of Two Deadly ... · RNA virus Biosafety level: 4 African...
Transcript of Molecular Epidemiology and Transmission of Two Deadly ... · RNA virus Biosafety level: 4 African...
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KirstyKwokStudyProgram:
MPhilinMicrobiology
Supervisor:Dr.MartinChan
DepartmentofMicrobiology
Friday,December9,2016
MolecularEpidemiologyandTransmissionofTwoDeadlyHumanViruses–TheEbolaVirusandLassaVirus
Andersen,K.etal.(Cell,2015)
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1995 1996 2016
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Single-strandedRNAvirus
Biosafetylevel:4
Africanviruses
Naturalreservoirs:Likelytobebats
AverageCasefatalityrate:~50%
Naturalreservoirs:Mastomys natalensis
80%infections:asymptotic
1in5infectionsàsevereoutcome(CFRà15to20%)
CFRcanbe>50%inoutbreakse.g.2016Nigeriaoutbreak189cases,89deathsàCFR53.9%
Ebolavirus(EBOV)
Lassavirus(LASV)
WHO,2016
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OverviewofEBOVandLASVgenome sequencingstudiesperformedduring2014–2016
Study Platform Method Sequencing location Caselocation No.ofseqs Virusofstudy
Baize,S. etal.(Apr.2014) Sanger Amplicon International Guinea 3 EBOV
Gire,S.K. etal.(Sep.2014) Illumina Direct International SierraLeone 79 EBOV
Hoenen,T. etal.(Apr.2015) Sanger Amplicon International Mali 4 EBOV
Bell,A. etal.(May.2015) Illumina Direct International UK 3 EBOV
Park,D.J. etal.(Jun.2015) Illumina Direct International SierraLeone 232 EBOV
Kugelman,J.R. etal.(Jul.2015) Illumina Direct In-country/Liberia Liberia 25 EBOV
Simon-Loriere,E. etal.(Aug.2015)
Illumina Direct International Guinea 85 EBOV
Carroll,M.W. etal.(Aug.2015) Illumina Direct International Guinea/Liberia 179 EBOV
Tong,Y.G. etal.(Aug.2015) BGISEQ-100 Amplicon ? SierraLeone 175 EBOV
Smits,S.L. etal.(Sep.2015) IonTorrent Amplicon In-country/SierraLeone SierraLeone 49 EBOV
Ladner,J.T. etal.(Dec.2015) Illumina Direct International Liberia 140 EBOV
Quick,J. etal.(Feb.2016) MinION Amplicon In-country/Guinea Guinea 137 EBOV
Hoenen,T. etal.(Feb.2016) MinION Amplicon In-country/Liberia Liberia 8 EBOV
Arias,A. etal.(Jun.2016) IonTorrent Amplicon In-country/SierraLeone SierraLeone 554 EBOV
Andersen,K.etal.(Aug.2015) Illumina Direct ? Nigeria,SierraLeone 183 LASV
Holmes,E.etal. (Nature,2016)
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Study Platform Method Sequencing location Caselocation No.ofseqs Virusofstudy
Baize,S. etal.(Apr.2014) Sanger Amplicon International Guinea 3 EBOV
Gire,S.K. etal.(Sep.2014) Illumina Direct International SierraLeone 79 EBOV
Hoenen,T. etal.(Apr.2015) Sanger Amplicon International Mali 4 EBOV
Bell,A. etal.(May.2015) Illumina Direct International UK 3 EBOV
Park,D.J. etal.(Jun.2015) Illumina Direct International SierraLeone 232 EBOV
Kugelman,J.R. etal.(Jul.2015) Illumina Direct In-country/Liberia Liberia 25 EBOV
Simon-Loriere,E. etal.(Aug.2015)
Illumina Direct International Guinea 85 EBOV
Carroll,M.W. etal.(Aug.2015) Illumina Direct International Guinea/Liberia 179 EBOV
Tong,Y.G. etal.(Aug.2015) BGISEQ-100 Amplicon ? SierraLeone 175 EBOV
Smits,S.L. etal.(Sep.2015) IonTorrent Amplicon In-country/SierraLeone SierraLeone 49 EBOV
Ladner,J.T. etal.(Dec.2015) Illumina Direct International Liberia 140 EBOV
Quick,J. etal.(Feb.2016) MinION Amplicon In-country/Guinea Guinea 137 EBOV
Hoenen,T. etal.(Feb.2016) MinION Amplicon In-country/Liberia Liberia 8 EBOV
Arias,A. etal.(Jun.2016) IonTorrent Amplicon In-country/SierraLeone SierraLeone 554 EBOV
Andersen,K.etal.(Aug.2015) Illumina Direct ? Nigeria,SierraLeone 183 LASV
Holmes,E.etal. (Nature,2016)
OverviewofEBOVandLASVgenome sequencingstudiesperformedduring2014–2016
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Whatcangenomicmolecularepidemiologystudiestellusaboutthevirus?
àItcanhelpustofindthetransmissionpatternofEBOV/LASV
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?
Repeatedspilloverfromreservoirs orsustainedhuman-to-human transmission?
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Andersen,K.etal.(Cell,2015)
EBOV: Samples’collectiondateisstronglycorrelatedwithroot-to-tipdistance
LASV:Nocorrelationbetweencollectiondateandroot-to-tipdistance
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Andersen,K.etal.(Cell,2015)
EBOV: Human-to-humantransmissioniscompatiblewiththiscorrelation
LASV:Transmissionislikelyfromacommonsourceofinfectioni.e.naturalreservoirs
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Gire,S.K.etal.(Science,2014)
WhatcangenomesequencingtellusaboutthemostrecentEBOVoutbreak?
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Gire,S.K.etal.(Science,2014)
ThemostrecentEbolaEpidemicislikelydueto asingletransmissionfromthenaturalreservoir,followedbyhuman-to-humantransmission!
Commonancestor
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Patientzero
An18-month-oldboyLocation:Meliandou,GuineaDateofonsetofsymptoms:26December2013Symptoms:Fever,blackstools,andvomitingResults:DiedtwodayslaterPossiblesourceofinfection:Thechildwasseenplayinginhisbackyardnearahollowtreeheavilyinfestedwithbats
WHO,2015BaizeS.etal.(NEJM,2014)
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Howdidtheoutbreakstart?
BBCNews,2014
PatientZero
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Gire,S.K.etal.(Science,2014)
2013– 2015EbolaEpidemicislikelydueto asingletransmissionfromthenaturalreservoir,followedbyhuman-to-humantransmission!
Commonancestor
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Andersen,K.etal.(Cell,2015)
WhataboutLASV?
LASV:Rodentstrainsareinterspersedwithhumanstrains
LASV:Multiplereservoirs-to-humantransmissioneventsinLASVinfections
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Andersen,K.etal.(Cell,2015)
WhataboutLASV?
LASV:Branchesdevelopinginpatients’strains
LASV:Human-to-humantransmissioneventsdosometimesoccurinLASVinfectionstoo
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Whatcangenomicmolecularepidemiologystudiestellusaboutthevirus?
àItcanhelpustomonitorthetransmissionsofEBOVacrossborders
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DoestransmissionofEBOVoccuracrossborder?
EBOV:From thisstudy,wecansee limitedEBOVexchangeacrosstheSierraLeoneanBorder
Park,D.J. etal.(Cell,2015)
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WhatwillweseeiffreeEBOVinterchangeoccurswithneighboringcountries?
Park,D.J. etal.(Cell,2015)
SierraLeoneàLiberia
LiberiaàSierraLeone
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Cangenomic molecularepidemiologystudieshelpustocontainanoutbreak?
Whatarethe publichealthusefulness of genomicmolecularepidemiology?
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GenomicEpidemiology
Monitorvirusevolution
ReconstructEBOVtransmissionchainandspreadintheepidemic
Identifypossibletransmissionroutes
GenomicEpidemiologyXPublicHealth
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Mate,S.E.etal.(NEJM,2015)
MolecularevidenceofsexualtransmissionofEBOV
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Thepowerofwhole genome molecularepidemiology
Video:https://vimeo.com/156668942
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Outbreakschronology:Ebolavirusdisease
CDC,2015CDC,2016
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William,E.D.etal.(Cell,2016) Richard,A.U.etal.(Cell,2016)
Whythe2013–2016EBOVoutbreakwassomuchlargerthanpreviousoutbreaks?
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William,E.D.etal.(Cell,2016)
Whythe2013– 2016EBOVoutbreakwassomuchlargerthanpreviousoutbreaks?
EvolutionofGP-A82VCoincideswithDramaticIncreaseinEBOVInfections
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Lessonslearnedandfuturedirectionsinoutbreakresponse
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LargestEBOVOutbreakinHistory
LackofResources
CulturalIssue
GP-A82VMutation
MultiplefactorscontributetoEBOVepidemic2013 – 2016
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WHOOneyearreport
“A"mysterious"diseasebegansilentlyspreadinginasmallvillageinGuineaon26December2013butwasnotidentifiedasEbolauntil21March2014”
WHO,2015
Delayeddiagnosisà Delayedalertà Delayedinfectioncontrolà EBOVOutbreak!
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Study Platform Method Sequencing location Caselocation No.ofseqs
Virusofstudy
Baize,S. etal.(Apr.2014) Sanger Amplicon International Guinea 3 EBOV
Gire,S.K. etal.(Sep.2014) Illumina Direct International SierraLeone 79 EBOV
Hoenen,T. etal.(Apr.2015) Sanger Amplicon International Mali 4 EBOV
Bell,A. etal.(May.2015) Illumina Direct International UK 3 EBOV
Park,D.J. etal.(Jun.2015) Illumina Direct International SierraLeone 232 EBOV
Kugelman,J.R. etal.(Jul.2015) Illumina Direct In-country/Liberia Liberia 25 EBOV
Simon-Loriere,E. etal.(Aug.2015) Illumina Direct International Guinea 85 EBOV
Carroll,M.W. etal.(Aug.2015) Illumina Direct International Guinea/Liberia 179 EBOV
Tong,Y.G. etal.(Aug.2015) BGISEQ-100 Amplicon ? SierraLeone 175 EBOV
Andersen,K.etal.(Aug.2015) Illumina Direct ? Nigeria,SierraLeone 183 LASV
Smits,S.L. etal.(Sep.2015) IonTorrent Amplicon In-country/SierraLeone SierraLeone 49 EBOV
Ladner,J.T. etal. (Dec.2015) Illumina Direct International Liberia 140 EBOV
Quick,J. etal.(Feb.2016) MinION Amplicon In-country/Guinea Guinea 137 EBOV
Hoenen,T. etal.(Feb.2016) MinION Amplicon In-country/Liberia Liberia 8 EBOV
Arias,A. etal.(Jun.2016) IonTorrent Amplicon In-country/SierraLeone SierraLeone 554 EBOV
Holmes,E.etal. (Nature,2016)
2014
2015
2016LackofsequencingcapacityinAfrica
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Whatareneededforfutureoutbreakresponsesintheaffectedcountries?
üHealthcareinfrastructureüHealthcaretrainingoflocalstaffüLocallaboratorycapacityüSharedsequencesdatabaseüPortablesequencingtechnologies
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Whatareneededforfutureoutbreakresponsesintheaffectedcountries?
üHealthcareinfrastructureüHealthcaretrainingoflocalstaffüLocallaboratorycapacityüSharedsequencesdatabaseüPortablesequencingtechnologies
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ImageReferencesSlide # Url
1 http://tree.bio.ed.ac.uk/research/molepi.pnghttps://www.usaid.gov/sites/default/files/nodeimage/Power-Africa-map-rev.png
2 https://upload.wikimedia.org/wikipedia/en/0/08/Outbreak_movie.JPGhttp://4.bp.blogspot.com/JJ466EDrfFA/Ub8yqkGN5OI/AAAAAAAAHMg/98wqYnz0NUY/s1600/Ebola+Syndrome+1.jpghttp://93daysmovie.com/wp-content/uploads/2014/11/93DaysWebPoster1.jpg
3 http://farm3.staticflickr.com/2237/2044987545_0e36ef42d7.jpg
6,17,20,27 http://tree.bio.ed.ac.uk/research/molepi.pnghttps://www.aacc.org/~/media/images/cln/articles/2012/april/dnasequencing.jpg?la=en
7 http://images.clipartpanda.com/batman-clipart-black-and-white-batman-20clip-20art--batman-clipart-8.pnghttp://images.clipartpanda.com/mickey-mouse-head-clipart-13555293131641649437untitled-hi.png
12 https://upload.wikimedia.org/wikipedia/commons/e/ed/Flag_of_Guinea.svghttp://www.unmultimedia.org/radio/english/wp-content/uploads/2014/10/meliandou1.jpg
27 https://thumbs.dreamstime.com/x/stop-ebola-modified-sign-virus-45915586.jpg
31,32 http://ngs-expert.com/wp-content/uploads/2014/06/4130_mini_ion_lab-copy.pnghttps://upload.wikimedia.org/wikipedia/commons/thumb/f/fa/Flag_of_the_People's_Republic_of_China.svg/2000px-Flag_of_the_People's_Republic_of_China.svg.pnghttp://az616578.vo.msecnd.net/files/2016/03/15/635936094413774872601650525_share.jpghttps://europa.eu/european-union/sites/europaeu/files/docs/body/flag_yellow_high.jpghttps://upload.wikimedia.org/wikipedia/en/thumb/a/a4/Flag_of_the_United_States.svg/300px-Flag_of_the_United_States.svg.pnghttp://plusquotes.com/images/quotes-img/Minion.jpg
34 http://flusolution.net/wp-content/uploads/2014/08/Photo-Ebola-Map-of-Africa.jpg
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Thankyou