Molecular Epidemiology and Transmission of Two Deadly ... Kirsty.pdfThe Ebola Virus and Lassa Virus...

KirstyKwokStudyProgram:

MPhilinMicrobiology

Supervisor:Dr.MartinChan

DepartmentofMicrobiology

Friday,December9,2016

MolecularEpidemiologyandTransmissionofTwoDeadlyHumanViruses–TheEbolaVirusandLassaVirus

Andersen,K.etal.(Cell,2015)

1995 1996 2016

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

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)

Study Platform Method Sequencing location Caselocation No.ofseqs Virusofstudy







Simon-Loriere,E. etal.(Aug.2015)

Illumina Direct International Guinea 85 EBOV




Ladner,J.T. etal.(Dec.2015) Illumina Direct International Liberia 140 EBOV






OverviewofEBOVandLASVgenome sequencingstudiesperformedduring2014–2016

Whatcangenomicmolecularepidemiologystudiestellusaboutthevirus?

àItcanhelpustofindthetransmissionpatternofEBOV/LASV

?

Repeatedspilloverfromreservoirs orsustainedhuman-to-human transmission?


EBOV: Samples’collectiondateisstronglycorrelatedwithroot-to-tipdistance

LASV:Nocorrelationbetweencollectiondateandroot-to-tipdistance


EBOV: Human-to-humantransmissioniscompatiblewiththiscorrelation

LASV:Transmissionislikelyfromacommonsourceofinfectioni.e.naturalreservoirs

Gire,S.K.etal.(Science,2014)

WhatcangenomesequencingtellusaboutthemostrecentEBOVoutbreak?


ThemostrecentEbolaEpidemicislikelydueto asingletransmissionfromthenaturalreservoir,followedbyhuman-to-humantransmission!

Commonancestor

Patientzero

An18-month-oldboyLocation:Meliandou,GuineaDateofonsetofsymptoms:26December2013Symptoms:Fever,blackstools,andvomitingResults:DiedtwodayslaterPossiblesourceofinfection:Thechildwasseenplayinginhisbackyardnearahollowtreeheavilyinfestedwithbats

WHO,2015BaizeS.etal.(NEJM,2014)

Howdidtheoutbreakstart?

BBCNews,2014

PatientZero


2013– 2015EbolaEpidemicislikelydueto asingletransmissionfromthenaturalreservoir,followedbyhuman-to-humantransmission!

Commonancestor


WhataboutLASV?

LASV:Rodentstrainsareinterspersedwithhumanstrains

LASV:Multiplereservoirs-to-humantransmissioneventsinLASVinfections


WhataboutLASV?

LASV:Branchesdevelopinginpatients’strains

LASV:Human-to-humantransmissioneventsdosometimesoccurinLASVinfectionstoo

Whatcangenomicmolecularepidemiologystudiestellusaboutthevirus?

àItcanhelpustomonitorthetransmissionsofEBOVacrossborders

DoestransmissionofEBOVoccuracrossborder?

EBOV:From thisstudy,wecansee limitedEBOVexchangeacrosstheSierraLeoneanBorder

Park,D.J. etal.(Cell,2015)

WhatwillweseeiffreeEBOVinterchangeoccurswithneighboringcountries?

Park,D.J. etal.(Cell,2015)

SierraLeoneàLiberia

LiberiaàSierraLeone

Cangenomic molecularepidemiologystudieshelpustocontainanoutbreak?

Whatarethe publichealthusefulness of genomicmolecularepidemiology?

GenomicEpidemiology

Monitorvirusevolution

ReconstructEBOVtransmissionchainandspreadintheepidemic

Identifypossibletransmissionroutes

GenomicEpidemiologyXPublicHealth

Mate,S.E.etal.(NEJM,2015)

MolecularevidenceofsexualtransmissionofEBOV

Thepowerofwhole genome molecularepidemiology

Video:https://vimeo.com/156668942

Outbreakschronology:Ebolavirusdisease

CDC,2015CDC,2016

William,E.D.etal.(Cell,2016) Richard,A.U.etal.(Cell,2016)

Whythe2013–2016EBOVoutbreakwassomuchlargerthanpreviousoutbreaks?

William,E.D.etal.(Cell,2016)

Whythe2013– 2016EBOVoutbreakwassomuchlargerthanpreviousoutbreaks?

EvolutionofGP-A82VCoincideswithDramaticIncreaseinEBOVInfections

Lessonslearnedandfuturedirectionsinoutbreakresponse

LargestEBOVOutbreakinHistory

LackofResources

CulturalIssue

GP-A82VMutation

MultiplefactorscontributetoEBOVepidemic2013 – 2016

WHOOneyearreport

“A"mysterious"diseasebegansilentlyspreadinginasmallvillageinGuineaon26December2013butwasnotidentifiedasEbolauntil21March2014”

WHO,2015

Delayeddiagnosisà Delayedalertà Delayedinfectioncontrolà EBOVOutbreak!

Study Platform Method Sequencing location Caselocation No.ofseqs

Virusofstudy







Simon-Loriere,E. etal.(Aug.2015) Illumina Direct International Guinea 85 EBOV





Ladner,J.T. etal. (Dec.2015) Illumina Direct International Liberia 140 EBOV





2014

2015

2016LackofsequencingcapacityinAfrica

Whatareneededforfutureoutbreakresponsesintheaffectedcountries?

üHealthcareinfrastructureüHealthcaretrainingoflocalstaffüLocallaboratorycapacityüSharedsequencesdatabaseüPortablesequencingtechnologies

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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Molecular Epidemiology and Transmission of Two Deadly ... Kirsty.pdfThe Ebola Virus and Lassa Virus...

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