Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
THE ANTIBIOTIC CRISIS
Mark WoolhouseCentre for Immunity, Infection and Evolution,
University of Edinburgh
UN RESOLUTION
M.E.J. Woolhouse, University of Edinburgh, March 2017
WORDS →ACTIONS→ CHANGE
• Raiseawareness• Improvesurveillance• Recogniselocalneeds• OneHealthapproach• UN-ledcoordinatingbody• Reportin2years’time
BACKGROUND
M.E.J. Woolhouse, University of Edinburgh, March 2017
NATURAL RESISTANCE
• 50-200tonnesbacteriaperperson
• Soil- Sourceof>80%antibiotics- Containshomologousresistancegenesforall
majorclassesofantibiotic- Forsbergetal.(2012)Science
• Antibioticsandantibioticresistancearenatural,ancientandubiquitous- D’Costa etal.(2011)Nature
• Antibioticproductionbyhumans175,000tonnesyr -1 =20tonneshr -1
• Antibioticproductionbybacteria>1moleculeper10Kbacteriumperhr?
M.E.J. Woolhouse, University of Edinburgh, March 2017 Woolhouseetal.(2015)Phil.Trans.B
USES OF ANTIBIOTICS
M.E.J. Woolhouse, University of Edinburgh, March 2017
• Communicablediseasesduetobacteria− Tuberculosis− Sexuallytransmitteddiseases− Respiratorytractinfections− (Some)diarrhoea− Healthcare-associatedinfections
• Endogenousbacterialinfections− Urinarytractinfections− Skinandsofttissueinfections− Infectiveendocarditis− Sepsis
• Prophylaxis− Burns,wounds− Caesareansections− Jointreplacements− Cancertherapy− Organtransplants
Antibioticsunderpinmuchofmodernmedicine
Antibioticshavesavedcountlesslives,andtheycontinuetodoso
AMR PRIORITIES
M.E.J. Woolhouse, University of Edinburgh, March 2017
WHAT’S THE PROBLEM?
DeathsduetonotusingantimicrobialsDeathsduetoAMR
Inthefuture Now
M.E.J. Woolhouse, University of Edinburgh, March 2017
EXCESSvsACCESS
RECOMMENDATIONS
M.E.J. Woolhouse, University of Edinburgh, March 2017
1) Globalpublicawareness campaign2) Improvesanitation andpreventthespreadofinfection3) Reduceunnecessaryuseofantimicrobialsinagriculture andtheir
disseminationintotheenvironment4) Improveglobalsurveillance ofdrugresistanceandantimicrobial
consumptioninhumansandanimals5) Promotenew,rapiddiagnostics toreduceunnecessaryuseof
antimicrobials6) Promotedevelopmentanduseofvaccinesandalternatives7) Improvethenumber,pay andrecognitionofpeopleworkingin
infectiousdisease8) Aglobalinnovation fundforearlystageandnon-commercialR&D9) Betterincentives topromoteinvestmentfornewdrugsand
improvingexistingones10) Buildanewglobalcoalition forrealaction– viaG20andUN
OUTLINE
• AMRburdenandsurveillance
• LivestockAMR
• Governanceandregulation
M.E.J. Woolhouse, University of Edinburgh, March 2017
OUTLINE
• AMRburdenandsurveillance
• LivestockAMR
• Governanceandregulation
M.E.J. Woolhouse, University of Edinburgh, March 2017
PUBLISHED ESTIMATES
CDC• USin2013• 16bacterialinfections
→ 23Kdeathsperyr→ 2Millnesses
M.E.J. Woolhouse, University of Edinburgh, March 2017
ECDC• EUin2009• 6 bacterialinfections
→ 25Kdeathsperyr→ 400Killnesses
O’NeillReview• Globalin2013• ExtrapolatedfromUS+
WHOestimatesforTB→ 700Kdeathsperyr
increasingto10Mdeaths peryr by2050
ANTIBIOTIC USAGE
M.E.J. Woolhouse, University of Edinburgh, March 2017
• Datafrom80countriescovering81%globalpopulation• Volume>70billionstandardunitsin2010• Globalconsumptionofantibioticsincreasedby36%between2000-2010• Brazil,Russia,India,ChinaandSouthAfricaaccountedfor76%ofincrease
VanBoeckel etal.(2014)LID
REDUCING USAGE
• Usagemuchhigherinprimarycare• AMRproblemmuchgreaterin
secondary/tertiarycare
• Point-of-decisiondiagnostics:– Virusorbacteria?– Beyondculture– Real-timegenomicsØ LongitudePrize
• Moreintelligentuse- Overkillstrategies- Combinationtherapies- Re-useandre-cycling
Imamovic &Sommer (2013)Sci TransMed
M.E.J. Woolhouse, University of Edinburgh, March 2017
? Settargets? Switchtonarrow-spectrumdrugs? Developalternatives
ALTERNATIVES TO ANTIBIOTICS
• PrebioticsandprobioticsCommerciallyavailablebutefficacyunclearandlikelyvariable
• Phagetherapy,e.g.lyticphagevsS.aureus
• Vaccination
M.E.J. Woolhouse, University of Edinburgh, March 2017
INCREASING RESISTANCE
M.E.J. Woolhouse, University of Edinburgh, March 2017
Sanchezetal.(2013)EID
Klebsiella pneumoniae intheUSA,1998-2010
M.E.J. Woolhouse, University of Edinburgh, March 2017 WHOreport(2014)
• Globalsurveyofnationalresistancedata
• Collatedestimatesofresistanceratestoselectedantimicrobialsforcommonbacteriainc.150countries
Ø Frequentreportsof>50%resistancefor:
− E.colivs3rd gencephalosporins− E.colivsfluoroquinolones− Klebsiella vs3rd gencephalosporins− Klebsiella vscarbapenems− S.aureusvsmethicillin
GLOBAL SURVEILLANCE
M.E.J. Woolhouse, University of Edinburgh, March 2017 WHOreport(2014)
• Lackofstandardmethodology
• Lackofdatasharing
• Significantgapsinresistancesurveillance
• Lessthan50%ofglobalpopulationunderanykindofsurveillanceatall
GLOBAL SURVEILLANCE
CAN WE DO BETTER?
• ICD-11
• Sentinelhospitals
• Sentinelclinicians
• Notifiable,e.g.XDR-TB,CREs
M.E.J. Woolhouse, University of Edinburgh, March 2017 Woolhouseetal.(2016)J.Glob.Hlth
Metagenomics+ResFinder
bioinformaticspipeline
GLOBALSEWAGESURVEILLANCE
M.E.J. Woolhouse, University of Edinburgh, March 2017
BUSIAFIELDLABORATORY,W.KENYA
M.E.J. Woolhouse, University of Edinburgh, March 2017
SURVEILLANCEINREMOTESETTINGS
OUTLINE
• AMRburdenandsurveillance
• LivestockAMR
• Governanceandregulation
M.E.J. Woolhouse, University of Edinburgh, March 2017
AMR IS A ONE HEALTH ISSUE
Multiplemodesofmovement:• bacteria• mobilegeneticelements
Multipledrug-bugcombinations
Woolhouse&Ward(2013)Science
M.E.J. Woolhouse, University of Edinburgh, March 2017
ANTIBIOTICS ON THE FARM
• Industrialagricultureworkswithverysmallmargins
• Antibioticsusedas:- metaphylaxis- “targeted”prophylaxis- and...
• Growthpromoters- Usedsince1950s- Achieveupto15-20%higherweightgain- Worksforantibacterials,butnotantifungalsorantivirals- Mechanismuncertain- Worksinchildrentoo
M.E.J. Woolhouse, University of Edinburgh, March 2017
CONSUMPTION ON THE FARM
EUgrowthpromoterban2006
Increasedmetaphylactic, prophylacticuse
→ Antibioticusage→ livestock:humans ≈ 1:1
M.E.J. Woolhouse, University of Edinburgh, March 2017
Elliot(2015)CDDEP
RESISTANCE ON THE FARM
M.E.J. Woolhouse, University of Edinburgh, March 2017
COLISTIN RESISTANCE
• Polymyxin classantibioticdiscoveredin1949• Widelyusedinagriculture(esp.China)but
littleusedinhumansduetonephro- andneuro-toxicity
• Newplasmid-mediatedcolistin resistancegene(mcr-1)identifiedinChinain2015[Liuetal.2016LID]
• Highprevalenceofmcr-1 in Ecoli isolatesfromfoodanimalsandretailmeat
• Sincereported in35othercountries,inmultiplegram–ve organismsandfrommanydifferentsources
• Oldestpositiveisolatesdatebackto1980’s(chickensinChina)[Shenetal.2016LID]
M.E.J. Woolhouse, University of Edinburgh, March 2017
Failureofglobalsurveillance?
BACTERIA IN HUMANS AND LIVESTOCK
Lowder etal.(2009)PNAS
ST5INHUMANS+POULTRY
CC97INHUMANS +CATTLE
Spooretal.(2013)mBio
Matheretal.(2013)Science
DT104INHUMANS +CATTLE
←Betweenspecies↓Withinspecies
M.E.J. Woolhouse, University of Edinburgh, March 2017
TWO-WAY TRAFFIC
M.E.J. Woolhouse, University of Edinburgh, March 2017
MANAGING AMR IN LIVESTOCK
M.E.J. Woolhouse, University of Edinburgh, March 2017
Voluntaryguidance
Legalpartialban
Blanketban→↓antibioticconsumption↓animalhealth↓welfare↓production↑prices? publichealthbenefit
TWO-WAY TRAFFIC
M.E.J. Woolhouse, University of Edinburgh, March 2017
LowtransmissionH→A HightransmissionH→A
vanBunnik&Woolhouse(inpress)RSOpenSci
- In many circumstances, curbing antibiotic consumption by food animals, as a stand-alone measure, will often havevery limited benefits for human health.- A better strategy is an integrated approach that tackles resistance in humans and food animals at the same time.
Impact
WHAT’S THE PROBLEM?
M.E.J. Woolhouse, University of Edinburgh, March 2017
DeathsduetonotusingantimicrobialsDeathsduetoAMR
Includesfoodsafetyandfoodsecurity
Withdrawinganimalantibioticscancausefarmorehumanillness-daysthanitwouldprevent:theestimatehumanbenefit:risk ratio…exceeds1000:1inmanycases.
ACTION PLANS
M.E.J. Woolhouse, University of Edinburgh, March 2017
• Improveawareness
• Developcapacityforsurveillanceandmonitoring
• Promotegoodpractice
• Strengthengovernance
− Provideinformation− Developregulatory
frameworks− ImplementOneHealth
approaches
CHINA: Reduceveterinaryprescriptionby50%UK: Reducefoodanimalconsumptionto50mg/kg“average”
OUTLINE
• AMRburdenandsurveillance
• LivestockAMR
• Governanceandregulation
M.E.J. Woolhouse, University of Edinburgh, March 2017
GOVERNANCE OF AMR
• IPAMRwillneedtobe:- Global internationalhealthregulations- Cross-sectormedicine,agriculture,environment- Interdisciplinary clinicalandveterinarymedicine,
epidemiology,microbiology,pharmacology,healtheconomics,internationallaw,socialscience
- Multi-agencyWHO,OIE,UN,WTO,OECD- Buyinmedics,patients,vets,farmers,industry,
governments- Agenda→roadmaptoimprovedantimicrobial
stewardshipandsustainablealternatives
Woolhouse&Farrar(2014)NatureM.E.J. Woolhouse, University of Edinburgh, March 2017
SETEVIDENCE-BASED,QUANTITATIVEGOALSANDTARGETS
GOVERNANCE OF AMR
• Targetsforusage- phaseoutgrowthpromotersinanimals- limitto≤medianDDDinhumans
• Targetsforresistance- noincreaseintertiarycaresetting
• Governanceandfinancing- HighLevelCoordinatingMechanism
[UN,WHO,OIE,WorldBank,non-stateactors]
- Globalfund
Laxminarayan etal.(2016)ScienceM.E.J. Woolhouse, University of Edinburgh, March 2017
UK
ACKNOWLEDGEMENTS
- BramvanBunnik- MargoChase-Topping- GilesEdwards(SMRSARL)- JeremyFarrar(WellcomeTrust)- RossFitzgerald(Roslin Institute)- CherylGibbons- DeborahHoyle- RamananLaxminarayan(CDDEP)
- DishonMuloi- HarishNair- MeghanPerry- StefanRooke- DeviSridhar- NickSparks(SRUC)- MingguiWang(Fudan)- MelissaWard- CatrionaWaugh
KEY POINTS
• Theproblemisurgentandweneedtotakeaction
• Evidencebaseispatchyandthisimpedespolicydevelopment
• Nomagicbullet;needconcertedR&Dandconcertedactionsacrossmultiplesectors
• Helpfultosettargets- butwhatshouldtheybe?
• EdinburghInfectiousDiseases communityisexceptionallywellplacedtomakeameaningfulcontributiontothiseffort
M.E.J. Woolhouse, University of Edinburgh, March 2017