The Global Response To AMR - Wellcome

Executive summaryAntimicrobial resistance (AMR) is a growingpublic health concern in every country in theworld. It already causes at least 700,000 deaths dueto drug-resistant infections per year globally, anumber that may increase to 10 million per year by2050 – unless significant action is taken. AMR is notonly reversing recent gains made in controllinginfectious diseases but also underminingimprovements in healthcare provision in general. Itsbroader health effects include threatening the safetyof many healthcare interventions that are today seenas routine, including chemotherapy, organtransplants and other major surgeries. Asantimicrobial drugs lose their efficacy due to AMR,risks of prolonged hospital stays or additionalsurgical interventions increase substantially. Theneed to deal with AMR will burden health systemsalready struggling with cost inflation, and thedamage to national economies resulting fromincreasing illness and death will further hit healthbudgets. These health and economic burdens willdisproportionately fall on low- and middle-incomecountries (LMIC), preventing attainment ofSustainable Development Goals.But this worrying scenario can be avoided, or at thevery least mitigated. A large global community ofactors spanning governments, multilateral agencies,civil society, and the private sector are workingtogether on AMR. They have had some successalready, but the scope for future progress hangs inthe balance. The AMR community needs to agree onhow the topic should be positioned relative to thebroader pandemic preparedness and recoveryagenda, and how to prioritise the most importantareas for action.This report provides a comprehensive update on thestatus quo, recent developments, and remainingcritical gaps in the AMR response globally. Itsummarises these findings in two overarchingchapters and underwrites these with profilescovering themed areas where work is needed, andfactors that will enable that work across the globalhealth landscape. It sketches what a critical path forthe global response to AMR could look like,including how to define, prioritise, and implementactions in order to achieve greatest impact.These findings are the result of interviews with over100 experts and reviews of over 250 documents.Most of the interviews were conducted in 2019,when the world looked very different. Covid-19 hasradically changed the landscape for healthcareand infectious diseases. It has put healthcare atthe top of national and global agendas and elevatedtopics such as disease surveillance from technical tomainstream policy conversations (while perhapsimpacting the resources and capacity to conductthem). The Covid-19 response has also seen a seachange in the global conversation on innovation andwho pays for it, perhaps lastingly. To account forthese effects, the views of more than 80 expertswere captured during July and August 2020.A core finding stands out: the next few years willdefine the trajectory of the long-term AMRresponse and how successful it can be.The AMR community has achieved notable recentsuccesses: AMR has achieved prominence on the globalpolitical agenda: It has moved from a largelytechnical topic to a political one – a preconditionfor building an enabling environment that securesfunding, awareness, and leadership. The 2016 UNGeneral Assembly Political Declaration raisedAMR’s international profile as a pressing concern.Some of the global momentum may have wanedsince then, especially given Covid-19, but politicalawareness of AMR remains – at least for now. The AMR community is a broad, multi-sectoralcoalition of actors aware of, and willing totackle, AMR: Among this community, there is anunprecedented commitment to an approachspanning sectors including human health, animalsand agriculture, and the environment. The discovery-stage and translational researchenvironment is robustly funded: Significantfunds have been made available for early-stageresearch since 2016, especially on newtherapeutics. Moreover, despite the Covid-19pandemic, additional push funding has beenlaunched in 2020, including the 1 billion AMRAction Fund.v The Global Response to AMR

This enabling environment for action on AMR is atrisk of irreparably weakening. Three critical gapsdrive this risk: Ambitions have not always translated intomeaningful action: A substantial uptick in theprominence of global discussion on AMR over thepast three to four years has not translated intobroader implementation of initiatives. This is trueespecially in LMICs, where AMR typically competesfor political attention and resources with otherpublic health topics. Actors outside of policymaking circles frequently perceive the AMRcommunity as a ‘talking shop’. Prioritisation is increasingly emerging as a gap:The ‘big tent’ approach of the AMR response todate has increased awareness among a broadrange of stakeholders. Yet experts across the AMRspace are concerned that the multifaceted natureof the issue, the complexity of its narrative, andthe multitude of possible interventions areparalysing the community, preventing impactfulaction. There are discrete problems for whichknown solutions exist; to prioritise effectively, thecommunity must align on a critical path ofsequenced steps towards implementation. The AMR agenda was at risk of losingmomentum even pre-Covid-19: In late 2019,experts felt that the AMR agenda was at risk oflosing significant momentum over the next 12 to 24months unless it could demonstrate impact. Severalmentioned the potential for short-term, smallsuccesses to demonstrate concrete impact andcommunicate the importance of AMR to an outsideglobal audience. Covid-19 has made this concernmore acute. AMR needs a new, focused narrative ina post-Covid-19 world that can rejuvenateattention, resources, and action towards impact.Covid-19 has radically altered the world’sconversation on public health. Experts universallyagreed that Covid-19 will affect the globalresponse to AMR in at least two ways: Covid-19 has exerted both upward and downwardpressure on the development of drug resistance ininfections through several mechanisms (forexample, experts observed increased use ofantibiotics in inpatient settings, but decreased usein outpatient settings) – the net effect remains tobe seen. The policy fallout from Covid-19 brings bothrisks and opportunities for the attention AMRreceives on a policy level, including funding,advocacy, and research. Opportunities may includeincreased understanding of infection preventionand control (IPC), increased surveillance and labcapacity (and awareness of its importance), or evena clearer pathway into finance ministries forpreventive healthcare conversations. Risks mayinclude suspended hospital surveillanceprogrammes, young research talent too oftendiverted towards viral infections, resourceconstraints for implementation, ineffectivestewardship, and a decrease in the availability offunding for the global health agenda.Accordingly, there is a clear need to rethink AMR’sposition as part of the global health agenda. Thisraises the question of what that agenda may look likepost-Covid-19. Broadly, experts perceived three(perhaps overlapping) possibilities: The status quo of a limited, technical, and nichepandemic preparedness and recovery agenda. An expanded pandemic preparedness andrecovery agenda, prominent in political and socialattention, and funded accordingly. A much broader, revitalised infectious diseasesagenda that focuses on preparedness andresponse to novel pathogens in tandem withtackling existing endemic and pandemic diseases(e.g. Tuberculosis and HIV).Crucially, experts were broadly confident that the firstoption was less likely than the other two; which ofthose two would be likelier is uncertain.vi The Global Response to AMR

Assuming that one of these does develop, there isthen the question of how the AMR agenda shouldbe positioned. Broadly, experts identified threeperspectives: The AMR agenda should tie itself to an inclusivepandemic preparedness and response agenda. The AMR agenda should remain distinctbecause AMR is better served by distinctivenarratives. The AMR agenda should remain distinctbecause linking AMR to a broad pandemicpreparedness agenda is not feasible.In choosing between these perspectives and findinga common path forward, there are several openquestions that should urgently be answered: Which perspective is best supported byavailable evidence and information? Which perspective can established actors in thecurrent AMR community align on? Which perspective resonates with externaldecision makers and potential funders? How, where, and to whom should a newlyrepositioned AMR agenda be communicated?In light of the perception that the AMR agenda was atrisk of losing momentum even before Covid-19, it isimperative to start a broad exploratory dialogue onthese questions sooner rather than later.A first sketch of a potential ‘critical path’ to impact– focusing on implementing a narrower set of trulycritical interventions – sets out two phases.The first phase, 2020–30, focuses on mitigating therisk of resistance and its consequences, and onexpanding the evidence base where gaps remain abarrier to action. Beyond 2030, the second phasewill build on established infrastructure to controlresistance and its consequences, moving intomaintaining resistance control through preventionand through maintaining and scaling best practices.The first phase prioritises seven focus areas foraction: Water, sanitation, and hygiene (WASH): Access toclean water and sanitation reduces the transfer ofresistant pathogens and prevents infection.Achieving this would depend on communicating aclear and actionable vision for the WASHcommunity. This will require attention but onlylimited additional resource commitments from theAMR community. Infection prevention and control: IPC measuresreduce the need for antibiotics and thus theirconsumption. Given the robust global agenda onIPC, there will be significant benefits frommainstreaming AMR awareness into existing IPCinterventions. This will require attention but onlylimited additional resource commitments from theAMR community. Therapeutic innovation: As resistance to existingtreatments continues to develop, new ones must bedeveloped continuously and sustainably. There iswidespread agreement that the current R&Decosystem has not produced enough drugcandidates for a sustained response, and largescale, global pull incentives to spur innovationappear further away than in 2016. Surveillance: Effective surveillance systems arecritical to understanding the problem, designingand implementing interventions, and assessing theeffectiveness of the response. Key gaps in existingsurveillance systems include capturing data that isactionable and utilising all existing data sources. H uman consumption of antimicrobials:Optimising human consumption of antimicrobialsrequires guaranteed access for those who needtreatment as well as adequate stewardship to limitoverconsumption. This is a natural priority givenrising consumption among humans and its role inresistance development. Yet behavioural changeamong both prescribers and patients has remainedhard to achieve.vii The Global Response to AMR

Vaccine development and access: By preventinginfection in humans and animals, vaccines play animportant role in reducing antimicrobialconsumption. While the case for vaccines tosupport the AMR response is clear in principle,more and better evidence is needed to mobiliseinvestment, particularly for vaccines for pathogensthat are of priority concern from an AMR standpoint. Antimicrobial use in animals: For a response thatis preventive, not just focused on treatment, aholistic perspective that includes other topicsacross the One Health spectrum is essential. Onesuch factor is that reducing drug-resistantinfections in humans requires ensuring appropriateantimicrobial use in animals.Other topics warrant attention and investment inthe near term, but may not be the focus of urgentaction. These include developing and ensuringaccess to (new) diagnostics, combatting lowquality or falsified antimicrobials, strengtheninghealth security systems and cooperation, limitingAMR in plants and in the environment, ensuringfood safety and security, improving drugdiscovery and translational research, and settingup clinical trial networks.In the second phase, beyond 2030 moving intomaintaining resistance control, some of these areasare likely to grow in importance. New evidence (e.g.on increased resistance transfer from animals tohumans) could propel topics to higher priority muchsooner. Each of these topics, including the prioritytopics, are discussed in detailed profiles inAppendix 1.In the move from prioritisation to implementation,specific strategies will vary widely across countries.While a systematic or comparative assessmentacross countries was outside the scope of thiseffort, deep-dive interviews with multiple in-countryexperts on national action suggested lessons fordifferent country archetypes. These findings onNational Action and Global Governance are alsodetailed in Appendix 1.In conclusion, prioritisation is increasingly emergingas a gap in the AMR response. The community mustalign on a more specific critical path to achieveimpact. This will involve mapping a set of key issuesto focus resources and attention on, and developinga perspective on the appropriate level andsequencing for implementation. Importantly, whichactions to support, or which to prioritise, will differfor actors in different areas of the AMR agenda.There is not a one-size-fits-all plan. All of thisbecomes even more important in the context ofCovid-19 and its impact on AMR. There are manyoutstanding questions, but regardless of how theseare answered, the response to AMR should notattempt to be all-encompassing in one step. Aneffective strategy will require a focus on a criticalpath of priority activities.viii The Global Response to AMR

GlossaryAcronymTermAMRAntimicrobial resistanceCARB-XCombating Antibiotic Resistant Bacteria Biopharmaceutical AcceleratorCDCUS Centers for Disease Control and PreventionCDDEPCenter for Disease Dynamics, Economics & PolicyCRECarbapenem-resistant EnterobacteriaceaeDALYDisability-adjusted life yearECRAIDEuropean Clinical Research Alliance on Infectious DiseasesEPAEnvironmental Protection AgencyFAOFood and Agriculture OrganisationFDAFood and Drug AdministrationFINDThe Foundation for Innovative New DiagnosticsGARDPGlobal Antibiotic Research and Development PartnershipGLASSGlobal Antimicrobial Resistance Surveillance SystemHICHigh-income countries1IACGInteragency Coordination GroupIPCInfection prevention and controlIPPCInternational Plant Protection ConventionLICLow-income countriesLMCLower-middle-income countriesLMICLow- and middle-income countries1MICMiddle-income countriesNAPNational Action PlanODAOfficial development assistanceOIEWorld Organisation for Animal HealthOECDOrganisation for Economic Co-operation and DevelopmentPCVPneumococcal conjugate vaccinesREDISSERegional Disease Surveillance Systems Enhancement ProgramSDGSustainable Development GoalUMCUpper-middle-income countries2USPUS PharmacopeiaWASHWater, sanitation, and hygieneWHOWorld Health Organisation1 ollowing the World Bank’s 2019–20 definition; cf. World Bank Data Team. New country classifications by income level: 2019–2020.FWorld Bank 2019 1 July. lassifications-income-level-2019- 2020.2Ibid.ix The Global Response to AMR

Introduction and contextAMR as an urgent public health concern.Antimicrobial resistance (AMR) is an essential publichealth concern and already the cause of at least700,000 deaths per year globally. Left unchecked,AMR is likely to become one of the world’s largesthealth threats, surpassing many other majorconditions, such as diabetes and cancer, in scale.3have a severe effect on economies around the world.The economic costs of AMR will burden healthsystems already struggling with cost inflation. TheWorld Bank estimates that AMR will reduce globalGDP by 1.1 to 3.8 per cent by 2050, and cause anannual shortfall of 1.0 trillion to 3.4 trillion by 2030versus the baseline.4 This estimate only considersAntibiotics are a cornerstone of modern medicineIn addition to direct health effects from drug-resistantinfections, AMR will have a detrimental impact on arange of other healthcare interventions, many ofwhich are routine procedures that are taken forgranted, such as surgery, chemotherapy, and organtransplants. If antimicrobials lose their efficacy due toAMR, it will significantly raise the chance of prolongedhospital stays and riskier surgical interventions forthese patients, especially where immune systems arealready weakened. This burden will disproportionatelyfall on low- and middle-income countries (LMIC). Inaddition to its impact upon human health, AMR willExhibit 1 – adapted from Review on AMRshocks to labour supply and livestock productivityand is likely to underestimate the total economicimpact. Moreover, a 2019 study by the Council forCanadian Academies, supported by the Governmentof Canada, found that 5,400 lives were lost andCanada’s GDP was reduced by Can 2 billion as adirect result of AMR in 2018.5 Beyond this, the costsof AMR can be catastrophic for affected individuals aswell. According to the World Bank, “in the highAMR-impact scenario, an additional 24 million peoplewould be forced into extreme poverty by 2030.”63 eview on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. J O’Neill andRWellcome Trust (contributors). London: Review on AMR; 2014.4 onas O et al. Drug-Resistant Infections: A threat to our economic future (Vol. 2): final report (English). Washington: World Bank; 2017J1 March. The O’Neill Review estimated a total production shortfall by 2050 of 100 trillion.5 ouncil of Canadian Academies. When Antibiotics Fail: The expert panel on the potential socio-economic impacts of antimicrobialCresistance in Canada. Ottawa: CCA; 2019. When-Antibiotics-Fail-1.pdf.6 Jonas O et al. Drug-Resistant Infections: A threat to our economic future (Vol. 2): final report (Engl

drug-resistant infections should be an integrated piece. While Covid-19 galvanises attention to the tremendous importance of infectious disease threats, airborne viral diseases are only one part of this broader category. Several AMR topics will benefit from this broader agenda. For example, the current focus on infection