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The History of Medicine Antimicrobial Resistance Issues Worldwide and the WHO Approach to Combat It Carmem Lúcia Pessoa-Silva, MD, PhD Health Security and Environment Cluster, WHO HQ, Geneva Hosted by Dr. Benedetta Allegranzi WHO Patient Safety Agency pessoasilvacl@who.int Sponsored by WHO Patient Safety Challenge Clean Care is Safer Care 2000 B.C. Here, eat this root. 1000 A.D. That root is heathen. Here, say this prayer. 1850 A.D. That prayer is superstition. Here, drink this potion. 1920 A.D. That potion is snake oil. Here, swallow this pill. 1945 A.D. That pill is ineffective. Here, take this penicillin. 1955 A.D. Oops bugs mutated. Here, take this tetracycline. 1960-1999 more oops Here, take this more powerful antibiotic. 2000 A.D. The bugs have won! Here, eat this root. WHO, 2000. Overcoming antibiotic resistance. 1 November 6, 2013 2 Impact of introduction of Penicillin on mortality in the USA Patients with pneumonia and bacteria in the blood Penicillin Aiello & Larson, LID 2002. Penicillin increased the chance of survival from 10% to 90% % survivors Untreated 3 Adapted from Austrian et al. Ann. 4 Int. Med 1964; 60, 759 Days Unavoidable reality More use = faster development of resistance 1944: Gonorrhea treatment Advice to World War II servicemen Source: Wikipedia Source: The evolving Threat of Antimicrobial resistance. WHO, 2012. Adapted from Albrich EID 2004. 6 1

70 years later Spread of metallo-beta-lactamases causing resistance in gram negative bacteria Source: The evolving Threat of Antimicrobial resistance. WHO, 2012. Adapted from Cornaglia et al. LID 2011. 7 8 Percentage of new TB cases with MDR-TB WHO HIV drug resistance report 2012 8 million people now taking ARVs in low middle income countries 450,000 new MDR-TB cases in 2012. About 170,000 deaths due to MDR-TB in 2012. By September 2013, 92 countries had reported at least one XDR-TB. Source: Global Tuberculosis Report. WHO, 2013. 2010: 6.8% people initiating antiretroviral treatment with drug resistant HIV Source: WHO HIV Drug Resistance Report. WHO, 2012. Artemisinin-Resistant Malaria Widespread resistance to earlier generation antimalarial medicines. Mekong subregion, 2007 2012 suspected or confirmed artemisinin resistance has been detected in therapeutic efficacy studies. Important factors Misuse in many settings & ways Clinical medicine, communities, agriculture Unrestricted sale & use of antimicrobial drugs Substandard or counterfeit inadequate dose Widely used in food animals Growth enhancement & therapeutic purposes Same classes of antimicrobials as used in humans Globalized distribution of food Food: important vector for spreading resistance 11 12 2

Now facing a global public health crisis Environmental contamination Contamination from agri-and aquaculture, hospitals and pharmaceutical industries leads to antibiotic exposure to the ecosystems. Increasing resistance to antimicrobial medicines bacteria viruses parasites Few new antimicrobial medicines in pipeline 13 14 Consequences of antimicrobial medicine resistance Reduced public health control over many infectious diseases Bacteria like tuberculosis, gonorrhea, pneumonia Viral diseases like HIV/AIDS Major tropical diseases like malaria.. Reduced safety net for patients undergoing medical procedures such as surgery, transplantation Impact on specific groups Vulnerable populations High morbidity and costs In the EU 2.5 million extra hospital days in 2007 25 000 deaths per year Overall about 1.5 billion per year Thailand > 140,000 cases/yr AMR infected patients 2.0 billion USD per year ECDC 2009. Joint technical report: the bacterial challenge time to react. Photo: CL Pessoa-Silva 15 16 Higher treatment costs when first line antimicrobials can't be used High costs: lives and resources 12 million cases of TB 630,000 involved multi-drug resistant TB strains. Only slightly more than 50% will be cured. Source: Containing antimicrobial Resistance. In WHO Policies perspectives on Medicines. WHO, 2005. 18 3

Economic Impact: beyond medical costs Who owns the AMR-problem? Significant impact of AMR on consumer income, employment, national savings, investment spending, healthcare delivery. Gross domestic product (GDP) losses: 1.4% to 1.6%. World Economic Forum 2013 Global Risks Report Roberts et al CID 2009; 49:1147-84. AMR is a social and economic issue beyond the health sector! 19 20 True scope of AMR much broader Global, social, multisectoral, ethical, security dimensions Need much higher engagement by many in all countries Governments: decision makers, regulatory authorities. Health sector: health systems, doctors, pharmacists.. Communities: consumers, patients, families Agriculture: farmers Industry: medicine companies.. Challenges Lack of capacity Laboratory, diagnostic, quality assurance, regulatory, and surveillance capacity Control over how antimicrobials are obtained and used Control of spread of drug resistant pathogens Utter poverty 21 22 WHO guidance Comprehensive plan, accountability, civil society engagement Strengthen surveillance and laboratory capacity Access to essential medicines of assured quality Rational use of medicines Enhance infection prevention and control The way forward: need for global action WHO AMR Strategic and Technical Advisory Group provided advice to WHO on the development of global strategies, including: Intersectoral engagement and partnering Fostering comprehensive national plans Strengthening the evidence on the magnitude of the AMR problem Better national and international regulatory mechanisms to foster optimal use of diagnostics, antimicrobial drugs and vaccines Prevention and control of infections Innovation for development of new tools to tackle AMR Social mobilization Foster innovation and R&D for new tools 23 24 4

AMR, Another "Tragedy of the Commons" WHD 2011 slogan "The Tragedy of the Commons" Garrett Hardin, Science, 162(1968):1243-1248. No quick or easy solutions: will require years of effective action to reduce AMR Key actions urgently needed Awareness & engagement beyond health community Behavioural change Development & application of innovative strategies Photo: Sharon Loxton at geograph.org.uk. 25 26 27 28 5