Martin Friede Vaccine workstream Liz Tayler AMR secretariat Global action plan on antimicrobial resistance

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1 WHO Global Action Plan on Antimicrobial Resistance Martin Friede Vaccine workstream Liz Tayler AMR secretariat

2 AMR a global health threat Resistant bacterial infections cause about deaths in the US and Europe. MDR/XDR TB also a major issue Estimated costs in the US Direct up to 20 billion USD per year Indirect up to 35 billion USD per year

3 Impact will be greatest in developing countries

4 Data is patchy

5 Five strategic objectives: 1. Improve awareness and understanding (WAAW) 2. Strengthen knowledge through surveillance & research 3. Reduce the incidence of infection (IPC\Sanitation) 4. Optimize the use of antimicrobial medicines 5. Ensure sustainable investment (R&D) National Action Plans

6 Implementation GAP: 10 work streams 1. Global communications campaign 2. Support National Action Plans of MS 3. Global Antimicrobial Resistance Surv System 4. Support measures to improve IPC 5. Monitor use & enhance stewardship of antibiotic use 6. Encourage R and D and explore new business models 7. Improve Point of Care diagnostics 8. Address the Environmental Drivers 9. Vaccines to prevent AMR 10.One Health Liaison

7 Global Action Plan Consult member states for the development of a research agenda to underpin development of new vaccines. Ensure that policy recommendations for new and existing vaccines take into account the prospects for restricted treatment options because of antimicrobial resistance and the additional benefits of reduced use of antimicrobial agents including antibiotics Work with partners and other organisations to facilitate the development and clinical evaluation of specific priority vaccines for the prevention of difficult to treat or untreatable actions Collaborate with OIE and FAO on animal vaccines to reduce foodborne disease in animals and humans

8 O Neil Review on AMR Vaccines and Alternative approaches Feb 2016 Recommendations Of vaccines and AMR. We are not moving nearly fast enough to develop them, recognise their potential, or use them appropriately Use existing products more widely in animals and humans Renew impetus for early research Sustain a viable market for needed products

9 Role of vaccines in AMR 1. Increase use of existing vaccines 2. Develop vaccines against high burden diseases currently treated systematically with antibiotics, but where resistance is not yet a problem. 3. Develop vaccines for diseases where resistance is becoming a problem

10 1. Increased use of EXISTING vaccines Expanded use of which vaccines in which population would contribute the most to reduced antibiotic use. Eg PCV use in children: 64% reduction in penicillin resistant strains ( ) Predict saving 11.4 million days of antibiotic use if global. What about the elderly? Where is antibiotic used the most?

11 Pneumonia hospital admissions by age Where are antibiotics most used? Would vaccinating adults be effective? Same vaccine or a new one? Griffin NEJM (2)

12 Antibiotic use and influenza infection Neuzil et al 2000 NEJM 342: Influenza accounts for 35% of outpatient visits in winter in children <3. Caused: 3-9 antibiotic courses per 100 children And 30% of excess (winter related) antibiotic prescription

13 Prioritisation Which existing vaccines, if used more, would impact antibiotic use the most? HiB, Pertussis, Neisseria, influenza? Need data!! Symptom burden X antibiotic use X pathogen causality X vaccine efficacy =???

14 2. Accelerate development of low-hanging fruit Vaccines for diseases currently treated with antibiotics but where resistance not yet an issue Group A Strep, Group B strep Otitis media (NTHi, M. catarrhalis).. others Need evidence: is this commercially viable? How many doses of antibiotic use would be avoided? At what cost?

15 Rational vs non-rational vaccine prioritization Acute otitis media: 700 million cases per year (most in under-5 year olds). Chronic OM: 31 million cases/yr -> hearing loss 0.3% AAFP guideline: 5-7 days of penicillin or erythromycin. Causative agents: Moraxella catarrhalis, non-typeable Haemophilus influenza, >50% of OM, >90% expressing b-lactamase. S. pneumonia >40%: vaccine reduces OM 7-34%. Is this sufficient justification to promote development of vaccines against M. catarrhalis and NTHi? Most OM resolves. New guidelines suggest limiting antibiotic treatment to symetrical OM / chronic OM.

16 Antibiotic use in the elderly: UTIs a major cause of use and resistance. Annual antibiotic prescription (UK) (Sundvall et al 2015) prescriptions/yr/ 100 patients <75 yr: 53/100 ~11% for UTIs >75 not in care home: 142/100 ~16% for UTIs >75 in care home: 199/100 ~33% for UTIs >75 in care, urinary catheter: 440/100 ~50% for UTIs Does this justify developing a vaccine? Primary pathogens: E. coli 50%, klebsiella, enterococci, staphylococci Would a vaccine have an impact? -immune senescence, immunity in urinary tract?

17 3. Vaccines for diseases where AMR is a problem TB S. aureus E. coli C. difficile etc

18 Issues, role for WHO S. aureus, P. aeruginosa (pseudomonas ), C. difficile Strong market drive numerous companies involved in R&D. Role of WHO? Advocacy, evidence (eg C. diff burden in LMICs?) Landscape of alternative interventions : eg passive immunization TB Major cause of antibiotic use MDRTB a major health problem and growing TB vaccines not receiving adequate financial push A priority!

19 Conclusions Essential that WHO leads and promotes the research agenda for use of vaccines to reduce AMR Gather evidence Establish policy Promote R&D of new vaccines which could reduce use of antibiotics Promote R&D of vaccines against pahtogens where antibiotics no longer working effectively eg TB Prophylactic vaccines Therapeutic vaccines to be used in combination with antimicrobials.