Losing Antibiotics Losing lives Losing economies Jørgen Schlundt Michael Fam Chair Professor Director NTU Food Technology Centre Nanyang Technological University

1,000 Major disease burden Major Deaths Burden The world: 700,000 deaths per year from antibiotic resistant bacteria

3 Switzerland Traffic Fatalities 2013 : 269 Switzerland: 800 deaths per year from antibiotic resistant bacteria Switzerland Traffic Fatalities 2013 : 269

Die from previously harmless infections United Nations 21 September 2016 agreed on a resolution warning of a potential post-antibiotic era where many will – again Die from previously harmless infections

(Note: annual global deaths from cancer: 7-8 million) Annual deaths from antimicrobial resistant bacteria Deaths per year 10 million 2050 700000 2020150 If left to continue at present pace, we will see a return to the pre-antibiotic era within the next 20-30 years (Note: annual global deaths from cancer: 7-8 million)

Where do we (mostly) use our antibiotics? Sick humans 15-25% Sick animals To grow healthy animals faster 50-70% (Estimated figures from USA)

The need for an evidence base “The effect of antimicrobial resistance policies seems variable … absence of progress partly due to an insufficient evidence base to inform policy makers about the effectiveness, generalisability, and cost-effectiveness of initiatives” From Paper 4 in the Lancet series: Antimicrobials; access and sustainable effectiveness 18 November 2015 DOI: http://dx.doi.org/10.1016/S0140-6736(15)00520-6

A number of (simple) steps to take Document use of antibiotics and occurrence of resistance Regulate all use of antibiotics Block Vet’s right to make a profit from dealing drugs Do the same for medical doctors Reduce stupid use of antibiotics significantly

New veterinary medicinal regulation adopted in 1995 Banning routine prophylactic usage and limiting Vet’s profit from the sale of drugs (which was close to 50% of a standard Vets total net income) New veterinary medicinal regulation adopted in 1995 Profit on therapeutics reduced In 1995 a law was passed, which banned the routine prophylactic usage of antimicrobials in animals, and which limited the veterinarians profit from the direct sale of drugs. This immediately led to a 40% drop in therapeutic drug use. However with time the effects of this intervention have been lost, and we are now back at the same level of therapeutic drug use as in 1994, taking into account the increased production of food animals in the same time period. Reduced the total usage of prescribed veterinary medicine by 30-40% from one year to the next

Effects on productivity of the Stop for Antimicrobial Growth Promoters (NTA = Non-Therapeutic Antimicrobials)

Lessons about resistant foodborne zoonoses from 10 years surveillance (DK) Close association between animal use and AMR. Close association between AMR in the food supply and AMR in foodborne human infections/commensals: AMRhuman ≈ x*AMRfood/animals + y*AMRimport + z*AMRtravel Significant impact of imported food and travel Growing use of antimicrobials in animal (incl. fish) production Antimicrobial growth promotion only banned in EU Vet profit only restricted in Scandinavia

Old-fashioned quantitative limits Import control Old-fashioned quantitative limits 12

Another Old Approach based on ‘Mutual Recognition Agreement’ MRAs can be time bound and depend upon agreements on ‘equivalence’ of the measures in place at a specific time. MRA’s are negotiated between two or more countries and as such become part of a broader negotiation. AMR is not static but constantly developing as more scientific evidence emerges so need for regular update   MRA’s will not necessary cover testing of all inputs that go into the exported product

Alternative approach based on ‘National treatment principle’ works for bacteria, can also work for AMR: A criterion based on assessment of risk (remember WTO SPS agreement): “Members may introduce measures resulting in a higher level of health protection than international standards, if there is a scientific justification …” Thus, countries are allowed to block import of products if based on an assessment of risk such imports results in a significantly increased health risk

HOW? The short version: From a batch of poultry x samples are analysed. The estimated relative risk of the batch is compared to the base-line risk in the country in question If the relative risk is substantially higher the batch is rejected

Determination of the Baseline Survey data from all products that the risk assessment include Represent total exposure from products and thereby also total cases from products included

Example (but from real life Example (but from real life!) relationship between Campylobacter load (cfu/g) and mean probability of illness 0,00033512 + 0,00170867c + 0,00047941c2 + 0,00057208c3 + 0,00050586c4 - 0,00012852c5 + 0,00000786c6 R2 = 0,99999801 P_ill = Polynomial fit

This is a risk-based Microbiological Criterion: A risk assessment is carried out for each individual batch Rejection/acceptance directly linked to risk Rejected lots should pose a significantly higher risk than average Rejection/acceptance is not based on specific number of positive and negative samples Judgment of relative risk estimate is a risk management decision

Advantages And: it works! Judgment is based on risk/output Flexible Cut-off level may be adjusted to the current situation Decision left to Risk manager, but transparent and based on assessment of risk And: it works!

Case by Case from 2007-2009

What we know we can do: Total antimicrobial consumption can be reduced without compromising productivity Specific drugs can be almost or entirely removed This will lead to reduction in resistance Still a lack of data quantifying the livestock (including fish) contribution to global AMR New risk-based quantitative criteria can enable future trade restrictions based on ‘national treatment’