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What are the main conclusions in the report on AMR headed by economist Lord Jim O’Neill and commissioned by former UK Prime Minister David Cameron?

Recommendations:

Specific steps to reduce antimicrobial demand are:

  1. A massive global public awareness campaign: this is to decrease the number of patients or farmers demanding antimicrobials as well as medical doctors and veterinarians prescribing them when it is not needed. O’Neill’s review estimates that the cost of such a global campaign would be between 40 and 100 million USD per year.
  2. Improve hygiene and prevent the spread of infection: hygiene is still a problem in the 21st century and is one of the essential steps to ensure a decrease in AMR. For the developing countries the focus will be on expanding access to clean water and sanitation. For countries that have already reached that stage the focus will instead be on hospital sanitation to prevent the rise of superbugs.
  3. Reduce unnecessary use of antimicrobials in agriculture and their dissemination into the environment: here the focus is on stopping non-therapeutic use of antibiotics. In other words, ending usage to improve growth or for preventative use. Three steps are proposed for this action
    • Follow the 10-year targets proposed in the AMR Review 2015
    • Restrict the use of certain highly-critical antibiotics
    • Improve transparency of the food sector when it concerns antibiotic use
  4. Improve global surveillance of drug resistance and antimicrobial consumption in humans and animals: surveillance is one of the cornerstones of infectious disease management, however it is under-utilised when it comes to AMR. After the Ebola crisis, several countries and organisations have begun to invest in this area which has created a model for other countries to build on. (Global Health Security Agenda for the US, Fleming Fund for the UK, and the Global AMR Surveillance System for the World Health Organisation). Cooperation between governments as well as open, transparent data sharing is critical for improving global surveillance.
  5. Promote new, rapid diagnostics to cut unnecessary use of antibiotics: Access to rapid and trustworthy diagnostic tools would limit the occurrences of wrongly prescribed antimicrobials and significantly reduce AMR. For O’Neill et al., it is rich countries that must lead the way here; he believes that by 2020 it should become mandatory for antibiotic prescription to follow informed testing. This would have the added benefit of providing incentives to diagnostic developers.
  6. Promote development and use of vaccines and alternatives: vaccines are already available today and can significantly reduce the occurrence of infections, thereby reducing the stress on antimicrobials. There are 4 main categories of vaccines relevant to AMR that we need to develop and these target: ‘community-acquired infections’ (prevent bacterial infections acquired by the general population); ‘hospital-acquired infections’ (prevent bacterial infections often developed in hospital contexts); viral infections (even though these do not require antibiotics, they are often misdiagnosed as such); and infections from animals (AMR Review 2016). However, other alternatives such as bacteriophages are also being developed. Actions needed are:
    • Use existing vaccines and alternatives more widely in humans and animals
    • Renew impetus for early-stage research
    • Sustain a viable market for vaccines and alternatives.

Examples of needed vaccines for community and hospital-acquired infections (AMR Review 2016):

  • Universal pneumococcal conjugate vaccine (against Streptococcus pneumoniae)
  • A vaccine against certain coli strains (no vaccines at the moment and only 2 are in the early stages of clinical development)
  • There are currently no licensed vaccines for bacteria considered by the US Centers for Disease Control and Prevention (CDC) to be our most urgent AMR threats – carbapenemase-producing bacteria (including Klebsiella (no vaccine candidates), E. coli (2 vaccine candidates in Phase I trials)), drug-resistant gonorrhoea (no vaccine candidates), and difficile (vaccines in clinical development).

Steps to increase the number of effective antimicrobial drugs to fight infections resistant to existing medicines

  1. Establish a Global Innovation Fund for early-stage and non-commercial research: The review proposes establishing a Global Innovation Fund endowed with up to 2 billion USD over 5 years by bringing together different initiatives of similar function that have emerged over recent years. (US via the Biomedical Advanced Research and Development Authority and Europe via the Innovative Medicines Initiative and Joint Programming Initiative for AMR programmes)
  2. Better incentives to promote investment for new drugs and improving existing ones: The antibiotic market is not very attractive to large pharmaceutical companies and the reduction of antibiotic usage necessary to tackle AMR will only compound the problem. Governments must play their part by, for example, resorting to national purchasing and distribution systems. The review proposes a “system of market entry rewards of around one billion USD per drug for effective treatments.”

A global coalition for action on AMR is needed for these steps to succeed. The review states that it could be done via the G20 and the UN.

Source: AMR Review 2016

Why is it said that AMR is a “global and multisectoral issue”?

AMR is global: Indeed, with globalisation and the movement of people and animals across the globe, microbes that ‘hitch a ride’ can also spread globally. If resistant bacteria develop somewhere in Europe, Asia etc., they could very quickly be transported by a carrier (human, animal, food) to another continent. A Swiss study demonstrated that 75% of 38 tourists travelling to India returned home with antibiotic-resistant bacteria in their guts. In addition, 11% of tourists had bacteria resistant to the last-resort antibiotic colistin (Bernasconi O, et al. 2016).

AMR is a multisectoral issue: The causes of AMR have roots in a variety of sectors, including health, food safety, agriculture, environment, and trade, making it a truly multisectoral issue. If these sectors do not act on the threat of AMR, it will not be solved (WHO,2018). To this end, the WHO has proposed their “One Health” approach which is designed to facilitate communication and cooperation between all relevant sectors in order to implement programmes, policies, legislation, and research to combat AMR (WHO).

Which countries have AMR on the top of their political agenda?

In 2010, the World Health Organisation (WHO) identified AMR as one of the top 10 public health crises that need to be addressed (WHO, 2010). At a United Nation General Assembly in 2016, world leaders committed to take a broad, coordinated approach to address AMR and its root causes (including but not limited to human health, animal health and agriculture) (WHO, 2016).

This is mirrored by the European Union with the EU One Health Action Plan coordinated by the European Commission as well as with the creation of National Action Plans by Member States (EC, 2017). However, because the EU One Health Action Plan is not legally binding, adoption of its recommendations has been a mixed bag. In a 2019 EPHA study, researchers found only 51% of surveyed EU countries had established a national action plan (NAP) that follows the One Health Plan (EPHA, 2019). While this was a necessary first step to place AMR on member state’s political agendas, further coordination with member states at the national level is still needed to fully implement these actions plans.

In 2014, G7 leaders committed to working alongside the WHO to establish a global action plan on AMR (European Observatory on Health Systems and Policies, 2015). The following year, WHO introduced the Global Action Plan that presented strategic objectives for governments to work towards in their policies against AMR (WHO, 2015). In Europe, several countries stand out for their commitment to fighting AMR. Of those, the UK, the Netherlands, France, Germany, and Sweden are prime examples. Since 2006, antibiotic usage in animal husbandry as growth promoters has been banned in all EU member states (Regulation IP/05/1687).

Under the Swedish EU presidency in 2009, antimicrobial development was made a priority (European Observatory on Health Systems and Policies, 2019). The UK, Denmark, Sweden, and Norway already publish joint annual AMR surveillance reports that are meant to facilitate cooperation and data sharing. The Netherlands has routinely had the lowest average systemic consumption of antibiotics as well the lowest mean consumption in hospitals within the EU/EEA population; the highest being Greece and Malta respectively (European Observatory on Health Systems and Policies, 2019).

Outside of Europe, the US, China, and India have also taken necessary strides to put political emphasis on the issue. All three countries as well as European countries have established an AMR surveillance system to track the progression of resistance in animals and humans (WHO, 2019). According to the WHO, both the US and China have enacted targeted nationwide policies that attempt to change the behaviours of key stakeholders over the last 2-5 years (WHO, 2019).

Individual countries that have put AMR at the top of their political agenda include:

 

What can policy makers do to help tackle AMR?

Policymakers are in one of the most crucial positions to aid in combatting AMR. As illustrated in the recommendations given by the 2016 AMR Review, policy makers must enact binding legislation that follows the path set forth by the EU One Health Action Plan. Any policy goals proposed should ensure that concrete, quantifiable steps are taken to regulate and spark innovation within the antibiotic industry as well as create awareness across relevant sectors and the general public to insist on proper antibiotic usage. You can find out more about your role in the fight against AMR here

What is the role of pharmaceutical companies in propagating AMR?

Unchecked manufacturing discharge into water systems has had a major impact not only on the safety of those water sources, but also on the people and animals that encounter the resistant bacteria. This problem is particularly salient in India and China where most active pharmaceutical ingredients (APIs) are manufactured (Changing Markets, 2016).

Studies from Hyderabad in India have shown that concentrations of pharmaceuticals routinely exceed the maximum regulatory limits or safe exposure levels (Larsson et al., 2007). Point-source pollution occurs when APIs and finished-dose antibiotics are produced in specific areas and cause excessively high concentrations which, in turn, encourages the development of drug resistance. Vulnerable populations living near manufacturing facilities and wastewater treatment plants are the most at risk for the damaging impacts of resistance. (Lübbert et al., 2017) (Al Jazeera, 2016) (Larsson, 2014)