Antimicrobial Resistance: What’s Next for the Global Action Plan

The review of the Global Action Plan for Antimicrobial Resistance at the upcoming (23-28 May 2016) WHA must consider the following: 1) More attention has to be focussed on public health measures that promote conservation and restoring of existing AB effectiveness. The principles espoused at Alma Ata in the Declaration on Health For All chart the path and apply to tackling ABR. Improvements in water and sanitation cannot be overlooked as important components of the primary health care (PHC) approach; 2) Other approaches to infection control and treatment are necessary to retain the effectiveness of current and emerging AB. These include vaccines (human and animal), diagnostic technologies and complementary and alternative technologies such as bacteriophages. Sub-therapeutic use of antibiotics in animal farming and agriculture must be phased out; 3) New AB while important must be affordable and accessible in LMICs. They must be available to the poorest of the poor. Their availability only in high income countries will not help the global response

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by  Shila Kaur

  Coordinator Health Action International Asia Pacific (HAIAP)

Antimicrobial Resistance: What’s Next for the Global Action Plan

 

Introduction

Last year in 2015, the World Health Assembly adopted the Global Action Plan (GAP) for Antimicrobial Resistance aimed at assisting countries to implement national action on antimicrobial resistance. Later in May this year, Health Ministers meeting at the 69th WHA will review the extent to which the GAP has been implemented nationally. In the interim we hear disturbing news of the discovery of a gene, MCR-1, which creates resistance to colistin, a powerful antibiotic of last resort.

The fact that this gene has the characteristic of being able to jump from one strain to other species of bacteria raises the spectre of many infections eventually becoming untreatable. According to a paper published in November 2015 in The Lancet Infectious Diseases journal, the gene discovered in China by Yi-Yun Liu et al was found in 166 out of 804 pigs at slaughter, 78 of 523 samples of chicken and pork being retailed and in 16 of 1,322 hospital patients.

The study indicates there is a chain in the spread of resistance from the use of colistin in livestock feed, to colistin resistance in slaughtered animals, in food and human beings. The study also showed that the gene is readily passed between common bacteria such as Escherichia coli and Klebsiella pneumonia.

The heavy use of colistin to promote growth in livestock is a driver of the growth and spread of this gene. The MCR-1 gene is now known to be found in Malaysia, Denmark, Thailand, Laos, Brazil, Egypt, Italy, Spain, England and Wales, the Netherlands, Algeria, Portugal and Canada.

Prior to the MCR-1 gene, the global health community was terrified when it learnt about the NDM-1 gene and horizontal gene transfer. In 2010, NDM-1 was found in only two types of bacteria – E Coli and K pneumonia. Within a few years, through horizontal gene transfer, NDM-1 had been found in more than 20 different species of bacteria.

What next?

An immediate logical action would be to ban the use of colistin in animal feed.

However for the long term and as part of the GAP, countries must already begin work to incorporate antimicrobial resistance as a national health priority. The GAP sets out five strategic objectives: to improve awareness and understanding of antimicrobial resistance; to strengthen knowledge through surveillance and research; to reduce the incidence of infection; to optimize the use of antimicrobial agents; and to develop the economic case for sustainable investment that takes account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions.

With respect to optimizing the use of antimicrobials (AM), GAP must consider:

Universal Access
As a key part of a comprehensive global solution, governments and donors must first prioritise universal access to affordable and effective AM. Securing access to quality AM is a core national responsibility. At least as far as access is concerned, countries should already begin dispensing this responsibility irrespective of the GAP and funding.

But there are challenges to access to AM in Low and Middle Income Countries (LMICs) which must be monitored. Some of these challenges for LMICs are:

• Most first line antibiotics (AB) are inexpensive; however with the emergence of resistance, treatment costs increase tremendously as second and third line AB are needed. The problem of resistance is compounded in LMICs where first recourse by the private sector is the use of second and third line AB, completely bypassing first line treatment. Not only this, the actual state of antimicrobial resistance (AMR) is not known or incomplete as surveillance or data collection is limited to the public sector. For example in Malaysia, data on AMR is not available from the private sector.

Therefore any surveillance system must include the private sector. And there is need to ensure that access to second and third line antibiotics is monitored in both the public and private sectors.

• The public sector is comparatively more rational in the dispensing of AB as it is not profit driven. However lack of clinical guidelines ( or knowledge on how to use guidelines), poor laboratory and point-of-care diagnostic services impede the appropriate management and handling of AB. Poor healthcare infrastructure including inaccessibility to primary healthcare services and lack of enforcement of regulations are additional obstacles.

– WHO could play a significant role here with technical assistance to countries that lack therapeutic treatment guidelines and regulations or the expertise to implement these if they exist.
– Drug Regulatory Authorities must be empowered to dispense their roles as enforcers of regulations in both the private and public sectors.
– Laboratory support and increased access to diagnostics are crucial. These rapid diagnostic tests must distinguish between bacterial and viral infections and between susceptible and resistant strains to certain AB. They must be sensitive, specific, rapid, inexpensive and easy to use, especially in remote locations.
Prizes for diagnostics such as the Longitude Prize and the proposed NIH-BARDA prize could be included in the WHO-DNDi Global Research and Development Facility to ensure that these can be extended to LMICs, by making them affordable and accessible.

• Balancing access with excess. When a new AB is introduced with few or no restrictions, this will certainly increase access but also its irrational use. Within the context of LMICs, restricting the use of new AB through regulations (prescription only laws) will further increase the existing lack of access for the poor in rural areas where providers are small pharmacies, grocery stores or private drug sellers.

– LMICs must look at appropriate forms of controlled distribution to protect against the irrational use of new AB and to preserve/conserve existing AB for future patients as long as possible. In order to do this there is need to invest in health systems strengthening. WHO can technically assist countries with exploring appropriate distribution models and their application.

– Advertising, marketing and promotion of AB further muddy the waters. Regulations must encompass distribution, marketing and sale of AB for human use in the private health sector (which is mostly unregulated in developing countries), for animal use and use in agriculture and aquaculture; as well as prescribing practices of health care providers, which means prohibiting of all forms of financial incentives for prescribers and dispensers, which have been major drivers of antibiotic resistance (ABR).
The voluntary Code of Conduct for the advertising and promotion of medical products for human use has clearly not worked. WHO must take action for a more binding Code to control the behaviour of drug companies.

Conserving and Restoring AB Effectiveness
In order to conserve and restore the effectiveness of AB, developing countries must give due attention to three areas:
1. The demand for AB in LMICS must be reduced:

• At the country level, AB use can be rationalized by reducing the need for AB through better public health, by curbing unnecessary use and by improving access where use is warranted. The burden of infectious diseases and the need for AB can be reduced through vaccination, improved water and sanitation and food safety. The principles espoused in the Alma Ata Declaration on Health For All chart the path and are very much still applicable to ABR. While funding for innovation and new AB is an acknowledged necessity, LMICs will not require additional funding for public health programmes that reduce demand for AB.
• WHO’s Expanded Programme on Immunization can easily incorporate vaccines against pneumococcal pneumonia and rotavirus with minor costs.
• Vaccinating food animals could be one way to also reduce AB demand in the veterinary sector especially in LMICs.
• AB cycling where AB are used for specific periods, followed by withdrawing them and then reintroducing them later may work for certain cases.
• Bacteriophages deserve a relook in view of ABR and the need for new approaches. Bacteriophages could be used in livestock for disease prevention and treatment, in diagnostics and in infection control and disinfection in hospitals and other sites.

National strategies should address incentives for conservation in hospital and community settings and in the agricultural sector. These must target healthcare providers, patients/consumers, farmers and animal food producers.

2. Reducing inappropriate and unnecessary AB use through AB stewardship programmes which encompass both human and animal use. Antibiotic stewardship programs (ASPs) can reduce inappropriate prescribing and provide other benefits, such as shorter therapies and lower hospital costs. Both persuasive (advice or feedback on prescribing) and restrictive (limits or required approvals) interventions improve physicians’ prescribing practices.

Many hospitals in LMICs do not have ASPs. According to the Center for Disease Dynamics, Economics & Policy (CDDEP), 2015, ASPs are present in 14 percent of African hospitals, 46 percent of Latin American hospitals and 53 percent of Asian hospitals. CDDEP further states that compliance with ASP policies and guidelines can be enforced through regulations restricting antibiotic sales and prescribing at the hospital level. In Vietnam, Chile, and South Korea, interventions that include regulations decreased antibiotic use and resistance. The same effect has been demonstrated to varying degrees in China.

3. Reducing and eventually phasing out sub-therapeutic antibiotic use in agriculture.
One important factor driving antibiotic resistance is the intensive use of antibiotics in the animal farming sector. This sector is known to consume more antibiotics than humans, and is less regulated. The few available studies on antibiotic resistance in livestock show that farm animals carry a large load of resistant organisms. In most LMICs, insufficient information is available on antibiotic use in agriculture or antibiotic-resistant organisms in animals. Documenting levels and patterns of antibiotic use in agriculture will provide a sound basis for reviewing and strengthening laws and regulations. Incentivizing the rational use of antibiotics is important in the veterinary field as well. Helping farmers optimize production as they transition to large scale farming, for example, could avoid reliance on antibiotics in place of improved water, sanitation, and immunization (Laxminarayan et al. 2015).

Changing social norms/behaviours
Central to preserving and conserving AB effectiveness in all countries, rich or poor, is changing behaviours about how and when to use AB. AB must be seen as an exhaustible medical tool to be used only when needed and appropriate. To do this patients/consumers, healthcare providers and the farming community must be engaged.

If smoking can be banned and is socially unacceptable in many countries, why not inappropriate AB use? Smoking kills, inappropriate AB use also kills.

However changing behaviour without complementary regulations will be a challenge.

It is time for an International Framework on AM control. What form this framework takes will have to be discussed through WHO’s leadership.

This is an area where Civil Society Organizations (CSO) can play a significant role at the country and local levels. Traditionally CSOs have provided information and awareness raising and they will continue to do so. CSOs invest time, effort/energy and resources into public/consumer education/campaigns. While governments need to invest in programmes to increase public/consumer awareness on rational use of AMs, these can be complemented through CSO involvement.

WHO should therefore continue to involve CSOs in this effort not just at the central/HQ level but also at the regional and national levels where impact is direct and most significant.

Conclusion
In view of the spectre of antibiotics of last resort becoming useless, there is urgent need to conserve and optimise the use of existing AM. To summarise, the review of GAP at the upcoming WHA must consider the following:

1. More attention has to be focussed on public health measures that promote conservation and restoring of existing AB effectiveness. The principles espoused at Alma Ata in the Declaration on Health For All chart the path and apply to tackling ABR. Improvements in water and sanitation cannot be overlooked as important components of the primary health care (PHC) approach.

2. Other approaches to infection control and treatment are necessary to retain the effectiveness of current and emerging AB. These include vaccines (human and animal), diagnostic technologies and complementary and alternative technologies such as bacteriophages. Sub-therapeutic use of antibiotics in animal farming and agriculture must be phased out.

3. New AB while important must be affordable and accessible in LMICs. They must be available to the poorest of the poor. Their availability only in high income countries will not help the global response.

 

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Health Action International Asia Pacific (HAIAP) aims to promote rational use of medicines and equitable health for all, with particular emphasis on the poorest of the poor. It is a network of more than 60 individuals and organizations ranging from powerful consumer organizations and development action groups and small grass roots organizations. Individuals who work with HAIAP consist mainly of health professionals comprised of doctors, pharmacists and academics. As the Coordinator of HAIAP, Shila Kaur responsibilities entail keeping members informed of network activities through HAI News and regular news mailings and emails; coordinating meetings, seminars, conferences; advocacy and lobbying; representation at meetings; coordinating research; fundraising and writing and publishing reports and publications.