Confidential: For Review Only Antimicrobials policy interventions in the food animal production in the Southeast Asia region Journal: BMJ Manuscript ID BMJ.2016.035858 Article Type: Analysis BMJ Journal: BMJ Date Submitted by the Author: 30-Sep-2016 Complete List of Authors: goutard, flavie luce; CIRAD, Department ES, UPR AGIRs; Kasetsart University Faculty of Veterinary Medicine, Bordier, Marion; CIRAD, Department ES, UPR AGIRs Calba, Clémentine; CIRAD, Department ES, UPR AGIRs Erlacher-Vindel, Elisabeth; World Organisation for Animal Health (OIE) Góchez, Delfy; World Organisation for Animal Health (OIE) de Balogh, Katinka; Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific Benigno, Carolyn; Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific Kalpravidh, Wantanee; Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific Roger, Francois; CIRAD, Department ES, UPR AGIRs; Kasetsart University Faculty of Veterinary Medicine, Vong, Sirenda; World Health Organization REgional Office for South-East Asia, Health Security and Emergency Response Keywords: https://mc.manuscriptcentral.com/bmj BMJ
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Confidential: For Review O
nly
Antimicrobials policy interventions in the food animal
production in the Southeast Asia region
Journal: BMJ
Manuscript ID BMJ.2016.035858
Article Type: Analysis
BMJ Journal: BMJ
Date Submitted by the Author: 30-Sep-2016
Complete List of Authors: goutard, flavie luce; CIRAD, Department ES, UPR AGIRs; Kasetsart University Faculty of Veterinary Medicine, Bordier, Marion; CIRAD, Department ES, UPR AGIRs Calba, Clémentine; CIRAD, Department ES, UPR AGIRs Erlacher-Vindel, Elisabeth; World Organisation for Animal Health (OIE) Góchez, Delfy; World Organisation for Animal Health (OIE) de Balogh, Katinka; Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific Benigno, Carolyn; Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific Kalpravidh, Wantanee; Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific Roger, Francois; CIRAD, Department ES, UPR AGIRs; Kasetsart University Faculty of Veterinary Medicine, Vong, Sirenda; World Health Organization REgional Office for South-East Asia, Health Security and Emergency Response
Keywords:
https://mc.manuscriptcentral.com/bmj
BMJ
Confidential: For Review O
nly
1
Antimicrobials policy interventions in the food animal production in the Southeast Asia
region
Flavie Goutard and colleagues call for concerted multi-sectoral measures through stronger policies to combat antimicrobial resistance. Flavie Luce Goutard1,2* senior epidemiologist
Marion Bordier1 PhD candidate
Clémentine Calba1 research assistant
Elisabeth Erlacher-Vindel3 Head , Science and New Technologies Department
1. CIRAD, UPR AGIRs, F-34398 Montpellier, France 2. Kasetsart University, 10900 Bangkok, Thailand 3. World Organisation for Animal Health (OIE), Paris, France 4. Food and Agriculture Organization of the United Nations, Regional Office for Asia and the Pacific, Bangkok, Thailand 5. World Health Organization, Regional Office for South-East Asia, New Delhi, India Guarantor*: [email protected]
Introduction
Antibiotics have been widely used in food animal production to treat sick animals, contain disease spread,
prevent bacterial contamination of the food chain, and increase production [1]. However, their misuse and
overuse in humans and animals leads to the emergence of antimicrobial resistance (AMR) [2]. In September
2016, the United Nations recognized the global rise of AMR as a threat to global health and human
development [3]. Recent projections estimated that by 2050 ~10 million people will die of AMR annually
worldwide if the current situation goes unchecked [4] ; the annual global gross domestic product would fall
by 1.1-3.8% with a major impact on global poverty; and the decline in global livestock production could
range from 3% to 8% per year [5]. Of national animal health systems evaluated in approximately 130
countries by the World Organisation for Animal Health (OIE) including Veterinary Services through its PVS
Pathway, more than 110 do not yet have appropriate legislations to regulate importation, manufacture,
distribution and use of antimicrobials agents. Consequently, antibiotics circulate uncontrolled like common
goods and are often falsified [6]. Furthermore, Van Boeckel et al. (2015) estimated that the antimicrobial
consumption for livestock would increase by 67% by 2030, to face growing demand for meat products in
middle-income countries [7]. This pattern is all the more true in a rapid growing economic area like the
World Health Organization (WHO) South-East Asia region (SEAR: Bangladesh, Bhutan, Democratic
People's Republic of Korea (DPRK), India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand,
Timor-Leste). With several countries as global farming and food industry exporters of meat and aquaculture
products [8], the region has embarked into intensive farming systems involving rising consumption of
fertilizers, antibiotics, and pesticides for which many farmers have limited technical knowledge. The
lack/weakness of regulation, adequate policy, and standards implementation for antibiotic usage in livestock
sector associated with low standards of hygiene and sanitation accelerate AMR emergence and dissemination
[2]. SEAR is thought to be the epicenter of AMR [9].
We determined challenges and needs regarding policy interventions to combat AMR in food animal
production in the SEAR with a focus on antimicrobial development/marketing, usage and resistances
monitoring. We reviewed official documents addressing antibiotics in food animal production in each SEAR
countries.
Evidences
We followed the PRISMA requirements [10] to conduct our literature review, using PubMed, Science Direct,
MEDLINE, LISTA, Web of Science and Scopus for the peer-reviewed publications; and Google Scholar for
the gray literature (see figure 1). We focused our search on English-speaking articles with available abstracts
published during 2010- April 2016. Our review, which complied with PRISMA requirements, used
additional search strategies (searches in the FAO legislative and policy database (Faolex) available at
http://faolex.fao.org/ and contacts with OIE national focal points for Veterinary Products and FAO contacts).
From the documents, we extracted information about: (i) drugs and medicine development and marketing,
(ii) drugs and medicine usage, and (iii) AMR surveillance and monitoring. For each record retrieved, we
captured data related to the competent authority in charge, the type of document (policy or legal document),
the objective(s), the key components and limitations. These results were crossed-checked with additional
information regarding policy implementation and law enforcement found in the other non official documents
[2,11–13].
Type of policy or legal documents available from the literature review – (see Table 1)
A total of 91 documents met the search criteria, of which 26 were official records addressing antimicrobial
development/marketing, usage, and resistances monitoring. Of these, 16 are legal instruments while 10 are
policies, related strategies, and action plans. Policy documents are usually more recent and up-to-date
regarding AMR issues than legal instruments, showing that the appropriate legal framework is not yet in
place to allow governments to implement the course of actions defined in their policy. Most topics in the
documents cover drug and medicine development and marketing (15/26), drug and medicine usage (15/26)
while few (5/26) address consumption and resistance monitoring/surveillance.
Country-specific analysis of policies, legislations and regulations – Gaps identification (see Table 2)
Antimicrobial agents’ development and marketing: Retrieved documents usually are not specific to AM, and some do not even mention them. Only for India, we identified a specific document for AM management, but
mainly targeting human drugs. Most of the documents covering drug development and marketing are
common to the human and veterinary sectors and are issued by authorities in charge of Public Health. We
identified texts specific to veterinary drugs in only Indonesia and Thailand. Prevailing legal and policy
instruments usually address three mains topics: (i) licensing and authorisation of drugs placed on the market;
(ii) requirements for drug manufacturers; (iii) requirements for distributing, selling and storing drugs.
Depending on the countries, requirements are more or less specific and detailed. Most countries require
licensing authorisation to release drugs, but few provide licensing criteria and precise description of
procedures. Policies retrieved from Nepal and Bangladesh underline the importance of science-based
assessment of drugs before market introduction. For drug manufacturing, obligation of licensing is
commonly addressed in the different records, but requirements are more or less strict depending on the
country. For instance, in four countries, Good Manufacturing Practices (GMP), as well as quality assurance
and control, are compulsory for drug manufacturers. Regarding drug storage and distribution, authorizations
are usually required by law, but requirements are poorly described. Official control measures carried out by
competent authorities are not commonly addressed. In Bhutan, the Medicines Rules and Regulation prescribe
pre-approval and routine GMP inspections to assess the conformance of pharmaceutical manufacturers to
GMP standards. In Bangladesh and India, the national policies provide for regular inspections of premises to
control manufacture and sale of drugs but, to date, prevailing legal instruments are outdated to allow their
programming. In Thailand, numerous official controls are carried out on the manufacturing and distribution
of veterinary medicines at all levels [14].
Antimicrobial usage (AMU): Two main issues are commonly addressed: i) antibiotics in animal feed for growth promotion and medicated animal feed, ii) rational AMU in healthcare and veterinary settings. In
2015, Thailand banned the use of all antibiotics as growth promoter in food animals and authorized
medicated feed only with a prescription [12]. This restriction has been enforced in the country since 1999
(amendment B.E. 2542) with the total prohibition of medicated feed in aquaculture [15]. Thai competent
authorities conduct regular official controls on antibiotic use in farms and holdings [14]. Sri Lanka and
Maldives are prohibiting therapeutic antibiotics as growth promoters or in medicated feed [11]. Bangladesh
banned as well (bills or law) the use of antibiotics as a feed additive for livestock but without means to
inforce proper controls of operators’ activities. All further countries authorize the use of antibiotics in animal
feed for curative or preventive therapeutic use or growth promotion. For India, Nepal, and Bhutan, we found
national roadmaps aiming to ban non-therapeutic use of antibiotics in feed within the next two to four years;
however these countries are still in the process of updating their legal documents to achieve these goals. Few
countries have national policies or regulations on AMU in food animals. India and Thailand as significant
seafood exporters specified a list of antibiotics banned from use in aquaculture, in line with their trade
partners requirements [15]. Specific provisions on AMU have been specified in regulatory documents, e.g.
recommendation on the prudent use of antibiotics (Nepal), or restrictions on the use of antibiotics intended
for human treatments (Indonesia). Indonesia and Thailand have developed a code of practice for the control
of the use of veterinary drugs in compliance with the Codex recommendations (CAC/REP 38-1993) [13]. In
Bangladesh, Bhutan, India and Nepal, the public health sector have prepared national policies with specific
strategies and roadmaps for the containment of AMR, targeting human and animal health with the
implementation of inter-sectoral committee and tasks force. These national policies recommend the
responsible use of antibiotics, the ban of over-the-counter (OTC) sales of antibiotics, the formulation of
current regulatory documents, good pharmacists practices (GPP), the development of standard treatment
guidelines (STGs) and promote education campaigns for sellers and end-users of antibiotics. These
recommendations are in line with OIE standards, but no legal documents were yet retrieved from the
literature search showing effective implementation.
Antimicrobial surveillance and monitoring in food animal production: Thailand seems to be the most advanced country with regards to surveillance strategies and implementation of AMU and AMR monitoring.
The Department of Livestock Development (DLD) constituted a multidisciplinary committee on AMR
containment with a specific working group on surveillance. In 2016 the DLD developed National Veterinary
AMR surveillance in line with Decision 2013/652/EU although its legal framework is yet to be established.
The objective of surveillance is to detect resistant bacteria and resistance genes in the food chain from
poultry and pigs with a focus on Salmonella spp., E. coli, Campylobacter jejuni as recommended by OIE. The policy to approve surveillance of AMU is planned but yet to be developed. All these actions are in line
with the Thailand Antimicrobial Resistance Containment and Prevention Program [16]. Bangladesh issued in
2011 a national strategy that provides a framework for interventions to slow the emergence and spread of
AMR for the next 10 years (implementation before 2020). National AMR surveillance for the veterinary and
fisheries sector in line with OIE standards is to start end of 2016. The monitoring of AMU at the animal
healthcare center is planned to start during 2017-2020. Alongside, a roadmap was developed to set-up
surveillance of antibiotic use and AMR in human health. In India, veterinary surveillance of AMR is not in
place yet. In human health there is no national surveillance of AMR and AMU; although surveillance is
conducted independently in some large and/or private hospitals. Official documents from Bhutan’s Drug
Regulatory Authority provided rules and regulations regarding medicines targeting human and animal health
but no specifics was found with respect to AMR in food animals. In the Bhutan Medicines Rules and
Regulation of 2012, no reference was made to AMR surveillance, but a monitoring system for adverse
reaction(s) of the drug use is described. Anyhow we found drafts of very recent policies documents which
are describing short-term plans to develop One Health-related AMR surveillance. Laboratory-based AMR
surveillance was set up in Nepal, including several public health facilities. Since 2011 the system has
included veterinary laboratories with samples from the poultry sector [11] but no surveillance data/records
were reported.
Policy-related best practices and global challenges for their implementation in food animal sector in
developing countries
While the pharmaceutical industry is to ensure the quality of antibiotics used in livestock, countries need
strong national regulatory framework to enforce compliance with good manufacturing practices and to
regulate licensing and sales. Other best practices should be science-based through risk assessment strategies
that focus on each antimicrobial agent. Policies must embrace the conditions of safe disposal of unused or
out-of-date antimicrobials. Finally, the policy and legislation should allow improved monitoring of drug
quality to curb the production of counterfeit and substandard antibiotics: there is indeed a need for an ad hoc legislation for the control (inspection) at many levels of the drug marketing chain - but this control should
not only target the farmers [17,18]. Policies should drive the development of surveillance on the use of
antimicrobial for terrestrial and aquatic animal health (and plants), on AMR in zoonotic agents and
commensal bacteria in food animals. Policy should encourage the development and use of standardised
diagnostic tools, alternatives to antibiotics and research for new anibiotics. Educational efforts for providers
(e.g. the veterinarians) and farmers must be continuous, developing appropriate materials and effective
communications strategies [19]. A participative approach that associates farmers in surveillance and
monitoring systems, especially of the AMU is crucial [20].
Recommendations to improve the design/implementation of best practice policies
Surveillance of AMR and antibiotic usage in animals are complementary and fundamental to monitor the
effectiveness of national AMR prevention and containment programs [21,22]. AMR surveillance in the
veterinary sector remains a challenge as veterinary services try to stretch their resources and capacities
beyond the ongoing surveillance on transboundary animal diseases to include AMR surveillance which
requires an active form of surveillance. Therefore, AMR surveillance needs to be teased out for countries to
understand what really needs to be done. There are various approaches to surveillance, namely: AMR in the
clinical context, related to non-therapeutic usage, residues, AMU for clinical cases and non-therapeutic
AMU. Understanding what each approach entails will allow the countries to prioritize and eventually help
shape policies.
Constant surveillance on AMU in food animals should be promoted, and especially in countries where the
ban of AM as growth promoter could drive producers to increase prophylactic use of AM. Following the
Global Action Plan on AMR, there is now an international consensus to ban antibiotics as growth promoters
in the absence of risk analysis [23]. Countries where legislation is still not in place to ban AM additives in
feed will face market limitations for products with promoters due to consumer pressure and export
restrictions. Integrating surveillance of AMR and AMU in both sectors remains a technical challenge due to
insufficient implementation of existing standards for surveillance [24]. WHO, OIE and FAO are
collaborating to address this issue.
Risk analysis, as recommended by the Codex Alimentarius and OIE guidelines [21,25,26], is an essential tool to evaluate the risk of AMR transmission on human health from animal food and feed, to identify specific
risk mitigation strategies, and to communicate about the complexity of this risk and the actions to be taken.
Anyhow, risk analyses are mainly implemented to assess the risk of introducing new veterinary drugs on
national markets. Critical data about risk factors for the emergence and transmission of resistance, and
pathways (foods, environments, contacts) of transmission (of resistant pathogens or resistances genomes) are
still fragmented. WHO, OIE and FAO have an important role to play in providing more applied example of
risk analysis studies assessing potential impact of AMR emergence and transmission on animal, human and
environmental health, including technical support to deal with risk management options, stakeholders’
communications and risk perceptions of end-users.
Many knowledge gaps regarding the use and impact of antimicrobial agents in agriculture are identified and
listed by Thanner et al. (2016). There is a need to develop a global approach/policy linking various private
sectors, government, veterinarians and farmers’ representatives, and researchers to address the knowledge
gaps. Above all, an integrated policy is required and could be operationalized under the One Health
umbrella. As resistant organisms exist in humans, animals, food, and the environment - and the main driver
of this resistance is antimicrobial usage - a “One Health” conceptual framework for surveillance and control
can be promoted [27].
Conclusion
The region lags behind when it comes to introducing key policies to combat AMR including surveillance of
AMR and AMU, training of professionals and farmers, or the implementation of independent national drug
regulatory authorities. Notably given the political and economic context, many countries have not been able
to enforce policies that have been in place including bans on e.g. OTC and growth promoters. Many reasons may explain the current situation including low awareness and immediate competing priorities; and a limited
understanding of the relationship between AMU and AMR in animals, humans and the environment.
Addressing these issues all together will lay a solid ground for policy and its enforcement. resistance
surveillance and monitoring, governmental bodies should propose a stronger political action to change
antibiotic usage by better informing the citizens and using a proactive and transparent approach to promoting
prudent use of antimicrobials in food-producing animals [28].
Combating AMR is complex for which interventions in one sector will not be effective to addressing the
problem as a whole. Efforts are required for concerted multi-sectoral measures through strong political
leadership and governance. The tripartite partnership between FAO, OIE and WHO, can strengthen its role
in the region by proposing a corpus rules and legislation to support the countries and their national policy.
This corpus of best practices should be rooted in a sound evidence base and sufficiently flexible to
accommodate different contexts [29].
Contributors and sources: SV conceived the article. FLG wrote the first draft. CC, FLG, FR conducted the
systematic literature review. All the authors contributed to the article. FLG is guarantor.
Competing interests: This work was commissioned by the WHO Regional Office of South-East Asia using
the UK Government’s Fleming Fund. The authors alone are responsible for the views expressed in this
article, which does not necessarily represent the views, decisions, or policies of the institutions with which
the authors are affiliated.
This an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial
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