Minutes of the 72nd Executive Committee Meeting,cdn.aphca.org/dmdocuments/AMR WS...

Proceedings of the International Workshop on the Use

of Antimicrobials in Livestock Production and Antimicrobial

Resistance in the Asia-Pacific Region

22-23 October 2012 Negombo, Sri Lanka

THE EIGHTEEN APHCA MEMBER COUNTRIES

AUSTRALIA MONGOLIA

BANGLADESH MYANMAR

BHUTAN NEPAL

INDIA PAKISTAN

INDONESIA PAPUA NEW GUINEA

IRAN PHILIPPINES

DPR KOREA SAMOA

LAO PDR SRI LANKA

MALAYSIA THAILAND

Negombo, Sri Lanka, 22–23 October 2012 i

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ii Negombo, Sri Lanka, 22–23 October 2012

For a copy of the report and correspondence, please contact:

Senior Animal Production and Health Officer and Secretary of APHCA FAO Regional Office for Asia and the Pacific (RAP) 39 Maliwan Mansion, Phra Atit Road Bangkok 10200, THAILAND E-mail: [email protected] FAO Homepage: http://www.fao.org APHCA Homepage: http://www.aphca.org

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Food and Agriculture Organization of the United Nations (FAO) nor the Animal Production and Health Commission for Asia and the Pacific (APHCA) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying or otherwise, without the prior permission of the copyright owner. Applications for such permission, with a statement of the purpose and extent of the reproduction, should be addressed to the FAO Regional Office for Asia and the Pacific (RAP), 39 Maliwan Mansion, Phra Atit Road, Bangkok 10200, Thailand

© FAO 2012

Negombo, Sri Lanka, 22-23 October 2012 iii

Table of Contents

Page

SESSION 1 -INTRODUCTION

Introduction .............................................................................................................................................. 1

Keynote - Epidemiology and Impact of AMR: Links Between Antimicrobial Use in Livestock and AMR in Human Pathogens and Impacts of AMR ............................................ 4

SESSION 2 - COUNTRY REPORTS

Australia ..................................................................................................................................................... 6

Bhutan ...................................................................................................................................................... 18

India .......................................................................................................................................................... 24

Indonesia ................................................................................................................................................. 30

Iran ............................................................................................................................................................ 40

Korea DPR ............................................................................................................................................... 43

Lao PDR.................................................................................................................................................... 46

Malaysia ................................................................................................................................................... 57

Myanmar ................................................................................................................................................. 66

Nepal ......................................................................................................................................................... 71

Pakistan ................................................................................................................................................... 78

Papua New Guinea ............................................................................................................................... 80

Philippines .............................................................................................................................................. 81

Samoa ....................................................................................................................................................... 86

Sri Lanka .................................................................................................................................................. 90

Thailand ................................................................................................................................................... 99

SESSION 3 - COUNTRY CASE STUDIES

An Integrated Surveillance Study of AMR in Salmonella subspp, Campylobacter spp, Escherichia coli and Enterococcus spp in Poultry in Cambodia ........................................ 106

Monitoring Antimicrobial Resistance in Food-borne Pathogens from Selected Species in Sri Lanka........................................................................................................................... 107

Acquisition of Multi-Resistance of Campylobacter jejuni Isolates with Antimicrobial Usage in Poultry ................................................................................................................................. 108

iv Negombo, Sri Lanka, 22–23 October 2012

Vancomycin Resistant Enterococci – Thailand Experience ............................................... 119

Antimicrobial Resistance at the Human-Animal Interface in Vietnam ......................... 124

SESSION 4 - APPROACHES TO AMR MANAGEMENT

Systems for Monitoring and Integrated Surveillance of Antimicrobial Use in Livestock and AMR in Different Parts of the World ............................................................. 134

Alternatives to Antimicrobials (ATAs) and Strategies for Minimizing Risk of AMR Development and Spread ................................................................................................................ 144

FAO and WHO Initiatives to Reduce the Risk of AMR Development and Spread ..... 145

OIE’s Contribution to the Promotion of Responsible and Prudent Use of Antimicrobials ..................................................................................................................................... 146

SESSION 5 - WORKING GROUPS

Priority Tasks at Country Level to Contain the Risk of AMR Development ................ 153

ANNEXES

Annex 1: Workshop Programme.................................................................................................. 157

Annex 2: List of Participants .......................................................................................................... 159

APHCA Workshop Proceedings

Negombo, Sri Lanka, 22-23 October 2012 1

Session 1 Introduction

Antimicrobial Use and Resistance

2 Negombo, Sri Lanka, 22–23 October 2012

Introduction

Joachim Otte

Senior Animal Health and Production Officer Regional Office for Asia and the Pacific

Food and Agriculture Organization of the UN Antimicrobial resistance (AMR) is a growing global threat across drug classes and around the world. Although much of the evolving antimicrobial resistance (AMR) can be attributed to (mis-)use of antimicrobials in humans, research by international scientific bodies supports the conclusion that the overuse of drugs in food animal production - in high-income countries, more than 80% of all antimicrobials produced are used in farm animals – is a threat for continued availability of effective treatment of human diseases. Resource-constrained countries are particularly vulnerable to AMR as they bear 95% of the global infectious disease burden and rely on effective antimicrobial medicines to treat these diseases. Little quantitative information is available about antimicrobial use (AMU) in rapidly growing livestock sectors of Asia-Pacific countries but research conducted in Asia clearly demonstrates that resistance to a range of compounds is fairly common in micro-organisms isolated from livestock and livestock products. Many previously easily curable infectious diseases are becoming increasingly difficult and costly to treat as single and multi-drug resistance grows. Turning the clock back to the days before penicillin will leave many lives at risk. In addition to the human cost, the health care bill for antibiotic resistance is staggering. One study estimated that antibiotic‐resistant infections annually cost US hospitals alone more than $20 billion. Again, little quantitative information on the human health cost of AMR in Asia has been generated. It is no exaggeration that we are at risk of losing one of the most important curative and preventive tools for human and animal disease management. And this happens at a time when animal and human population densities continue to increase overall, but to complicate things further in a highly clustered fashion, which results in increased risk of transmission, which allows pathogens to spread and mutate ever more quickly. Society can no longer rely mainly on the expectation that a continuous stream of new antimicrobials will come onto the market, as pharmaceutical companies find it increasingly difficult justify the investment into research and development in this area in an extremely competitive global market. AMR is a complex problem and the contributing factors to its emergence and spread are diverse and multifaceted. Numerous stakeholders from across multiple sectors have a role to play in AMR



containment. Unfortunately, coordinated containment activities have been lacking, especially at the national and regional level. Microbes do not respect borders and no individual country or country group can contain AMR on its own. Strategic coalitions and partnerships are required to advance sustained AMR advocacy and containment at the regional, country, and local levels. Therefore, the Animal Production and Health Commission for Asia and the Pacific (APHCA) is combining its 36th Annual Session with an International Workshop on ‘Antimicrobial Use and Resistance in Livestock Production in the Asia-Pacific Region’ to be held in Negombo, Sri Lanka. The objectives of the workshop are:

To obtain an overview of the extent of antimicrobial use (AMU) in livestock production in the Asia-Pacific region (quantities, compounds, production systems);

To obtain an overview of existing legal framework regulating AMU use in livestock production and instruments for enforcement in Asia-Pacific countries;

To obtain an overview of sources of data on antimicrobial resistance (AMR) in the Asia-Pacific region;

To review evidence linking AMU in livestock with AMR in pathogens isolated from humans, preferably from the region;

To familiarize participants with systems for monitoring and integrated surveillance of AMU in livestock and AMR in different parts of the world;

To provide an update on alternatives to antimicrobials (ATAs) and strategies for minimizing risk of AMR development and spread;

And finally, to jointly define actions towards responsible antimicrobial use in livestock production in the region.

Details of the workshop structure and programme are provided in the annex.



Keynote - Epidemiology and Impact of AMR: Links Between Antimicrobial Use in Livestock and AMR in Human

Pathogens and Impacts of AMR

Jaap Wagenaar

[in preparation]



Session 2 Country Reports



Australia

Mark Schipp

Chief Veterinary Officer Department of Agriculture, Fisheries and Forestry

This country report provides a brief description of Australia’s regulatory and monitoring framework for antimicrobials used in livestock.

The legal framework and institutional arrangements for regulating antimicrobial use in livestock production and instruments for enforcement

All antibiotics for use in livestock must be registered with the Australian Pesticides and Veterinary Medicines Authority (APVMA) (www.apvma.gov.au). The APVMA, an independent statutory authority within the portfolio of the Department of Agriculture, Fisheries and Forestry (DAFF), is responsible for managing and administering the government’s regulatory responsibilities under the National Registration Scheme. The APVMA regulates agricultural and veterinary chemical products up to the point of sale, and the States/Territories are responsible for the control of use of the products. The APVMA is also responsible for licensing manufacturers of veterinary chemical products, monitoring compliance in the marketplace and for reviewing registered chemical products to ensure that they continue to meet contemporary standards. The APVMA statutory powers are provided in the Agricultural and Veterinary Chemicals Code Act, 1994 (the Agvet Code). For a product to be registered with the APVMA, it must undergo an assessment. This is to determine that the product works as intended, and that scientific data confirms that when used as directed on the product label, it will have no harmful or unintended effects on people, animals, the environment or international trade. All antibiotics registered by the APVMA undergo an antimicrobial resistance risk assessment. In doing this the APVMA seeks advice from the National Health and Medical Research Council (NHMRC) and other experts. A role of the NHMRC is overseeing the administration of antibiotics for veterinary use that are classified as 'high importance' in human medicine. The mechanism used by the APVMA to assess and manage the risk of antimicrobial resistance posed by veterinary use of antibiotics is found in its Manual of Requirement and Guidelines (MORAG) Vol 3 Part 10 Special Data: Antibiotic Resistance. (http://www.apvma.gov.au/morag_vet/vol_3/part_10_special.php). This manual

http://www.apvma.gov.au/

http://www.apvma.gov.au/morag_vet/vol_3/part_10_special.php



describes the general requirements for submitting antimicrobial resistance data for the registration of veterinary chemical products that contain antimicrobials. Under the current APVMA requirements, all new antimicrobials, changes in the dosage form or use pattern, and major extension of the use patterns of existing antimicrobials, must be assessed to determine the likelihood of resistance developing and transferring from animals to humans and the impact on public health. Imported antibiotics also need to meet biosecurity import requirements. Import requirements are managed by the Australian Government Department of Agriculture, Fisheries and Forestry (DAFF) (http://www.daff.gov.au/aqis/import/biological). Regulation of antimicrobial supply and usage in livestock, including instruments for enforcement, is managed at the jurisdictional level (Australian states and territories). An example is the Victorian Agricultural and Veterinary Chemicals (Control of Use) legislation (http://www.dpi.vic.gov.au/agriculture/farming-management/chemical-use/veterinary-chemicals). Almost all antibiotics used in livestock production in all states/territories for therapeutic/prophylactic purposes require a prescription by a veterinarian. DAFF and the states and territories are currently developing a model for the harmonisation of state and territory veterinarian prescribing and compounding rights. The harmonised model has the potential to provide a more efficient and responsive system to control antibiotic usage in animals. A model is expected to be presented to the Council of Australian Governments for their consideration in the near future. The regulation of veterinary antimicrobials in Australia can be looked at in three broad areas:

1. Importation of antimicrobial substances 2. Registration of veterinary antimicrobials 3. Post registration activities.

Importation of antimicrobial substances

Antimicrobial raw materials (active constituents) used in the formulation of antimicrobial products are not manufactured in Australia and are therefore imported from overseas. Importers must hold a permit covering each consignment. Permits are issued by the Therapeutic Goods Administration (TGA) under the Australian Customs (Prohibited Imports) Regulations (Customs Act 1901) and checked by the Australian Customs Service at the point of entry. A person must not import into Australia an unregistered agricultural or veterinary chemical product or an unapproved active constituent, including antimicrobial, unless it

http://www.daff.gov.au/aqis/import/biological

http://www.dpi.vic.gov.au/agriculture/farming-management/chemical-use/veterinary-chemicals

http://www.dpi.vic.gov.au/agriculture/farming-management/chemical-use/veterinary-chemicals



has either been exempted from the importation provisions or the importer has obtained a Consent to Import from the APVMA, as mandated in the Agricultural and Veterinary Chemicals (Administration) Act 1992. This provision allows the APVMA to more effectively control imported agricultural and veterinary chemicals including antimicrobials at a single point (Customs barrier), rather than at multiple points in the marketplace. In addition, antimicrobial agents of biological origin must be assessed and approved by DAFF which determines the quarantine requirements for these agents before they can be imported. Registration of veterinary antimicrobials

The registration of veterinary chemical products including antimicrobials entails detailed technical evaluation and risk assessment of all information against legislative criteria. The criteria that the APVMA must consider and be satisfied of before a product is registered are included in section 14 of the Agvet Code. The evaluation determines whether the use of the product in accordance with its instructions for use:

would not be an undue hazard to the safety of people exposed to it during its handling or people using anything containing its residues; and

would not be likely to have an effect that is harmful to human beings; and

would not be likely to have an unintended effect that is harmful to animals, plants or things or to the environment; and

would not unduly prejudice trade or commerce between Australia and places outside Australia; and

would be effective according to the criteria determined by the APVMA for the product.

In satisfying itself of the above matters, the APVMA must also undertake a detailed technical assessment of matters pertaining to the active constituent and the formulation of the product. The evaluation of a product also includes the assessment of the Relevant Label Particulars (RLPs) as specified in the Agvet Code. Specialist staff in the APVMA assesses the chemistry and manufacture of the active constituent and the product to ascertain product quality and set a shelf life for the product. The APVMA also assesses the residues data of the product to establish a maximum residue limit (MRL), withholding period and export slaughter interval. Efficacy and safety evaluation are carried out by the APVMA, states and territory departments of agriculture and primary industry and external experts. The APVMA seeks specialist advice from a number of Commonwealth agencies but ultimately responsibility for decision making rests with the APVMA.



The Office of Chemical Safety (OCS) of the department of health assesses toxicology and sets dietary limits and acute reference dose for the active constituent. The OCS also assesses occupational health and safety aspects of the product and develops safety instructions and first aid instructions for the product. Based on the toxicological evaluation produced by the OCS, the Australian Chemical Committee on Scheduling (ACCS) determines the poison schedule classification for the chemical. The scheduling classification determines the level of control over the availability of drugs and poisons including agricultural and veterinary chemicals including antimicrobials. The classification determines whether a product should be available over-the-counter or as prescription only medicine. With each poison classification, or ‘schedule’, come appropriate label statements and controls. Antimicrobials available as prescription only are classified as schedule 4 (S4) prescription animal remedies (PARs), and must be prescribed by a registered veterinarian for animals under his/her care. Persons distributing, wholesaling or retailing PARs must be licensed by the relevant State/Territory health department. A public consultation process must take place for every proposed new product, or proposed major extension to existing use. On completion of the evaluation and public consultation, if APVMA is satisfied that the product is safe and effective and that the label contains adequate instructions, registration is granted. For the registration of veterinary antimicrobials, there is a formal mechanism in place to assess and manage the risk of antimicrobial resistance posed by veterinary use of antibiotics. Up until three years ago, antimicrobial resistance risk analysis was conducted by the National Health and Medical Research Council (NHMRC) subcommittee, the Expert Antimicrobial Group on Antimicrobial Resistance (EAGAR). In more recent years the NHMRC has had an advisory role, and the APVMA uses external experts to conduct antimicrobial resistance risk analyses. The APVMA also seeks advice from the state and territory primary industry departments. Taking into account the advice received, the APVMA decides whether or not the risk of antimicrobial resistance is manageable. In deciding whether or not to grant an application for registration, special attention is paid to those antibiotics for veterinary use that are classified as 'high importance' in human medicine. Consequently, for example, the fluoroquinolone family of antibiotics which is classified as 'antimicrobial of high importance' in human medicine is not registered for use in food-producing animals in Australia even though these antibiotics are approved for such use in countries with comparable regulatory regimes. All new applications for registration of antimicrobials for use in animals, major extensions of use, and any reviews of currently registered antibiotics, are assessed against Part 10 Special Data Requirements, as detailed in the APVMA’s Manual of



Requirements and Guidelines (MORAG), Volume 3 Part 10 www.apvma.gov.au/morag_vet/vol_3/part_10_special.php Special Data: Antibiotic Resistance. Part 10 outlines the types of studies, data and information that are necessary to characterise the potential for development of antimicrobial resistance associated with the proposed use of antimicrobial products in animals. The information includes:

Description of the antimicrobial active constituent/product including general attributes. Class of antibiotic and the chemical relationship to other members of the antibiotic's class and related classes.

Mechanism and type of antimicrobial action, including antimicrobial activity of the antibiotic in order to determine the overall spectrum of activity,

Pharmacokinetic / pharmacodynamic profile of the active constituent after administration of the product(s).

Antimicrobial resistance mechanisms and genetics

Antimicrobial agent activity in the intestinal tract Part 10 also calls for a qualitative risk analysis of the probability of diseases occurring in susceptible humans due to infection with antibiotic resistant pathogens arising from proposed use of the antimicrobial antibiotics in animals, and the consequences of such disease. Depending on the outcome of this qualitative assessment, applicants then have the option of developing a quantitative risk assessment. Post registration activities

Post registration activities relating to the regulation of veterinary medicines including antimicrobials include:

Control of use

Antimicrobial sales information

Antimicrobial resistance surveillance

Adverse experience report program (pharmacovigilance)

Compliance activities

Auditing and licensing of manufacturing facilities

Chemical review The APVMA is responsible for the evaluation and registration process and for regulation of antibiotics up to and including the point of sale. While the scope of the APVMA does not extend to controlling product use, the conditions of use specified on product label by APVMA form part of the State/Territory control-of use regimes. State/Territory health, agriculture and primary industries departments provide further controls over the supply and use of the products, through relevant legislation:

health legislation - enables registered veterinarians to prescribe PARs, licenses sellers of PARs and regulates conditions of supply of PARs, including scheduling classifications;

http://www.apvma.gov.au/morag_vet/vol_3/part_10_special.php



health, agriculture/ primary industries legislation - allows registered veterinarians to practise through registration by veterinary surgeons boards under veterinary surgeons legislation, which regulates professional standards and behaviour, including the responsible use of drugs.

agriculture/primary industries legislation - enables control of the use of registered products, off-label use, trace-back and regulatory action associated with violation of permitted residue levels.

Veterinarians are allowed by law to use products ‘off-label’. This includes prescribing, using or authorising a client to use a registered drug or veterinary chemical in a manner outside the range of uses permitted by the approved label directions – such as species of animal, dosage or treatment interval – but not contrary to a specific label restraint. Veterinarians are permitted to exercise professional judgement in the ‘off-label’ use or supply of most drugs or other veterinary medicines. This gives veterinarians access to beneficial drugs which may be registered for human use or which have limited registration for veterinary use. A number of legal limits have been placed on the ‘off label’ prescribing of drugs by veterinarians under national control-of-use principles adopted by most State/Territory. These primarily relate to treatments for defined food-producing species (excluding horses), and are less stringent for companion animals. In most jurisdictions use of any product for companion animals is permitted, but supply for their treatment is usually restricted to human pharmaceuticals or products compounded by the veterinarian or on the veterinarian’s prescription. There are a number of programs administered by various authorities that monitor the use and effectiveness of antimicrobial control strategies. Veterinarians, as the prescribing professionals, play a key role in ensuring prudent use of antimicrobials consistent with species-specific judicious and prudent use guidelines developed by the Australian Veterinary Association (AVA). In all cases these advocate that when reaching a decision to use antimicrobials for therapy, veterinarians should strive to optimise therapeutic efficacy and minimise resistance to antimicrobials to protect public and animal health. The AVA also has in place a Code of Practice for the use of antimicrobial drugs in food animal veterinary practice. The Code aims to raise awareness among veterinarians of antimicrobial resistance and minimise the development of resistance through the responsible use of antimicrobial agents, particularly antibiotics. Farmers participate in various on-farm programs that require them to declare the veterinary treatments their livestock have received. Food safety issues are monitored by various commercial bodies plus State and Commonwealth Government agencies through the application and monitoring of maximum residue limits.



The APVMA also administers the Adverse Experience Reporting Program that allows the APVMA to monitor the performance of veterinary medicines including antibiotics. In addition, the APVMA administers the Manufacturers' Licensing Scheme, a quality assurance program with the primary objective of assuring, and giving confidence in, the quality of veterinary medicines manufactured and supplied in Australia. For veterinary chemical products manufactured overseas the registrant must demonstrate that the product is manufactured to quality standards (i.e. Codes of Good Manufacturing Practice – GMP) comparable to those applying to veterinary chemical products manufactured in Australia.

The extent of antimicrobial use in livestock production

The total quantity (in metric tonnes of active constituent) of antimicrobial agents used in food-producing animals in Australia is provided in table 1.

Table 1. Quantity of antimicrobial agents used in Australia 2007 to 2010

Year Quantity (MT)

2007 298.9

2008 277.5

2009 228.9

2010 358.9

2011 data not yet available

*this data is based on sales data provided voluntarily by registrants of veterinary antimicrobial products. Data is provided in a specified format including agent class, route of administration, and species

*the majority of usage is as growth promotants/prophylaxis

*more details can be found at: http://www.apvma.gov.au/publications/reports/docs/antimicrobials_1999-2002.pdf

http://www.apvma.gov.au/publications/reports/docs/antimicrobials_1999-2002.pdf



Table 2. Total quantity of sales (active ingredient in metric tonnes) of veterinary antimicrobials by route of administration 2005–06 to 2009–10

Route of administration

05/06 % 06/07 % 07/08 % t 08/09 % 09/10 %

Feed 243.2 82.2 191.7 78.5 211.7 83.0 155.3 85.5 226.5 83.1

Water 46.5 15.7 47.7 19.5 37.5 14.7 20.9 11.5 41.5 15.2

Injectable 3.6 1.2 3.0 1.2 3.1 1.2 2.7 1.5 2.9 1.1

Intramammary 1.6 0.6 0.9 0.4 2.0 0.8 2.3 1.2 1.1 0.4

Other 0.9 0.3 0.9 0.4 0.7 0.3 0.4 0.2 0.6 0.2

Total 295.8 244.2 255.0 181.7 272.7

*excludes coccidiostats and polyethers

Antimicrobials that are approved for use as growth promotants in animals include:

Category Active constituent

Glycophospholopids Flavophospholipol Macrolides Tylosin and kitasamycin (growth promotant

claims currently under review) Olaquindoxalines Olaquindox Oligosaccharide Avilamycin Polyethers/Ionophores Monensin sodium and salinomycin sodium

Other antimicrobials are not permitted to be used as growth promotants. Antibiotics registered for therapeutic/prophylactic use in food producing animals:



Current and planned arrangements for monitoring of antimicrobial use in livestock, antimicrobial residues in livestock products and surveillance for antimicrobial resistance in animal pathogens

The APVMA monitors antimicrobial use in livestock. The data under heading 2 above is collected by the APVMA. Monitoring of antimicrobial residues in livestock products is the responsibility of the industry funded Australian Government National Residue Survey (NRS) (http://www.daff.gov.au/agriculture-food/nrs). Residue monitoring provides an estimate of the occurrence of residues in products (using systems based on sampling and statistical probability); confirms (or otherwise) that residues in products are below set limits; and alerts responsible government authorities and industry if, and when, limits are exceeded, so that corrective action can be taken. An example of corrective action is the refusal of export certification of meat under the Export Control Act 1982 (Commonwealth). Recent surveillance for AMR in animal isolates has included the DAFF ‘Pilot Surveillance Program for Antimicrobial Resistance in Bacteria of Animal Origin.’ This survey was published in 2007 and is publically available at: http://www.daff.gov.au/__data/assets/pdf_file/0004/950431/AMR-pilot-survey-

http://www.daff.gov.au/agriculture-food/nrs

http://www.daff.gov.au/__data/assets/pdf_file/0004/950431/AMR-pilot-survey-report.pdf



report.pdf. Surveys, research, and other input into animal origin AMR have also been recently undertaken by some state and territory governments and universities. Australia currently has no ongoing formalized system for the monitoring and surveillance of antimicrobial resistance in animal isolates. For human isolates, the Australian Group on Antimicrobial Resistance (AGAR) (http://www.agargroup.org) tests and gathers information on the level of AMR in bacteria causing important and life threatening infections in Australia. The monitoring and surveillance of AMR in Australia is currently under review by the Australian Health Protection Principal Committee Antimicrobial Resistance Sub-Committee, managed out of the Australian Commission on Safety and Quality in Health Care (http://www.safetyandquality.gov.au). The broader objective of the sub-committee is the development of a national strategy to minimise antimicrobial resistance. SAFEMEAT (a partnership between the red meat and livestock industry with Australian Government and state and territory governments) in June 2012 endorsed funding for research to quantify the prevalence of antimicrobial resistant bacteria in the red meat supply chain. The details of this work are yet to be formalized. Issues of AMR have also recently gained significant public and professional attention in Australia through public forums such as the 2011 Antimicrobial Resistance Summit hosted by the Australian Society for Infectious Disease (http://www.asid.net.au/News.aspx?NewsID=65) and Australian Society for Antimicrobials (http://www.asainc.net.au). There have been numerous other forums similarly dedicated to AMR since then also.

Patterns and extent of antimicrobial resistance in animal pathogens

The APVMA collects information annually from registrants on the quantity of antimicrobials sold in Australia. This information is voluntarily supplied by registrants. It is reasonable to assume that there is a close relationship between the quantities of antimicrobials sold and amounts used in animals in Australia. The 2007 DAFF ‘Pilot Surveillance Program for Antimicrobial Resistance in Bacteria of Animal Origin’ indicated resistance to antibiotics of critical importance to human medicine was non-existent or low in bacteria isolated from food-producing animals in Australia. A more detailed summary of AMR in Australian animals can be found in the paper ‘Antibiotic Resistance in Australian Animals in 2010 – What Lies Ahead’ presented by Professor Mary Barton of the University of South Australia to the APVMA Science Fellows Symposium in 2010

http://www.agargroup.org/

http://www.safetyandquality.gov.au/

http://www.asid.net.au/News.aspx?NewsID=65

http://www.asainc.net.au/



(http://www.apvma.gov.au/news_media/docs/symposium_2010/4_mary_barton_summary.pdf). Further information is contained in a presentation given by Professor Mary Barton of the University of South Australia, titled ‘Antibiotic stewardship into the future? The livestock industries’, which can be found at http://www.asid.net.au/images/Barton_Fri_14.05.pdf

http://www.apvma.gov.au/news_media/docs/symposium_2010/4_mary_barton_summary.pdf

http://www.apvma.gov.au/news_media/docs/symposium_2010/4_mary_barton_summary.pdf

http://www.asid.net.au/images/Barton_Fri_14.05.pdf



Bhutan

Naitan Wangchuk

Chief Livestock Officer Dpt. of Livestock, Livestock Production Division

Introduction

Livestock is crucial for the agrarian communities for food as well as non-food functions. With steady increase of demand for livestock products (fig.1), role of livestock is getting oriented more towards food functions, thereby, driving livestock farming system from subsistence to intensified system. In 2010, 69 percent of milk, 80 percent of egg and 27 percent of meat demand was met from internal production (Wangchuk 2012). To enhance internal production more intensification is desired. But, one of the undesirable consequences of intensification is exposure of food animals to antimicrobials for various purposes.

Figure 1. Livestock product demand trends (2007 -2010)

Source: Livestock statistics 2007-2010

Usage of antimicrobials were approved for treatment, prevention of diseases, promotion of growth and enhancing feed efficiency through various routes of administration—feed, water, injection – either to individual animals or groups (McEwen and Fedorka-Cray 2002). Use of antimicrobials resulting into emergence of diseases resistance in zoonotic enteropathogens, commensal bacteria and bacterial pathogens is elaborately discussed (Hur, Jawale et al. ; McEwen and Fedorka-Cray 2002; Ellerbroek, Narapati et al. 2010). However, studies on antimicrobial use and its consequences in Bhutan are scant, which perhaps could be due to the lack of appropriate technologies,



adequate infrastructures, and competent human resources to strengthen the national food safety standards and usage of drugs. Study of the prevalence of Salmonella spp. and drug resistant in imported chicken carcasses in Bhutan by Dahal, Ellerbroek et al. (2008) shows prevalence of Salmonella of 13% with Salmonella enteritidis as the most frequently isolated serotype (84.62%) followed by Salmonella typhimurium (15.38%). Among the seven antimicrobials tested, resistance for nalidixic acid was highest, followed by amoxicillin and cephalexin. The above findings show the evidence of risk associated with use of antimicrobials in food animals and it is essential to have enabling legal framework and institutions in place to implement the food safety standards and monitor the use of antimicrobials in food animals.

Legal framework and institutional arrangements

The broad legal framework on antimicrobial use and resistance is provided by the acts and regulations related to drugs (RGOB 2003; RGOB 2008) and food safety ((BAFRA 2005; BAFRA 2007). Under the broad frame work of Bhutan Medicines Rules and Regulations, National Center for Animal Health – the national referral center – has developed the approved list of antimicrobials (NCAH 2011) to be used. For each antimicrobial, specific guideline (NCAH 2011) is provided on its use. Regulation on drugs is effectively implemented and monitored spearheaded by Drug Regulatory Authority of Bhutan (DRA). Institutional arrangement on Drug regulation is illustrated in figure 2.

Figure 2. Institutional arrangements for regulation of drugs *ADR: Adverse Drug Reaction



Similarly to drug regulation, there is a sound legislation and institutional arrangement to regulate food safety for the consumers. Food Act of Bhutan (2005) and Food Rules and Regulation of Bhutan (2007) provide the legal basis for implementing food safety standards. Section 43.2 of Food Rules and Regulations of Bhutan 2007 emphasizes on food safety requirements: “Food should be deemed safe, unadulterated and uncontaminated if it has been produced, processed, transported, stored, distributed and prepared according to relevant codes of hygiene and technological practices and if it complies with the safety requirements of relevant standards, both established by the Codex Alimentarius Commission and with relevant national requirements. National requirement take precedence if there is a difference between the two.” Despite of having a good institutional arrangement (Figure 3) and strong legal instruments, it is unable to operate and deliver sophisticated and yet important services, such as analysis and monitoring of antimicrobial prevalence and resistance in food animals due to lack of technical capacity, adequate human resources and appropriate equipment. National Food Testing Laboratory under BAFRA has to upgrade its capacity to deliver laboratory services to the public.

Figure 3. Institutional arrangements and food safety functions

Extent of antimicrobial use in livestock production

Table 1 shows the type and amount of antimicrobial used in 2011. Unlike in other countries, antimicrobials in Bhutan are specifically used for therapeutic purpose only.



The mode of administration varies between oral and injection. Antimicrobials are administered to large and small animals and poultry. Table 1. Types of antimicrobial use in livestock production (Source: drug demand and

procurement information of National Center for Animal Health)

Name of Drug Composition Presentation Amount (units per

presentation)

Type Mode of use

Large animals

Amoxycillin trihydrate

1.5gm/bolus 1.5gm x2's 1,000 Therapeutic Oral

Ampicillin + Cloxacillin

1 gm + 1gm 2gm vial 3,000 Therapeutic Injection

Cephalexin 1.5gm/bolus 1.5gm x 2's 1,000 Therapeutic Oral Oxytetracycline

LA 200 mg/ml 30ml vial 2,000 Therapeutic Injection

Strepto-penicillin

2.5g 25vials pkt. 1,000 Therapeutic Injection

Sulphadimidine 33.33% 100ml vial Therapeutic Injection Sulphadimidine 5gm per

100gm 4's strip 1,000 Therapeutic Oral

Trimethoprim + sulphadiazine

400mg.2gm 10boli strip 2,000 Therapeutic Oral

Trimethoprim + sulphadiazine

80mg,400mg per ml

30ml vial 1,000 Therapeutic Injection

Small animals

Ampicillin 250mg 250mg vial 3,000 Therapeutic Injection Benzathine penicillin LA

600,000iu 600,000iu vial

4,000 Therapeutic Injection

Cephalaxin dry suspension

125mg/5ml 30ml bottle 1,000 Therapeutic Oral

Enrofloxacin tab

150mg tab 10 x 10's 1,000 Therapeutic Oral

Large&small animals

Amikacin 250mg/ml 5ml/vial 1,000 Therapeutic Injection Cefotaxime 1G/vial 1 G vial 1,100 Therapeutic Injection

Cefotaxime 500mg tab 10 x 10 S 1,100 Therapeutic Oral Erythromycin

inj. 100 mg in 1 ml

50 ml vial 1,000 Therapeutic Injection

Gentamicin inj. 40 mg in 1 ml

30 ml vial 1,000 Therapeutic Injection

Metronidazole injection

500mg/ml 100 ml 1,000 Therapeutic Injection

Oxytetracycline SA

50 mg/ml 50ml vial 1,000 Therapeutic Injection

Poultry Tetracycline Hcl W/S

5gm per 100gm

100gm sachet

12,000 Therapeutic Oral



Monitoring of antimicrobial use, antimicrobial residues in livestock products and surveillance of AMR in animal pathogens

The report on drug use and its performance are collected every six month by National Center for Animal Heath. Sensitivity test is conducted to find out the appropriateness of antibiotic usage to pathogen. Type of antimicrobials to be used is broadly guided by Bhutan Medicines Rules and Regulations 2005 and National Veterinary Drug Formulary 2011. Antimicrobial surveillance at national level has never been carried out but there is a system to tackle any adverse drug reaction noted in the field. Adverse drug reaction is reported to National Pharmaco Vigilance Center (NPVC) which forwards the report to Drug Regulatory Authority (DRA) for further actions (figure 2). Regulations on the use of drugs are improving under the guidance of DRA and NCAH, but there is limited capacity to test residues in food products at National Food Testing Laboratory (NFTL) which needs to be improved simultaneously to effectively monitor and analyze antimicrobial use and resistance in pathogens. Besides strengthening the capacity of existing laboratories, there is a need to have additional laboratories at different regions in the country with adequate and competent human resources to conduct sensitivity tests of drugs and residues in food products. In general, awareness on effects of injudicious use of antibiotics is lacking among public and even among the decision makers. Although drugs for animals are procured, distributed and dispensed by professionals, there is still a need to advocate on sensible use of drugs.

Patterns and extent of AMR in animal pathogens

It is difficult to get the patterns and extent of AMR in pathogen due to lack of testing facilities in the country on antimicrobial residues in foods and resistance in pathogens. There is immediate need to upgrade the existing laboratories and set up more laboratories with adequate facilities and competent human resources to systematically monitor and trace the use of antimicrobials in food and understand the resistance of pathogens to antimicrobials.

References

BAFRA (2005). Food Act of Bhutan, 2005. Thimphu: 2-33.

BAFRA (2007). Food Rules and Regulation of Bhutan 2007. Thimphu: 1-20.

Dahal, N., L. Ellerbroek, et al. (2008). Prevalence and antimicrobial resistance of Salmonella in imported chicken carcassess in Bhutan. The 15th Congress of FAVA; FAVA -OIE Joint Symposium on Emerging Diseases, Bangkok, Thailand.

Ellerbroek, L., D. Narapati, et al. (2010). Antibiotic Resistance in Salmonella Isolates from Imported Chicken Carcasses in Bhutan and from Pig Carcasses in Vietnam. Journal of Food Protection; 73(2): 376-379.



Hur, J., C. Jawale, et al. (2012). Antimicrobial resistance of Salmonella isolated from food animals: A review. Food Research International 45(2): 819-830.

McEwen, S.A. and P.J. Fedorka-Cray (2002). Antimicrobial Use and Resistance in Animals. Clinical Infectious Diseases 34(Supplement 3): S93-S106.

NCAH (2011). Essential Veterinary Drug List, DOL. Thimphu: 1-39.

NCAH (2011). Nation Veterinary Drug Formulary, DOL. Thimphu: 1-180.

RGOB (2003). The Medicines Act of the Kingdom of Bhutan. RGOB: 2-21.

RGOB (2008). Bhutan Medicine Rules and Regulation 2005. RGOB: 1-47.

Wangchuk, N. (2012). Livestock production trends. Thimphu, DOL.



India

Kaithathara Vijayakumar Joint Commissioner (LH)

Dpt. Animal Husbandry, Dairying and Fisheries

Introduction

It was the discovery of Penicillin in 1928 by Sir Alexander Fleming, a Scottish biologist which changed the course of the history of mankind in harnessing infections. By conquering some of the ancient scourges of the world, it turned out to be the most potent weapon to fight infection and the most effective life saving drug. The discovery of penicillin opened up a new saga of antibiotics to the world, spawned the huge pharmaceutical industry and also unleashed the enigma of antimicrobial resistance. Today, antimicrobial resistance in pathogens causing important infectious diseases is a matter of great public health concern globally and in India. One of the main reasons for this is the injudicious widespread use and the availability of practically all antimicrobials ‘over the counter’ (OTC) for human as well as for animal use. Reliable Indian data on antimicrobial resistance (AMR) for important pathogens of public health importance is an essential pre-requisite for developing appropriate guidelines for the use of antimicrobials in the country. Currently there is no accepted national database for antimicrobial resistance except in places where there is a specific national control programme. Though the use and misuse/ overuse of antibiotics in humans have been established as the main reason for development of antimicrobial resistance, the use of antibiotics in food animals has also become an important concern. The use of antibiotics in animals can be majorly divided into four categories such as:

Therapeutic,

Prophylactic,

Metaphylactic,

Growth Promoting Use. Growth promoters are usually administered in relatively low concentrations depending on the drug and species treated. Scientific evidences suggest that the repeated use of these performance enhancing antibacterial growth promoters (AGPs) may contribute to the development of drug resistance. Therefore, it is of paramount importance that countries develop legislations and regulations for use of AGPs.



Initiatives in India

In India the manufacturing of antibiotic drugs for human and veterinary purposes are regulated by Central Drug Standard Control Organization (CDSCO) under Drugs and Cosmetics Act of 1940 and the rules therein. However, there is as such no regulation particularly for use of antibiotics as animal growth promoter. The Food Safety and Standards Authority of India (FSSAI) under the Ministry of Health and Family Welfare is the main authority for laying down science based standards for articles of food and to regulate their manufacture, storage, distribution, sale and import, to ensure availability of safe and wholesome food for human consumption and for matters connected therewith as per the rules specified by Food Safety and Standard Act, 2006 (FSSA, 2006). It is the responsibility of FSSAI to adopt Good Manufacturing Practices, Good Hygienic Practices, Hazard Analysis and Critical Control Point and such other practices as may be specified by regulation. The various provisions which may have direct or indirect implication for AGPs are:

As per Section 16 (2)(b) of FSSA, 2006: The Food Authority specify the limits for use of food additives, crop contaminants, pesticide residues, residues of veterinary drugs, heavy metals, processing aids, myco-toxins, antibiotics and pharmacological active substances and irradiation of food.

The Section 16 (3)(b) of FSSA, 2006: The Food Authority shall also search, collect, collate, analyse and summarise relevant scientific and technical data particularly relating to incidence and prevalence of biological risk, residues of various contaminants, identification of emerging risks and also includes many others also.

The Section 21(1) of FSSA, 2006 specifies “No article of food shall contain insecticides or pesticides residues, veterinary drugs residues, antibiotic residues, solvent residues, pharmacological active substances and micro-biological counts in excess of such tolerance limit as may be specified by regulations.”

The Section 2.3.2 in Food Safety and Standard (Contaminants, Toxins and Residues) Regulations, 2011 of FSSA, 2006 specifies the limits for antibiotics and other pharmacologically active substances on the sea foods including shrimps, prawns or any other variety of fish and fishery products. According to this clause he following limits are prescribed as Tolerance limit for antibiotics in sea food.

Sl.No. Name of Antibiotic Tolerance limit mg/kg (ppm)

1. Tetracycline 0.1

2. Oxytetracycline 0.1

3. Trimethoprim 0.05

4. Oxolinic acid 0.3



This rule also prohibits the use of any of the following antibiotics and other Pharmacologically Active Substances in any unit processing sea foods including shrimps, prawns or any other variety of fish and fishery products namely All Nitrofurans, Chloramphenicol, Neomycin, Nalidixic Acid, Sulphamethoxazole, Aristolochia spp. and preparations thereof, Chloroform, Chlorpromazine, Colchicine, Dapsone, Dimetridazole, Metronidazole, Ronidazole, Ipronidazole, other Nitromidazoles, Clenbuterol, Diethylstilbesterol, Sulphonamide drugs, Fluroquinolones and Glycopeptides.

Similarly Export Inspection Council (EIC) under Ministry of Commerce and Industry has also set up rules stipulating upper permissible limits for certain antibiotics and anthelmintics like Albendazole and Fenbendazole in milk and milk products and MRLs for antibiotics in egg (EIC/Milk-E.I./Feb2008 Issue 5).

As per EIC, the following antibiotics and other pharmacologically active substances are prohibited in manufacture of feed, medication for chicken/poultry or in any stage of production of egg powder which include Chloramphenicol, Dimetridazole, Metronidazole, Nitofuran metabolites and anticoccidials including Nitroimidazoles (GOI order S.O.1442 dated 19.12.03).

An insertion to Rule 97 to the Drug and Cosmetics Rules, 1945 which came in to force in 17.01.2012 specifies that the container of a medicine for treatment for food producing animals shall be labeled with the withdrawal period of the drug for the species on which it is intended to be used. Provided that if the specific withdrawal period shall not be less than seven days for eggs or milk, twenty eight days for meat from poultry and mammals including fat and offal, five hundred degree days for fish meat.

Antimicrobial resistance monitoring

Antimicrobial resistance in pathogens causing important communicable diseases has become a matter of great public health concern globally including our country. Resistance has emerged even to newer, more potent antimicrobial agents like carbapenems. The factors responsible for this are widespread use and availability of practically all the antimicrobials across the counter meant for human, animal and industrial consumption. There are definite policies and guidelines for appropriate use of antimicrobials at national level in specific national health programmes being run in the country. In order to monitor antimicrobial resistance it is necessary to have regulations for use and misuse of antibiotics in the country, creation of national surveillance system for antibiotic resistance, mechanism of monitoring prescription audits, regulatory provision for monitoring use of antibiotics in human, veterinary & industrial sectors and identification of specific intervention measures for rational use of antibiotics.



In this regard a task force has been constituted with the following terms of reference: 1. To review the current situation regarding manufacture, use and misuse of

antibiotics in the country. 2. To recommend the design for creation of a national Surveillance System for

Antibiotic Resistance. 3. To initiate studies documenting prescriptions patterns & establish a Monitoring

system for the same. 4. To enforce and enhance regulatory provisions for use of antibiotics in human &

veterinary and industrial use. 5. To recommend specific intervention measures such as rational use of antibiotics

and antibiotic policies in hospitals. 6. Diagnostic Methods pertaining to Antimicrobial Resistance Monitoring.

For monitoring use and misuse of antibiotics: Schedule H of the drug and cosmetics act contains a list of 536 drugs which are required to be dispensed on the prescriptions of a registered medical practitioner. In order to have separate regulation to check unauthorized sale of antibiotics, a separate schedule as Schedule H1 may be introduced under the Drugs and Cosmetics Rules to regulate the sale of antibiotics exclusively. Corresponding provisions under the Rules could be framed for their implementation. A system of colour coding of third generation antibiotics and all newer molecules may be put in place restricting their access to only tertiary hospitals. Appropriate steps should be taken to curtail the availability of fixed dose combination of antibiotics in the market.

For strengthen diagnostics for AMR monitoring: The current methods as well as newly developed ones will be utilized for AMR surveillance with a robust quality assurance system put in place through a neutral central institute.

Aims of the national policy for containment of antimicrobial resistance

a) Understanding emergence and spread of antimicrobial resistance and the factors

influencing it. b) Establish a nationwide well coordinated antimicrobial programme with well

defined and interlinked responsibilities and functions of different arms of the programme.

c) Rationalizing the usage of available antimicrobials. d) Reducing antibiotic selection pressures by appropriate control measures. e) Promotion of discovery of newer and effective antimicrobials based on current

knowledge of resistance mechanisms. f) Rapid and accurate diagnosis of infections and infectious diseases.



Points of action

1. Establish government commitment and support for nation-wide antimicrobial program and within it the policy and set up national focal point for collaborations and compilation.

2. Establish a National Alliance for prevention and control of antimicrobial resistance.

3. Institute a surveillance system that captures the emerging resistance, seeks and envisions trends in its spread and correlates with utilization of antimicrobial agents in community as health care set ups.

4. Promote rational usage of antimicrobial agents. 5. Strengthen infection prevention and control measures-healthcare associated and

community based 6. Support research in developing newer antimicrobial agents and improving usage

of available ones, based on pharmacological properties. 7. Educate, train and motivate all stake holders in rational and appropriate usage of

antimicrobials and its regulation. 8. Establish a Quality System and a National registry for Antimicrobial resistance for

bacteria, fungi and viruses at national focal point. 9. Co-development of antimicrobial agents with pharmaceuticals and leaving the

distribution, sales and promotion with the government.

To conclude

In livestock production, antibiotics are dispensed to animals for a number of different reasons viz. therapeutic treatment, disease prophylaxis and growth promotion. The administration of antibiotics against bacterial populations is a significant driving force for selection of resistant forms of bacteria, which can spread from one organism to another. There is, therefore, an important question of whether the use of antibiotics in animal food production poses a threat to human health. In particular, the worry is that resistant forms of bacteria may spread from animals and/or the environment (ground water/ surface water/ soil) to humans. It is pertinent to note that there is lack of quality database on use of antibiotics and the problem of AMR has little recognition. The indiscriminate and inappropriate use of antimicrobials has resulted in rapid increase of AMR. To add to this there is no regulation in India to monitor use of antibiotics in food animals intended for human consumption. To redress the situation the National policy for containment of AMR in India has suggested for the institution of an ‘Inter-Sectoral Co-ordination Committee’ to give specific recommendations which is in progress. The consultations made by the committee are in line with the strategy of WHO to ensure prudent use of antimicrobials to combat development of AMR. They include:



1. Develop and promote guidelines to minimize and contain AMR arising from use of antimicrobials in food producing animals

2. Develop a list of critically important antimicrobials (CIA) for human health as well as for treatment of food producing animals in order to guide risk management strategies.

3. Provide technical support and capacity building in monitoring AMR through research projects, training activities and reference services of the WHO Global Food borne Infections Network (GFN).

4. Establish and perform pilot studies to address lack of data for risk assessment. 5. Measures for improving animal health to reduce/restrict antibiotic use and to

create awareness through IEC campaigns. 6. Develop regulations and advisories considering the Indian scenario on the use of

antimicrobials with continuous supervision, audit and feedback. 7. Ban in a phased manner the non-therapeutic / growth promoter use of

antimicrobials to prevent the development of AMR.



Indonesia

Imron Suandy and X Suparno

Quality Control for Livestock Services, Directorate of Veterinary Public Health and Post-Harvest

Ministry of Agriculture, Republic of Indonesia

Introduction

Indonesia is one of the countries where the agriculture sector can be considered to be a main national income resource. The agriculture development has been a main focus of the national development programs. In 2009, agricultural sector contributed as much as 15.3% to the National GDP and it is considered as the big two after the sectors manufacturing industry. To support agriculture development the government has established some policies and recently some programs have been set up to accelerate growth of agriculture production and the transformation of the agriculture system from traditional small holder farming to modern business agriculture industries. As a result of the intensification and commercialization of animal food production, however it has been created several consequences for public health concern. Antimicrobial residue in food of animal origin and development of antimicrobial resistance via food of animal origin has become a big challenge to public health. Thus, the residue problems should be controlled systematically to prevent from potential risk on human health and to eliminate distortion of trade. Moreover, the growing problem of antimicrobial resistance has become a significant public health concern worldwide. The World Health Organization (WHO) has concluded that antimicrobial resistance is a serious and complex worldwide problem. To address this problem, the WHO recommended a global surveillance system in veterinary and human. The Ministry of Agriculture (MOA) through the Directorate General of Livestock Services (DGLS) is responsible for controlling livestock production including animal health and quality of livestock products. The regulations based on Animal Health and Animal Husbandry Law no.18, 2009 which stipulated the authority to control animal health and livestock production, including veterinary public health. In connection with the use of veterinary drugs in aquaculture the law is effective and being referred, however the authority is under the Ministry of fisheries.



Regulatory framework to control antimicrobial resistance and residue of veterinary drugs in livestock products

In order to control the antimicrobial resistance and the residue of veterinary drugs in livestock products, the initiatives were focused on 2 main aspects: Strengthening of veterinary drugs control and improving the quality of livestock products. A. Control of veterinary drugs

Legal aspects The veterinary drugs controls have been regulated in Indonesia since 1912 under

The Ordinance no.432 and 435, and it were reviewed in 1937 under the Ordinance no. 541. In 1949, under the ordinance no. 419 the veterinary drugs control has been specifically pointed out and the drugs were classified to strong drugs and free drugs.

The Animal Health and Animal Husbandry Law No. 18, 2009, article 22 mentioned about the restriction use of veterinary drugs (such hormones and antimicrobials intended for human medicine).

Article no.49 - 54 chapters 2nd of Law no. 18, 2009 defined about veterinary drugs, it is described that the control of manufacturing, storage, distribution and used of veterinary drugs are under the government authority.

The Government Regulation no. 15, 1977 chapter IV article 7 defined the competency of the Ministry of Agriculture to control the veterinary drugs.

The Government Regulation no. 78, 1992 defined the control of veterinary drugs such as biologics, pharmaceuticals and premixes products including raw materials for veterinary drugs preparation.

The Veterinary Drugs Inspector and the operation procedure for controlling of veterinary drugs were established with the decree of Minister of Agriculture no. 15, 1994.

The veterinary drugs classifications, list of drugs can be used as feed additives and the prohibition to use Chloramphenicol and Hormone Growth Promoters in food producing animals were stipulated in the decree of Minister of Agriculture no. 806, 1994.

The regulations on the veterinary drugs used in aquaculture were cited in the decree of the Minister of Oceanic and Fisheries no. 26, 2002 and no. 4158, 2003.

Institutions

The control and administration of veterinary drugs are conducted by the Sub directorate of Veterinary Drugs Control which belongs to Directorate of Animal Health of the Directorate General of Livestock Services.

The Veterinary Drugs Commission was established to give advice on the policy related to veterinary drugs, and the Veterinary Drugs Assessment Committee to conduct technical assessment on administration of veterinary drugs.

The quality control and assay of veterinary drugs are carried out at the Veterinary Drugs Assay Laboratory. The laboratory is designed to conduct the



test and to issue the quality certificate for the products to prove that they meet the requirements.

The Veterinary Drugs Inspectors are placed at province and district livestock service office to carry out the control and inspections related to veterinary drugs in their work area.

Control systems The control of veterinary drugs covers the administration and registration system, assay system, Good Manufacturing Practice, monitoring and surveillance system, monitoring of drug side effect and the prudent use of veterinary drugs.

The registration of veterinary drugs requires an approval based on a document explaining the nature and characteristics of a drug. The safety, efficacy and quality of the drug being proposed should be assessed clearly by the Veterinary Drugs Assessment Committee and/or Veterinary Drugs Commission.

The veterinary drugs assay system has been established since the veterinary drug assay laboratory began to operate in 1985 (decree of MOA no.328, 1985) under a cooperation with the government of Japan. The assays are conducted for the drugs being registered and for monitoring of distributed drugs.

Good Manufacturing Practice (GMP) was introduced in 1999 by establishing the guideline for implementation of GMP (decree of MOA no. 466, 1999) and the guideline of operational procedures for GMP (decree of DGLS no. 247, 1999). The rules of GMP will come into effect in the year 2005, and all manufacturers will be subject to audit and inspections. By implementing GMP, the quality of veterinary drugs is controlled during the production process involving raw materials, facilities, process, quality controls and other relevant factors required by Good Manufacturing Practice (GMP).

The monitoring and surveillance programs are conducted to confirm the quality of veterinary drugs in distribution, in storages, in the markets, and at the farms. Samples are collected and sent to assay laboratory by the veterinary drugs inspectors of the district or province livestock offices, or are conducted directly by the assay laboratory.

The potential side effects of veterinary drugs are monitored particularly for drugs which have been used for long time or for drugs which are reported to induce abnormal symptoms in animals including effects on microorganism, environment and human health.

The prudent use of veterinary drugs was outlined in the code of practice for using veterinary drugs. To promote the prudent use of veterinary drugs, code of practices were prepared to be harmonized with the Codex Code of Practice for Control of the Use of Veterinary Drugs (CAC/RCP 38-1993). The code of practices was also designed to cover regulations on the use of veterinary drugs in feed, and the use of veterinary drugs by an authorized company, institution or personnel. The enforcement of compliance to withdrawal times were put as priority.



Veterinary drugs business and trade: The regulations have been issued in order to control and promote business and trade of veterinary drugs. Any company involved in business and trade of veterinary drugs should be authorized, and a license will be granted to the company which has to meet the requirements according to the regulations. The Contribution of the Veterinary Drugs Association on controlling and promoting business and trade of veterinary drug in Indonesia are significant.

The veterinary drugs inspectors have the authority to conduct the inspection and all control aspects related to veterinary drugs in their working area.

B. Quality control of livestock products

Legal aspects Law no.18, 2009, Chapter IV, article no. 56 stated about veterinary public health

authority; and article no. 58 mentioned with regard the obligation of control, monitoring, testing, standardization and registration of food of animal origin.

Food Law no. 7, 1996, article no.20 and 21 stated the food quality assurance and laboratory testing for food. According to the law, for all parties producing and distributing food for sale and trading purpose, it is obligatory to manage a quality assurance system. Before it’s distributed the food products are subject to laboratory examinations at the designed laboratory.

Consumer Protection Law no. 8, 1999, article no.19 lined out the responsibilities of the producers to protect consumers from deviations of their products.

Government regulation no.22, 1983 covers the Veterinary Public Health aspects The establishment and operations of the Quality Control Laboratory for Livestock

Products were stated in decree of MOA no. 426, 1994. Institutions

The quality control of food products is managed under the authority of the Ministry of Agriculture for livestock products, the Ministry of Oceanic and Fisheries for marine and fish products and the Food and Drugs Control Agency for most processed foods. Some other institutions such as Ministry of Health and Ministry of Trade are also involved.

Under the Ministry of Agriculture, there is Sub-Directorate of Residues which belongs to the Directorate of Veterinary Public Health of the Directorate-General of Livestock Services. The Sub-Directorate of Residues conducts the control of residue of veterinary drugs in livestock products.

The Quality Control Laboratory for Livestock Products (QCLLP) was established in 1994 and is designed to laboratory analysis and confirmation of residues and microbial contaminants in livestock products. This laboratory was than established as National Reference Laboratory for quality control of livestock products.

There are 8 Laboratories of Animal Diseases Investigation Center covering 8 regions of the national area; they have been promoted as Veterinary Assay



Laboratories with additional competency on analysis of residues and microbial contaminants.

The Veterinary Public Health Laboratory located in districts and provincial areas are operated to carry out simple tests of livestock product.

The Veterinary Public Health Inspectors are placed at provincial and district livestock service offices to carry out the control and inspection related to the quality of livestock products.

The Livestock Products Sampling Officers are trained and appointed to carry out the sampling operations of livestock products for laboratory examinations.

The National Veterinary Research Laboratory conducts research and development of methods of analysis for residue of veterinary drugs.

Residue control system

To improve the quality of livestock products the government launched the quality assurance program called "ASUH" meaning Aman (safe), Sehat (healthy), Utuh (wholesomeness) and Halal (edible under religious rules).

The animals should be slaughtered at the slaughter houses or other places designed specifically to meet the criteria for slaughter house under the inspection of the authorized officers.

The animals are subjected to examination of the drug administration and health conditions under the control of veterinarians before their slaughtered.

Veterinary Control Numbers are issued in order to improve the quality assurance of food safety by implementing the minimum requirements for sanitation and hygiene. The numbers are issued to the institutions such as slaughtered house, processing plant and private such as importer, cold storage and processing plant.

HACCP principles were introduced and socialized since 1998; however the implementation of the principles is still under preparation. Following demand for export purposes some company have implemented the principles already.

Monitoring and surveillance of residue and microbial contaminants, the programs called "PMSR" have been established since 1998. The samples are collected and tested by the institutions and laboratories involved in the control of livestock products. The results of monitoring are evaluated at the annual meeting of PMSR, and the data are used for strategic planning of the programs. The programs were prepared to improve the national monitoring and surveillance system.

Laboratory accreditation programs based on ISO-17025 was one of the efforts which has been implemented to provide testing laboratories with a recognized Good Laboratory Practice status and valid test results.

SNI-BMR is a national standard for maximum residue limit (MRL) of veterinary drugs which adopted from Codex MRL, so that the risk analysis procedure were provided and approved at the international level.



Initiative control program for antimicrobial resistance

Although only limited research on resistant bacteria to antimicrobial has been conducted in Indonesia, unfortunately, the DGLS have not yet had a regular program for monitoring and surveillance of antimicrobial resistance. The initiative activity concerning the issue has been started by QCLLP since 2011.

In 2011, the QCLLP conducted a study to monitor the antimicrobial resistance in sentinel bacterial isolated from poultry meat from one of poultry pocket area in West Java.

In 2012, the program was continued to all Java Island (still in progress). Hopefully, based on the available data it will be proposed as a regular program in next year following the OIE guidelines on Harmonization of National Antimicrobial Resistance Surveillance and Monitoring Program.


The key priority of the Indonesian government for the livestock sector is the expansion of the poultry industry, in particular the broiler industry. It’s revealed that the share of antimicrobials used in livestock production was dominantly in poultry farms rather than others (as shown in figure 1 below).

Figure 1. Distribution of antimicrobial use by animal species

Source: ASOHI 2011

Remarkably, the veterinary drugs were used as feed additive have a highest market share in Indonesia, although the trend was a bit decreasing in 2011 (see table 1).



Table 1. Market share of veterinary drugs in year 2010 – 2011

2010 2011

Value (billion Rp.)

% Value (billion Rp.)

%

Biological agents 617.6 30.8 693.8 32.1

Pharmaceuticals 461.5 23.1 489.7 22.6

Feed additives 921.2 46.1 980.0 45.3

Total 2,000.3 2,163.5 Source: ASOHI, 2011

Based on the data from the DGLS, number of exported of veterinary drugs tent to be increasing in each years. The same trend was also shown for number of export. Although the data up to August 2011 was shown decreasing, but the ASOHI have been predicted it will rise.

Table 2. Balance of export and import of veterinary drugs year 2009 -2010 (US$)

2009 2010 2011*

Export 4,704,648 5,346,775 12,025,932

Import 41,731,023 46,465,313 30,611,856 * Data were updated up to August 2011; Source: Directorate General of Livestock Services

Findings of monitoring program for antimicrobial residues and resistance

Monitoring of antimicrobial residues in food of animal origin

The National monitoring program was conducted and prioritized in livestock pocket production area in country. Further action must be taken will be recommended to local authority as responded of result finding. The data below were resulted from QCLLP monitoring program, as national laboratory reference on veterinary public health services.



Figure 2. Number and type of samples taken for antimicrobial residue

testing 2010 and 2011 The data of monitoring program resulted from QCLLP mentioned that the antibiotic residue was prevalent in each year. The results were showed a varieties trend of residue on group of antimicrobials in each year. In year 2012, the residues of macrolides and aminoglycoside group tend to be increasing (as shown in figure below).

Figure 3. Proportion of samples positive for antimicrobial residues 2010-2012

Monitoring of antimicrobial resistance

A study was conducted to monitor the antimicrobial resistance of sentinel bacteria (E. coli) isolated from broiler meat in one area of main poultry pocket production in West Java by QCLLP in 2011. In general, resistance patterns reflected the commonness of use of antimicrobials in the farms. Although chloramphenicol is a prohibited antimicrobial for use in food animals resistance could be detected (see figure below).



Figure 4. Results of antimicrobial resistance testing

The study also showed that the prevalence of multidrug resistance was highest in four drugs combination of antimicrobial. The combination of tetracycline, erythromycin, and ampicillin was the pattern most frequently observed.

Figure 5. Prevalence of multidrug resistance

Fund to support AMR control program

Main source of fund is supplied by central government budget via APBN (Anggaran Pendapatan dan Belanja Negara) or National Budget that can be divided into two kinds. First, budget from APBN straight come to DGLS, and the budget from APBN via other government institutions. Sometimes there is an external budget from international organization, but not significant in terms of amount and frequency. Unfortunately, there



are a limited budget have been prioritized to support AMR control program in particular.

Conclusions

The system for the control of residues of veterinary drugs in Indonesia has been designed and established, however, there are still many problems to be faced which need to be phased out, relating to facilities, human resources, and laws enforcement. The intervention strategies for controlling antimicrobials used on farms should be reconsidered. It is required to set up a routine monitoring and surveillance program, and improve farming practices in order to reduce the development of antimicrobial resistance and minimize the likelihood of transfers of antimicrobial resistance genes to other microbes in the food chain. These conditions should be considered to assure the continuity of agriculture developments in country, to prevent distortions on international trade and ultimately to secure the safety of consumers.



Iran

Seyed M. Azizian Director General

Bureau of Pharmaceuticals, Therapy and Laboratories

Legal framework and institutional arrangements The legal framework and institutional arrangements regulating antimicrobial usage is based on governmental guidelines. Every drug has a Master File (DMF) and this file contains all important information about safety, efficacy and potency, residue limits in milk and meat as well as about all limitations and particularly withdrawal times. Important information such as dosage, route of administration, period of use, contraindications has to be notified on the labels. If a farmer or veterinarian does not act in conformity with the law, rules and regulations, the legal authority system (I.V.O) will counter with them because of public health hazards.


The extent of antimicrobial drugs used in livestock production in 2011 is displayed in Table 1.

Table 1. Antimicrobial use in livestock in Iran in 2011

Species Formulation Quantity Unit

Poultry Oral Solution 1,700,000 litre

Soluble Powder & Premix 1,900,000 kg

Cattle, sheep & goats

Injection solution 8,189,000 vial

Injection powder 4,500,000 vial

Intra-mammary ointment 1,300,000 syringe

Tablet, oblet, bolus 53,000,000

The main sources of the above antimicrobial drugs are domestic manufacturers while only a minor percentage is imported. Close to 1,000,000 kg of active ingredient were used in 2011 to produce the above quantities of antimicrobial drugs.



Monitoring of antimicrobial use, antimicrobial residues in livestock products and surveillance of AMR in animal pathogens

Current arrangements and plans for monitoring of antimicrobial use in livestock refer to guidelines that approved for monitoring of usage, residues, MRL (Maximum Residue Limits) in meat and milk. We recently provided a national plan for monitoring of AMR. The Authority System (IVO) is in force to ensure that the residues of drugs and their metabolites in meat and milk do not exceed legal limits. At present, general arrangement for antibiotic residues is only based on the limitation imposed in the labels of drugs.


Because AMR may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs, the rates of antimicrobial resistance in bacteria causing serious infections are rapidly rising. Because of this rapidly rising resistance, many infectious diseases are now untreatable and for this reason a study on antimicrobial resistance patterns was carried out in Iran in 2011. In this study, which covered all provinces of the country, nearly 6,000 antimicrobial sensitivity tests were carried out. Results of the study are similar to those found in studies in other countries. The main findings can be summarized as follows:

Most AMR found in broiler farms appears in E. coli;

AMR to ‘old’ antimicrobial drugs such as Oxytetracycline and Flumequine was high, reaching up to 80 %;

AMR to ‘old’ antimicrobial drugs was also high (up to 70%) in regions with low density of breeding farms. There is a direct relation between the use of antibiotics and appearance of resistance;

In isolates from young chicken, AMR was mainly found to ‘old’ antibiotics such as Oxytetracycline-Flumequine, but with increasing age, in addition to an increase of resistance to old antimicrobial drugs, increasing AMR levels is observed to ‘new’ antimicrobial drugs such as Doxycycline-Dano Floxacine-Florfenicol

Analysis of antibiogram records showed that E. coli is the major bacteria isolated from chicken, but Salmonella, Proteus, Citrobacter, Pseudomonas, Klebsiella and Serratia were also isolated. AMR in E. coli was most common against Oxytetracycline (up to 80%), Enrofloxacin (up to 60%) and Flumequine (up to70%). It is necessary to mention that because of E. coli is the most important agent causing economic loss in poultry production, E. coli was examined against more antibiotics such as Oxytetracycline, Flumequine, Enrofloxacine. AMR patterns to mentioned antibiotics depends on isolated bacteria species.



Figure 1 displays the extent of AMR found in E. coli and Salmonella spp isolates in 2011. For E. coli, the highest resistance related to Oxytetracycline (nearly 90%) and lowest resistance related to Colistin (10%). In contrast, only 10% of Salmonella isolates displayed resistance to Oxytetracycline. This may be due to the high prevalence of E. coli and second the long period of use of Oxytetracycline. With respect to Colistin, the short period of use may be the most important reason for low resistance levels in E. coli. In relation to salmonella resistance to this antibiotic it may be inherited.

Figure 1. Percentage of E. coli and Salmonella spp. isolates in Iran resistant to

Oxytetracycline, Flumequine, Enrofloxacin and Colistin in Iran In comparison to ‘old’ antimicrobial drugs, micro-organisms still exhibit high levels of susceptibility / low levels of resistance to ‘new’ antimicrobial drugs such as Doxycycline, Florfenicol and Fosfomycin calcium. Based on the above results a national monitoring plan for AMR is envisioned and supposed to be implemented every year.



Korea DPR

Jo K. Guk

Head Epidemiological Surveillance Branch, MOA

Introduction

During the past decades, several industrialized animal farms have been built under the wise leadership of the great leader comrade Kim Jong Il and animal production is increasing under the wise leadership of the dear general Kim Jong Un in our country. This requires the use of much more antimicrobials in animal production but they are not supplied sufficiently now, because the quantity and quality of most antimicrobials produced in our country are poor and many of them are imported. The number of food-producing animals are about 15,700,000 in our country now. The numbers related to animal species are as follows.

Table 1. Number of food-producing animals

Species Number

Cattle 576,000

Pigs 2,857,000

Sheep 168,000

Goats 3,689,000

Legal framework and arrangements for the use of antimicrobials

We now have a legal framework and arrangements on the manufacture, distribution, importation and use of veterinary medicinal products. The veterinary and anti-epizootic law, the veterinary medicinal agents management law and the animal quarantine law provide the legal framework and arrangements on the use of antimicrobials in animal production. However, a legal framework and institutions on marketing authorization of antimicrobials in the country is still lacking. Antimicrobials are provided according to the supply plan of the government.



Extent of antimicrobial use in animal production

The total quantity (in metric tonnes) of antimicrobial agents used in food-producing animals for 2007 to 2011 is indicated in the following table.

Table 2. Total quantity of antimicrobials used in food-producing animals

Year Quantity (MT)

2007 15.8

2008 15.6

2009 16.4

2010 16.5

2011 16.5

The class of antimicrobials used in our country usually includes Oxytetracycline, Tetracycline, Penicillin, Streptomycin, Tylosin, Flurazolidone, Norfloxacin and Sulfadimedoxine. Penicillin and Streptomycin are produced (as one million IU / g) in our country. Oxytetracycline is also produced in our country but most of it is not refined and of low biological activity (about 3,000 to 10,000 IU / g). Tetracycline, Tylosin, Furazolidone, Norfloxacin and Sulfadimedoxine are imported, mainly from China. Several types of antimicrobial agents are used in animal production. These and their mode of use are displayed in the table below.

Table 3. Types and mode of use of antimicrobial agents in food-producing animals

Antimicrobial Presentation Purpose of use Mode of application

Penicillin, Streptomycin

Powder in ampoule or vial

Disease treatment Injection

Norfloxacin, Tetracycline

Powder in ampoule or vial

Disease treatment Injection

Oxytetracyclin, Tylosin

Powder Growth promotion and treatment

Additive in feed and drinking water

Sulfadimedoxine, Furazolidone

Powder Treatment and control of disease

Additive in feed

Arrangements for monitoring of antimicrobial use, residues and resistance

An official system for collecting quantitative data on antimicrobial agents used in animals has been established since 1997. MOA is in charge of this system. Information on the antimicrobial agent used in animals is collected by the veterinary and anti-epizootic department, the animal production department, the central veterinary station,



provincial veterinary stations, the animal quarantine office, veterinary medicine manufacturers and veterinary research institutions. Regulatory monitoring systems and programs for antimicrobial use, antimicrobial residues and antimicrobial resistance have not yet been fully implemented. Information on the use of antimicrobials is reported to the veterinary stations all over the country, but the information includes only some data of animal disease treatment using antimicrobial agents, namely what disease was treated, which antimicrobial was used, how it was used and how it worked. Antimicrobials as additives in feed are used according to their brand and instruction of individual researcher. The monitoring of antimicrobial residues in livestock products and surveillance of antimicrobial resistance in animal pathogens is only conducted for particular reasons and not as general routine.

Antimicrobial resistance in animal pathogens

We have not surveyed the patterns and extent of antimicrobial resistance. Sometimes, antimicrobials to treat animal diseases, mainly digestive disorders, have proved to be less or non-effective. Considering this, we have been suspecting that that pathogens with AMR exist in our animals and animal products, but their characteristics have not been investigated.



Lao PDR

Thongphun Theungphachan

Head Livestock & Fisheries Products Quality Assurance Unit

NAHC, DLF

Introduction

The Lao PDR has a land area of 236,800 square kilometres and a human population of 6,201,000 giving it the lowest population density in East Asia. A landlocked country, Lao PDR is bordered by Vietnam (2,069 Km in the east), Cambodia (435 Km in the south), China (505 Km in the north), Myanmar (236 Km north-west) and Thailand (1,835 Km in the west) with the Mekong River serving as much of the border with Thailand. About two-thirds of the country is mountainous which creates transportation difficulties while at the same time producing many rivers and vast hydropower potential. Lao PDR is a tropical country, whose climate is affected by monsoon rains from May to September alternating with a dry season from October to April. The Lao PDR is a predominantly rural society with 85% of the population depending on agriculture for their livelihood with most of the rural households producing food mainly for their own consumption. Agriculture accounts for 52% of GDP with livestock and fisheries contributing 18%. Culturally, the Lao PDR is immensely diverse with more than 46 officially recognized ethnic groups. Broadly, the country can be divided into lowland and upland (or sloping lands) zones, and these provide different challenges and opportunities for development. Lowland areas are planted to paddy rice and are the most important rice cropping areas in the Lao PDR. They occur mainly along the Mekong and its tributaries, and this area is referred to as the Mekong Corridor. Agriculture in these areas is becoming more and more market-oriented with market forces driving the process of agricultural intensification and diversification. Upland villages in the sloping lands zone are more remote, have poorer road and market access and villagers rely predominantly on subsistence farming. While poverty has been reduced considerably in the Mekong Corridor, people in the sloping lands zone have been by-passed by economic growth and many are still living in poverty. The Lao government wants to increase livestock production to reduce poverty and increase protein consumption from 22 to 50 kg per person in rural areas and from 33 to 70 kg per person in urban areas. The National Growth and Poverty Eradication Strategy identifies targets of an average meat supply of 70 kg/capita/year and increased exports to the value of US$50 million by 2020.



Given that 95% of livestock are local breeds produced by smallholders under low input/low output systems for domestic use and local trade, questions remain about the potential for producers to:

(1) lift productivity to reduce their poverty levels; (2) increase production to meet growing domestic demand; and (3) contribute to export markets.

The demand for meat in the Lao PDR and other Southeast Asian countries has grown consistently over the last decade and is likely to continue to do so for the foreseeable future. About 75% of cattle and buffalo produced are consumed domestically and the remaining 25% are exported. Thailand is a major market for live cattle and buffalo with the Lao PDR supplying approximately 20% of the demand, accounting for approximately 100,000 animals per year. Other major suppliers are Myanmar and Cambodia. Pigs and poultry are produced mainly for home consumption and local markets. There is strong demand pull for meat which will increase in future. In 2011-2012, there were approximately 1,363,972 buffalo and 1,904,177 cattle, 3,464,187 pigs, 894,255 goats and 40,110,232 poultry. Density of cattle and buffalo is lower in the northern region than in the central and southern regions. Per capita pig density is higher in the lowland and highland areas than in uplands. Livestock are raised in extensive, low input systems that take advantage of naturally occurring feed resources. All livestock types are native breeds well adapted to the extensive production systems in which they are raised. Livestock production is clearly in the hands of smallholder farmers with about 95% of all animals being reared by these producers. Smallholder farmers operate mixed farming systems, growing both crops and rearing animals. Ways of feeding and managing animals have evolved in response to the predominant cropping system and the available feed resources. These include fallow cropland, communal areas along roads, rivers, areas around fields and villages, dedicated grazing land, secondary forests and other non-cropped communal land. Additionally, crop by-products such as rice straw are also fed to ruminants. Commercial livestock production has developed only around major population centers such as Vientiane, supplying meat, eggs and milk to the urban population.

Legal and regulatory framework

Current livestock regulations

Regulation No.0036/DLF dated January 2000 of the Department of Livestock and Fisheries is a comprehensive set of rules governing most aspects of animal raising and management in the Lao PDR. The regulation provides for the marking and registration of livestock, the movement of animals and their products and veterinary supplies in and



out of and internally within the Lao PDR, and contains conditions relating to animal disease prevention and vaccination, the slaughter of animals and meat inspection, and the conservation of breeding stocks. Of particular relevance are the following points:

➮ The legal requirements to import livestock, feed and veterinary supplies are onerous:

an official application has to be made 15 days before importation and should be accompanied by another form to the DLF (different forms for different products) also accompanied by a certification / license from the exporting country including, in the case of veterinary drugs, samples of the drugs. The imported goods have to be checked at border checkpoints. The regulations of the Ministry of Trade and Ministry of Finance also have to be followed.

➮ The legal requirements for export of animals or their products require, in addition to

the equivalent requirements for importation, another set of forms and requirements for movement within the Lao PDR to the border. Thai Government regulations also have to be followed.

➮ Within the Lao PDR, irrespective of whether for export or not, all cattle and buffalo

have to be vaccinated against HS and, in some areas, additionally for Anthrax and Black Quarter.

➮ Pigs must be vaccinated against CSF, chickens against NCD and Fowl Cholera, and

ducks against Fowl Cholera and Duck Plague.

➮ There are comprehensive conditions relating to reporting of disease epidemics and

the subsequent control of the epidemics including restriction on animal movements in declared epidemic zones. There are particular conditions relating to Anthrax, Black Quarter, CSF and FMD. These are all notifiable diseases. For all of these notifiable diseases, rules are given for destruction of infected animals, for disinfecting the area and vaccination of unaffected animals within the five km radius Epidemic Zone. Repeated vaccinations are not specified. Of particular interest is the restriction of movement of livestock in declared Anthrax and FMD epidemic zones which is 14 days after the day on which the last animal with symptoms is observed for Anthrax and 21 days for FMD. In addition to the specific requirements of the Regulation 0036/DLF, provinces impose special directives on the livestock industries in their areas of control. Provincial directives are not consistent among provinces. In some provinces, directives regulate the importation of production animals through a restricted number of approved traders, taxes are imposed on the importation of feed and animals, and vaccine importation from Thailand is banned.



The conditions of Regulation No.0036/DLF are generally not enforced. However, provincial directives appear to be more consistently enforced. The livestock industry in the lowland areas adjacent to Thailand appears to be operating profitably under somewhat free enterprise conditions in the absence of appreciable enforcement of legal regulations. Strict enforcement of existing regulations would hamper the export of livestock and would hamper the production of industrial animals for local consumption.

➮ The Law on Livestock Production and Veterinary Matters No 110/OP, 18 August 2008:

The objectives of the LVL are to regulate the organization, management and inspection of livestock production and veterinary services; regulate the management and control of animal diseases; provide consumer protection from animal diseases transmissible to humans; protect national livestock resources and increase supply of quality livestock to the domestic and export markets; and ensure sustainable environmental protection.

➮ Decree on Livestock Management in Lao PDR No. 85/PMO dated 31 May 1993.

• Regulation on Livestock Management in Lao PDR No. 0004/MAF and Instruction on Livestock management in Lao PDR No. 0005/MAF dated 02 January 1997;

• Technical Norm/Guideline on Livestock and Livestock Products Management in Lao PDR No. 0036/MAF dated 24 January 2000;

• Different Orders, Announcements, and Instructions have been issued by MAF and DLF.

➮ The mentioned decree, regulation and technical norm provide for: Ear tagging and

registration of livestock; movement of animals, their products, within the country, import and export, transit through the country; the regulation also regulates the supply of veterinary drugs and equipment; the conditions relating to animal disease prevention, control and vaccination; slaughterhouses and meat inspection and the conservation of breeding stocks. Foreseen legislation activities

Draft specific legislation to be implemented the LVL such as:

• Regulation on slaughterhouse and meat inspection; • Regulation on animal disease prevention and control; • Regulation on animal and animal product movement management These three documents have been submitted to the National Science and Technology organization.



Continued dissemination of the LVL by organizing the workshop with different sectors in each province throughout country;

Draft the regulation on veterinary association; Draft the regulation on livestock production association; Draft the regulation on veterinary services such as: Veterinary clinics; vaccine and

medicine production; animal vaccines, veterinary drug and veterinary equipment shops; establishment of veterinary professional schools.


Lao PDR is a developing country and the majority of the antibiotics used in livestock and fisheries is as therapeutic agents to treat infections of bacterial diseases in intensive and extensive farming systems. They may also be used as prophylactic agents. Antibiotics are also used to counteract the adverse consequences of stress responses. They may also be used as prophylactic agents in the water of healthy birds and as growth promoters at sub-therapeutic concentrations in feed. Bacitracin, Bio-tetra, Bio-tylo, Chlortetracycline, Tylosine, Neomycin, Oxytetracycline, and others are used for these purposes. Sub-therapeutic dosing in feed increases the rate of weight gain and improves the efficiency of converting feed to meat. In Lao PDR antimicrobial use in the livestock and poultry sectors is a common practice. Available data suggest that antimicrobials are used in most phases of swine and poultry production and that usage has been increasing, most frequently through in-feed additives. When antimicrobials are used for therapeutic and prophylactic purposes, they help treat and prevent disease in exposed animals. When used at low levels in animal diets and feed for sub-therapeutic (essentially nonmedical) purposes, antimicrobials help improve animal growth rates and feed efficiency, and also help reduce mortality and morbidity and may improve reproductive performance. Some studies show that higher growth rates from sub-therapeutic antimicrobials have positively influenced producer incomes and resulted in higher per-animal net returns. However, certain bacteria are becoming increasingly resistant to these drugs, and that antimicrobial resistance may be transferred from animals to humans through the consumption or handling of meat that contains resistant bacteria. Public health experts also attribute such resistance to a number of other causes, such as overuse of antimicrobial drugs by medical professionals and their patients. Many antimicrobials are approved for treatment or growth promotion in the Lao PDR. Antimicrobials used in livestock / fisheries as therapeutic agents to treat infections are: Pen-step, Dufamox 15% LA, Oxtetracycline 20% LA, Bio-Tetra 10% WSP (Powder), Bio-Tetra 200 LA, Enrofloxacin, Oxtacin-En 5%, Bio-tylo 200, Bio-Tycosone, Genta-tylosin, LA, Bio-analzine, Bio-TMPS 48%, Bio-Primix, Spira-Tylocol, Enrovita, Kinococ, Bio-New



Diarrhea Stop, Dexon-A, Triprim, Gentavet, Kanamycin, Oxycline, Bio-b12, Betamycine, Vioxin, Losin, sulfonamides and others. Antiseptics and disinfectants used in livestock products: Potasium Permanganate, Blue Spray Tetrave, Formaldehyde solution 40%, Alcohol 90, Dertodine, Biodine, Negasunt. Vitamins and minerals: Fer+Genta-Tylo, Oxytocin, Multivitamins Inj, Bio-B Complex Inj, Vitadex B 12 Inj, Vit AD3 E Inj, Three Mix (Powder), Three Mix (Solution), Anti-stress, Swine mineral, Chicken mineral, Royalfac. Cattle and Buffalo: There is an opportunity to considerably increase cattle and buffalo production in Lao PDR. Remote upland areas are well suited to breed / supply cattle and buffalo which can then be fattened for sale closer to markets. In the Mekong Corridor, available feed resources are limiting expansion of cattle and buffalo production, particularly in areas where irrigation enables farmers to grow two rice crops. Foot and Mouth Disease, Hemorrhagic Septicemia, Samonellosis, E. coli sp, Blackleg, B. Anthracis may also be involved. Although many antimicrobials are available to treat enteric diseases, little information is available describing which of these drugs are being used and at what frequency. Poultry. Chicken population increased from 20 million in 2010 to 40 million chickens in year 2011-2012; the industry grew to be highly integrated, with few companies controlling most birds, feed mills, farms, and slaughter and processing facilities. Poultry are typically raised under confinement in pens containing 200 to 20,000 birds. Integration led to standardized management practices, including drug treatment policies and procedures, and to many successes in the prevention and control of infectious diseases. Many problematic infectious diseases are controlled with antimicrobials (Enrovita, Oxtetracycline, Bio-Tetra, Bio-New Diarrhea Stop, Bio-TMPS) and anti-coccidial drugs. Vitamins and minerals (e.g., bio-vitamin, anti–stress, chicken mineral compounds) are used for prevention and treatment in water to an entire flock (usually thousands of birds contained within a single barn) because single-bird treatment is not practical. Swine. Swine are usually raised in confinement, either from birth through slaughter (farrow-finish) or in age segregated management systems (i.e. nursery, grower, finishing), with many farms of both types practicing all-in, all-out management to control infectious diseases. Average herd size is increasing; in 2011, 50 % of pigs were raised on farms of 200 to 1,000 pigs. Antimicrobials used for growth promotion or disease prevention and prophylaxis are typically removed at the finishing stages of production. Therapeutic treatments are also administered in feed, although producers also treat individual swine. Most pigs receive



antimicrobials in feed after weaning (“starter rations”), when they are most vulnerable to infectious diseases such as Classical Swine Fever, Foot and Mouth Disease, round worm, piglet diarrhoea, Erysipelas, Porcine Reproductive and Respiratory Syndrome (PRRS / Blue Ear), Cysticercosis. Several antimicrobials (e.g., Bio-Tycosone, Bio-Primix, Bio-analzine, Bio-New Diarrhea Stop, sulfonamides, tetracyclines, Fer+Genta-tylo) are used to treat and prevent pneumonia, an important problem among swine. Gentamycin, Bio-New Diarrhea Stop, sulfonamides and neomycin are used to treat bacterial diarrhea. Other important problems are caused by organisms such as E. coli and Salmonella spp. Overall, the antimicrobials used most frequently in swine are tetracyclines, Gentamycin, tylosin, and sulfamethazine or other sulfas. Opportunities to improve pig and poultry production clearly exist, but expansion is somewhat limited by the relatively small (albeit increasing) size of the domestic market. Farmers in the Lao PDR are unlikely to be able to produce pigs and poultry competitively for large-scale export, although some trade opportunities may develop for districts near borders with the People’s Republic of China, Thailand and Viet Nam. While the Lao PDR has a comparative advantage in ruminant (cattle, buffalo and goat) production, this is not the case with pigs and poultry.

Current and planned arrangements for monitoring of antimicrobial use in livestock antimicrobial residues in livestock products and surveillance for antimicrobial resistance

Antimicrobial residues

Presently antimicrobials are used in livestock / fisheries as therapeutic agents to treat infections, bacterial diseases of livestock and aquatic animals in intensive and extensive farming systems. Livestock / fisheries products are very important for Lao people, they are a source of income for the family and saving bank for the villages in rural areas and source of protein for consumers health in the country. But meat products may be contaminated with antibiotics. Antibiotics are widely used in veterinary medicine and subsequently drug residues may persist in food derived from animals, which may pose an adverse health effect for the consumer. Department of Livestock and Fisheries apply methods fail to detect the maximum residue limits in animal and fisheries products. Recently for detection of antimicrobial use in livestock / fisheries products used standard determined by OIE table 1.



Table 1. Maximum residue limits (milk: mg/l, meat: mg/kg)

No Description Fresh milk

Shrimp Chicken Pork Beef Fish

1 Amoxillin 0.001 0.004 0.004 0.004 0.004

2 Ampicilin 0.001 - - - - -

3 Bacitracin 0.56 - 0.4 0.2 - -

4 Chlotetracycline 0.05 0.2 0.2 0.2 - 0.2

5 Eritromycin 0.5 - 0.4 0.4 - -

6 Gentamycin - - 0.2 0.4 - -

7 Kanamycin 2.0 - - - - -

8 Neomycin - - 1.0 2.0 - -

9 Oxytetracycline 0.1 0.2 0.4 0.4 0.2 0.2

10 Rifampicin 0.01 - - - - -

11 Penicillin 0.001 0.004 0.004 0.004 0.004 0.004

12 Streptomycin - - 0.5 0.5 - -

13 Sulfadimathoxine 0.5 0.125 0.5 0.5 0.5 -

14 Tetracycline 0.1 0.1 0.2 0.2 - 0.1

15 Tylosin 0.0625 - 0.125 0.125 - -

Accuracy(%) 91.7 92 95 92 - 92

Sensitivity(%) 100 80 90 66.7 - 80

Specificity(%) 90.5 92.6 100 97.6 - 92.6

Kappa Coefficient (%) 0.70 0.46 0.90 0.70 - 0.46

Monitoring of food products from animal origin for the presence of antimicrobial residues is preferably done using test kits for determination of drug residue in meat. The methods because of their high cost-effectiveness and low cost appropriate services. AMR in animal pathogens

Antimicrobial resistance is also a concern for animal health, but little is known about the magnitude of this problem. The antimicrobial resistance in exclusive animal pathogens is poor with surveillance of zoonotic diseases.



Antimicrobial susceptibility testing of bacterial isolates not only allows for discrimination between isolates, but for assessment of developing resistance. Susceptibility testing methods include disk diffusion. For the antimicrobial susceptibility test dish use in ADDL (NAHC) import two brand Difco and Oxoid. Few data are available on the prevalence of resistance in the bacteria because of lack of resources, lack of facilities and equipment for testing; perceived low priority, lack of coordination for collection and antimicrobial testing methods; and concerns about sampling bias because most bacterial infections are barriers. The National Animal Health Center performs analyses of animal parasites and diseases and tests and certifies the safety of unprocessed livestock products and animal feed. The Center is divided into five diagnostic units: Avian Influenza (since 2004 with FAO support), bacteriology, parasitology, serology, and rabies but its analytic program is limited by its operating budget. The Animal Feed Laboratory collects and analyzes samples from the feed mills. Fish disease diagnosis is being done by Namxuang Aquaculture Development Center and Living Aquatic Resource Research Center. There is, however, no capacity for pesticide and chemical residue testing in meat and fish products. The diagnostic infrastructure also includes six animal disease diagnostic laboratories in the provinces that can perform simple parasitological tests. Most of the diagnoses, however, are performed only at the NAHC laboratory; the provincial laboratories provide support in the collection and preservation of samples. On the northern border with China, there is a small laboratory (in collaboration with China) already with equipment but not yet operational. The NAHC is weak with regard to the number of trained staff. They have only general veterinarians and para-vets with a general agricultural training at the Agricultural College (diploma) or the Faculty of Agriculture (Bachelor of Science); there are no specialists for pathology. The quality assurance system of the Animal Feed Laboratory is likewise hampered by limited staff, inadequate equipment and methods of analysis, and the often unavailable chemicals and reagents. Department of Livestock and Fisheries, National Animal Health Centre responsibility for Disease Control and Prevention, Animal Disease Surveillance, susceptibilities of zoonotic pathogens from animal to animal to human health, specimens from healthy farm and from raw product of food-producing animals at slaughter and processing plant. The National Animal Health Center (NAHC) of the Department of Livestock and Fisheries is the key to providing diagnostic services and the capacity of NAHC to provide field support for livestock projects is crucial to the success of a project. While support for the laboratory and diagnostic capability is likely to continue with assistance from ACIAR, OIE and the EU Livestock Project, the field capacity of NAHC needs to be supported by all projects requiring this services.



A primary obstacle to gauging Lao PDR ability to prevent, contain, or manage AMR was the lack of a defined Lao target for performance. Most Lao PDR reports were less descriptive in nature, reporting rates or numbers of AMR cases or drug use. There existed a tension between the desire to create standardized surveillance programs that allowed for international comparison with those that can provide tailored local data, trading off standard methods and centralized laboratories with the flexibility required to address local issues.


The Lao PDR is a predominantly rural society with approximately 85% of the population depending on agriculture for their livelihood. Subsistence farming is common with 94% of households producing food mainly for their own consumption. Smallholder farmers operate mixed farming system such as pigs and poultry producing largely for home/village consumption and local markets. Ways of feeding and managing animals have evolved in response to the predominant cropping system and the available feed resources. These include fallow cropland, communal areas along roads, rivers, areas around fields and villages, dedicated grazing land, secondary forests and other non-cropped communal land. Additionally, crop by-products such as rice straw are also fed to ruminants. Commercial livestock production has developed only around major population centers such as Vientiane, supplying meat, eggs and milk to the urban population. Commercial pig and poultry farms are found near population centers such as Vientiane. Most of these agribusinesses are small cottage industries with few employees. In general, production costs tend to be high since semi-intensive pig and poultry production is dependent on concentrate feed which, in many cases, is imported from Thailand. Concentrate feeds are mixed with locally available feeds such as rice bran and brewers grain to reduce production costs. In several cases, commercial pig and poultry production is attached to rice mills. Commercial pig and poultry production in the Lao PDR is disadvantaged by higher feed costs for monogastric animals (pigs and poultry) than neighboring countries which have access to cheaper ingredients for concentrate feeds (e.g. by-products of industrial crops such as sugarcane, cassava and coconuts, and port access for importation) and a larger domestic market. Gold Coin, the only larger scale (150 tons per day) animal feed producer in Lao PDR is unlikely to be able to compete with Thai feed mills given the higher cost of raw materials and transport costs. Antibiotics have been used widely in poultry and pig farms in order to treat and prevent infectious bacterial diseases. They have also been used at low levels in feed as growth promoters. Such practice has improved pig and poultry performance effectively and



economically but an increase in numbers of antibiotic-resistant bacterial strains like Escherichia coli, Staphylococcus spp. and Enterococcus spp. did occur which can be transmitted from pig and poultry to humans through the food chain with serious consequences on public health. The present situation underlines the increased public and governmental interest in eliminating sub-therapeutic use of antibiotics in poultry and livestock products; particularly those that are also used to treat humans. There is need for more rational use of antibiotics in animal production and more prudent use in humans. It is important to take concerted action to improve antibiotic resistance surveillance capacity worldwide with a view to monitoring the emerging resistance genes and their transfer in both animal and human strains. Department of Livestock and Fisheries is a very comprehensive set of rules governing most aspects of animal raising and management in the Lao PDR. The Regulation provides for the marking and registration of livestock, the movement of animals and their products and veterinary supplies in and out of and internally within the Lao PDR, and contains conditions relating to animal disease prevention and vaccination, the slaughter of animals and meat inspection, and the conservation of breeding stocks. Department of Livestock and Fisheries lack of standardized methods is a major problem in evaluating and making recommendations to address the problem of antimicrobial resistance. Lack of methods for antimicrobial susceptibility testing for livestock/aquatic pathogens, and their interpretation. Lack of maximum concentration of residue resulting from the use of veterinary drug (expressed in mg/kg on a fresh weight basis) that is legally permitted or recognized as acceptable in livestock/fish products.



Malaysia

Akma Ngah Hamid

Director Central Region Veterinary Laboratory (CRVL)

Dpt. of Veterinary Service

Introduction

Antimicrobials are essential drugs and used in human and veterinary medicine to treat and prevent disease, and for other purposes including growth promotion in food-producing animals. However, using small amounts of antimicrobials over long period of time leads to the growth of bacteria that are resistant to the drugs’ effects, endangering humans who become infected but cannot be treated with routine antibiotic therapy. The more antimicrobials are used, the more likely antimicrobial resistant (AMR) to develop among pathogens and among commensal bacteria in an exposed population of animals. Antimicrobial resistance is a global public and animal health concern that is influenced by both human and non-human antimicrobial usage. This issue of AMR is now a significant health problem and each year in the European Union alone, over 25 000 people died from infections caused by antibiotic-resistant bacteria. Antibiotic resistance also posed problem in food safety where the use of antibiotic in food animals for treatment, disease prevention or growth promotion allow resistant bacteria and resistance genes to spread from food animals to humans through the food-chain (WHO, 2011).

Organisation of the department of veterinary services

The Department of Veterinary Services (DVS) is a Federal Government agency under the Ministry of Agriculture Malaysia. The DVS functions are documented in Minister Function Act 1969 and are as follows:

i. To control, prevent, and eradicate animal and zoonotic diseases. ii. To promote the growth and development of livestock, livestock products,

and animal feed productions. iii. Inspection of meat, milk, eggs, animal feed, abattoirs and animal based

processing plants. iv. To control importation / exportation of animals, animal produce and

quarantine. v. To provide training for livestock and pets industries.



vi. To promote the growth and development of livestock production, animal health and veterinary public health.

vii. To promote research on animal diseases and animal genetic resources. viii. To ensure the welfare of all animals and conservation of animal genetic

substances. The function of DVS listed in no. iii and no. iv indicate that livestock, livestock products and livestock based products are under DVS jurisdiction (inspections and supervisions). Beside domestic products, DVS also deal with importation products especially livestock based products and livestock products. It is important for DVS to design import control safety system to monitor the incoming products from importing country to Malaysia. Being a Muslim majority population in Malaysia, the Muslim consumers expect not only safe and quality food imported or produced, but also halal (prepared according to Islamic rites). Food safety and quality programs conducted by DVS are focusing on a farm-to-table approach, in order to eliminate or reduce food-borne hazards. This holistic approach was focusing on the control of food-related risks which involves control of every step in the chain, from raw material to food consumption. With regards to this holistic approach, the Department of Veterinary Services (DVS) conducted a certification programs, inspections and accreditation system as well as implementation of legislation to support Malaysia food safety and quality management system. The Livestock Farm Practices Scheme (SALT) was introduced by the DVS in 2003 on Good Animal Husbandry Practices (GAVP). The objective of SALT is to ensure the production of safe and wholesome food from farms practicing GAHP, operated in a sustainable and environmental friendly conditions and yield produces that are of good quality and safe for consumption. The SALT recognition is in the form of certificate and logo. To be certified, the farm must comply with the SALT requirements stated by the DVS. The SALT logo is a mark of quality given to livestock farms awarded under the Veterinary Inspection and Accreditation Programme of the Department of Veterinary Services, Ministry of Agriculture Malaysia. The criteria for the certification of SALT are based on GAHP, Animal Health Management, Bio-security, good infrastructure and prudent use of drugs. This Scheme covers all types of livestock such as beef cattle, dairy cattle, broiler chicken, layer chicken, breeder chicken, deer, goat, sheep and pig. Table 1 showed the organisation chart of DVS Malaysia.



Table 1. Organisation chart of the department of veterinary services, Malaysia

Usage of antimicrobials in livestock

There are 97 different type of antimicrobials registered with the National Pharmaceutical Control Bureau Ministry of Health, Malaysia (NPCB, MOH). Most of the registered drugs are used in poultry and pig farm and less in cattle and goat farm. Table 2 showed some of the group of veterinary drug which is registered with NPCB.

Table 2. Registered antimicrobials for use in livestock

Group of Drug Active Ingredient No. of Products

β-lactam Ampicillin, Amoxycillin 8

Cephalosporins Ceftiofur, Cefadroxil Cefadroxil 3

Tetracycline Chlortetracycline, Oxytetracycycline, Doxycycline 13

Sulphonamide Sulfamethazine, Sulfadiazine,

Sulfachloropyrazine, Sulfadimethoxine, Sulfaquinoxaline

8

Macrolide Tylosin, Erythromycin, Spiramycin, Tylvalosin 10

Aminoglycoside Neomycin, Gentamicin 2

Fluoroquinolone Flumequine, Enrofloxacin 8



Monitoring program of antimicrobial residues

Monitoring of veterinary drug residue in food of animal origin are based on the number of animal slaughtered from the previous year and the species of animals. In Malaysia, monitoring of antimicrobials are based on EEC Directive 1990 and also on the capability of the laboratory to conduct the test. Currently the capabilities of the Veterinary Public Health Laboratory (MKAV/DVS) are limited to Group A5, A6, B1 and B3. Some of substances in other group are under development of the test method such as stilbenes. Table 3 shows the routine monitoring of veterinary drug which is carried out in the livestock. For monitoring of the antimicrobial Group B list, agar diffusion technique is used as a screening method whereas for antimicrobial Group A list, HPLC or LCMS-MS is used. If antimicrobial Group B list was found positive, the sample will proceed for further confirmation using HPLC or LC MS-MS.

Table 3. Monitoring of veterinary drug in Malaysia - Group of antimicrobial, substances, technique and matrix/species of livestock

Group of Antimicrobial

Substances Technique Matrix / Species

Sulphonamide, Tetracycline, Aminoglycoside, Macrolide, Quinolone β-lactam

- Microbiology - Six Plate Test - Five Plate Test

Chicken, Cattle, Pig, Milk, Egg

Tetracycline

OTC, TC, CTC, DC, 4-eCTC HPLC Chicken, Cattle, Pig

Sulphonamide

SDZ, STZ, SP, SMERZ, SMZ, SMT, SIN, SMOPZ

HPLC Chicken, Cattle, Pig

Quinolone Sarafloxacin, Difloxacin, Ofloxacin, Enrofloxaxin, Danofloxacin, Ciprofloxacin, Norfloxacin

LC-MS-MS Chicken, Cattle, Pig

Kloramfenikol (CAP) CAP LC-MS-MS Chicken, Cattle, Pig, Milk, Egg

Nitrofuran Nitrofurazone, Furazolidone, Furaltadone, Nitrofurantoin

LC-MS-MS Chicken, Cattle, Pig, Milk, Egg

Beta-agonist Brombuterol, Cimaterol, Cimbuterol, Clenpenterol, Clenbuterol, OH -methyl Clenbuterol, Isoxuprine, Mabuterol, Mapenterol, Ractopamine, Salbutamol, Terbutaline, Tulobuterol, Zilpaterol

LC-MS-MS Chicken, Cattle, Pig



Monitoring of veterinary drug residues in animal feed in Malaysia will be implemented in year 2013 according to the Animal Feed Act 2009. Sampling plan, number and type of feed sample, type of testing, feed millers, importers and distributors will be identified and monitored based on the Act. Table 4 shows the frequency and sampling plan for the monitoring of veterinary drugs in Malaysia according to the species of livestock. Table 5 showed the percentage of samples tested, number of sample, number of slaughter houses or processing plants for the Group A list which is banned and not allowed to be used in food-producing animal including Chloramphenicol, Nitrofurans and Beta agonists (NPCB, MOH 2009). Table 6 showed the percentage of samples tested, number of samples, number of slaughter houses or processing plants for the Group B list which is allowed to be used in food-producing but MRL shall be followed.

Table 4. Yearly monitoring of veterinary drugs in Malaysia

Species of animal Percentage or number of samplesa

Group of substances

Group Ab Group Bc

Poultry/Duck 1 sample for every 200 tonne or 100 sample for each group of substances

50% 50%

Bovine 0.4% 0.25% 0.15%

Porcine 0.05% 0.02% 0.03%

Goat/Sheep 0.05% 0.01% 0.04% a. based on the number of livestock slaughtered from the previous year

b. banned drug (Nitrofurans, Beta agonist, Rectopamine, Chloramphenicol, Steroid)

c. drug which has MRL (Tetracyline, Sulfa and Contaminants such as Pesticide, Heavy Metal,

Mycotoxin)



Table 5. Yearly monitoring of banned drugs in Malaysia

Species of animal

Group of substances

Number of Slaughter

Houses

Percentage or number of

sample

Number of samples collected

Poultry/Duck

Chloramphenicol

21 1 sample/ per 200 tonne of production

144

Nitrofurans 144

Beta-Agonist 125

Bovine

Chloramphenicol

30 0.25

60

Nitrofurans 60

Beta-Agonist 60

Porcine

Chloramphenicol

6 0.02

24

Nitrofurans 24

Beta-Agonist 24

Goat/Sheep

Chloramphenicol

0.01

59

Nitrofurans 59

Beta-Agonist 59

Table 6. Yearly monitoring of antimicrobial residues (MRL)

Species of animal

Group of substances

Number of slaughter house

Percentage of sample

Number of samples

Poultry/Duck Antimicrobial 21 1 sample/ per 200 tonne of production

675

Bovine Antimicrobial 30 0.15 90

Porcine Antimicrobial 6 0.03 59

Goat/Sheep Antimicrobial 29 0.04 59

Pattern of AMR in animal pathogens

The human, animal and plant sectors have a shared responsibility to prevent or minimise AMR on both human and non-human pathogens. Veterinary drug residue in food of animal origin and antimicrobial resistance are two main problems if veterinary drugs are not properly managed in animal production. Most of the problems related to drug residue and drug resistance occurred or start at animal production level, where the usage of veterinary drugs are not properly managed and withdrawal periods are not monitored. Hence, management of veterinary drugs in animal production is a proactive



program to control veterinary drugs usage and prudent use of veterinary drug to prevent the occurrence of veterinary drug residue in food and also antimicrobial resistance. Preliminary study of AMR in 2012 was carried out on both food-producing animals and foods. Different strains of Salmonella species and Disk Agar Diffusion Method was used in this study. AMR Salmonella in food-producing animals

Thirty eight (38) isolates of different species of Salmonella is isolated from chicken cloacal swab were used for Antimicrobial Susceptibility testing. Cloacal swabs were collected from the poultry farm which is supervised under SALT programme. The poultry farm involved in this study is located at the central zone of Malaysia which consists of 4 states. Figure 1 and Figure 2 show the AMR Salmonella in chicken. From this study, 13.5% of Salmonella were resistant to Tetracycline, 5.4% Polymixin B and Erythromycin, and 2.7% to Chloramphenicol, Penicillin G and Trimethoprim.

Figure 1. AM susceptibility of Salmonella isolates from chicken



Figure 2. AMR in Salmonella isolates from chicken AMR Salmonella in food

Forty three (43) isolates of difference species of Salmonella was tested. The salmonella pathogen was isolated from 43 samples of food samples such as beef, mutton and chicken. About 62.8% of salmonella (27/43) was isolated from the imported products (44.2% beef and 18.6% chicken). Figure 3 shows the AMR Salmonella in the 43 isolates whereas Figure 4 shows the AMR in the imported beef, imported chicken and domestic chicken (25.6%).

Figure 3. AMR Salmonella isolates from food



Figure 4. AMR Salmonella in domestic chicken, imported chicken and imported beef

References

National Pharmaceutical Control Bureau Ministry of Health, Malaysia (2009). Registration Guideline of Veterinary Products (REGOVP); Version 2, March 2009.

WHO (2011). Tackling antibiotic resistance from a food safety perspective in Europe, World Health Organization, Geneva, 2011.



Myanmar

Pyi Sone1 and Ye Htut Aung2

1General Manager Livestock, Feedstuff and Milk Products Enterprise

2Professor, Department of Medicine, University of Veterinary Science, Yezin, Myanmar

Introduction

Livestock production in Myanmar was gradually developed since 1991. Estimation of cattle, pig and poultry population was 14.02, 10.30 and 172.61 million, respectively, in the year 2011-2012 (LBVD Reports 2012). Antimicrobials have been widely used in livestock production for a quite long time and are a necessary tool for appropriate care of food animals in Myanmar. In food-producing animals, the main purposes of antimicrobial uses include treatment of diseases, prevention of infections and promotion of growth. While most antimicrobial agents are generally mixed into feed or water, some are also administered to individual animals. It has been well known that imprudent and overuse of antimicrobial substances is responsible for widespread of multiple drug resistance among bacteria of animal origins.

Legal framework

Although Food and Drug Authority (FDA) has been founded in Myanmar, it is still to be established a legal framework and institutional arrangements for regulating antimicrobial use in livestock production and instruments for enforcement. Up to date, therefore, antimicrobials have been broadly used in livestock production by consulting veterinarians and according to the experience of livestock farmers.

Antimicrobial use in livestock production

Most of antimicrobials used in livestock production are imported from Asian and European countries. The major classes of antimicrobials, used in livestock production in Myanmar are Beta-Lactams, Tetracycline, Fluoroquinolone, Aminoglycoside, Macrolides and Sulphonamides. Major sources of the antimicrobials are China, Thailand (Neo, Otta), Korea (Choong Ang Biotech, Samyang Anipharm), India (Cipla, Agio Pharmaceuticals), Bangladesh, Spain (Invesa, Dex Iberica), Belgium (VMD), and Germany (Bremer Pharma, Bayer). The major antibiotics, used in poultry production, are oxytetracycline, doxycycline, chlortetracycline, enrofloxacin, amoxacillin, colistin, erythromycin, sulphadiazine, trimethoprim and neomycin. While enrofloxacin is particularly used for prevention and



treatment of bacterial diseases of the respiratory tract, amoxicillin and colistin are mainly used for prevention and treatment of bacterial diseases of gastro intestinal tract. Most of antimicrobials are given in drinking water. Anybody can buy antimicrobials freely in Myanmar. Therefore, the major existing problem, leading to inappropriate use of antimicrobials, is that most of poultry farmers use antimicrobials without any consultation from veterinarians. Most of poultry producers use antimicrobials as preventive measures for bacterial diseases. Nobody consider withdrawal period of antibiotics, which they used in their food animals. Therefore, antibiotics residues are frequently encountered in the poultry meat and eggs. Chlortetracycline is still used as feed additive for growth promoter by some poultry feed producers. The pattern of antimicrobials use in cattle and pig production are quite similar. In cattle and pig production, penicillin, streptomycin, lincomycin, enrofloxacin, gentamycin and kanamycin are major antibiotics used for parenteral administration. Some in feed antibiotics are still used as growth promoter in fattening pig production.

Studies of AMR, drug residues and microbial contamination

Since there is only one University of Veterinary Science in Myanmar, most of the research such as monitoring of antimicrobial use in livestock, antimicrobial residues in livestock products and surveillance for antimicrobial resistance (AMR) in animal pathogens were mainly conducted by the University of Veterinary Science, Yezin, Myanmar. Since poultry meat is consumed by the majority of the people irrespective of race and religious in Myanmar, most of the studies were conducted with poultry and poultry products. Different species of Salmonella were isolated from poultry meat from retail poultry meat market. Among 36 Salmonella suspected isolates from different specimens of poultry, six isolates were identified as Salmonella by biochemical tests and serotype was confirmed by agglutination test with the specific antisera. The isolated Salmonella serovars were Salmonella pullorum (1), Salmonella enteritidis (2), Salmonella senftenberg (1), Salmonella newport (1) and one unknown serotype. Then the isolated Salmonella serovars were tested for susceptibility to five antimicrobial agents; Chloramphenicol (30 mcg), Neomycin (30 mcg), Norfloxacin (10 mcg), Tetracycline (30 mcg) and Streptomycin (10 mcg). All of the tested Salmonella serovars were most susceptible to Chloramphenicol (100%) and resistant to Tetracycline (100%). The degree of resistance to antibiotics varied with the tested Salmonella serovars (Su Su Khin, 2005). Another study also investigated antibiotic resistance to 6 antimicrobials with Salmonella isolates from chicken meat. Resistance percentage of Salmonella isolates were 79.5, 82.1, 87.2, 74.4, 33.3 and 100 to ampicillin (10 µg), chloramphenicol (30 µg), ciprofloxacin (5 µg), cotrimoxazole (25 µg), gentamycin (10 µg) and tetracycline (30 µg), respectively. Among the six antimicrobial drugs, tetracycline was found highly resistance by Salmonella species. Gentamycin showed the lowest resistance by Salmonella isolates from chicken meat (May Thet Hnin Oo, 2009).



According to the study with isolation of Escherichia coli from poultry meat, the isolated E. coli were resistant to chloramphenicol (30μg), ciprofloxacin (5μg), neomycin (30μg) and tetracycline (30μg). In this study, E. coli isolates were found to be the most susceptible to gentamycin and resistant to chloramphenicol. The degree of resistance to antibiotics varied with the tested E. coli serovars (Khin Nge Aung, 2005). Thirteen strains of Escherichia coli were isolated from the broilers with typical post-mortem lesions of colibacillosis from the commercial broiler farms in Mandalay region. Serological typing by rapid slide agglutination test indicates 4 serotypes namely O44:K74, O26:K60, O124:K72, and O55:K59. Antibiotic resistance pattern of 13 isolates showed the highest resistance frequencies with ampicillin, chloramphenicol, oxytetracycline, and neomycin (69.23 to 61.53%). Moderate resistance frequencies to antibiotics was observed with ciprofloxacin (46.15%). Gentamycin showed the lowest resistance frequencies (7.6%) (Khine Thwe Latt, 2005). Since antibiotic residues in food animals always threaten to consumers’ food safety, Fluoroquinolone residues in chicken muscle were screened using microbial inhibition test. According to the survey data, 6.67% of poultry meats from retail market were positive for antibiotic residue (Khin Thida San, 2005). In the other study, the presence of antibiotic residues in chicken muscle, liver and kidney purchased from three retail markets from central Myanmar were also investigated by using microbial inhibition test, Swab Test on Animal Food. Antibiotic residues positive samples were observed as 6/72 (8.3%), 7/72 (9.7%) and 0/72 (0%) in liver, kidney and muscle samples, respectively, from all locations (Ohnmar Hnin, 2009). The common pathogens of clinical and subclinical mastitis cases in crossbred and local cows were also investigated in the Mandalay region. The major isolates were Staphylococcus aureus (25%), Staphylococcus epidermidis (2.5%), Streptococcus spp (22.5%), Aerococcus spp (32.5%), Corynebacterium spp (7.5%), and Bacillus spp (10%). The frequency of isolations of genus Staphylococcus, Streptococcus and Aerococcus is significantly higher (P<0.05) than Corynebacterium and Bacillus. There is no significant difference among genus Staphylococcus, Streptococcus and Aerococcus. Sensitivity to the most commonly use antibiotics were also tested in this study. Among 6 different antibiotics, Norfloxacin and Streptomycin have a significantly wider range of spectrum (P<0.05) than Penicillin G, Oxytetracycline, Chloramphenicol, and Cephalexin base on the efficiency of antibiotic sensitivity to 13 different bacteria species (Aye San May, 2008).



C.pyogenes

5.0%

C.ulcerans

2.5%

B.cereus

10.0%

Staph. aureus

25.0%

Staph. epidermidis

2.5%

A.viridans

32.5%

Str. uberis

2.5%Str. dysgalactiae

2.5%Str. pyogenes

5.0%

Str. mutans

5.0%

Str. agalactiae

5.0%

Str. mitior

2.5%

Staph. aureus

Staph. epidermidis

Str. Mutans

Str. agalactiae

Str. mitior

Str. dysgalactiae

Str. pyogenes

Str. Uberis

A.viridans

C.pyogenes

C.ulcerans

B.cereus

Figure 1. Pathogenic bacteria species isolated from clinical and subclinical mastitis

(Source: Aye San May 2008) Isolation of E. coli from fresh beef samples of retail market was carried out in the central parts of Myanmar. E. coli were isolated from 93.33% of fresh beef samples. Serotyping of E. coli by rapid slide agglutination test revealed that 37 out of 120 isolates (30.83 %) were E. coli O157. Resistance to three commonly use antimicrobials were tested with isolated E. coli O157. Resistance of E. coli O157 isolates to ciprofloxacin (5μg), gentamycin (10 μg), and trimethoprime-sulfamethoazole (25 μg), were 25%, 87.5% and 12.5%, respectively (Yin Yin Kyawt, 2008). Antibiotic resistance of E. coli isolated from rectal swab samples of piglets was also investigated in Nay Pyi Taw region, administrative city of Myanmar. E.coli isolates resistant to Ampicillin and Oxytetracycline was 100% constantly throughout the experimental period, while E.coli isolates resistant to Chloramphenicol, Ciprofloxacin, Gentamycin and Sulfamethoxazole/ Trimethoprim were 75%, 75%, 83.3% and 91.6%, respectively (Min Maung Cho, 2008).

Conclusions

For many decades, antibiotic resistance has been recognized as a global health problem. It has now been escalated by major world health organizations to one of the top health challenges facing the 21st century. The use of antimicrobials in livestock production is thought to significantly contribute to this phenomenon, but little is known about the true causes of antimicrobial resistance. Some of its causes are widely accepted, for example, the overuse and inappropriate use of antibiotics for nonbacterial infections and inadequate antibiotic stewardship in the clinical arena. The lack of relevant scientific data means that risk managers must take precautionary measures, even though the underlying causes of public health risks associated with resistant bacteria



may not have been adequately identified. However, it has been widely accepted that resistant bacteria in animals are one source of antimicrobial resistance (AMR) for people.

References

Aye San May (2008). Clinical and subclinical mastitis related to environmental risk factors. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Khaing Thwe Latt (2005). Study on the aetiological, clinico-pathological and therapeutic aspects of experimental Colibacillosis in broiler chickens. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Khin Thida Sann (2005). Screening of fluaroquinolone residues in muscle of chickens using microbial inhibition test. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Khin Nge Aung (2005). Study on Sensitivity of Escherichia coli isolates from village chickens in Yezin area to six antibiotics. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

LBVD report (2012). Yearly report of Livestock Breeding and Veterinary Department, Ministry of Livestock and Fisheries, Nay Pyi Taw, Myanmar.

May Thet Hnin Oo (2009). In Vitro study of the resistance pattern of six antimicrobial drugs to Salmonella isolated from chicken meat in Yezin, Pyinmana and Tatkon area. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Min Maung Cho (2008). Antibiogram of Escherichia coli isolated from post-weaning piglets fed with or without feed additives containing chlortetracycline. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Ohnmar Hnin (2009). Screening the antibiotic residues in chicken muscle, liver and kidney samples within Nay Pyi Taw area. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Su Su Khin (2005). Isolation and identification of Salmonella species from poultry source in Yangon markets. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.

Yin Yin Kyawt (2008). Occurrence of Escherichia coli 0157 in fresh beef and rectal swab of cattle in middle Myanmar. M.V.Sc Thesis. University of Veterinary Science, Yezin, Myanmar.



Nepal

Ram K. Khatiwada

Deputy Director General Department of Livestock Services

General information

Nepal is a Himalayan country sharing boundary with Tibet of China on North and India on East, West, and the South. The total land area of the country is 147,181 square kilometers. About 65.6% of the people residing in the country are engaged in agriculture. The natural forest in the country constitutes about 39%. Geographically country is divided into following three regions, namely:

Mountain: Mountainous region is located in the north part of the country, covering 35% (51,817 Sq. Km.) of total area. The altitude of the region varies from 4800 and above asl. Yak/Nak, sheep, alpine goats (Chyangra) and mule rearing form the way of life of people in this region.

Hill: This region extends from east to west which is located in the middle part of the country, covering about 42% (61,345 Sq. Km.) area. Hilly region ranges from 300 to 4800 m asl. People of diverse ethnic groups, caste and cultures share their common way of living. Agro-based livestock industries and horticultural production in the region are the main source of income of the people.

Terai: Terai region is located in the southern part of the country, covering about 23% (34,019 Sq. Km.) of the total area. This region serves as a main source of food supply to other region of the country.



Importance of livestock

Livestock is an integral part of agri-production system, which plays a vital role in national economy. This sector contributes about 11% to the national GDP and 27% to Agricultural Gross Domestic Products (AGDP). It is an important sector contributing in employment and poverty reduction. Subsistence level of livestock farming is predominant in the rural areas of the country however commercialization has slowly gained its pace near the cities with the growth in consumption capacity. It has also helped to increase the number of cross bred animal. Detail of estimates of livestock population is summarized as follows:

Table 1. Nepal livestock populations (million)

Year Cattle Buffalo Goat Sheep Pig Poultry

05/06 7.00 4.20 7.42 0.81 0.96 23.2

06/07 7.04 4.36 7.84 0.81 0.98 23.9

07/08 7.09 4.49 8.13 0.80 1.01 24.6

08/09 7.10 4.60 8.40 0.80 1.00 24.4

09/10 7.19 4.83 8.84 0.80 1.06 25.76

Growth % 0.3 3.3 4.3 -0.2 1.9 5.2 Source: MOAD, Nepal

Activities of veterinary services

Prevalence of a number of infectious and parasitic diseases in livestock population is the major constraints affecting production and productivity of the livestock resulting into substantial economic loss in livestock industry of Nepal. Nepal has continuously been putting its efforts for prevention and control of major animal diseases. There is a network of national veterinary services at central, regional and district levels. Under the Department of Livestock Services (DLS), Directorate of Animal Health is assisted by its different units at central level. Veterinary services at regional and district levels are being delivered through five Regional Directorates of Livestock Services, five Regional Veterinary Laboratories and one National Avian Diseases investigation Laboratory, eight Animal Quarantine Offices with 24 Animal Quarantine Check posts, 5 Regional Livestock Training Centers and 75 District Livestock Services Offices. Moreover, there are 359 Livestock Service Centers and 640 Livestock Sub-Service Centers to provide veterinary services at the sub-district level. They deliver animal health, breeding, nutrition, training and extension services to the livestock farmers.



Organogram of Veterinary Services in Nepal

Ministry of Agriculture Development (MoAD)

Regional Directorate of

Livestock Services (5)

District Livestock

Services Office (DLSO)

75

Livestock Service

Center/Sub-service

Center (LSC/LSCC) 999

Department of Livestock Services

Veterinary Epidemiology Center

Central Biological Production

Lab.

National FMD and TADs Lab.

Central Veterinary Hospital

Directorate of Animal Health (DAH)DoLP DLSTEDLMP

Veterinary Public Health

Office

Vet. Drug Admin. & Quality

Control Office

Rabies Vaccine Production Lab.

Central Veterinary Laboratory

5 Regional Labs

Central Animal Quarantine

Office

AQO 8,

Check-Posts 24

AICP

1 National Avian lab

Figure 1. Organogram of veterinary services in Nepal

Veterinary Service in Nepal is being implemented with legal basis provided by Animal health and Livestock Services Act, Slaughterhouse and Meat Inspection Act, Nepal Veterinary Council Act, Bird Flu Disease Control Order.



Organogram of Laboratories

Ministry of Agriculture Development

Department of Livestock Services

Directorate of Animal Health

CENTRAL VETERINARY LABORATORY

Regional

Veterinary

Laboratory

Biratnagar

Janakpur

Pokhara

Surkhet

Dhangadhi

National Avian Disease

Investigation Laboratory

Chitwan

FMD & TADS Lab

Figure 2. Organogram of veterinary laboratories in Nepal

Legal framework regulating drug use

Government of Nepal has promulgated the Drug Act 1978, to prohibit the misuse or abuse of drugs and allied pharmaceutical materials as well as the false or misleading information relating to efficacy and use of drugs and to regulate and control the production, marketing, distribution, export-import, storage and utilization of those drugs which are not safe for the use of the people, efficacious and of standard quality. To implement and fulfill the aim of Drug Act 1978 and various regulations under it, Government of Nepal established Department of Drug Administration (DDA) in 1979. Department of Drug Administration is the only authority responsible for regulating drug use in Nepal. DDA is responsible for regulating all types of medicines including veterinary, allopathic, ayurvedic and homeopathic drugs in the country. There is no separate organization for regulating veterinary medicines in Nepal. Veterinary Standards and Drug Administration Office has been established under the Directorate of Animal Health in Nepal to regulate the drug use but due to absence of Veterinary Drug Act, the office is not functioning as dreamed. Still the VSDAO has been involved in regulating veterinary vaccines imported in the country. Veterinary Inspectors are designated in each district by the Ministry of Agriculture Development. Designated veterinary inspectors regularly visit the drug stores and monitor their functioning but in the absence of the veterinary drug act they cannot act at the spot and has to report it to DDA for any legal actions.



Drug use in Nepal

A study conducted by the DDA in 2006 has shown that allopathic drugs worth 2 billion and 250 million rupees were imported into Nepal through 52 importers. Similarly, ayurvedic / unani drugs worth 342 million rupees, veterinary drugs worth 70 million rupees and homeopathic drugs worth 5 million were imported. Allopathic drugs worth 6 billion 276 million rupees in retail value were sold. Likewise ayurvedic / unani drugs worth 557 million rupees, veterinary drugs worth 155 million rupees and homeopathic drugs worth 19 million rupees were sold in the same year. Same study has shown that from the domestic production allopathic drugs worth 3 billion 442 million rupees in retail value were sold. Similarly, ayurvedic / unani drugs worth 62 million rupees and veterinary drugs worth 14 million rupees were produced from the domestic industries who provided the data. Ayurvedic / unani medicines worth 172 million rupees and veterinary drugs worth 80 million rupees in retail value were sold. On an average 20% of total sales by domestic industries was offered as bonus or deals.

Figure 3. Share of drug supply by import and domestic sources

Antimicrobial resistance surveillance and monitoring

Laboratory based Antimicrobial Resistance Surveillance (AMR) was started in Nepal in 1999, with the aim of monitoring the resistance trends of selected bacterial pathogens. In a developing country like Nepal, surveillance of pathogens exhibiting antimicrobial resistance is essential to:

Trace source and spread of drug resistance.

Formulate appropriate antibiotic policy guidelines.

Provide susceptibility data to physicians for directing treatment.

Co-ordinate clinicians with laboratory personnel

Detect emergence of resistance and monitor resistance patterns



To implement measures for prevention of AMR.

Participating laboratories for AMR surveillance in Nepal

National Public Health Laboratory (NPHL), Teku, Kathmandu

Western Regional Hospital, Pokhara

Manipal Teaching Hospital, Pokhara

Kanti Children's Hospital, Kathmandu

Tribhuwan University Teaching Hospital (TUTH), Kathmandu

Patan Hospital, Lalitpur

BPKIHS, Dharan

Mission Hospital Tansen, Palpa

Lumbini Zonal Hospital, Butwal

Dhulikhel Hospital, Kabhre

Mechi Zonal Hospital, Jhapa

Bheri Zonal hospital, Nepalgunj

Seti zonal Hospital, Dhangadi

Mid-Western Zonal Hospital, Surkhet

Central Veterinary Laboratory, Kathmandu

Kist Medical College, Kathmandu

KMC Medical College and Teaching Hospital, Kathmandu

Kathmandu Model Hospital, Kathmandu

Mahakali Zonal Hospital, Kanchanpur

Importance of AMR surveillance in animal health

Antibiotics are valuable and most utilized therapeutic agents in vet practice

Emergence of multi-drug resistance in many diseases (mastitis, pyometra, colibacillosis, tuberculosis etc) has limited therapeutic options for the practitioners

Introduction of drugs of higher generation is frequently done to handle the resistance problem, which has increased cost of treatment.

Constraints

Antimicrobial resistance problem is more frequent in the developing countries like Nepal where indiscriminate, inadequate and inappropriate use of antimicrobials and self-medication are quite common. The major constraints for AMR in Nepal include

lnadequate understanding among the veterinary practitioners about AMR



lack of consensus among the human and veterinary medical practitioner on AMR surveillance

management of infectious and contagious diseases in the developing world is hampered by the lack of reliable antimicrobial surveillance data

AMR Surveillance in Nepal for selected bacterial pathogen from medical side

The AMR surveillance started in 1999 in Nepal with the technical assistance from Bangladesh and the National Public Health Lab Act as a national focal point for AMR surveillance in Nepal. Vibrio, Shigella, Streptococcus, Haemophilus, E. coli, Neisseria, Salmonella have been studied for AMR in Nepal but the program has been mostly done with the human pathogens while studies on animal pathogens have started only recently from 2011. National Public Health Laboratory is coordinating the activity and the veterinary laboratories are working in coordination with the NPHL on AMR surveillance.

Way ahead

Rationalize the use of available antimicrobial agents with support of Antimicrobial Susceptibility Testing (AST) for the prevention and containment of AMR

Regional participation in AMR as pathogens are common in the region (SAARC)

Public awareness on empirical use of antibiotics

Frequent monitoring of the laboratories involved in diagnosis

Frequent monitoring of the pathogens from hospitals and treatment centers for AMR

Multi-sectoral collaboration at the human-animal interface

Regular monitoring of the distribution of antibiotics in the country



Pakistan

Muhammad A. Javaid

Section Officer M/o NFS&R

Introduction

Pakistan is an agricultural country. This sector provides employment to 45 percent of the population and provides input for agro-based industry. It accounts for 23 percent share in the Gross Domestic Product (GDP) of the country. Agriculture income creates demand for industrial products. The livestock sub-sector has emerged as a priority sub-sector only recently on policy formulation. Historically, livestock has been a subsistence sector dominated by small holders to meet their needs of milk, food and cash income on daily basis. In the rural areas, livestock is considered as a more secure source of income for small farmers and landless poor. It has become important source of employment generation in rural areas. The sector is mitigating income variability in the rural areas as crop sector is more dependent on uncertain vagaries of mother-nature. The poverty incidence in Pakistan is determined by income variability and thus livestock is the best hope for poverty alleviation as it can uplift the socioeconomic conditions of our rural masses. Livestock accounted for approximately 55.1 percent of the agriculture value-added and 11.5 percent to GDP during 2010-11. Currently, Pakistan has 67.3 million large ruminants (cattle and buffaloes), 89.6 million small ruminants (sheep and goats) 1,230 million poultry. The major animal products include 46,440,000 tons of milk, 3,095,000 tons of meat and 12,457 million eggs.

Antimicrobial use

Infectious diseases cause heavy economic losses to the livestock industry, resulting in high mortality, morbidity, reduced productive and reproductive efficiencies. Different classes of antimicrobials are used for therapeutic purposes. However, some antimicrobials are in use as growth promoters in livestock production.

Antimicrobial classes used are:

Penicillins

Lincosamide

Macrolides

Aminoglycosides

Sulfonamides

Flouroquinolones



Tetracyclines

Penicillins

Lincosamide

Macrolides

Aminoglycosides

Sulfonamides

Fluoroquinolones

Tetracyclines Macrolides

The macrolides whose activity stems from the presence of a macrolide ring. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the class of natural products are produced by Streptomyces erythreus (erythromycin is natural product) Aminoglycosides

An aminoglycoside is a molecule or a portion of a molecule composed of amino-modified glycoside. Several aminoglycosides function as antibiotics that are effective against certain types of bacteria. They include Amikacin, Arbekacin, Gentamycin, Kanamycin, Neomycin etc. They are produced by Streptomyces and Micromonospora. Aminoglycosides bind to ribosomes and interfere with protein synthesis (bacteriocidal). Sulfonamides

Sulfonamides are the basis of several groups of drugs. The original antibacterial sulfonamides, sometimes called sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant. Sulfonylurea and Thiazide are newer drug groups based on the antibacterial sulfonamides. Sulfonamides act on the protein synthesis chain. Fluoroquinolones

Fluorquinolones are derivatives of previous earlier antibiotic (nalidixic acid) and inhibit DNA gyrase (bacteriocidal) Current control for antibacterial use in animals in Pakistan

Import and registration are controlled. List of leading market seller drugs in Pakistan

Most sold antimicrobials in Pakistan are: Oxytetracycline, Gentamycin, Amoxycilin, Enrofloxacin, Flumequine, Norfloxacin, Tylosin, Ampicillin, Procaine Penicillin, Sulfonamides



Papua New Guinea

Gibasa B. Asiba

National Agriculture Quarantine and Inspection Authority Veterinary Services

[In preparation]



Philippines

Rubina O. Cresencio

Director Bureau of Animal Industry

Legal framework regulating antimicrobial use in livestock production and instruments for enforcement

There are two main branches or agencies that are involved in the regulations on the use of antimicrobials in the country. One is the Department of Agriculture (DA) through the Bureau of Animal Industry (BAI) and the Department of Health through its Food and Drug Administration (DOH-FDA). Both of these agencies are clothed with their respective mandates or laws that are the basis of their respective regulatory functions. At the DA-BAI, the main law that governs its regulatory powers is an Act No. 3105 of 1925, authorizing the Director of BAI subject to the approval of the Secretary of Agriculture to promulgate regulations for the preparation, sale, traffic in shipment and importation of viruses, serum, toxins or analogous products used for the treatment of domestic animals. Republic Act (RA) No. 1071 of 1954 regulates the sale of veterinary biologics and medicinal preparations. This law prohibits any agency or store to sell to the public veterinary biologics, and medicinal preparations other than from registered pharmacists or drugstores, biological laboratories, veterinary clinics and government veterinary agencies. Another law was enacted in 1956 known as the Livestock and Poultry Feeds Act. This law provided for the regulation and control of the manufacture, importation, labeling, advertising and sale of livestock and poultry feeds. At the DOH side, the most current law enacted and that affected the regulatory activities of the BAI is RA No. 9711 or the Food and Drug Administrative Act of 2009, mandating the FDA (formerly called the Bureau of Food and Drugs) in regulating and monitoring of establishments and products including veterinary drugs and other health products. In order to fully implement the FDA law and in order not to create disruption in the current delivery of regulatory services, a Memorandum of Agreement was undertaken, authorizing the BAI to continue its regulatory activities for veterinary drugs and products that are used or mixed or incorporated in feeds and drinking water. On the other hand



FDA regulates all veterinary injectables and individually administered dose of antimicrobials for animals. Other related law is the Consumer Act of the Philippines passed in 1992, provided for among others, consumer safety and quality standards on agricultural and veterinary products or commodities. This law reinforces the other laws as it provides for inspection of animals, animal products and by-products, meat and meat products, feeds and biological, and testing or analysis of such products which maybe are dangerous or harmful to the consuming public. The regulatory activities in general consist of registering of all existing establishments that are manufacturing, distributing and or selling veterinary drugs and products. It also includes actual inspection of feed establishments and facilities, sample taking and conduct of laboratory analysis to ensure the quality of feed products and that these should not contain banned chemicals. Administrative sanctions and penalties are imposed for companies that violate the provision of these laws. Other legal issuances issued by the DA are in the form of Administrative Orders (AOs). One of these is an AO No. 24 establishing the National Veterinary Drug Residues Control Program. This is an inter-agency initiative to ensure the rational use of antimicrobials and other veterinary drugs and chemicals in animal production. This is also in response to the need of ensuring that foods of animal origin, meat, milk and eggs are safe for human consumption. This regulation spelled out and redefined the responsibilities of the various stakeholders including the livestock and poultry producers and the Local Government Units, on the rational use of veterinary drugs. Other DA agencies involved in the program are the Bureau of Fisheries and Aquatic Resources (BFAR), National Meat Inspection Service (NMIS), National Dairy Authority (NDA) and the Philippine Carabao Center (PCC), Bureau of Agriculture and Fisheries Products Standards (BAFPS), Food Development Center (FDC). The FDA is also supporting this program through its representation in the Committee. Currently, there is a proposed bill or law that is in the pipeline and hopefully soon to be enacted, called the Food Safety Act of the Philippines. This will pave the way to a much better coordination in addressing food safety issues including controlling veterinary drug residues and AMRs.


Antimicrobials are principally used for treating sick animals and controlling infectious animal diseases. On the registered products at the BAI, the following are so far the top three (3) antimicrobials sold in the market and their estimated volume of usage based on available records of the BAI:



1. Chlortetracycline – 847,000 kg. 2. Bacitracin – 199,090 kg. 3. Tiamulin Hydrogen Fumarate – 197,958 kg.

Most of these chemicals are imported and are used in controlling diseases and infections in pigs and chicken. These are usually mixed or incorporated in feeds and water. Based on an industry study and analysis conducted in 2011, the sale and use of veterinary drugs both for medication and vaccination is projected to grow by 4.4-5.5% per year from 2010-2015. This is to meet the projected increase or growth of the livestock industry particularly the swine and poultry sector. Based on this analysis we can also infer that there will also be a corresponding increase in the pharmaceutical industry.

Surveillance and monitoring of antimicrobial residues and resistance

The different commodity offices or organizations of the DA provides actual monitoring of veterinary residues. NMIS conducts drug residues testing for meat, BFAR for fishery products and on a limited scale the NDA and PCC for milk and milk products that are produced by their farmer –cooperators or program beneficiaries. Their findings are shared with the BAI, with the latter tracing areas with high levels of drug residues. Very recently, the DOH has initiated in creating a Technical Working Group for the Development of the National Anti- Microbial Resistance Policy. This in response to the World Health Organization’s call to fight AMR which now poses a global threat due to the persistent misuse and poor management of anti-microbial medicines. The six-point policy package includes: (1) committing to develop a master plan to combat anti-microbial resistance; (2) strengthening surveillance and laboratory capacity; (3) ensuring uninterrupted access to essential medicines of assured quality; (4) promoting rational use of medicines in patient care and animal husbandry; (5) enhancing infection prevention and control; and (6) fostering innovation and research to develop new tools and drugs. The membership comes from various agencies of the government, but many of which comes from the DA and the DOH. A Technical Working Group was created and was tasked to: supervise the gathering and review of information on AMR with the end in mind of formulating appropriate policies. With this and the other initiatives at hand, better and much improved policies and programs on monitoring of AMR will be affected.



Types and extent of AMR

So far the extent and level of AMR in the country has not been established. Much work and resources should be invested by the government, however there have been limited studies conducted so far, such as the study conducted on Campylobacter jejuni isolates with AMR usage in poultry by the College of Veterinary Medicine at the University of the Philippines. This paper will be presented in this conference by Dr. Loinda Baldrias. Routine Salmonella testing of feeds is being undertaken by the BAI as part of regulatory activities and to support the animal production food safety program of DA. Eventually collaborative studies will be undertaken more vigorously with universities and research institutions.

Other initiatives to control AMR

The current effort of the government of improving trade and competitiveness and its participation to the World Trade Organization is driving competent authorities to put in place programs not only in addressing AMR but measures in addressing Sanitary and Phyto-Sanitary Measures. For instance, through the BAFPS, the DA is promoting the farm certification program on Good Agriculture Practices (GAP) and Good Animal Husbandry Practices (GAHP). GAHP standard and certification program sets out the minimum requirement for animal food production farms. Among the requirement is traceability and documentation of veterinary drugs and medicines used. The standard also calls for the strict observance of the withdrawal period. The Philippines Codex Sub-Committees on Veterinary Drugs and Animal Feeding are another mechanisms where AMR is also discussed and considered. As a result of these consultative processes, gaps are identified and appropriate policies and programs are formulated. For instance, HACCP-based inspection principles is now being introduced in the current inspection system of the BAI for feed manufacturers and establishments. Advocacies from veterinary professional organizations are helping in creating an awareness through seminars and talks on food safety. Another development in the country is the promotion of organic agriculture which the current Secretary of Agriculture is the author of the law. Through this Organic Agriculture law funds were made available for its promotion including support for organic certification program, trainings and strengthening the research and development.

Conclusion

Much work is needed in elucidating the level of AMR in the country and this entails costs, manpower resources and policy reviews. The level of coordination and



collaboration should also be enhanced especially in tapping other institutions such as universities to complement existing manpower complement in the government agencies involved in AMR work. The current developments in the government and commitment to International standards augurs well in pursuing the needed steps in improving work on AMR.



Samoa

Tony Aiolupo

Senior Meat Inspector Animal Production and Health Division

Ministry of Agriculture and Fisheries

Introduction

An estimated 75% of Samoans belong to about 18,000 agriculturally active households, the majority of which produce mainly, or entirely, for home consumption, and only about 1,100 are commercial producers engaged in any type of formal marketing activities. In the livestock sub-sector, it is largely subsistence in nature, and with the exception of small segments of large-scale cattle production is dominated by household production. Almost all rural households raise backyard poultry (chicken) and pigs, and some 6,000 households own cattle. The main livestock animals raised for domestic consumption in Samoa are cattle, poultry, pigs, goats and more recently sheep. The most up to date data available on the main animal species used for meat consumption are listed below and sourced from the National Agricultural Census took place in 2009.

Livestock Type Cattle Pigs Chicken Sheep

Number 42,219 152,140 307,028 500

Cattle production

Samoa has approximately 6,000 cattle farmers representing 35 percent of agricultural households. Two-thirds of cattle are located on Upolu Island with one-third on Savaii Island and production is entirely on natural pasture grazing system. The number of cattle has gradually increased as the result of increased interest in commercial farming over the past ten years. Cattle breeds are mostly Droughtmaster and Santa Gertrudis crosses with some Brahman crosses. Pig Production

The Agriculture Census 2009 estimated that there were 152,140 pigs compared to 167,000 recorded from the 1999 Agricultural Census reflecting a drop in number of pig population. Virtually all pigs in Samoa are of the indigenous breed and are kept under free range scavenging conditions, supplemented by crop, fruit and household wastes.



The average pig owning household keeps 5-10 breeding sows and spend the good part of day to collect crop wastes for pig feeding. Pigs reach a market weight of 65 kg about nine months old after weaning. Although no serious infectious pig diseases currently exist in Samoa, piglet mortality can still range up to almost 50 percent due to exposure and poor nutrition. Poultry production

As of 2009, it is estimated by the Agriculture Census that the total number of chicken was 307,028 which is a drop from 431,000 which was recorded in 1999. Virtually all chicken are of indigenous-exotic breed crosses. Almost every rural household keeps a small scavenging poultry flock ranging from 5 to 25 chickens with offspring. Mortality from hatching to adult is nearly 50% as the result of predators, poor nutrition and exposure. Free ranging hens lay about 40-50 eggs per year, depending on their age and level of nutrition. The hatchability of these eggs ranges from 50% to 75%. Except for occasionally occurring Fowl Pox and Marek’s Disease both of which respond to vaccination Samoan poultry have not been exposed to significant infectious disease. Sheep production

A recent livestock development initiative in 2004 has been launched for the development of sheep farming using a tropical bred sheep, Fiji Fantastic breed (based on the Barbados Blackbelly breed) patented by Fiji under funding assistance from FAO food security project. MAF is currently assisting the farmers through the breeding and provision of extension services to selected sheep farmers. Furthermore, the 2009 Agriculture Census has recorded 500 sheep compared to the initial stock of 44 in 2004.

Antimicrobial use and antimicrobial resistance

There is very limited knowledge and information available on the use of antimicrobial drugs in livestock production in Samoa. Veterinary drugs instead for therapeutic use only (injured and sick animals) are commonly used and available. On the other hand, there are no antimicrobial drugs uses as feed additives in livestock production as ruminant production entirely depends on natural pasture grazing whereas pigs and chickens are raised free ranged mainly at the village level. All veterinary drugs are all imported from mainly Australia and some from New Zealand, and are registered under the Food and Drug Act which is administered by the Ministry of Health. This Act regulates and authorizes the official registration of these drugs. Veterinary drugs (antibiotics) are administered and used only under the discretion and supervision of the Government Veterinarians assisted by Para-Veterinarians and other designated staff members in the Animal Production and Health Division of MAF.



Table 1. Commonly used antibiotics in livestock production in Samoa

Name of Antibiotic Active Ingredients Types of Animals

Oxytetrin LA Injection Oxytetracycline (as the dehydrate) Cattle, sheep, pigs

TYLO 200 Tylosin Tartrate All livestock

Amphoprim Injection Trimethoprim, sulphadimethylpyrimidine

Cattle, sheep, pigs, horses, dogs and cats

GENTA 50 Gentamion All livestock

There are no data available on antibiotic use and resistance due to various reasons such as:

- Lack of surveillance and data collection program - Lack of technical veterinary and animal health expertise - Lack of proper diagnostic technique - Limited funding (budget) - Perceived low priority (not included mandatory management plans) - Very limited public awareness

Needs

Having very limited information and knowledge on the use of antibiotics for livestock production and impact on both animal and public health, it is highly recommended that through the mandatory Veterinary Services available within the Animal Production and Health Division (APHD) of the Ministry of Agriculture and Fisheries (MAF), immediate priority should be on developing an action plan embracing viable practices and approaches that promote public awareness that lead towards the development of positive indicators to suggest potential negative impacts as a result of using antibiotics in livestock production, general food (meat) safety status at primary production at the farm level and across the food (meat) distribution and supply chain including imported meat and meat products. Some of the initial actions recommended to be taken include, - Incorporate emphasis on anticipated work towards prioritizing antibiotic use and

monitoring into the Division’s (APHD) management plan - Introduce as a technical issue for public awareness into existing mandatory food

regulated authorities and committees (Samoa National Codex Committee, L-MAC, Q-MAC, PHAMA, etc)

- Establishment of a Database to compile data collected from surveillance program on the use of antibiotic drugs for livestock production. Collected data should include the types and classes of antibiotics, the quantity used, cost, as well as other the



relevant information on potential drug resistance that would have occurred over time.

- Conduct Public Awareness Campaign and disseminate relevant information through the Division’s on-going training program for farmers and food supply chain operators/handlers and consumers about antibiotic and antimicrobial resistance, including the maintenance of good hygienic practices and recommended husbandry and welfare practices.

- Develop efficient and effective policy or effective and efficient legal enforcement on the use of antibiotics in livestock production with special emphasis on imported meat especially to consider that Samoa import 60% of meat for public consumption and about 50% is chicken imported from the USA on an annual basis.



Sri Lanka

W.K. de Silva

Director-General Dpt. of Animal Production & Health

Executive summary

Traditionally, livestock is an integral part of the agriculture sector in Sri Lanka which plays a significant role in supplementing animal protein requirement of the human nutrition. Livestock are spread throughout all regions of Sri Lanka with concentrations of certain farming systems in particular areas due to cultural, market and agro climatic reasons. Poultry farming has been shown leading the animal production sector over dairy and pork. Under the present circumstances, livestock production sector almost totally depends on imported pharmaceuticals, vaccines and equipments except FMD, HS, NCD, Brucellosis and BQ vaccines produced at the Veterinary Research Institute of the Department. Key legal instrument which control manufacture, import, export and use of pharmaceuticals and biological products in the country is Animal Diseases Act No 59 of 1992 and its regulations. Antimicrobials have been categorised under the pharmaceuticals and hence, are covered by the provisions of the Act. Section 32 of the Act grants provisions to appoint a “Veterinary Drug Control Authority” (VDCA) to assist the Director General as a specialized body to regulate veterinary drugs and biologicals. VDCA composed of a Registrar and a group of experts who receive and evaluate application made for import, manufacture and sale of pharmaceutical and biological products of which DG/DAPH function as the Chairperson. Animal feeds are another possibility which certain antimicrobials may use as feed additives as growth promoters or as prophylactics. In order to regulate animal feeds in the country, a legal instrument is in operation named “ Animal Feed Act No 15 of 1986” and the purpose of the act is to regulate, supervise and control the manufacture, sale and distribution of animal feeds in the country. Accordingly the Department of Animal Production & Health has banned number of pharmaceutical products from using on food animals in the country and the banned products include, Nitrofurans, Dapsone, Ronidazole, Chloramphenicol, Carbadox, Olaquindox, injectable aminoglycosides, growth promoter anabolics, synthetic androgens, synthetic estrogens, synthetic steroids, therapeutic antibiotics indicated as growth promoters or prophylaxis and preparations having vitamin, mineral, amino acid



mixed with therapeutic antibiotics as a measure of preventing public health hazard caused by potential residues of drugs in milk, meat and eggs. Government of Sri Lanka through its National Development Agenda has committed to achieve self reliance of food of animal origin as well as pledged to assure the food security and food safety. Under the Ministry of Livestock and Rural Community Development, the Department of Animal Production and Health has developed the plans for the coming years to implement activities pertaining to monitoring of antimicrobial residues in food of animal origin, monitoring of antimicrobial resistance as well as to create an awareness among veterinarians and farmers on the importance of prudent use of antimicrobials. As a responsible State Organization, Department of Animal Production and Health is always receptive to the international community and hence are always agreeable with APHCA, FAO and OIE to implement appropriate proposals under the state development agenda as well.

Country background

Sri Lanka is a tropical agricultural island located in the Indian Ocean to the south-west of Bay of Bengal. Geographically the country is located between latitude 50 and 100 N and longitude 790 and 820 E. The country lies in close proximity to the south-eastern coast of India with which it shares a continental shelf and a narrow strip of water (Palk Strait) has, however, separated two countries. Traditionally, livestock is an integral part of the agriculture sector in Sri Lanka which plays a significant role in supplementing animal protein requirement of the human nutrition. Presently, the agricultural sector contributes around 10.4 percent of National Gross Domestic Production (GDP) in 2011 while livestock sub sector contributes around 1% of national GDP. The livestock sector contribution to the agriculture GDP was 8.65%. As far as livestock statistics are concerned, there are about 1.4 million cattle, 0.5 million buffalos, 0.4 million Goats, 15.4 million poultry and 0.08 million pigs in the country with negligible number of sheep, ducks and other species. Livestock are spread throughout all regions of Sri Lanka with concentrations of certain farming systems in particular areas due to cultural, market and agro climatic reasons. As far as the production is concerned, the country produced 286.7 million liters of milk in 2011 which was 191.9 in 2010 and is a 33% increase of production over the previous year. Eggs produced in the country in 2011 were 1717.9 Million. In 2011, country produced 116.76 metric tons of chicken meat and the chicken meat availability was 5.57 kg/person/year while eggs availability was 81.78/person/year at the end of 2011. Cattle and buffalo farming are distributed throughout all regions of the country and in the up and mid-country, cattle keeps primarily for milk. In the low country wet zone and



in the coconut growing area buffalo farming is an integral part of agriculture providing draft power, weed control and manure as well as being used for milk production. In the dry zone these species are regarded as a source of insurance by the small-holders as they provide a store of wealth and access to cash by means of animal sales, and milk. Ruminant production systems in the country are mostly related to the environment based on their dependency on pasture and fodder. In the hill and mid country mainly intensive management systems could be observed while intermediate zones showing semi extensive systems of management while the dry zone areas keeping cattle mostly under extensive systems. Two categories of poultry farming could be observed as commercial farming as well as backyard farming and commercial ventures are small, medium and large scale operations. The intensive poultry production systems are concentrated mainly in Western and North Western part of the country as a commercial venture due to their easy access to market facilities and input availability with improved infrastructure facilities. The extensive production systems are scattered throughout the island as a backyard system. Pig farming is concentrated in the Western coastal “pig belt” as intensive systems with 10-15 fatteners and as extensive systems. Under the extensive pig farming, small farmers keep 1to 2 pigs as a scavenging system. Under the present circumstances, livestock production sector almost totally depends on imported pharmaceuticals, vaccines and equipments except FMD, HS, NCD, Brucellosis and BQ vaccines produced at the Veterinary Research Institute of the Department. The pharmaceutical and equipment supply industry is totally run by the private sector and as there is no price control system for animal drugs in the country, the prices are fluctuated with world market prices and the foreign exchange rates. Feed production is also in the hands of the private sector and depends mainly on imported raw materials.

Legal framework

Key legal instrument which control manufacture, import, export and use of pharmaceuticals and biological products in the country is Animal Diseases Act No 59 of 1992 and its regulations. Antimicrobials have been categorised under the pharmaceuticals and hence, are covered under the provisions of the Act. Director General of the Department of Animal Production and Health is the legally empowered officer for the general administration of this Act and should be essentially a registered veterinarian of the country. According to the section 17 of the Act, no person shall manufacture any veterinary drug veterinary biological product in Sri Lanka except under of veterinary authority or a license issued in that behalf. The license issued so is valid only for a period of one year unless it is cancelled or suspended prior to completion of the period. This will maintain



the authority of the Department to oversee manufacturing of drugs and is therefore able to prevent the possibility of releasing undesirable products to the market to be used on livestock. The section 21 of the Act prohibits import of any veterinary drug without a proper approval of the Director General. Further strengthening the provisions of the Section 21, Section 31 has further provide the implementing authority to not to recommend the issue of a permit to any person for the import of any veterinary drug or veterinary biological product unless such person produces a certificate from the Chief Veterinary Surgeon or a veterinary surgeon authorized by him in the country of origin of the product, certifying the safety of such drug or veterinary biological product. This section prevents unauthorized or discontinued products for sales in the country of origin to dump in Sri Lanka in the form of imported veterinary products. Therefore this section provides the opportunity to prevent entry of recently banned antimicrobials for the purpose of prevention and using as growth promoters. Section 32 of the Act has granted opportunity to appoint a “Veterinary Drug Control Authority” to assist the Director General as a specialized body in reviewing the requests make for manufacture or import of pharmaceutical products. Accordingly Director General function as the Chairman of the Committee and a Veterinary Surgeon employed under the Department of Animal Production and Health appointed by the Minister concern of the discipline function as the Registrar as well as the Secretary of the Committee. In addition six specialized personnel in the disciplines of clinical practice in State and Private sectors, microbiology and immunology, parasitology, pharmacology, nutrition, reproductive physiology and endocrinology also would be appointed by the Minister concern to function in the Committee. Additionally there is an opportunity to appoint another veterinarian to represent the local pharmaceutical industry as well. According to the Act the period valid for such an appointed member except Director General is limited to three years unless leave or removed prior to completion of the period. The same section of the Act very clearly indicates the powers of the Veterinary Drug Control Authority and they are as follows.

a. Exercise control over the manufacture, import, export, sale and use of veterinary drugs and veterinary biological products;

b. Ensure the efficient and safe use of veterinary drugs and veterinary biological products on animals

c. Determine whether licenses shall be granted for the manufacture or importation of veterinary drugs and veterinary biological products;

d. Advise the Minister on any matter he may refer to the Authority for advice or any other matter which it considers necessary to bring to the notice of the Minister;



e. Promote research which the Authority considers necessary to test or improve veterinary drugs and veterinary biological products;

f. Disseminate information relating to the safe and efficient use of veterinary drugs and veterinary biological products ; and

g. Carry out or cause to be carried out, tests on veterinary drugs and veterinary biological products already licensed or pending issue of a license whenever necessary in the opinion of the Authority.

Export of veterinary pharmaceuticals and biological are governed by the provisions of the section and accordingly no person shall export any animal, animal product, veterinary drug, veterinary biological product, semen or embryo except under the authority of a permit issued by the Controller of Imports and Exports on the recommendation of the Director General of Animal Production and Health. For the purpose of implementing the Act effectively the Minster concern make regulations in respect of all matters which are required by this Act to be prescribed or in respect of which regulations are authorized to be made and in particular in respect of all or any of the maters namely the mode and manner in which an application for a license may be made and to decide the fees payable for the issue and renewal of a license. Animal feeds are another possibility which certain antimicrobials may use as feed additives as growth promoters or as prophylaxis. In order to regulate animal feeds in the country a legal instrument is in operation named “ Animal Feed Act No 15 of 1986” and the purpose of the act is to regulate, supervise and control the manufacture, sale and distribution of animal feeds in the country. In order to implement the functions of the Act, an Animal Feed Advisory Committee has been established under the Department of which a Veterinary Officer attached to the Department function as the Registrar while Director General functions as the Chairman. Licensing of raw materials intended to be imported, registration of feeds, registration of feed mills, monitoring the industry and identification of issues pertaining to the industry are the main functions of the committee.

Institutional arrangements

Department of Animal Production and Health is the primary organization which is responsible for regulating matters pertaining to antimicrobial manufacture, import sale and use in the country. Under the Department, a technical division entitled “Division of Veterinary Regulatory Affairs” has been established and presently Veterinary Drug Control Authority functions under this division. Main functions implement by the Veterinary Drug Control Authority at present are limited to evaluation of applications receive for manufacture and import, registration of products, notification of registered products and clearing of invoices for routine imports. On receiving applications, they are submitted by the Registrar to the Veterinary



Drug Control Committee and evaluated at the committee meetings held at least six times a year. Approved products are informed to the Controller of Imports and Exports as well as to the applicant for consequent action. Import applications are mainly for two purposes namely for purpose of sales that is called “free sales license” and for using on the animals exclusively owned by the importer called “user permits”. Free sales license are valid for a period of three years from the date of issue and user permits are valid for the particular consignment only. All the licensing process are fee involved and free sales permit will be issued on payment of approximately US$50 while user permits are issued on payment of approximately US$ 10 provided that the applications meet the country requirement. Based on global and local requirements, Veterinary Drug Control Authority time to time considers elimination of products especially antimicrobial products for the best interest of public health. Accordingly the Department of Animal Production & Health of Sri Lanka has banned a number of pharmaceutical products from using on food animals in the country and the banned products include, Nitrofurans, Dapsone, Ronidazole, Chloramphenicol, Carbadox, Olaquindox, injectable aminoglycosides, growth promoter anabolics, synthetic androgens, synthetic estrogens, synthetic steroids, therapeutic antibiotics indicated for growth promotion or prevention of infections and preparations having vitamin, mineral, amino acid mixed with therapeutic antibiotics as a measure of preventing public health hazard caused by potential residues of drugs in milk, meat and eggs.

However, it has to mention here that there is no proper system for market vigilance, adverse reaction reporting and residue monitoring so far but the Department is in the process of developing systems through bringing in modifications to the regulations of the Animal Diseases Act. Therefore, in order to bridging the gap, Department conducts educational programs targeting farmers, potential users and pharmaceutical industry regularly on responsible use and sales of antimicrobial products in view of minimizing residues in food commodities and preventing it from developing resistant strains.


Poultry subsector in Sri Lanka approximately up to 80% operates under intensive management system and use variety of antimicrobials, anthelmintics and anti-coccidial drugs depending on the requirement. Drugs in the poultry sector are administered through oral route and products are available either in liquid form or powder form. Along the western coast of the island pig farming is considered as a popular livestock species depending on socio-cultural and religious status and can be seen reared in intensive and extensive systems. Next to the poultry subsector, pig farming also utilizes a considerable amount of antimicrobials and anthelmintics. The main route of administering antimicrobials in pig sector is parenteral.



Comparatively dairy industry uses less amounts of antimicrobials except in cases of difficult parturition process. Based on their physiological complexicity, antimicrobials are used through parenteral route but to a limited extent. The main way of using antimicrobials are as treatment for clinical mastitis and the details of antibiotic sensitivity profile is given under “Section 7”of the paper. Table 1 below shows the quantities of antimicrobials imported into the country in 2011.

Table 1. Imports of antimicrobials into Sri Lanka in 2011

Nr. Active ingredient Quantity (kg)

1 Enrofloxacin 2,696

2 Amoxycillin 6,130

3 Tylosine 3,026

4 Sulphadiazine 5,264

5 Trimethoprim 1,300

6 Oxytetracycline 1,032

7 Chlortetracycline 900

8 Neomycin 808

9 Bactrim 710

10 Doxycycline 658

11 Flumequine 560

12 Penicilin 76

13 Ceftiofor 8

Total 23,168

Current and planned arrangements Department of Animal Production and Health as the implementing organization of the laws and regulations pertaining to veterinary pharmaceutical usage in the country has well recognized the importance of the issues of antimicrobial resistance and residues in food of animal origin. Currently the Department is in the process of updating the regulations governing the subject. It has been planned to regularize the monitoring process related to pharmaceuticals (which include antimicrobials as well) from the point of registration to usage in the farm by adopting various measures. Registration of pharmaceutical importers, stockers, retail vendors has been included into the newly drafted regulations. In addition the registration process itself also has further strengthened by introducing a renewal process every three years after registration. Pharmaceutical manufacturing and re-packing also are under scrutiny so as to prevent adulteration and assure the quality of the product which reach the user. The department has enhanced the attention towards strengthening its programs in the field of food safety as well. In order to bring the program to the track, animal identification



and farm registration activities are kept in place and fast track programs are underway with the assistance of Provincial Departments. The department has already launched the activities in the discipline of Veterinary Public Health and antimicrobial residue monitoring at the field level has been recognized as a program which would be implemented at the Veterinary Research Institute in the coming year.

Patterns and extent of AMR animal pathogens

At present, studies on antimicrobial resistance and sensitivity are largely limited to testing of milk samples obtained in the field prior to initiate treatment for mastitis through veterinary investigation centres. In addition veterinary investigation centres perform ABST for field samples receive from Divisional Veterinary Surgeons in the course of antimicrobial treatment for OPD as well as out bound cases. In 2012, veterinary investigation centres have performed 1,609 ABST, which 790 were milk samples and 819 other laboratory samples. The organisms commonly identified are mainly Staphylococus, E. coli and coliforms. Irrespective of the organism, ABST results of 576 milk samples tested for mastitis at ten veterinary investigation centres were evaluated to generate basic understanding of the antimicrobials resistance. The primary picture is as depicted in Table 2.

Table 2. Number of samples detected as resistant to antimicrobials in ABST, 2012

Antimicrobial Agent Total %

Amoxycillin 101 17.53

Enrofloxacin 97 16.84

Gentamycin 18 3.13

Oxytetracycline 142 24.65

Cephalexin 143 24.83

Cloxacillin 161 27.95

Penicillin 205 35.59

Sulpha+Trimethoprim 27 4.69

Neomycin 8 1.39

Doxycycline 10 1.74

Ampicillin 59 10.24

Streptomycin 12 2.08

Sulphamethoxazole 10 1.74

Chloramphenicol 15 2.60

Tetracycline 4 0.69

Erythromycin 4 0.69

Total 576



According to the results, it has been indicated that resistant has been developed against the antibiotics of penicillin group including Amoxycillin, Cephalexin, Cloxacillin, Penicillin and Ampicillin. In addition it indicates the resistance against Enrofloxacin as well. According to the present regulations, macrolide group of antimicrobials are not permitted to be used in food producing animals through parenteral route and in the results less resistance against macrolides could be observed as well. Considering the alarming situation in relation to resistance this could be recognized as an area which needs further research as well as intensive attention in view of averting the risk of developing generalized resistance of large number of disease causing bacteria which could be introduced to human through the food chain. At present Faculty of Veterinary Medicine and Animal Science is engaged in routinely performing studies in relation to antimicrobial resistance and residues while providing a service to the livestock production sector as well as to the aquaculture sector and those details have not been included in this paper.



Thailand

Sasi Jaroenpoj

Senior Veterinary Officer Bureau of Livestock Standards & Certification

Department of Livestock Development

Legal framework and institutional arrangements for regulating antimicrobial use in livestock production and instruments for enforcement

Drug Act B.E. 2510 (1967) and its five revised versions are the legislations used for licensing of manufacturing, importing and selling and registration of human and animal drugs (including vaccine).

Food and Drug Administration (FDA), Ministry of Public Health is responsible for licensing, registration and pharmacovigilance of veterinary medicinal products and the Department of Livestock Development (DLD), Ministry of Agriculture and Cooperatives is responsible for control the usage and post-marketing surveillance of veterinary medicinal products. The FDA also empowers the relevant officials of the DLD and the Department of Fisheries (DOF) to enforce the Drug Act relating to the post-marketing of veterinary drugs/biologics.

The main roles of the FDA and the DLD on regulating of veterinary medicinal products can be summarized into 2 parts as follows:

(a) Pre-marketing control: is under responsibility of the Bureau of Drug, FDA, Ministry of Public Health and the Bureau of Drug and Narcotic, Department of Medical Science, Ministry of Public Health. Their roles are to issue the notifications, establish quality standards, and conduct inspection and testing before approval and granting the licenses for business operation and the certificates for veterinary medicinal products registration.

(b) Post-marketing monitoring and surveillance: is under responsibility of the FDA and the DLD. These are to check and monitor whether the approved products in the market conform to the proclaimed quality and safety. The activities also cover the surveillance programs for watching of unforeseen hazards, abuse, or any unsafe use of veterinary medicinal products. In addition, there are the offices under the DLD to perform the veterinary drug administration work, veterinary drug assay and veterinary biologic assay. These are done in collaboration with the FDA for veterinary drugs/biologics supervision.

Meanwhile, the drug law is under the amendment process provided that the Veterinary Drug Committee of Ministry of Agriculture and Cooperatives shares



responsibility with the FDA of Ministry of Public Health on veterinary medicinal products.


Table 1 shows the amount of antimicrobial drugs use in animals in Thailand during 2007 - 2010.

Table 2 shows the veterinary medicinal products in animal health market in Thailand, 2011.

Table 3 shows the statistic of licenses for pharmaceutical industry in 2005.

Table 1a. Amount of single preparation antimicrobial drugs used in animals in

Thailand, 2007 to 2010

Group Dosage form Unit Single preparation

2007 2008 2009 2010

ANTI-INFECTIVE ANTIDIARREAL

injection lits 0.4 0.0 0.8 0.0

water soluble lits 7.0 11,377.0 0.0 6,384.0

premix kg 703,853.2 1,201,977.2 818,333.4 1,111,090.7

tablet tab

TETRACYCLINES injection kg 712.3 705.0 690.8 523.5

injection lits 25,904.7 28,860.1 23,095.9 17,668.5

water soluble lits 1,100.0 1,100.0 4,850.0 49,440.0

premix kg 4,513,492.0 3,709,097.4 3,231,802.0 5,218,148.5

spray lits 0.0 0.0 1,128.9 0.0

tablet tab 0.0 6,000.0 8,400.0 0.0

PENICILLINS injection kg 0.0 0.1 0.0 0.1

injection lits 60,887.1 65,691.9 70,616.5 98,757.7

premix kg 457,094.7 6,727,090.1 813,088.7 1,161,709.6

CEPHALOSPORINS injection kg 190.0 253.8 763.1 582.2

injection lits 1,872.3 1,130.4 1,335.0 1,424.1

premix kg 16,190.0 22,530.0 5,370.0 12,244.0

tablet tab 96,880.0 86,240.0 0.0 66,150.0

TRIMETHOPRIM premix kg 0.80 0.50 0.00 0.00

MACROLIDES injection lits 13,604.8 12,080.2 10,703.1 15,717.3

injection kg 4,078.0 2,309.0 6,632.0 8,471.0


premix kg 584,640.5 669,202.2 703,968.7 880,499.1

QUINOLONES

injection lits 41,005.0 34,828.7 40,773.1 43,335.9


premix kg 27,537.6 19,986.7 15,566.6 24,769.1

tablet tab 706,878.0 803,176.0 755,094.0 1,398,690.0

AMINOGLYCOSIDES

injection kg 174.9 613.845 261.375 627.97

injection lits 76,639.11 85,638.99 82,525.77 82,175.66

water soluble lits 474.66 359.1 720.6 354.24



Group Dosage form Unit Single preparation

2007 2008 2009 2010

premix kg 92,751.90 27,948.10 27,265.80 29,053.79

spray lits 470.50 950.00 469.30 2,433.40

tablet tab 0.0 40.0 0.0 10.0

OTHER ANTIBIOTICS premix kg 207,822.0 355,905.0 417,664.5 774,423.2

SULPHONAMIDES

injection lits 1,526.7 1,115.3 1,639.1 1,480.0


premix kg 4,036.0 4,964.0 7,091.0 5,931.9

COCCIDIOSTATS

injection lits 12,916.7 20,060.1 21,050.9 20,832.7


premix kg 1,647,478.3 2,208,161.6 2,518,637.9 3,749,443.5

ANTHELMINTICS injection kg 37.1 65.6 15.2 8.3

injection lits 18,205.5 18,874.7 20,607.5 21,385.2

water soluble kg 9,346.3 6,444.5 2,167.7 162,386.8


premix kg 113,411.3 117,537.4 125,473.5 166,659.5

tablet tab 578,124.0 700,820.0 686,164.0 1,205,510.0

wax kg

ANTI-MALARIALS premix kg 5.0 205.0 3,005.0 300.0

SCABIES & ECTOPARASITICS

tablet tab 9,000.0 13,560.0 13,410.0 13,470.0

Table 1b. Amount of antimicrobial drugs used in animals in combined preparations in

Thailand in 2007 to 2010

Group Dosage form Unit Combined preparation

2007 2008 2009 2010

ANTI-INFECTIVE ANTIDIARRHEA

injection lits

water soluble lits

premix kg 2.5 21.5 2.5 17.0

tablet tab 21,000,000.

0 27,000,000.0 22,500,000.0 46,023,900.0

TETRACYCLINES spray lits 8,004.4 10,001.6 6,003.2 7,828.8

COCCIDIOSTAT

injection lits

water soluble lits

premix kg 170,400.0 192,000.0 342,000.0 406,800.0

ANTHELMINTICS injection lits 9,228.0 4,869.1 2,526.4 6,669.2

water soluble lits 0.0 0.0 377.1 56.6

premix kg 92,311.6 4,977.5 3,922.8 7,246.7

tablet tab 4,114,708.0 6,563,458.0 5,783,070.0 7,454,420.0

wax kg

18.4 11.3 15.4

ANTIFUNGALS shampoo lits 6,400.00 14,400.0 16,800.0 25,600.0

ANTIBACTERIAL COMBINATION

injection kg 3,893.0 153.5 4,613.2 4,477.4

injection lits 121,294.1 123,758.7 155,952.5 149,494.4

water soluble lits 749.7 1,036.3 150.1 446.4

premix kg 737,138.1 1,719,772.3 2,015,493.4 1,814,732.8



Group Dosage form Unit Combined preparation

2007 2008 2009 2010

spray kg 4,296.0 2,721.6 5,208.0 0.0

tablet tab/cap 1,703,160.0 1,665,000.0 3,095,080.0 482,000.0

ear paste kg 315.0 346.5 616.5 1,458.0

ear drop lits 1,117.9 1,259.6 1,715.5 1,357.1

TRIMETHOPRIM + SULPHONAMIDES

injection lits 16,400.1 17,964.9 21,048.2 21,750.7


premix kg 696,372.7 461,696.1 426,992.5 542,979.8

tablet tab 118,080.0 131,840.0 511,200.0 671,900.0

Table 2. Veterinary medicinal products in animal health market in Thailand, 2011

(million THB)

Product Total Poultry Pigs Cattle Dogs /

cats Shrimp / fish

Feed mill

Vaccines 2,979 1,238 1,272 0 469 0 0

Antimicrobial (FA) 2,703 149 2,554 0 0 0 0

Antimicrobials (WS) 954 440 0 299 0 216 0

Antimicrobials (Inj.) 1,027 0 1,027 0 0 0 0

Antibacterial Pet 108 0 0 0 108 0 0

Coccidiostats 173 173 0 0 0 0 0

Endoparasiticides 562 88 67 294 113 0 0

Ectoparasiticides 739 91 99 56 493 0 0

Endectocides 80 0 0 0 80 0 0

Feed Additives 6,943 0 0 62 163 240 6,479

Vit.-Min. Premixes 3,052 829 945 0 0 1,278 0

Supportives (WS) 513 513 0 0 0 0 0

Supportives (Inj.) 279 0 279 0 0 0 0

Disinfectants 2,112 309 109 0 0 1,695 0

Others 1,467 0 0 187 200 1,080 0

TOTAL 23,692 3,828 6,352 897 1,627 4,509 6,479

Table 3. Statistic of licenses to pharmaceutical industry in 2005

Type Amount

1. License to manufacture modern drugs 166

2. License to manufacture traditional drugs 879

3. License to import modern drugs 600

4. License to import traditional drugs 172

5. License to sell modern drugs 8,801

6. License to sell ready–packed modern drugs 4,528

7. License to sell ready–packed modern veterinary drugs 640

8. License to sell traditional drugs 2,096 * For manufacturer / importer of veterinary medicinal products 170



Current and planned arrangements for monitoring of antimicrobial use in livestock, antimicrobial residues in livestock products and surveillance for antimicrobial resistance in animal pathogens

The Drug Acts B.E. 2510 (1967) and its amendments Sec. 85 stipulated that "The Licensee to produce drugs or license to import drugs into the Kingdom must submit an annual report concerning the production or importation of drugs that the formulation has been registered each formula in the form prescribed in the Ministerial Regulation within 31th March of the following year". Therefore, the available data to estimate the use of antimicrobial drugs from the Thai FDA is the quantities of the antimicrobial agents manufactured and imported.

To control the use of veterinary medicines in farm animals, the prescriptions from farm veterinarians who look after animal health and farm management are required following the Ministerial Notifications of Ministry of Agriculture and Cooperatives on Livestock Farm Standard of Thailand on 3 November B.E. 2542 (1999), 15 May B.E. 2545 (2002) 21 May B.E. 2546 (2003) and 28 December B.E. 2552 (2009). These Ministerial Notifications stipulated that the livestock standard farms (the farms certified for GAP by the DLD) must have the farm veterinarians to look after animal health. He/she must be qualified in accordance with the Veterinary Practitioner Act B.E. 2545 (2002) and passed the farm veterinarian training course of the DLD and licensed by the DLD. The animal treatment of the farm veterinarians must comply with the Code of Practice for Control of the Use of Veterinary Drugs (TAS 9032-2009) issued by Ministry of Agriculture and Cooperatives which is in compliance with the Code of Practice for Control of the Use of Veterinary Drugs (CAC/REP 38–1993) of Codex. The farm veterinarian must have his/her prescription records kept at least two years, and presented when required by the DLD.

Surveillance of antimicrobial residues in livestock has been carried out by the DLD following the DLD Order No. 349/2547 (2004) in which the Residue Monitoring Committee has been appointed. The committee is responsible for drawing up residue monitoring plan for livestock, coordinating the monitoring activities of the central, regional, provincial and district livestock offices and collecting data to evaluate the results and the residue control system. If non-compliance is found, the result will be immediately reported to the officers who submitted the samples so that the officer is able to take immediate action. The non-compliant farm and farm veterinarian will be under investigation and measures will be taken according to the DLD Notification on Residues Control Measures.



Results of the residue monitoring programme in 2011

Sample Source of sample

Total no. of samples

No. of non-compliant samples

Residues

Poultry feed Farm 304 0 -

Pig feed Farm 1,297 15 Tetracyclines*, Sulphonamides*

Poultry muscle Farm, Slaughterhouse

5,555 4 Anticoccidal*

Poultry liver Farm, Slaughterhouse

942 0 -

Poultry fat Farm, Slaughterhouse

450 0 -

Pig muscle Slaughterhouse 800 12 Tetracyclines*

Pig liver Slaughterhouse 390 6 β-agonists**

Pig fat Slaughterhouse 99 0 -

Honey Farm 134 0 -

Remarks: * MRLs are exceeded ** β-agonists are banned substances in Thailand

Surveillance of AMR in animal pathogens conducted by the DLD includes:

(a) Samples from slaughterhouses (E.coli, Salmonella spp., Campylobacter spp. Staphylococcus aureus, Clostridium perfringens, Listeria monocytogenes, Enterococci)

(b) Samples from diagnostic cases (E.coli, Salmonella spp., Staphylococcus spp.)


Methicillin-resistant Staphylococcus aureus (MRSA) in milk: 807 isolates of coagulase positive staphylococci from milk samples were tested for MRSA using multiplex PCR method, 10 isolates (1.2%) were MRSA positive

Vancomycin-resistant enterococci (VRE) in poultry meat production chain: during 2007-2011, 17,363 samples from various sources of whole poultry meat production chain were tested for VRE, 3 samples (0.1%) were VRE positive



Session 3 Country Case Studies



An Integrated Surveillance Study of AMR in Salmonella subspp, Campylobacter spp, Escherichia coli and

Enterococcus spp in Poultry in Cambodia

Patrick Otto

[In preparation]



Monitoring Antimicrobial Resistance in Food-borne Pathogens from Selected Species in Sri Lanka

P. Abeynayake

[In preparation]



Acquisition of Multi-Resistance of Campylobacter jejuni Isolates with Antimicrobial Usage in Poultry

Loinda R. Baldrias1

Professor College of Veterinary Medicine

University of the Philippines Los Banos

Abstract

The antimicrobial profiles of 12 Campylobacter jejuni isolates recovered from poultry ceca were determined using the Kirby Bauer method. The isolates came from chickens detected to be positive for antibiotic residues. These showed multi-resistance, being resistant to more than 7 out of 14 different antibiotics tested. Statistical analysis showed a significant relationship between antibiotic usage in poultry production and the development of microbial resistance. Observed multi-resistance among C. jejuni isolates adds to the evidence on emergence of resistant bacteria in animals following administration with antibiotics, either prophylactically or therapeutically. The growing resistance to different antibiotics, which is being observed to be higher in developing countries, appears to be a similar trend in the Philippines, where the use of antimicrobial drugs in humans and animals is relatively unrestricted. This is of public health relevance as antibiotic resistance among bacteria from foods of animal origin may have an impact on antibiotic–associated bacterial infection of humans.

Introduction

Development and use of antimicrobial agents were considered among the most important measures leading to the control of bacterial diseases in the 20th century (Cohen, 1992). Antibiotics have greatly enhanced human life expectancy, reduced mortality, improved the quality of life and almost won the war against many infectious diseases. However, reports of antibiotic-resistant bacteria isolated from farms and animal carcasses are raising concerns that antibiotic use in agriculture may play a role in selecting for antibiotic resistance among foodborne bacteria (Nawaz et al., 2001; Alfredson and Korolick, 2007). The emergence of antimicrobial resistance is a very controversial issue. Some claim that indiscriminate use of antibiotics in agriculture, either as growth promotants or for performance enhancement, has created a reservoir of resistant organisms in the environment that could infect humans through the food

1 Research supported by the Department of Agriculture Bureau of Agricultural Research (DA-BAR), Philippine Council of Health Research and Development (PCHRD), Philippine Council of Advanced Research in Science and Technology Development (PCASTRD) and Commission on Higher Education (CHED).



chain. On the other hand, it is also possible that abuse of antibiotics in human medicine may be largely responsible for the increase in antibiotic resistance. Among food-borne illnesses from foods of animal origin, campylobacteriosis is now considered the leading gastrointestinal infection throughout the world, even exceeding salmonellosis (Rosef and Kapperud, 1983 and Walker et al., 1986; Steel et al., 1998; Altekruse et al., 1999; Alfredson and Korolick, 2007). Their significance, as causative agents of foodborne diseases in man, is well documented by various food-borne outbreak reports (Engberg et al., 2001). Most cases of Campylobacter enteritis do not require antimicrobial treatment, but a substantial portion of these infections does require treatment, particularly if it is severe and prolonged. There are, however, reports on the emergence and spread of resistance spectra among Campylobacter strains, particularly C. jejuni, which is recognized as the most important etiologic agent of acute diarrheal Campylobacteriosis in humans worldwide (Gibreel et al., 1998; Smith et al., 1999; Saenz et al., 2000; Engberg et al., 2001; Alfredson and Korolick, 2007). This study investigates a possible link between the use of antibiotics in poultry production and the development of antibiotic resistance using local C. jejuni isolates from chickens from commercial and backyard raisers that were detected to be positive for antibiotic residues.

Materials and methods

Antimicrobial sensitivity testing of Campylobacter Isolates. Local putative Campylobacter isolates, recovered from the ceca of randomly selected freshly dressed chicken at dressing plants of commercial and backyard chicken producers, were confirmed to be C. jejuni by polymerase chain reaction using specific primers CL2 and CR3 (Ng et al., 1997; Magistrado et al., 2001). Pure cultures of twelve revived C. jejuni isolates were subjected to antimicrobial susceptibility testing using the Kirby Bauer method (Atlas et al., 1988; NCCLS, 1981 and 1998; Lucey et al. 2000). The 14 antimicrobial substances used for sensitivity/resistance testing were: ampicillin (10 μg), cephalothin (30 μg), chloramphenicol (30 μg), ciprofloxacin (5 μg), colistin sulphate (10 μg), erythromycin (15 μg), gentamycin (10 μg), nalidixic acid (30 μg), norfloxacin (10 μg), spectinomycin (10 μg), streptomycin (25 μg), and tetracycline (30 μg) from MAST Diagnostics, U.K.; trimethoprim (1.25 μg) and sulfamethazine (25 μg) from SIGMA, Italy. Their patterns of antibiotic resistance were analyzed (Baldrias and Raymundo, 2009). Antibiotic residue detection using the Four Plate Test (FPT). Data from Four Plate testing of liver samples from the same study population of freshly dressed chickens at dressing plants of commercial and backyard raisers were analyzed for type of antibiotic residues (Baldrias et al., 2008). Statistical Analysis. Chi-square and Pearson correlation (Noether, 1991) was used to determine if a relationship existed between the percent antibiotic resistance of the C. jejuni isolates (Baldrias and Raymundo, 2009) and the type of antibiotic residue as



inferred by Four Plate Test (Baldrias et al., 2008). This was to examine an association between the antimicrobial profile of isolates with the antibiotic usage (by type of antibiotic residue detected) of the same chicken population from commercial and backyard raisers, computed using Chi-square with continuity correction and linear regression as used by Schmidt et al (2001).

Results and discussion

On determining the frequency of detection by type of antimicrobials (Table 1), as inferred by the Four Plate Test, it was found that penicillin type of antibiotic ranked highest in occurrence at 53.1% for both backyard (62.8%, 49/78) and commercial (44%, 37/84), followed by aminoglycosides. Both producers, then varied on the frequency for tetracyclines and sulfonamides. However, the least frequent type of antibiotic detected for both producers were the macrolides at 21.6%. The number of chickens positive for penicillin, tetracycline, sulfonamide and aminoglycoside antibiotics was significantly higher at 5% level of significance for backyard raisers than for commercial producers. In contrast, no significant difference was found between both producers for number of chickens positive for macrolides. It was observed, however, that in many instances, more than one type of antibiotic residue was detected in the liver samples, possibly indicating simultaneous dosing of a combination of two or more antibiotics.

Table 1. Suspected type of antibiotic detected in fresh chilled chicken by producer using Four Plate Test

COMMERCIAL (n=84)

BACKYARD (n =78) (N=162)

SUSPECTED TYPE OF ANTIBIOTIC

NO. OF POSITIVE

% POSITIVE

NO. OF POSITIVE

% POSITIVE

PERCENT (%)

POSITIVE X

2 VALUE

Penicillin 37 44.05 49 62.82 53.09 0.0167421* Tetracycline 27 32.14 43 55.13 43.21 0.0031686* Sulfonamide 22 26.19 47 60.26 42.59 1.1BE-05* Aminoglycoside 25 29.76 47 60.26 44.44 9.50BE-05* Macrolide 23 27.38 12 15.38 21.60 0.1289373

Legend: * = significant at p < .05 level of significance

Resistance profiles (along with the measured zones of inhibition) of the 12 C. jejuni from commercial (C. jejuni isolates V5, V7, V19 and V26) and backyard producers (52c, 53m, 55c, 57b, 60c, 64c, 65b and 68c) are presented in Table 2. The 14 antimicrobial agents chosen for the test are those being used for treating clinical cases of gastroenteritis in both man and animals, had a broad spectrum of activity, and routinely used for sensitivity testing in diagnostic laboratories (National Committee for Clinical Laboratory Standards, 1981 and 1998). They are also similar to those used by Lucey et al. (2000). All of these isolates showed multi-resistance (being resistant to more than 7 different antibiotics tested). For commercial producers, two (V5 and V26) of the four (50%)



isolates came from chickens detected to be positive for antibiotic residues. These two isolates showed resistance to all (100%) antibiotics tested. For backyard raisers, all isolates came from chickens positive for antibiotic residues by FPT (Baldrias et al, 2008). On the specific percentage of resistance to the different antibiotics (Figure 1 and Table 2), all 12 C. jejuni isolates were resistant to trimethoprim (100%); 91.7% were resistant to cephalothin, ciprofloxacin, colistin, gentamicin, nalidixic acid, sulphamethazine, streptomycin, and tetracycline; 83.3% to ampicillin; 75% to chloramphenicol and norfloxacin; and 66.7% to spectinomycin. In contrast, only 33.3% of the isolates were resistant to erythromycin. The 100% resistance to trimethoprim among all C. jejuni isolates is an important finding, as resistance to trimethoprim had been increasingly observed for C. jejuni by Gibreel and Skold (2000) and Lucey et al. (2000). Gibreel and Skold (2000) related this to the acquisition of foreign resistance genes (dfr1, dfr9 or both) that code for resistant variants of the enzyme dihydrofolate reductase — the target of trimethoprim (Alfredson and Korolick, 2007). These dfr genes were found to occur as integron cassettes inserted in the chromosome of the clinical isolates examined by these workers.

Legend: Amp = Ampicillin Kf = Cephalothin C = Chloramphenicol Cip = Ciprofloxacin

Col = Colistin sulphate E = Erythromycin Gm = Gentamicin Na = Nalidixic acid

Nor = Norfloxacin Spc = Spectinomycin Sul = Sulphamethazine Sm = Streptomycin

Tet = Tetracycline Tm = Trimethoprim

Figure 1. Percent total antimicrobial resistance of 12 Campylobacter jejuni isolates from poultry of commercial and backyard producers to different types of antibiotics



9

Table 2. Antibiotic resistance profiles and zones of inhibition (mm) of Campylobacter

jejuni isolates from poultry of commercial and backyard producers.

ANTIBIOTIC TESTED

C. jejuni isolates from commercial producers

C. jejuni isolates from backyard producers

V5 V7 V19

V26 52c 53m 55c 57b 60c 64c 65b 68c

ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP ZI RP

Ampicillin, 10 μg 7 R 15 S 0 R 5 R 0 R 0 R 0 R 0 R 0 R 13 I 0 R 1 R

Cephalothin, 30 μg 6 R 15 I 0 R 1 R 2 R 0 R 1 R 0 R 0 R 12 R 3 R 1 R

Chloramphenicol, 30 μg 5 R 1 R 0 R 4 R 3 R 0 R 18 S 3 R 5 R 5 R 15 I 17 I

Ciprofloxacin, 5 μg 7 R 7 R 12 R 11 R 0 R 15 R 0 R 0 R 1 R 15 R 18 I 0 R

Colistin sulphate,10 μg 1 R 1 R 4 R 4 R 0 R 15 S 9 R 0 R 4 R 5 R 3 R 7 R

Erythromycin,15 μg 7 R 10 R 0 R 10 R 19 S 17 I 20 S 17 S 19 S 14 S 18 S 20 S

Gentamicin,10 μg 6 R 6 R 12 R 8 R 0 R 17 S 7 R 0 R 2 R 10 R 5 R 9 R

Nalidixic Acid, 30 μg 0 R 0 R 7 R 7 R 3 R 0 R 2 R 0 R 2 R 6 R 0 R 3 R

Norfloxacin, 10 μg 6 R 7 R 15 I 12 R 2 R 16 I 2 R 0 R 2 R 17 I 15 I 2 R

Spectinomycin, 100 μg 5 R 5 R 12 R 10 R 4 R 16 S 18 S 1 R 5 R 0 R 12 S 20 S

Suphamethazine, 25 μg 0 R 0 R 0 R 12 R 0 R 17 S 0 R 10 R 12 R 0 R 2 R 5 R

Streptomycin,10 μg 4 R 5 R 15 S 7 R 1 R 0 R 1 R 0 R 1 R 7 R 0 R 1 R

Tetracycline, 30 μg 4 R 10 R 8 R 9 R 5 R 0 R 0 R 0 R 1 R 16 S 0 R 1 R

Trimethoprim, 2.5 μg 5 R 5 R 0 R 5 R 2 R 0 R 0 R 0 R 1 R 0 R 0 R 2 R

No. of antibiotics resistant to

14 12 12 14 13 8 11 13 13 10 9 11

% AMR 100.0 85.7 85.7 100.0 92.9 57.1 78.6 92.9 92.9 71.4 64.3 78.6

Legend: ZI = zone of inhibition (mm); RP = resistance profile; Interpretation: R= resistant; S = susceptible; I = intermediate (based on NCCLS, 1981 and 1998; Atlas et al., 1988; and Quinn et al., 1994)

The multi-resistance of C. jejuni isolates from chickens in this study reflects a similar trend for increasing frequency of resistance being observed by other investigators from other countries (Alfredson and Korolick, 2007). For example, Saenz et al. (2000) in Spain found that on 1997-1998, C. jejuni strains recovered from broilers were resistant to cephalothin, ampicillin, gentamicin, and tetracycline. Resistance to ciprofloxacin (a quinolone antibiotic) in the present study is also reflective of the high frequency of resistance being observed among Campylobacter strains in other countries. Altekruse et al. (1999) in Minnesota on 1997 also cited C. jejuni resistance to ciprofloxacin in his locality. The licensing of fluoroquinolone for use in poultry in 1995 was observed to coincide with reports on emergence of quinolone-resistant strains of C. jejuni (Khachatorians, 1998; Altekruse et al., 1999; Alfredson and Korolick, 2007; Kabir, 2010). Among the features used for identification of C. jejuni in diagnostic laboratories are its resistance to cepthalothin and susceptibility to nalidixic acid (Carter and Cole, 1990). As such, the observed high level of resistance to cephalothin was an expected finding. However, the high level of resistance to nalidixic acid vouches for the increasing



occurrence of nalidixic acid-resistant strains of C. jejuni, as reported by Saenz et al., (2000). The growing resistance to different antibiotics, which is being observed to be higher in developing countries, appears to be a similar trend in the Philippines, where the use of antimicrobial drugs in humans and animals is relatively unrestricted. Likewise in Malaysia, Selaha (2002) found that 76 C. jejuni isolates, recovered by cloacal swabs of chickens from 10 broiler farms, were resistant to at least one of the seven antibiotics tested. Multiple resistance was also observed in 58 (76.3%) isolates with ten (13.1%) resistant to all antibiotics tested. Comparably similar results were observed for resistance to tetracycline; 91.7% in this study and 100% in Selaha‘s study (2002). Least resistance was also observed for erythromycin; 33.7% in this study and 23.7% in Selaha’s (2002), among the antibiotics tested. The low resistance (33%) to erythromycin (a macrolide) by C. jejuni isolates validates the observation that among the antibiotic residues (Baldrias et al, 2008), macrolides were the least frequent type of antibiotic (21.6%) detected for both commercial and backyard producers. This may provide another good association between antibiotic usage in poultry production and development of microbial resistance. Similarly, Hernandez and Raymundo (1988) also observed a clear association between higher level of resistance of Escherichia coli isolates and feeding pigs diets supplemented with antibiotics, as compared to pigs not given antibiotics in their feeds. Likewise, Bradbury and Munroe (1985) raised the concern that a relationship might be present between antibiotic use in feeds and in the development and presence of antibiotic resistance among bacteria of food-producing animals. This is of public health relevance as antibiotic resistance among bacteria from foods of animal origin may have an impact on antibiotic–associated bacterial infection of humans (Kabir, 2010). Observed multi-resistance among C. jejuni isolates adds to the evidence on emergence of resistant bacteria in animals following the administration of antibiotics, either prophylactically or therapeutically. For instance, in the survey conducted by Evangelista (1994), all of the participating poultry farms in the survey indicated using antibacterials in their operations. Use of antibiotics may have created a heavy selective pressure causing microorganisms, like C. jejuni, to undergo needed changes to adapt to the new antibiotic environment (Rowe-Magnus and Mazel, 2002; Alfredson and Korolik, 2007; Kabir, 2010). Using Chi-square test, an analysis was conducted to determine if a relationship does exist between the type of antibiotic residue (Baldrias et al, 2008) and percent antibiotic resistance of the C. jejuni isolates (Baldrias and Raymundo, 2009). Pearson correlation (X2 values in Table 3) showed that a statistically significant relationship (p < .05) exists between the occurrence of penicillin type of residues in chickens sampled with the existence of antibiotic resistance of C. jejuni isolates, particularly for cephalothin (a beta-lactam antibiotic) with a P-value = 0.02 and for erythromycin (a macrolide) with a P-value = 0.028.



Similarly, a significant relationship was also present between the detection of tetracycline type of antibiotic residue and with resistance to erythromycin of C. jejuni isolates (P-value = .001). Likewise, for the aminoglycoside residue with erythromycin (P-value = .030). The P-value or probability values are herein specified to provide a better appreciation on the observation of associations between antibiotic residue and resistance of C. jejuni isolates, in the light of the 0.05 level of significance cut-off. This provides an objective measure of the strength of evidence, such that if the P-value is smaller than the level of significance, then the result is highly significant (Ott and Mendenhall, 1990; Noether, 1991). When reporting results of a statistical investigation (rather than stating whether or not a given hypothesis is rejected), it is currently much preferred to report the actual P-value associated with the experimental evidence. This makes the report more informative so that the reader can decide whether to accept or reject the hypothesis being tested. For trimethoprim, no statistics can be computed as all the isolates showed 100% resistance to this antibiotic. A 100% level of resistance is, without a doubt, biologically significant. The general guideline observed by the Philippine Generics law of 1988 on antibiotic supplementation of animal feeds follows the recommendation of the Swann Report of 1969 that antibiotics used to treat infections in humans are not to be used as animal-food additives. This is based on the concept that structurally similar drugs would have the same target of action and is, therefore, subject to cross-resistance within the same class of related antibiotics. For instance, the initial expectation was that penicillin residue will be related to the occurrence of ampicillin resistance; or aminoglycoside residue with resistance to aminoglycoside antibiotics, like streptomycin, kanamycin or gentamicin. However, the relationship revealed between the occurrence of antibacterial residues in the liver samples (Baldrias et al, 2008) and multi-resistance of C. jejuni isolates (Baldrias and Raymundo, 2009) to chemically unrelated antibiotics raises a very important concern of cross-resistance that antibiotics can confer to other classes of antibiotics. As presented in Table 3, statistically significant relationships were established between detection of penicillin type residue with resistance to cephalothin (a cephalosporin) and erythromycin (a macrolide); between tetracycline type residue with erythromycin resistance, and between aminoglycoside residue and erythromycin resistance. The relevance of these observed relationships might be related to the example cited by Courvalin (2001) on apramycin, an antibiotic used exclusively in animals because it had an unusual structure. It was not expected to be recognized by aminoglycoside-modifying enzymes in bacteria. However, enterobacteria of animal origin became resistant to apramycin by synthesis of a plasmid-mediated 3-N aminoglycoside acetyltransferase type IV, which confers resistance to gentamicin (Chalus-Dancia et al., 1986). Following spread in animal strains, the plasmid was later found in clinical isolates from hospitalized patients (Chalus-Dancia et al.1991). As such, use of antibacterials in food-producing animals may, in turn, result to spread of resistant bacteria from animals to humans. Spread of resistance may involve transfer of



antibiotic-resistant genes from bacteria in animals to human pathogens, and even strains of resistant bacteria that are zoonotic that can cause disease in man (Alfredson and Korolick, 2007). The occurrence of multi-resistant pathogens is currently creating a dilemma in the treatment of infections, not only in animals, but also in human medicine.

Table 3. Pearson Chi-square values for type of antibiotic residue detected in relation to percentage of resistance to antibiotic tested

ANTIBIOTIC TESTED

% RESISTANCE of

C. jejuni ISOLATES

X2 VALUES FOR TYPE OF ANTIBIOTIC RESIDUE DETECTED

Penicillin Tetracy-

clines Sulfas

Aminogly-cosides

Macrolides

Ampicillin 83.3 .166 .584 .584 .584 .640

Cephalothin 91.7 .020 * .140 .460 .140 .753

Chloramphenicol 75.0 .371 .157 .157 .157 .546

Ciprofloxacin 91.7 .640 .460 .140 .460 .753

Colistin sulphate 91.7 .640 .460 .460 .460 .753

Erythromycin 33.3 .028* .001* .083 .030 * .140

Gentamicin 91.7 .640 .460 .460 .460 .753

Nalidixic Acid 91.7 .640 .460 .140 .460 .753

Norfloxacin 75.0 .371 1.00 1.00 .157 .546

Spectinomycin 66.7 .273 .083 .386 .083 .460

Suphamethazine 91.7 .640 .460 .460 .460 .753

Streptomycin 91.7 .640 .140 .460 .460 .753

Tetracycline 91.7 .640 .460 .140 .460 .753

Trimethoprim** 100

Legend: * Significant relationship exists at p < .05 level of significance between type of antibiotic residue and percent antibiotic resistance of the Campylobacter jejuni isolates **No statistic computed because trimethoprim is a constant with all isolates showing resistance.

Significant findings gained from occurrence of multi-resistance among the C. jejuni isolates (Baldrias and Raymundo, 2009) and their relationship with detection of antibiotic residues (Baldrias et al., 2008), indicating antibiotic exposure of the sampled chicken population, provides proof that development of multi-resistance among the isolates may be a response to selective pressure or stresses created by exposure to antimicrobials. Thus, this study shows concrete evidence of a definite association between the development of antimicrobial resistance and usage of antibiotics in poultry production.

Acknowledgements

Dr. Loinda R. Baldrias would like to express her deepest gratitude to the Department of Agriculture Bureau of Agricultural Research (DA-BAR), the Philippine Council of Health Research and Development (PCHRD), the Philippine Council of Advanced Research in



Science and Technology Development (PCASTRD) and the Commission on Higher Education (CHED) for providing the funds needed for the research.

References

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Baldrias LR, Gatchalian-Yee M and Raymundo AK. 2008. Detection of antibiotic residues in dressed chicken from commercial and backyard producers using Four Plate Test. Philippine Journal of Veterinary Medicine 43: 39-48.

Baldrias LR and Raymundo AK. 2009. Antimicrobial resistance profile of local Campylobacter jejuni recovered from ceca of dressed chickens of commercial and backyard raisers in Laguna, Philippines. Philippine Journal of Veterinary Medicine 46: 87-94.

Bradbury WC and Munroe DLG. 1985. Occurrence of plasmids and antibiotic resistance among Campylobacter jejuni and Campylobacter coli isolated from healthy and diarrheic Animals. Journal of Clinical Microbiology. 22(3): 339-346.

Carter GR and Cole JR. 1990. Diagnostic Procedures in Veterinary Bacteriology and Mycology. 5th ed. USA. Academic Press, Inc. pp. 541-544; 549-559.

Chaslus-Dancla E, Martel J L, Carlier C, Lafont JL and Courvalin P. 1986. Emergence of 3-N-acetyltransferase IV in Escherichia coli and Salmonella typhimurium isolated from animals in France. Antimicrobial Agents Chemotherapy 29:239-43.

Chaslus-Dancla E, Pohl P, Meurisse M, Marin M and Lafont JL. 1991. High genetic homology between plasmids of human and animal origins conferring resistance to the aminoglycosides gentamicin and apramycin. Antimicrobial Agents Chemotherapy 35:590-3.

Cohen, M.L. 1992. Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 257: 1050-1078.

Courvalin P. 2001. The antibiotic food-chain gang. Emerging Infectious Diseases. 7(3): 2001.

Engberg J, Aarestruip FM, Taylor DE, Gerner-Smidt P and Nachamkin I. 2001. Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance



mechanisms and trends in human isolates. Emerging Infectious Diseases 7(1): 24-34.

Evangelista EF. 1994. Assessment of drug use in selected poultry farms in the Philippines and a preparation of a drug formulary for poultry. Undergraduate thesis. University of the Philippines Los Baños, Laguna, Philippines.

Gibreel A and Skold O. 2000. An integron cassette carrying dfr1 with 90-bp repeat sequences located on the chromosome of trimethoprim-resistant isolates of Campylobacter jejuni. Microbial Drug Resistance 6(2): 91-98.

Gibreel A, Sjogren E, Kaijser B, Wretlind B and Skold O. 1998. Rapid emergence of high-level resistance to quinolones in Campylobacter jejuni associated with mutational changes in gyrA and parC. Antimicrobial Agents Chemotherapy 42: 3276-3278.

Hernandez MAS and Raymundo AK. 1988. Incidence and conjugal transfer of antibiotic resistance in Escherichia coli from pig feces. Philippine Agriculturist 71(4): 403-408.

Kabir SML. 2010. Avian Colibacillosis and Salmonellosis: A Closer Look at Epidemiology, Pathogenesis, Diagnosis, Control and Public Health Concerns. Int. J. Environ. Res. Public Health 79:89-114.

Khachatourians GG. 1998. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria. Canadian Medical Association Journal 159 (9): 1129-1136.

Lucey B, Crowley D, Moloney P, Cryan B, Daly M, O’Halloran F, Threlfall EJ and Fanning S. 2000. Integronlike structures in Campylobacter spp. of human and animal origin. Emerging Infectious Diseases J. 6 (1): 1-8.

Magistrado PA, Garcia MM and Raymundo AK. 2001. Isolation and polymerase chain reaction-based detection of Campylobacter jejuni and Campylobacter coli from poultry in the Philippines. International J of Food Microbiology 70: 197-206.

National Committee for Clinical Laboratory Standards (NCCLS). 1981. Performance standards for antimicrobial disc susceptibility tests. Approved standard. National Committee for Clinical Laboratory Standards, Villanova, Pa. Vol. 1, p. 141-156.

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Ng LK, Kingombe CIB, Yan W, Taylor DE, Hiratsuka K, Malik N and Garcia MM. 1997. Specific detection and confirmation of Campylobacter jejuni by DNA hybridization and PCR. Applied and Environmental Microbiology 63(11): 4558-4563.



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Vancomycin Resistant Enterococci – Thailand Experience

Pennapa Matayompong

Department of Livestock Development, Ministry of Agriculture and Cooperatives

Introduction

Enterococci, the normal flora of the gastrointestinal tract of animals and humans, have over the years become the organisms of public health concern. Although they are not considered as primary pathogens, they are worldwide common cause of nosocomial infections such as urinary tract infections, wound infections and bacteraemia. This is due to their ability to acquire high-level resistance to antimicrobial agents, in particular vancomycin which is the last-line antibiotic for resistant infections. Vancomycin is active against most Gram positive bacteria. It has been critically important for treatment of patients with severe infections with multi-drug resistant enterococci and methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin-resistant enterococci (VRE) are several combinations of bacterial strains of the genus Enterococcus that have developed resistance to antibiotic vancomycin. To become vancomycin-resistant, vancomycin-sensitive enterococci obtain DNA in the form of plasmids or transposons which encode genes that confer vancomycin resistance. High-level vancomycin resistant enterococci have been documented for Enterococcus faecalis and Enterococcus faecium clinical isolates. E. faecalis and E. faecium are the most common in the human gastrointestinal tract and E. faecium in production animals. Detection of VRE is not only from hospital sources but also from food animals, environment and waste water. In the past, avoparcin was used as an animal growth promoter, particularly in broilers and pigs. Both avoparcin and vancomycin are the glycopeptide antimicrobial agents with similar chemical structure. Several studies indicated that the use of avoparcin is associated with a high prevalence of VRE in feces of exposed animals and in meat products; and the humans coming into contact with the animals (farm workers, butchers) are also shown to carry VRE of identical clones. The emergence and dissemination of VRE in food animals and the food supply caused many countries to ban the use of avoparcin in animal feed. A link between avoparcin use and the prevalence of VRE in Europe has been demonstrated in which a decreased VRE colonization rate in healthy Europeans was found after the avoparcin ban in 1997. Thailand experience on VRE is that the export of Thai chicken meat to Japan in July 1998 was severely disrupted following the outbreaks of VRE in Japanese hospitalized patients.



Japan is the main importing country of frozen chicken meat from Thailand. A connection between Japanese outbreaks and imported chicken meat was suggested. The Japanese researchers with the support of Japanese Ministry of Health, Labour and Welfare conducted an investigation of VRE in imported and domestic chicken meat. The results showed that while VRE had never been isolated from domestic chicken meat, a high frequency of VRE were isolated from imported chicken meat which were about 20% and 30-50% from Thailand and France, respectively, where avoparcin was used in animal feed. The VRE strains isolated from French chicken meat exhibited high-level vancomycin and teicoplanin resistance and the VRE strains isolated from Thai chicken meat exhibited high-level vancomycin resistance and relatively low-level teicoplanin resistance. The VRE strains isolated from three patients at the two hospitals showed the same characteristics as the VRE strains from the Thai chicken meat. The research results were suddenly published by the Japanese media which resulting in a tremendous scare of Japanese consumers. The Thai chicken meat and its products were refused from Japanese market and the importation was suspended. The Thai government took immediate action by banning the use of avoparcin in animal feed and prohibiting import of avoparcin mixed feed on 15 July 1998. The measures for VRE control and surveillance have been established by the Department of Livestock Development (DLD) for the whole chain of poultry meat production. These measures have been implemented until the present day. The Japanese have been satisfied with the measures applied and resumed import of frozen chicken meat and its products from Thailand. Since 1998, the VRE surveillance in Thailand has been conducted in breeder farms, hatcheries, broiler farms, poultry slaughterhouses and poultry meat product processing plants. The following is the sampling plan for the VRE tests.

Breeder farms: samples of feces (60 piles/house, pooled into 1 sample, sampling 10% of poultry houses in a farm), drinking water (1 sample/farm), feed (1 sample/farm) and water for cleansing (1 sample/farm) – samples are collected when birds are at the age of laying eggs

Hatcheries: samples of meconium from day old chicks (10 chicks/egg incubator, pooled into 1 sample, sampling 10% of total incubators in a hatchery), swabs of hatching trays after cleaning and disinfection (swabs of 10 trays pooled into 1 sample per hatchery)

Broiler farms: samples of feces (60 piles/house, pooled into 1 sample, sampling 10% of poultry houses in a farm), drinking water (1 sample/farm), feed (1 sample/farm), water for cleansing (1 sample/farm) – samples are collected when birds are over 30 days old

Poultry slaughterhouses: samples of cloacal swabs (swabs of 60 birds/farm pooled into 1 sample, 5 farms/plant), carcass swabs after evisceration but before inside-outside washing (swabs of 5 carcasses/shift pooled into 1 sample), finished product of fresh chicken meat (1 sample/day)

Poultry meat product processing plants: samples of poultry meat products (5 samples pooled into 1 sample)



All samples are tested for VRE at the Veterinary Public Health Laboratory of the Department of Livestock Development. Antimicrobial susceptibility test is conducted to determine the minimal inhibition concentration (MIC) of enterococci to vancomycin and teicoplanin using the Agar Dilution Technique following the National Committee for Clinical Laboratory Standards (NCCLS, 1997 and 2000). Table 1 and Table 2 show the results of VRE tests in poultry meat production chain in Thailand during 2001-2004 and during 2005-2012, respectively.

Table 1. Results of VRE tests in poultry meat production chain in Thailand, 2001-2004

Source 2001 2002 2003 2004

Breeder farms No. of tested farms

306

339

373

363

No. of VRE contaminated farms (%)

20 (6.5%)

5 (1.5%)

1 (0.3%)

12 (3.3%)

Hatcheries No. of tested hatcheries

250

238

291

251

No. of VRE contaminated hatcheries (%)

17 (6.8%)

8 (3.4%)

0 4 (1.6%)

Broiler farms No. of tested farms

815

780

875

678


48 (5.9%)

22 (2.8%)

13 (1.5%)

10 (1.5%)

Feed (breeder & broiler farms) No. of tested samples

1,179

1,187

1,236

1,130

No. of VRE contaminated samples (%)

32 (2.7%)

9 (0.8%)

4 (0.3%)

11 (1%)

Water for cleansing (breeder & broiler farms) No. of tested samples

1,696

1,749

1,918

1,656 No. of VRE contaminated samples (%)

32 (1.9%)

3 (0.2%)

1 (0.1%)

4 (0.2%)

Cloacal swabs No. of tested farms

660

912

858

794


70 (10.6%)

30 (3.3%)

22 (2.6%)

15 (1.9%)

Chicken meat No. of tested samples

1,054

1,208

1,211

1,070


68 (6.5%)

12 (1%)

3 (0.3%)

8 (0.8%)

Chicken meat products No. of tested samples

413

469

585

499


0 2 (0.4%)

1 (0.2%)

3 (0.6%)



Table 2. Results of VRE tests in poultry meat production chain in Thailand, 2005-2012

Year No. of tested samples No. of VRE contaminated samples

2005 7,012 48 (0.7%)

2006 6,227 17 (0.3%)

2007 3,196 0

2008 3,426 0

2009 3,789 0

2010 3,919 0

2011 3,033 3 (0.1%)

2012 (Jan-Sep) 1,898 0

After the prohibition of avoparcin use in feed in 1998, the occurrence of VRE decreased remarkably. Since 2007, no VRE contamination has been found in the samples collected from various sources of poultry meat production chain except in 2011 in which 3 samples of fresh chicken meat collected from a slaughterhouse were positive for VRE. The predominant VRE (MIC ≥ 64 µg/ml) found during 1998-2006 were E. faecalis and E. faecium, particularly in the samples related to live birds. However, the VRE found in fresh chicken meat in 2011 were E. durans with MIC more than 64 µg/ml. As there is a potential risk of VRE resistant genes transfer from food animals to humans and from enterococci to other Gram-positive bacteria including Staphylococcus aureus, the continuation of VRE surveillance in the whole poultry meat production chain is still needed although the current VRE prevalence is very low. This is to ensure the safety of poultry meat from Thai poultry industry supplying to both domestic and export markets. Additionally, during August 2005-July 2006, Chalermchaikit et al. had studied the prevalence of VRE in environment, animal feeds and raw meats in Thailand. Samples of ark shell, chicken meat, pork, beef, pet food, chicken feed and pig feed sold in local markets were collected for VRE tests. The results revealed that VRE (MIC ≥ 8 µg/ml) were found in ark shell samples 6.6%, chicken meat 5%, pork 3%, beef 13%, dog feed 0.93% and chicken feed 0.89%. None of VRE was found in cat feed and pig feed samples. The VRE identified from ark shell samples were E. faecium (60%), E. faecalis (20%), E. gallinarum (12%) and E. casseliflavus (8%); from chicken meat samples were E. gallinarum (60%) and E. faecalis (40%); from pork samples were E. gallinarum (66.7%) and E. faecium (33.3%); from beef samples were E. gallinarum (53.8%), E. faecalis (38.5%) and E. faecium (7.7%); from dog feed and chicken feed samples were E. gallinarum. The pattern of glycopeptide (vancomycin and teicoplanin) resistance of most VRE isolates indicated that they likely contained the resistant genes of either vanB or vanC except only one isolate from chicken meat sample that vanA gene would exist. The significance is that vanA acquired high resistance to both vancomycin and



teicoplanin, vanB acquired moderate level resistance to vancomycin and sensitive to teicoplanin, and vanC acquired only partly resistance to vancomycin and sensitive to teicoplanin. From this study, the results could give a preliminary conclusion that VRE is not a public health threat in Thailand. The VRE found in ark shell reflected that the contamination of VRE in environment could be derived from communities, hospitals, pets and/or animal farms. Therefore, the prudent use of antimicrobial in humans and animal industries and the routine surveillance of antimicrobial-resistant pathogenic bacteria have to be continued.

Acknowledgements

Special thanks is given to the Veterinary Public Health Laboratory of the Department of Livestock Development for providing the data.

References

Chalermchaikit, T, K. Korthammarit, S. Srisagna, K. Siriwattanachai. 2008. Thai Feed Mill Association Journal. 119:50.

Fisher, K., and C. Phillips. 2009. The ecology, epidemiology and virulence of Enterococcus. Microbiology. 155:1749.

Hammerum, A. M., C. H. Lester, and O. E. Heuer. 2010. Antimicrobial-resistant enterococci in animals and meat: a human health hazard? Foodborne Pathog Dis. 10:1137.

Kanarat, S. 2004. Vancomycin resistant enterococci and detection and identification techniques.

Nilsson, O. 2012. Vancomycin resistant enterococci in farm animals – occurrence and importance. Infection Ecology and Epidemiology. 2:16959.

Ozawa, Y., K. Tanimoto, T. Nomura, M. Yoshinaga, Y. Arakawa, and Y. Ike. 2002. Vancomycin-resistant enterococci in humans and imported chickens in Japan. Appl. Environ. Microbiol. 68:6457.



Antimicrobial Resistance at the Human-Animal Interface in Vietnam

Nguyen Vinh Trung1,2, Juan J Carrique-Mas1, Ngo Thi Hoa1, Thai Quoc Hieu3, Nguyen

Thi Nhu Mai4 , Ha Thanh Tuyen1, Juliet Bryant1, James Campbell1, Anita Hardon5, Jaap Wagenaar6, Constance Schultsz1,2

1Oxford University Clinical Research Unit, Ho Chi Minh City – Vietnam,

2Academic Medical Center, University of

Amsterdam – The Netherlands, 3 Sub-Department of Animal Health, Tien Giang – Vietnam,

4 Preventive Medicine

Center, Tien Giang – Vietnam,5Faculty of Social and Behavioral Sciences, University of Amsterdam – The Netherlands,

6Faculty of Veterinary Medicine, Utrecht University - The Netherlands

Introduction

Antimicrobial resistance (AMR) is a growing problem in human as well as veterinary medicine. The use of antimicrobial agents, both in animals and humans, is a major contributing factor in the selection and dissemination of resistant bacteria. Food-producing animals can act as a reservoir of resistant bacteria, and animal food products are a major cause of food-borne infections in humans (Collignon and Powers, 2009). In addition, resistant organisms may spread from animals to humans either by direct contact or indirectly, through food, water, and the use of animal waste as fertilizer (Marshall and Levy, 2011). Chickens are one of the most suspected sources of antimicrobial resistant bacteria, such as Escherichia coli and Salmonella (Boogard 2001; Johnson and Scannes 2007). In Vietnam it is estimated that 8.3 million households (about 33% of the population) are involved in poultry farming, with chickens being the most common source of poultry meat (Stéphanie 2008). However there is little information on the use of antimicrobial agents in animal production and the prevalence of antimicrobial resistance in back-yard and medium size of chicken production, which makes up most of poultry production in the country. Moreover, knowledge regarding associations between use of antimicrobial agents in animal husbandry and the occurrence of resistance in both chicken and humans is limited. The VIBRE project integrates the study of antimicrobial resistance in animals and humans by investigating the prevalence of antimicrobial resistant E. coli and non-typhoidal Salmonella isolated from chickens and humans (farmers and non-farmers). In addition, this study aims at estimating the relative contribution of antimicrobial drug usage to AMR in animal back yard farming and in the human population, by detailed comparisons of prevalences and genetic relatedness of AMR determinants in animals and humans in the same geographical region.



Materials and methods

Study site and population

This study is carried out in the province of Tien Giang, located in the Mekong delta region of Vietnam. Three districts were selected since they contain >60% of the medium size farms in this province. The study population is 204 farms/households that keep chickens, equally divided into two categories: small-scale (10-200 chickens) and medium-scale (200-2,000 chickens). In addition, two sets of matched individuals are sampled to represent rural (n=204) and urban (n=102) populations not involved in poultry farming in Tien Giang. This will allow the comparison between antimicrobial resistance between chickens, chicken farmers and non-farming individuals in the same province. Participant recruitment and sample collection

Small-scale and medium-scale farms were selected randomly. Farm were visited and included by the Sub-Department of Animal Health (SDAH) in Tien Giang. Boot swabs and hand swabs were used to collect chicken faeces. Thus, the farm was the sampling unit instead of individual chicken. The person with primary responsibility for the selected farm or household was identified and this person was the respondent in the survey. Rural and urban non-poultry keeping individuals were matched by age and gender to the population of farmers sampled, and were recruited by Preventive Medicine Center in Tien Giang Province. Fecal samples were collected by trained study personnel by using rectal swabs. Written informed consent was obtained from all participants. The study was approved by the Oxford University Tropical Research Ethical Committee and the review committees of Department of Agriculture and Rural Development and Department of Health in Tien Giang. Antimicrobial usage survey

Antimicrobial usage in the participant household as well as in chicken farming was characterised through interviews using structured questionnaires. The interviews were conducted by trained study personnel. Interviewers asked farmers to give them insight in the antimicrobials commonly used in their household through inventories of medicine cabinets, including both antimicrobials for animal and for human use, as it is assumed that commonly used medicines are kept in medicine storages or cabinets. AMR E. coli isolation

Fixed volumes of faecal suspensions were inoculated on MacConkey plates and MacConkey plates supplemented with ceftazidime (2 mg/L), nalidixic acid (16 mg/L), or gentamicin (8 mg/L), and incubated at 37°C overnight. From each plate, suspected colonies were counted and a random selection of 5 (non-selective agar plate) and 2



(selective agar-plates) were sub-cultured and identified using a short biochemical set. Strains of E. coli were saved and tested for AMR. Salmonella isolation

After pre-enrichment in buffered peptone water at 370C for 18 hours, 100µL of pre-enrichment broth was inoculated onto modified semi-solid Rappaport-Vassiliadis agar and overnight incubated at 420C. Then these broths were sub-cultured on Rambach and XLD agar plates and incubated at 37°C overnight. Suspected colonies of different morphologies were identified using a short biochemical sets. Identity was confirmed using polyvalent antisera. One colony of each morphology per sample was saved for further analysis. Antimicrobial susceptibility testing

For the determination of antimicrobial susceptibility, the disk diffusion methods was performed according to the Clinical and Laboratory Standard Institute (CLSI) guidelines. The following antimicrobials were tested: ampicillin (10µg), ceftriaxone (30µg), ceftazidime (30µg), chloramphenicol (30µg), ciprofloxacin (5µg), ciprofloxacin (1µg), trimethoprim-sulphamethoxazole (10µg), gentamicin (10µg), amikacin (30µg), tetracycline (30µg), meropenem (10µg). Potential production of extended spectrum betalactamases (ESBL), as indicated by resistance to ceftriaxone and/or ceftazidime, and/or by an inhibitory effect of clavulanic acid, was confirmed using a double disc diffusion test. Resistance was defined according to breakpoints as defined by CLSI (M100-S21, 2011). Identical methods were used for Salmonella and E. coli isolates.

Preliminary results and discussion

Sampling for the VIBRE project is ongoing, and due to be completed in April 2013. By September 2012, about half of the target study population was sampled (comprising 100 chicken farms – equally divided into two categories, 92 rural individuals and 46 urban individuals). These data forms the basis for this preliminary report. As shown in the baseline characteristics of the first 100 farms visited, a very high proportion of farms of both types used antimicrobials and commercial feed as well as practiced disinfection during production (Table 1). In 18% of small-scale farms chickens were able to move outside of the farm and in only 2% chicken were fully confined in house or pen.



Table 1. Baseline characteristics of 100 farms included in the VIBRE project

Antimicrobial usage in chicken farms and family households

Of the 100 chicken farms observed, sixty-four (64%), comprising 34 (68%) of the medium-scale farms and 30 (60%) of the small-scale farms, antimicrobials used for chicken, were present in the medicine cabinet (Table 2). In 238 households, sixty-three (26.5%) had antimicrobials in their family medicine cabinet – including 24 (24%) of the farmer households and 24 (16%) and 15 (32%) of the rural and urban households, respectively (Table 3).

Medium-size farms (N=50)

Small-size farms (N=50)

Median (IQR) age of farm manager (years) 42 (37 – 49) 52 (43 – 56) Number of farms managed by male 34 (68%) 26 (52%) Highest level of education attained by farm manager

1. No schooling 0 1 (2%) 2. Primary school 9 (18%) 19 (38%) 3. Secondary school 31 (62%) 17 (34%) 4. High school 9 (18%) 13 (26%) 5. Post high-school degree 1 (2%) 0

Median (IQR) number of years of experience in chicken farming 5 (3 – 10.75) 10 (4 – 18) Production type

1. Meat 14 (28%) 34 (68%) 2. Eggs 36 (72%) 0 3. Dual purpose 0 16 (32%)

Median (IQR) number of chickens 1500 (1000 – 1988) 80 (60 – 120) No. of farms with chickens confined in pen/house 24 hours 46 (92%) 1 (2%) No. of farms where chickens have access outside (of the farm) 0 9 (18%) No. of farms that followed vaccination

1. HPAI 49 (98%) 48 (96%) 2. Newcastle 50 (100%) 44 (88%) 3. Fowl Cholera 35 (70%) 26 (52%)

No. of farms with other animal species 1. Duck 12 (24%) 27 (54%) 2. Pigs 15 (30%) 28 (56%) 3. Cattle/buffalo 8 (16%) 10 (20%) 4. Dog 36 (72%) 47 (94%) 5. Fish 24 (48%) 30 (60%)

No. of farms with change of boot/shoes when accessing chicken houses 41 (82%) 26 (52%) No. of farms that had foot bath/foot dip 36 (72%) 24 (48%) Type of cleaning and disinfection practice

1. During production 48 (96%) 40 (80%) 2. Terminal 1 (2%) 10 (20%) 3. Both (1&2) 1 (2%) 0

No. of farm that used antibiotics in the current flock(s) 34 (68%) 30 (60%) No. of farm that used disinfectants in the current flock(s) 50 (100%) 47 (94%) No. of farm that used commercial feed in the current flock(s) 49 (98%) 38 (76%) Source of water for chickens

1. Municipal supply 38 (76%) 40 (80%) 2. Well 17 (34%) 16 (32%) 3. River 0 2 (4%)



In chicken farming, tetracyclines, (fluoro)quinolones, polypeptides and penicillins groups were the most commonly used for the prophylactic and therapeutic purposes (Table 2), while cephalosporins, macrolides, aminoglycosides and (fluoro)quinolones were mainly used in humans (Table 3). Table 2. Number (percentage) of chicken farms where antimicrobials were present in

the medicine cabinet

Table 3. Number (percentage) of households where antimicrobials were present in the

family medicine cabinet

Prevalence of resistant E. coli isolates

There was a very high prevalence of resistant E. coli in both chicken and humans (Table 4). The prevalence of gentamicin resistance and nalidixic acid resistance was higher in chicken farms than in humans, whereas 3rd generation cephalosporins resistance was detected mainly in humans – especially in the rural control group. This is likely to be associated with the common usage of cephalosporins in human population.

Antimicrobial groups No. of medium farms (N=34)

No. of small farms (N=30)

Total No. of farms (N=64)

Macrolides 13 (38%) 4 (13%) 17 (27%)

Penicillins 10 (29%) 8 (27%) 18 (28%)

Phenicols 6 (18%) 1 (3%) 7 (11%)

Quinolones 12 (35%) 9 (30%) 21 (33%)

Tetracyclines 13 (38%) 13 (43%) 26 (41%)

Aminoglycosides 2 (6%) 4 (13%) 6 (9%)

Sulfonamides 3 (9%) - 3 (5%)

Polypeptides 8 (24%) 11 (37%) 19 (30%)

Lincosamides 2 (6%) - 2 (3%)

Antimicrobial groups No. of farmer households

(N=24)

No. of rural households

(N=24)

No. of urban households

(N=15)

Total No. of households

(N=63)

Aminopenicillins 7 (29%) 5 (21%) 3 (20%) 15 (24%)

Cephalosporins 10 (42%) 20 (83%) 6 (40%) 36 (57%)

Lincosamides 1 (4%) - 1 (7%) 2 (3%)

Macrolides 5 (21%) 6 (25%) 4 (27%) 15 (24%)

Quinolones 1 (4%) 2 (8%) 1 (7%) 4 (6%)

Sulfonamides - - 1 (7%) 1 (2%)

Tetracycline - 1 (4%) 1 (7%) 2 (3%)



Table 4. Prevalence of resistant E. coli

Antimicrobial drug tested

No. of study subjects with resistant E. coli (%)

Medium-scale farms (N=50)

Small-scale farms (N=50)

Medium-scale farmers

(N=50)

Small-scale farmers (N=50)

Rural individuals

(N=92)

Urban individuals

(N=46)

3rd

generation Cephalosporins

6 (12,0%) 13 (26,0%) 14 (28,0%) 20 (40,0%) 45 (48,9%) 20 (43,5%)

Gentamicin 41 (82,0%) 47 (94,0%) 41 (82,0%) 35 (70,0%) 60 (65,2%) 29 (63,0%)

Nalidixic acid 28 (56,0%) 23 (46,0%) 18 (36,0%) 17 (34,0%) 41 (44,6%) 21 (45,7%)

ESBL confirmed

3 (6,0%) 7 (14,0%) 12 (24,0%) 13 (26,0%) 39 (42,4%) 16 (34,8%)

Contribution of antimicrobial resistance phenotypes to overall population of E. coli

Overall, 1471 E. coli isolates were selected randomly from the non-selective plates. The susceptibility of these isolates to 12 antimicrobials is shown in Table 5. Multi- drug resistance - defined as resistance to at least 3 different classes of antimicrobials - was observed in all types of study subjects, and this proportion was higher in chickens (80%) compared with humans (50%). The results demonstrate the high level of resistance to antimicrobials in E. coli with the exception of a low frequency of resistance to amikacin and no resistance to meropenem. E. coli isolates from chickens had a higher rate of resistance to tetracycline, ampicillin, trimethoprim-sulphamethoxazole, chloramphenicol and ciprofloxacin compared to isolates from humans; whereas a higher frequency of resistance to ceftriaxone was notable in humans. The prevalence of multi-drug resistant E. coli in our study is lower than those from Van et al. (2008) who also conducted an investigation of antimicrobial resistant E. coli from chicken faeces in Vietnam in 2008 and concluded that about 95% of the isolates was multi-drug resistant. This difference is most likely primarily due to low number of isolates studied (20) in the study from Van et al. Moreover, sixty-nine E. coli isolates comprising 67 isolates from humans and 2 isolates from chickens produced extended spectrum beta-lactamase (ESBL) and interestingly 42 of those isolates were among the human non-farming rural group. The common usage of cephalosporins is probably an explanation for the highest rate (9.8%) of the ESBL producing E. coli isolates in this group.



Table 5. Frequency of resistant E. coli isolates in each of the study groups

Antimicrobial No. of resistant E. coli isolates (%)

Medium-scale farms (N=206)

Small-scale farms (N=220)

C 136 (66.0%) 134 (60.9%) CAZ 7 (3.4%) 4 (1.2%) AMC 6 (2.9%) 6 (2.7%) CRO 5 (2.4%) 1 (0.5%)

MEM 0 0 CIP1 103 (50.0%) 44 (20%) CIP5 63 (30.6%) 24 (10.9%) TE 198 (96.1%) 203 (92.3%)

SXT 164 (79.6%) 143 (65.0%) AK 2 (1.0%) 3 (1.4%) CN 47 (22.8%) 34 (15.5%)

AMP 163 (79.1%) 155 (70.5%) Resistance to ≥ 1 antibiotic 202 (98.1%) 207 (94.1%)

Multi-drug resistance* 164 (79.6%) 160 (72.7%) ESBL positive 1 (0.5%) 1 (0.5%)

*Resistance to at least 3 different classes of antimicrobials

C: chloramphenicol (30µg), CAZ: ceftazidime (30µg), AMC: amoxicilin/clavulanic acid (30 µg), CRO: ceftriaxone (30µg), MEM: meropenem (10µg), CIP1: ciprofloxacin (1µg), CIP5: ciprofloxacin (5µg), TE: tetracycline(30µg), SXT: trimethoprim-sulphamethoxazole (10µg), AK: amikacin (30µg), CN: gentamicin (10µg), AMP: ampicillin (10µg)

Table 5. Frequency of resistant E. coli isolates in each of the study groups (cont.)

Antimicrobial

No. of resistant E. coli isolates (%) Medium-scale

farmers (N=215)

Small-scale farmers (N=228)

Rural individuals

(N=427)

Urban individuals

N=175

C 88 (40.9%) 68 (29.8%) 125 (29.3%) 56 (32.0%) CAZ 2 (0.9%) 9 (3.9%) 20 (4.7%) 1 (0.6%) AMC 4 (1.9%) 11 (4.8%) 20 (4.7%) 6 (3.4%) CRO 6 (2.8%) 15 (6.6%) 51 (11.9%) 13 (7.4%)

MEM 0 0 0 0 CIP1 44 (20.5%) 55 (24.1%) 82 (19.2%) 29 (16.6%) CIP5 25 (11.6%) 41 (18.0%) 67 (15.7%) 19 (10.9%) TE 154 (71.6%) 161 (70.6%) 302 (70.7%) 104 (59.4%)

SXT 107 (49.8%) 112 (49.1%) 228 (53.4%) 81 (46.3%) AK 3 (1.4%) 2 (0.9%) 0 0 CN 22 (10.2%) 26 (11.4%) 48 (11.2%) 25 (14.3%)

AMP 127 (59.1%) 125 (54.8%) 219 (51.3%) 81 (46.3%) Resistance to ≥ 1 antibiotic 176 (81.9%) 187 (82.0%) 335 (78.5%) 132 (75.4%)

Multi-drug resistance* 107 (49.8%) 116 (50.9%) 198 (46.4%) 83 (47.4%) ESBL positive 6 (2.8%) 7 (3.1%) 42 (9.8%) 12 (6.9%)

*Resistance to at least 3 different classes of antimicrobials

C: chloramphenicol (30µg), CAZ: ceftazidime (30µg), AMC: amoxicilin/clavulanic acid (30 µg), CRO: ceftriaxone (30µg), MEM: meropenem (10µg), CIP1: ciprofloxacin (1µg), CIP5: ciprofloxacin (5µg), TE: tetracycline(30µg), SXT: trimethoprim-sulphamethoxazole (10µg), AK: amikacin (30µg), CN: gentamicin (10µg), AMP: ampicillin (10µg)



Prevalence and antimicrobial resistance phenotypes of non-typhoid Salmonella isolates

The prevalence of non-typhoid Salmonella was 50%, 44%, 5.0%, 5.4% and 2.2% for medium-scale chicken farms, small-scale chicken farms, farmers, rural and urban individuals, respectively (Table 6). The percentage Salmonella positive chicken farms in our study is higher than the 38.5% reported by An et al. (2006). One possible explanation is the difference in sampling method, which was pooled samples from only 5 to 10 chickens on the farm, whereas in our study boot swabs were used in order to make sure a larger number of individual faecal droppings were collected.

Table 6. Prevalence of Salmonella in chicken farm and humans

Subject Total no. of subjects No. of subjects positive

for Salmonella (%) No of Salmonella isolates studied

Medium-scale farms 50 25 (50.0%) 50 Small-scale farms 50 22 (44.0%) 36

Farmers 100 5 (5.0%) 5 Rural individuals 92 5 (5.4%) 5 Urban individuals 46 1 (2.2%) 1

Of the 86 Salmonella isolates from chicken, 35 (40.7%) showed antimicrobial resistance. Resistance was most observed to tetracycline (32.6%) and trimethoprim-sulphamethoxazole (20.9%), followed by chloramphenicol (20.9%), ampicillin (18.6%), gentamicin (2.3%) and ciprofloxacin (1.2%). Multi-drug resistance was also found in 15 (17.4%) of the Salmonella isolates from chicken. In the human populations, the same tendency was observed.

Table 7. Antimicrobial resistance in Salmonella isolates from different study subjects

Antimicrobial

No of resistant Salmonella isolates (%)

Medium-scale farms

(N=50)

Small-scale farms

(N=36)

Farmers

(N=5)

Rural Individuals

(N=5)

Urban individuals

(N=1)

C 11 (22.0%) 7 (19.4%) 1 (20.0%) 1 (20.0%) 0 CAZ 0 0 0 0 0 AMC 0 0 0 0 1 (100.0%) CRO 0 0 0 0 0

MEM 0 0 0 0 0 CIP1 0 1 (2.8%) 0 0 0 CIP5 0 0 0 0 0 TE 16 (32.0%) 12 (33.3%) 2 (40%) 1 (20.0%) 0

SXT 12 (24.0%) 6 (16.7%) 1 (20%) 2 (40.0%) 0 AK 0 0 0 0 0 CN 1 (2.0%) 1 (2.8%) 0 0 0

AMP 10 (20.0%) 6 (16.7%) 1 (20.0%) 0 0 Resistance to ≥ 1 antibiotic 22 (44.0%) 13 (36.1%) 2 (40.0%) 2 (40.0%) 1 (100.0%)

Multi-resistance* 10 (20.0%) 5 (13.9%) 1 (20.0%) 1 (20.0%) 0 *Resistance to at least 3 different classes of antimicrobials



Acknowledgements

This study was funded by WOTRO (The Netherlands organization for Scientific Research) and ZoNMw (The Netherlands Organization for Health Research and Development) (Project number 205100012) and by the Wellcome Trust, UK.

References

An V., et al. (2006). Distribution of Salmonella enterica serovars from humans, livestock and meat in Vietnam and the dominance of Salmonella Typhimurium Phage Type 90. Veterinary Microbiology, 2006. 113:p153-158.

Bogaard, A. (2001). Antimicrobial resistance of faecal E. coli in chicken, chicken farmers and chicken slaughterers. Journal of Antimicrobial Chemotherapy, 2001. 47: p. 763-771.

Collignon, P. and Powers, J. (2009). World Health Organization ranking of antimicrobials according to their importance to human medicine: a critical step for developing risk management strategies for the use of antimicrobials in food production animals. Clinical Infectious Diseases, 2009. 49: p. 132-141.

Johnson, R. and Sannes, R. (2007). Antimicrobial Drug-resistant Escherichia coli from humans and chicken products, Minnesota and Wisconsin, 2002-2004. Emerging Infectious Diseases, 2007. 16(6): p. 838-846.

Marshall, J. and Levy S. (2011). Food animals and antimicrobials: impacts on human health. Clinical Microbiology Review, 2011. 24:p.713-733.

Stéphanie D. (2008). A general review and description of the chicken production in Vietnam. 2008: Agricultural Publishing House.

Van, H., et al. (2008). Safety of raw meat and shellfish in Vietnam: An analysis of Escherichia coli isolations for antimicrobial resistance and virulence genes. International Journal of Food Microbiology, 2008. 124(3): p. 217-223.



Session 4 Approaches to AMR Management



Systems for Monitoring and Integrated Surveillance of Antimicrobial Use in Livestock and AMR in Different Parts

of the World

Dirk U. Pfeiffer

Veterinary Epidemiology & Public Health Group, Royal Veterinary College, University of London

Summary

The inevitable challenge presented by the emergence and spread of antimicrobial resistance requires an integrated global effort. Antimicrobial usage in production and companion animals still plays a limited role, but this is likely to become more important. The mitigation of this threat includes the development of surveillance systems that are more effective than what is currently available. Encouraging developments have occurred in this respect in some higher income countries and regions. But more work is to be done, with some urgency, in particular in dealing with the threat posed by usage in animals (and humans) in low to middle income countries. The design of risk-based surveillance systems needs to be encouraged, informed on sound transdisciplinary risk assessment. Value chains for trade in antimicrobials need to be described. Regional approaches will be important, and in the short to medium term regional sentinel network may have to be developed funded by national and international governmental and non-governmental organisations, recognising the global public good nature of the threat.

Context

There is widespread recognition that the emergence of antimicrobial resistance (AMR) represents a major challenge to humanity for which there currently is no workable solution or on the horizon. It is therefore paramount that strategies are developed that will in the short to medium term extend the time during which current antimicrobials (AM) are effective in humans and animals and to develop alternative approaches to antimicrobial treatment and prevention (Hunter 2012; Anonymous 2012a; Choffnes, Relman, and Mack 2010). The goal of extending effectiveness of currently available AMs will have to be based on rationalising their usage. This will require prudent use of AMs, better informed treatment choices, better compliance amongst patients and animal owners and reduction of antimicrobial use in animals as well as reserving selected AM for human use (Choffnes, Relman, and Mack 2010). In addition, effective surveillance will be required and better disease prevention as well as innovation in terms of control and



prevention (Anonymous 2012a). The World Health Organisation has recognised the strategic priority to apart from dealing with usage in humans to also contain AMR associated with usage of AM in production animals (Aidara-Kane 2012). The World Organisation for Animal Health (OIE) has specified necessary standards for dealing with this challenge from an animal health perspective in Chapters 6.7 to 6.10 of the OIE Terrestrial Animal Health Code (Anonymous 2012b). This paper discusses the role of surveillance in animals for preserving antimicrobial effectiveness, with an emphasis on approaches that will be applicable for low to middle income countries.

General methodological principles

Animal health surveillance aims at generating data to be used for informing activities in relation to disease risk management. The surveillance strategy itself is informed by risk assessment, but it also generates data that will be integrated into risk assessments. A surveillance strategy describes the implementation of a surveillance system that will usually be targeted at a particular disease, and typically the system will comprise of several components. For example, a bovine tuberculosis surveillance system may consist of two main components: On-farm disease surveillance by tuberculin testing of cattle and post-mortem surveillance at abattoirs. Each surveillance system component will be characterised by a particular data source, data collection method and diagnostic tools. Data collection methods can be broadly grouped into early warning (passive or scanning surveillance) and strategic (or active) surveillance. Within each of these two groups there are a wide range of methods as shown in Table 1.

Table 1. Examples of different types of surveillance system components

Early warning (passive or scanning) Strategic (active)

farmer or veterinary reporting probability-based methods

laboratory submissions observational and intervention studies

community animal health service purposive methods

syndromic surveillance risk-based surveillance

molecular surveillance sentinel surveillance

participatory surveillance

The Animal Health and Veterinary Laboratories Agency (AHVLA) in the United Kingdom identified the generic requirements against which the performance of a surveillance system can be evaluated (Anonymous 2012c). The specific objectives of a surveillance system for livestock diseases may include 1. detection of exotic, new and emerging disease, 2. declaration of freedom from disease and/or 3. monitoring of endemic disease (case detection, prevalence estimation). The systems effectiveness can be expressed in terms of cost-effectiveness or based on its sensitivity to detect and therefore accurately quantify risk. Both aspects will be affected by the surveillance system design in terms of its components, their linkages, the data analysis and outputs



generated. The data quality and quantity is often the most important constraint within such systems, apart from usually limited quantitative analyses for each surveillance system component and primarily qualitative integrated analyses for the whole system being performed. Data quality and quantity are strongly influenced by stakeholder commitments towards the objectives of the surveillance system.

Livestock production and disease risk management

Worldwide increases in demand for high value food items including meat and other livestock associated products demand has, so far, largely been met by a combination of a shift towards short-cycle species (poultry and pigs), increasing individual animal productivity and an increase in animal numbers. In particular, China has experienced an enormous increase in meat production that is much higher than in any other region of the world (Figure ).

Figure 1. Temporal pattern in total meat production comparing China with all other regions of the world (data source: FAOSTAT)

The resulting increased density of animals within farms as well as their regional concentration leads to an increased risk of spread of infectious diseases within farms and regional livestock populations. Apart from extensive human global movement patterns, agricultural trade has also increased significantly, such that global agro-food trade networks will facilitate fast transcontinental spread of any food-borne hazards (Hosseini et al. 2010; Ercsey-Ravasz et al. 2012). Risk management options include improvements in animal husbandry, which require training and investment in facilities, and / or preventive usage of AM or vaccines. Particularly the latter has been attractive



to farmers due to relatively low cost and immediate productivity benefit. An additional reason for widespread usage of antimicrobials in food animal production is their growth-promoting effect.

Surveillance of antimicrobial resistance

Any risk management policies in relation to AMR will have to be informed by data on AM usage as well as resistance. The usage data is needed to be able to predict emergence risk, and therefore is essential for prevention. The detection of treatment-resistant microbes is necessary to be able to initiate specific responses, including the containment of the spread of such pathogens. The data sources, quantity, quality and their cost will vary significantly between both outcomes. It is also very clear now that the emergence of AMR requires cannot be tackled by single countries but rather by a coordinated global effort (Walker et al. 2009). In some settings, systems integrating human and animal health surveillance may be more cost-effective, as recommended by the WHO Advisory Committee on Integrated Surveillance of Antimicrobial Resistance (AGISAR) (Anonymous 2011a). As an example, this is the philosophy of the Danish DANMAP system (Korsgaard and Agerso 2012). An overview of different AM surveillance approaches can be found in Silley et al (2012). Table 2 presents the factors that need to be considered when designing an integrated AMR surveillance and monitoring system based on recommendations by AGISAR (Anonymous 2011a). Table 2. Factors to be considered in the design of integrated AMR surveillance systems

1. Study population – Humans, retail meats, food producing animals

2. Sampling strategy a. Representativeness b. Sampling bias c. Frequency of testing d. Sample size e. Sample source

3. Culture methodology a. Target organisms b. In vitro antimicrobial susceptibility testing methods c. Antimicrobials to be used in susceptibility testing

4. Data management and reporting a. Database design for appropriate data extraction b. Type of data to be reported c. Analysis and interpretation of data d. Information sharing e. Confidentiality policies should be established to protect proprietary data

The design of AMR or any type of surveillance system in low to middle income countries needs to be informed by carefully conducted transdisciplinary risk assessments which will allow identifying the most important risk pathways, potential surveillance data



sources and key data gaps. To emphasize the difference to integrative scientific research (interdisciplinary research), transdisciplinarity refers to involving non-academic stakeholders in the risk assessment process (van den Hove 2007; Tress, Tress, and Fry 2005; Max-Neef 2005). It is likely that such risk assessments need to be conducted using qualitative approaches and may have to involve expert opinion (Anonymous 2010).

Surveillance of antimicrobial sales/usage/consumption in animals

AM sales for animals can be monitored in countries with well regulated pharmaceutical trade, such as most higher income countries where manufacturers or retailers can provide this data. The specificity and timeliness of the data may vary, i.e. type of antimicrobial and the target species. AM usage is more difficult to monitor, since it requires information on dose and species from the end user, the veterinarian or farmer. Estimates can be generated by relating sales to animal species density, although this may have to be adjusted where significant trans-boundary movement of livestock occurs. The European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), for example, has produced population weighted sales of veterinary antimicrobial agents in 9 EU countries for 2005-2009 (European Medicines Agency 2011). The numerator has been standardized overall sales data of antimicrobial veterinary medical products (VMPs) at package level (DDD = Defined Daily Dose = assumed average maintenance dose per day or PDD = Prescribed Daily Dose). The denominator is the population correction unit (PCU) based on the estimated weight of livestock and slaughtered animals, and it is a proxy for animal biomass at risk of being treated with antimicrobial VMP. An example of results from a descriptive analysis are shown in Figure 2. The number of countries that will contribute to this surveillance system is reported to have increased to about 20 for 2010.

Figure 2. Temporal pattern in tetracycline sales in 9 EU countries (from: European Medicines Agency, 2011. 'Trends in the sales of veterinary antimicrobial agents in nine

European countries (2005-2009)' (EMA/238630/2011))



Denmark established the Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (DANMAP) in 1995 to monitor AM consumption as well as AMR in humans and animals (Korsgaard and Agerso 2012). This programme also has an explicitly stated emphasis on analysis and identifying cause-effect relationships. An example of a descriptive analysis is presented in Figure .

Figure 3. Temporal pattern of antimicrobial consumption for humans and animals in Denmark (from Korsgaard and Agerso, 2012)

The design of a surveillance system for AM sales/usage needs to include decisions in relation to the type of product, whether complete data or a sample will be collected and what analytical output will be generated. For example, the ESVAC focusses on detecting change in quantity over time or in space across European countries, standardised by livestock biomass at national level. The utility of the surveillance system outputs needs to be considered in relation to the usefulness for the outputs for policy making. The situation is particularly challenging in countries with poorly regulated trade in AMs for humans and/or animals, and where there are often significant illegal sales without prescription, in tainted products as well as those prohibited for animal use. It is likely that useful surveillance of sales or usage will be very difficult in such situations, which probably includes the majority of low to middle income countries around the world. Major challenges are ineffective regulation due to poor compliance and enforcement. In addition, there is poor reliability of livestock population data. Any data on legal sales/usage will be affected by data quantity and poor quality. But much more importantly, there will be widespread illegal trade/usage, probably with a transboundary dimension, and usually this data is not easily quantifiable.



In these settings, it may be necessary to include targeted collection of qualitative data to complement any available quantitative sales or usage data. This could be done through focus groups or participatory data collection. Stakeholders involved in AM trade could be targeted in this context. An understanding of the value chain for the AM trade is required in order to determine most effective data collection approaches and possible interventions, as has been done for livestock and other commodities (Anonymous 2006; Anonymous 2012d). It should also be possible to use spatial modelling methods to generate maps of estimated AM usage, using a combination of predictor variables including livestock biomass, productivity and other geo-referenced factors likely to influence usage, such production system, veterinary infrastructure etc.. An assumption will have to be that moderate to high livestock density populations in regions with poor veterinary infrastructure cannot be maintained without significant antimicrobial usage. Such models should be able to provide crude predictions and could be used to inform risk-based surveillance activities.

Surveillance of antimicrobial resistance in animals

Surveillance systems for AMR in animals can be either pathogen specific or syndromic. Specific microbial organisms can be used as indicators, such as Campylobacter, Salmonella, E. coli or Enterococcus. Pathogen profiling methods can be used to inform that decision (Sintchenko, Iredell, and Gilbert 2007). Sample submission can be voluntary or compulsory, and data sources can be on-farm, slaughter house or food products. The samples can be based on animals which did not respond to treatment, but this is likely to provide an incomplete picture due to lack of incentive for further diagnostic assessment. An alternative is to target commensal bacteria in healthy animals which is more likely to generate representative data assuming the animals have been selected appropriately. There are major challenges to delivery of effective AMR surveillance in low to middle income countries. Passive surveillance will be inadequate due to both lack of reporting incentives and poor laboratory infrastructure. While in medical settings there may be a bias towards detection of resistant isolates, this is unlikely to be the case in animals due to significant underreporting. It would therefore be necessary to collect representative data through tailored surveys. But these are often impractical, since large sample sizes would be required to generate representative data which will be resource-intensive. Any existing data is likely to be based on small numbers of laboratory submissions which are inherently biased. Also, there is usually limited laboratory capacity and poor quality assurance. As a consequence, poor quality prevents pooling of data from multiple locations (and probably even retrospectively from the same location) for integrated data analyses that would allow identification of spatial and temporal trends. If such analyses are still to be conducted they should only be used to inform more in-depth investigations. As an alternative, regional surveillance could be conducted based on



sentinel surveillance networks which operate according to quality assured standards (Arita et al. 2004). If the system is capable of quantifying some frequency measure of AMR, it is necessary to decide what this data will be used for. If it is to trigger containment activities, evidence-based methods will have to be used to decide what level that will be. Lot quality assurance sampling (LQAS) is a sampling method used widely in industry to identify excessive fault proportions in production lines. It requires relatively small sample sizes but still needs decisions in relation to undesirable levels of AMR. As with AM sales and usage, spatial modelling methods could be part of the risk assessment used to inform the design of a risk-based AMR surveillance system. Livestock population density and its temporal change will be important indicators, as will information on spatial and temporal patterns of livestock trade. With that information, locations of sentinel populations could be identified for conducting repeated surveys, such as at specific abattoirs and livestock markets.

Policy development

The policies underpinning these surveillance systems need to recognise the need to change human behaviour. Policies which do not generate useful data should not be implemented, since they will damage the acceptance of the policy amongst stakeholders and compromise the credibility of the responsible regulatory authority. Compliance of stakeholders with the policy measures is unlikely to be achieved if the policy is purely based on regulatory or fiscal measures, partly because it cannot be enforced in low to middle income countries. Instead, alternative policy instruments influencing choices made by individuals should be identified (Anonymous 2011b). Such approaches are used in social marketing and behavioural economics. They will require an in-depth understanding of the locally relevant drivers of individual behaviour, and these will have cultural, economic as well as other dimensions. The process of conducting transdisciplinary risk assessments will be helpful in this context. During the policy development, the aspect of informal AM trade and usage could be developed by considering methodologies applied in the context of, for example, illegal wild animal or drug trade. If behaviour change is not considered feasible, it will not be possible to generate ‘representative’ national data. Instead, policies based on focussed regional sentinel surveillance networks should be developed, supported by local and international funds.

Conclusions

Surveillance and monitoring of AM usage and AMR associated with livestock, even in high income countries, is still an area of development, and different models have been developed, and the most effective ones were implemented in a very small number of high income countries. It is very clear that surveillance in low to middle income



countries represents a major challenge, for which new approaches need to be developed. Risk-based approaches informed by sound transdisciplinary risk assessments that identify spatially and potentially temporally distinct entities in the livestock production system and AM trade value chains suitable for data collection may provide a mechanism for still being able to generate data for understanding regional and potentially national patterns of emergence risk in such settings. The global public good nature of the threat of AMR justifies the involvement of national and international governmental and non-governmental organisations in the delivery of surveillance in low to middle income countries.

References

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———. 2012a. The Evolving Threat of Antimicrobial Resistance: Options for Action. World Health. Geneva, Switzerland.

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Arita, Isao, Miyuki Nakane, Kazunobu Kojima, Namiko Yoshihara, Takashi Nakano, and Ahmed El-Gohary. 2004. “Personal View Role of a Sentinel Surveillance System in the Context of Global Surveillance of Infectious Diseases Personal View.” Lancet Infectious Diseases (4): 171–177.

Choffnes, Eileen R, David A Relman, and Alison Mack. 2010. Antibiotic Resistance: Implications for Global Health and Novel Intervention Strategies: Workshop. Washington, DC: National Academies Press. http://www.nap.edu/catalog/12925.html.



Ercsey-Ravasz, Mária, Zoltán Toroczkai, Zoltán Lakner, and József Baranyi. 2012. “Complexity of the International Agro-food Trade Network and Its Impact on Food Safety.” PloS One 7 (5) (January): e37810. doi:10.1371/journal.pone.0037810. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3365103&tool=pmcentrez&rendertype=abstract.

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Alternatives to Antimicrobials (ATAs) and Strategies for Minimizing Risk of AMR Development and Spread

Jaap Wagenaar

[In preparation]



FAO and WHO Initiatives to Reduce the Risk of AMR Development and Spread

Awa Aidara-Kane and Patrick Otto

[In preparation]



OIE’s Contribution to the Promotion of Responsible and Prudent Use of Antimicrobials

Hnin Thidar Myint, Tomoko Ishibashi, François Diaz*, Elisabeth Erlacher-Vindel*

OIE Regional Representation for Asia and the Pacific *OIE Headquarters, Paris (France)

The OIE and its history with antimicrobials

The World Organisation for Animal Health (OIE) is an intergovernmental organisation with 178 Member Countries, whose mandate is to improve animal health, veterinary public health including the sanitary safety of animals and animal products at production level, and animal welfare worldwide. Within its mandate, the OIE has recognised the need to tackle the issue of antimicrobial resistance already in the late 1990s and the OIE organised two international conferences on antimicrobial resistance, one in 1999 and the other in 2001. In addition, an OIE ad hoc Group on antimicrobial resistance was given mandates such as development of risk assessment methodology for the potential impact on public health of antimicrobial resistant bacteria of animal origin, development of guidelines for prudent use of antimicrobials in animal husbandry, and standardisation and harmonisation of laboratory methodologies used for the detection and quantification of antimicrobial resistance. As of today, five Chapters in the Terrestrial Animal Health Code, four Chapters in the Aquatic Animal Health Code, and one Chapter in the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (2012 versions) have been adopted by the World Assembly of Delegates. Regarding the mechanism by which bacteria acquire antimicrobial resistance, some aspects are known and others are yet to be revealed. One of the most troubling questions from the veterinary viewpoint is the extent to which the use of antimicrobials in animals leads to the generation of antimicrobial resistance. We know that antimicrobials are used in human medicine, veterinary medicine, animal production, aquaculture and horticulture and all sectors have therefore a shared responsibility to prevent or minimize antimicrobial resistance selection pressures on both human and non-human pathogens. It is our responsibility to pursue risk management options for sustainable use of antimicrobials in animals, while giving due consideration to the risk of generating antimicrobial resistant bacteria. Antimicrobial resistance is one of many issues where the OIE has been working in collaboration with the FAO and WHO. The WHO/FAO/OIE tripartite initiatives for expert consultations on antimicrobial resistance started in 2003 and one of the results is the development of an OIE list on veterinary important antimicrobials that was adopted in 2007 and that is currently under review. Both FAO



and WHO are participating in this update. The tripartite cooperation led to the meeting of the OIE/FAO/WHO Consultative ad hoc Group on Collaborative Activities on Antimicrobial Resistance, organized in 2009 in OIE Headquarters in Paris with the aim of finding common areas for cooperation and maintaining good communication in this field. Follow up meetings to further develop collaborative activities and improve coordination, were held in the WHO Headquarters and in the FAO Headquarters (August 2012).

Major OIE activities

(1) OIE Standards and publications Since first adoption in 2004, the number of Chapters related to antimicrobials in the OIE Terrestrial Animal Health Code (http://www.oie.int/international-standard-setting/terrestrial-code/access-online/) has been completed and existing texts revised. The FAO and WHO participates in these updates. In its 2012 version, the following Chapters are contained in Section 6 Veterinary Public Health: - Chapter 6.6. Introduction to the recommendations for controlling antimicrobial

resistance; - Chapter 6.7. Harmonisation of national antimicrobial resistance surveillance and

monitoring programmes (update adopted in May 2012); - Chapter 6.8. Monitoring of the quantities and usage patterns of antimicrobial agents

used in food producing animals (update adopted in May 2012); - Chapter 6.9. Responsible and prudent use of antimicrobial agents in veterinary

medicine (under review could be proposed for adoption in May 2013); - Chapter 6.10. Risk assessment for antimicrobial resistance arising from the use of

antimicrobials in animals (under review, has been circulated for Member Country comments).

To help laboratories determine which in vitro antimicrobial susceptibility testing methodology to use, the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (http://www.oie.int/international-standard-setting/terrestrial-manual/access-online/) provides General Guidelines in Part 3: - Guideline 3.1 Laboratory methodologies for bacterial antimicrobial susceptibility

testing (adopted in May 2013) Given the importance of and concerns over the use of antimicrobials in aquaculture, over the last several years guidelines have also developed and adopted in the Aquatic Animal Health Code (http://www.oie.int/international-standard-setting/aquatic-code/access-online/): - Chapter 6.2. Introduction to the recommendations for controlling antimicrobial

resistance;

http://www.oie.int/international-standard-setting/terrestrial-code/access-online/

http://www.oie.int/international-standard-setting/terrestrial-code/access-online/

http://www.oie.int/international-standard-setting/terrestrial-manual/access-online/

http://www.oie.int/international-standard-setting/terrestrial-manual/access-online/

http://www.oie.int/international-standard-setting/aquatic-code/access-online/

http://www.oie.int/international-standard-setting/aquatic-code/access-online/



- Chapter 6.3. Principles for responsible and prudent use of antimicrobial agents in aquatic animals (adopted in May 2011);

- Chapter 6.4. Monitoring of the quantities and usage patterns of antimicrobial agents used in aquatic animals (adopted in May 2012);

- Chapter 6.5. Development and harmonisation of national antimicrobial resistance surveillance and monitoring programmes for aquatic animals (adopted in May 2012);

- A chapter on risk assessment is under development. These standards should be respected for promoting prudent use of antimicrobials and for conducting scientifically valid resistance surveillance and monitoring. The OIE List on veterinary important antimicrobials adopted in 2007 and published on the OIE Website is currently under review and both FAO and WHO are participating in the update. All information is available at: http://www.oie.int/en/our-scientific-expertise/veterinary-products/antimicrobials/ In addition, the last OIE Scientific and Technical Review published in April 2012 (VOLUME 31 (1)) was dedicated to “Antimicrobial resistance in animal and public health”. It contains a wide range of scientific articles about mechanisms for resistance, surveillance and monitoring of resistance and consumption in human and animals, consequences of resistance, risk assessment and containment, all available free at: http://web.oie.int/boutique/index.php?page=ficprod&id_produit=1074&fichrech=1&lang=en. (2) PVS Pathway and legislation missions The OIE well recognises that, like all other aspects of the animal health system, responsible and prudent use of antimicrobials can be supported by “good governance” of a country’s Veterinary Services. The OIE PVS Pathway, starting with a PVS Evaluation by an OIE-certified expert team using the OIE-developed PVS tool, followed by a GAP analysis and other specific activities, has been helping Member Countries identify their gaps and target for a wide range of critical competencies. PVS analysis includes many “critical competencies” related to the capability of responsible use of antimicrobials, notably: II-9 veterinary medicine and biologicals; II-10 residue testing; and VI-2 implementation of legislation and regulation and stakeholders’ compliance. The “One Health PVS” mission, which is currently at a pilot stage, is being developed to focus more on the capability of Veterinary Services to manage issues involving both animal health and public health. Needless to say, the capability of collaboration with the public health authority for responsible use of antimicrobials is one of the important issues. As a follow up to an evaluation of the Performance of Veterinary Services (PVS) using the OIE PVS Tool, and at the request of Members, the OIE conducts missions to help governments that wish to modernise the national veterinary legislation and thereby

http://www.oie.int/en/our-scientific-expertise/veterinary-products/antimicrobials/

http://www.oie.int/en/our-scientific-expertise/veterinary-products/antimicrobials/

http://web.oie.int/boutique/index.php?page=ficprod&id_produit=1074&fichrech=1&lang=en

http://web.oie.int/boutique/index.php?page=ficprod&id_produit=1074&fichrech=1&lang=en



help the veterinary services to meet the OIE standards. After an initial ‘identification’ mission the country may request a longer term collaboration with the OIE, under a formal agreement, with the objective of modernising the national veterinary legislation. As with other elements of the OIE PVS Pathway, legislation missions are undertaken by experts who are trained and certified by the OIE for this purpose. Mission reports are confidential unless/until the country authorises release to Donors or other OIE partners.

PVS

Gap Analysis

PVS

Evaluation

PVS Pathway

Follow-Up

Missions

PVS Pathway

Follow-Up

Missions

One Health

Veterinary

Legislation

Public / Private

Partnerships

Veterinary

Education

Laboratories

« Diagnosis» « Prescription»

« Treatment »

The OIE collaborates with

governments, donors and other

stakeholders

including

Veterinary Services’

Strategic Priorities

43 (3) OIE National Focal Point system As the OIE’s mandate has broadened, there has been need to develop support for OIE Delegates to more actively participate in OIE activities. Thus, a system of OIE National Focal Points for specific subject areas was created. In 2009, the World Assembly adopted Resolution XXV regarding veterinary products, which recommends each OIE Member Country to nominate a National Focal Point for the OIE on matters related to veterinary products (it should be noted that such Resolution also recommends each OIE Member Country to promote responsible and prudent use of antimicrobials). The OIE has organised regional capacity building workshops for National Focal Points for Veterinary Products in all OIE regions. In addition to providing National Focal Points with information about the OIE’s work in the subject field and how to help their Delegates, these workshops allow them to develop a network among themselves. In the region of Asia and the Pacific, two workshops have already been held for National Focal Points for Veterinary Products, one in June 2011, followed by second round training in July of this year in Bangkok. While the first round covered general topics, the second round programme allocated substantial time to the issue of antimicrobials: 1) Chapters 6.7 and 6.8 of the OIE Terrestrial Animal Health Code on antimicrobial resistance: detailed presentation, implementation, 2) Strategy of the OIE regarding Veterinary products and 3) Workshop: Monitoring of antimicrobial resistance and quantities used in animals -12



designated Focal Points for Veterinary Products, 14 country representatives and 2 OIE Delegates representing 28 countries for the Region participated in the workshop whose success was evidenced by the participants’ active discussion. (4) OIE Reference Centres For the OIE to develop standards, publish scientific information and support members’ capacity building, the contribution of Collaborating Centres is indispensable. In addition to the three Collaborating Centres on Veterinary Medicinal Products (in France, Japan and USA) a Reference Laboratory on antimicrobial resistance supports the OIE’s activities concerning veterinary medicinal products.

Ongoing and future activities

While continuing its work of revising the existing standards and the list of Critically Important Antimicrobials to incorporate recent scientific developments with participation of the WHO and FAO, the OIE is organising a Global Conference on the Responsible and Prudent Use of Antimicrobial Agents for Animals, International Solidarity to Fight against Antimicrobial Resistance, in Paris (France), from 13 to 15 March 2013. In addition to the two conferences in early years around 2000, the OIE hosted in September 2012 the “International Symposium on Alternatives to Antibiotics” with the aim to present the main outcomes to the participants of the OIE Global Conference on the Responsible and Prudent Use of Antimicrobial Agents for Animals in March 2013. The conference objectives are: • present an overview of the current situation regarding antimicrobial use in animals

and antimicrobial resistance; • inform on initiatives taken by the OIE and other international organisations to

promote prudent and responsible use of antimicrobial agents in animals at a national, regional and international level;

• promote good governance practices, including national legislation and regulatory frameworks for import, registration, distribution and use of quality veterinary drugs worldwide, by using the OIE PVS Pathway in evaluating and strengthening national Veterinary Services and their compliance with OIE standards;

• encourage international cooperation to help all Member Countries to effectively implement measures for responsible and prudent use of antimicrobial agents in animals;

• foster and strengthen cooperation with Veterinary Statutory Bodies and the veterinary profession for the respect of OIE standards on prudent use in animals worldwide;

• explore the opportunities to improve data collection in animal antimicrobial usage and antimicrobial resistance;

• present research on new molecules and scientific findings on the alternatives that could be used in animal production replacing antimicrobial agents.



Further information is available at http://www.oie.int/eng/A_AMR2013/ introduction.htm. Based on the experience of the Focal Point Trainings and as a part of the preparation for the Global Conference, the OIE developed a questionnaire on monitoring of the quantities of antimicrobial agents used in animals and requested OIE Delegates and Focal Points to reply before end June of 2012. Questions start from the situation of legislation and use of antimicrobial agents and then move to details such as data sources and systems. Out of 178 Countries, 145 have submitted responses. The survey results will be presented at the Global Conference. The OIE Regional Representation for Asia and the Pacific, in consultation with OIE Headquarters, is considering how to reflect the Conference’s recommendations in the regional context to support members in the years to come.

http://www.oie.int/eng/A_AMR2013/%20introduction.htm.

http://www.oie.int/eng/A_AMR2013/%20introduction.htm.



Session 5 Working Groups



Priority Tasks at Country Level to Contain the Risk of AMR Development

Mike Nunn

Research Program Manager, Animal Health Australian Centre for International Agricultural Research

Group composition and task

Two working groups were formed as follows Facilitator: V. Ahuja Facilitator: C. Benigno Delegates: Bhutan, India, Iran, Myanmar, Nepal, Pakistan, Sri Lanka

Delegates: Australia, Indonesia, Korea DPR, Lao PDR, Malaysia, Philippines, Samoa, Thailand

Resource persons: P. Abeynayake, A. Aidara-Kane, T. Myint, M. Nunn, D. Pfeiffer

Resource persons: L. Baldrias, P. Otto, K. Sakurai, T.N. Vinh, J. Wagenaar

The groups were asked to develop a list of priority actions to be undertaken by / in their respective country and regional country grouping (SAARC, ASEAN, SPC) to contain risk of AMR development and spread. Areas to consider were, e.g. awareness raising (general public, policy makers), legal framework and instruments, technical capacities and human resources, stakeholder engagement and behaviour change etc.

Consolidated results

Each working group reported back to a plenary session and the outputs were synthesised into a common list of potential actions in an approximate order of priority. Delegates acknowledged the importance of AMR and agreed that the international workshop was a useful and timely reminder of the need for animal health authorities in the Asia–Pacific region to give greater attention to AMU and AMR. Delegates noted that there is a wide variation in the awareness of and capacity to manage the risks from AMR across APHCA member countries. However, they agreed that the case studies presented during the workshop demonstrated both that AMR was a problem in countries in the Asia–Pacific region and that appropriate action could and should be taken to ensure prudent use of antimicrobials in animals to reduce the risks from AMR. Delegates recognised that although AMR is a global problem local action in each APHCA member country was needed to underpin regional and global risk reduction measures.



The synthesis of feasible local actions identified is shown in Figure 1. Delegates noted that it was not feasible to undertake all of these quickly but recognised that it was important to undertake a situational analysis to understand the roles and motivations of all stakeholders in antimicrobial value chains in their respective countries. They noted that AMU is not just a technical issue and that addressing it and the risks from AMR also required consideration of social, economic, environmental, ethical and policy factors. Figure 1: Local in-county actions to reduce risks from AMR identified in the workshop

1. Undertake a situational analysis (to improve understanding of what is occurring with AMU and AMR) to understand the roles and motivations of all stakeholders in antimicrobial value chains in their respective countries;

2. Establish a National Task Force on Antimicrobials that is multidisciplinary and cross-sectoral to provide a forum to lead policy development and support action on AMU and AMR;

3. Improve awareness at different levels (including farmers and farmer organizations; veterinarians, para-veterinarians, veterinary faculty staff members; policy-makers; consumers and civil society);

4. Develop, review and improve practical legislation and regulatory frameworks, including compliance capacity, for AMU and AMR: • Develop national policy; • Develop guidelines and regulations to encourage responsible and prudent use of

antimicrobials (e.g. on prescription for both animal and human AMU). 5. Build capacity (of both human resources and laboratory infrastructure) for

monitoring AMU and surveillance of AMR: • Review current national capacity; • Explore options for capacity-building to fill gaps identified.

6. Undertake monitoring and surveillance of AMU and AMR: • Collect data on AMU (e.g. types and of volume of antimicrobials used, purpose of

use); • Design and undertake targeted surveillance for AMR; • Explore options for developing a national programme for monitoring AMU and

surveillance of AMR. 7. Promote alternatives to AMU, particularly improved infection control, good

husbandry practices, and farm biosecurity; 8. Develop and implement communications and public awareness on AMU and AMR. Delegates recognised the need to work to establish, where not already in place in their respective countries, a broadly based multidisciplinary national taskforce on AMU and AMR. They noted that having a broadly based multidisciplinary and cross-sectoral National Taskforce on Antimicrobials would help to facilitate a number of other actions identified (e.g. increasing awareness). They also noted that some support was available from WHO for countries to take action to reduce risks from AMR, and that both FAO and



OIE produce useful guidance including a range of standards and guidelines for good practice. Delegates recognised the need for relevant legislation and regulatory frameworks, including compliance capacity, which they noted was limited in a number of countries in the Asia–Pacific region. However, they recognised that developing or reviewing legislation was longer-term action that first required broad consensus on national policy. Delegates also recognised the need for capacity-building (of both human resources and laboratory infrastructure) for monitoring AMU and surveillance of AMR, but acknowledged that this was also an action that would require longer-term planning and investment. Delegates agreed that they would each progress a number of local actions identified in the workshop that were relevant to their respective countries, and report progress at the next APHCA meeting. APHCA Secretariat is requested to pursue the issue with the three countries that were not represented at the Session / Workshop. Delegates noted that some of the local actions identified in the workshop actions would require external funding support, particularly in terms of longer-term actions such as capacity-building. They acknowledged that it would be useful for some priority be given to exploring mechanisms for obtaining external funding to support undertaking some longer-term actions in a number of APHCA member countries. Delegates agreed that it would be useful for APHCA to facilitate obtaining external funding to support undertaking some longer-term actions in a number of APHCA member countries.



Annexes



Annex 1: Workshop Programme

Day 1, 22 October 2012 Session 1: Opening and Introduction

14:00 – 14:15 Objectives of the workshop & introduction of participants

J. Otte (FAO)

14:15 – 15:00 Keynote: Epidemiology and impact of AMR: Links between antimicrobial use in livestock and AMR in human pathogens and repercussions of AMR

J. Wagenaar (University of Utrecht)

15:00 – 15:15 Tea break and group photo

Session 2: Country Reports

15:15 – 16:45 Australia M. Shipp

Bhutan N. Wangchuk

India K. Vijaykumar

Indonesia I. Suandy

Iran S.M. Azizian

Korea DPR L.H. Nam

Lao PDR T. Theungphachan

Malaysia A.N. Hamid

16:45 – 17:00 Break

17:00 – 18:15 Myanmar P. Sone

Nepal R.K. Khatiwada

Pakistan M.A. Jaivid

Philippines R. Cresencio

Samoa T. Aiolupo

Sri Lanka W.K. de Silva

Thailand S. Jaroenpoj

19:30 – Dinner hosted by Government of Sri Lanka



Day 2, 23 October 2012

Session 3: Country Case Studies

09:00 – 09:30 An integrated surveillance study of AMR in Salmonella subspp, Campylobacter spp, Escherichia coli and Enterococcus spp in poultry in Cambodia

P. Otto (FAO, Rome)

09:30 – 10:00 Monitoring antimicrobial resistance in food borne pathogens from selected species in Sri Lanka

P. Abeynayake (U. of Peradeniya)

10:00 – 10:30 Relationship between multi-resistance of Campylobacter jejuni isolates and antimicrobial usage in poultry in the Philippines

L. Baldrias (UP Los Banos)

10:30 – 11:00 Coffee break

11:00 – 11:30 Vancomycin resistant enterococci – Thailand experience

P. Matayompong (Department of Livestock Development)

11:30 – 12:00 Antimicrobial resistance at the human-animal interface in Vietnam

T.N. Vinh (Oxford University & Can Tho University)

Session 4: Approaches to AMR Management

13:30 – 14:15 Systems for monitoring and integrated surveillance of antimicrobial use in livestock and AMR in different parts of the world

D.U. Pfeiffer (Royal Vet. College)

14:15 – 15:00 Alternatives to antimicrobials (ATAs) and strategies for minimizing risk of AMR development and spread

J.A. Wagenaar (University of Utrecht)

15:00 – 15:15 Tea break

15:15 – 16:00 WHO and FAO initiatives to reduce risk of AMR development

Awa Aidara-Kane (WHO)

The OIE’s contribution to promote responsible and prudent use of antimicrobials

Tidar H. Myint (OIE)

Session 5: Working Groups to Develop Recommendations and Plan(s) of Action

16:15 – 17:15 Facilitated working groups to develop action points / plans for AMR risk management

V. Ahuja & C. Benigno (FAO)

17:15 – 17:45 Working groups reporting back to plenary

17:45 – 18:15 Wrap-up and closure J. Otte (FAO)

19:00 – Dinner hosted by FAO-APHCA



Annex 2: List of Participants

Delegates AUSTRALIA Dr Mark Schipp Chief Veterinary Officer Department of Agriculture, Fisheries and Forestry GPO Box 858 Canberra ACT 2601 Tel.: +61-(2) 6272 4644 Mobile: +61-439 605 503 Fax: +61-(2) 6272 3150 E-mail: [email protected]

AUSTRALIA Dr Mike J. Nunn Research Program Manager, Animal Health Australian Centre for International Agricultural Research 38 Thynne St, Bruce, ACT 2617, Australia GPO Box 1571, Canberra, ACT 2601, Australia Tel.: +61-(2) 6217 0540 Mobile: +61-409 650 546 E-mail: [email protected]

BHUTAN Dr Naiten Wangchuk Chief Livestock Officer Department of Livestock Livestock Production Division Ministry of Agriculture and Forest PO Box 113, Thimpu Tel.: +975-(2) 335401 Mobile: +975-17666061 Fax: +975-(2) 322401 E-mail: [email protected]

INDIA Dr Kaithathara Vijayakumar Joint Commissioner (LH) Dpt. Animal Husbandry, Dairying and Fisheries Room No. 29C, Krishi Bhawan Dr. Rajndra Prasad Road, New Delhi Tel.: +91-(11) 2338419 Fax: +91-(11) 23384190 E-mail: [email protected]; [email protected]

INDONESIA Dr Imron Suandy Quality Control Laboratory for Livestock Products, JL Pemuda No 29A Tanas Sareal Bogor, West Java, 16161 Tel.: +62-8568987687 Fax: +62-(251) 8353712 E-mail: [email protected]

INDONESIA Dr Suparno Quality Control Laboratory for Livestock Products, JL Pemuda No 29A Tanas Sareal Bogor, West Java, 16161 Tel.: +62- Fax: +62-(251) 8353712 E-mail:

mailto:[email protected]









Delegates IRAN Dr Seyed M. Azizian Director General Bureau of Pharmaceutical, Therapy and Laboratories Tel.: Fax: E-mail: [email protected]; [email protected]

KOREA DPR Dr Li H. Nam Director Animal Production Department MOA Songyo-i dong, Songyo District Pyongyang Tel.: +8-(502) 3818278 E-mail: [email protected]

KOREA DPR Mr Jo K. Guk Head Epidemiological Surveillance Branch MOA Songyo-i dong, Songyo District Pyongyang Tel.: +8-(502) 3818278 E-mail: [email protected]

LAO PDR Dr Thongphun Theungphachan Head Livestock & Fisheries Products Quality Assurance Unit NAHC, DLF Tel.: +856-(20) 22287121 Fax: +856-(21) 244476 Email: [email protected]

MALAYSIA Dr Akma Ngah Hamid Director Central Region Veterinary Laboratory (CRVL) Department of Veterinary Service Jalan Nilai-Banting, Bandar Baru Salak Tinggi 43900 Sepang, Selangor Darul Ehsan Tel.: +603-8706 3810 (Dir) Tel.: +603 8706 8681/3811 (Gen) Fax :+603 8706 8675 E-mail: [email protected]

MYANMAR Dr Pyi Sone General Manager Livestock, Feedstuff and Milk Products Enterprise Station Rd., Insein Township Yangon Tel.: +95-(01) 640488 Fax: +95 (01) 503024 E-mail: [email protected]

NEPAL Dr. Ram K. Khatiwada Deputy Director General Department of Livestock Services Maritlar Bhawon, Lalitpur Tel.: +977-(1) 5542644 Mobile: +977-9851093956 Fax: +977-(1) 5542915 E-mail: [email protected]

PAKISTAN Dr Muhammad A. Javaid Senior Officer Ministry of National Food Security Pak Secretariat Islamabad Tel.: +925-19208360 Fax: E-mail: [email protected]












Delegates PHILIPPINES Dr Rubina O. Cresencio Director Bureau of Animal Industry Visayas Avenue, Diliman Quezon City 1100 Tel.: +63-(2) 926 6883 / 925 9228 Fax: +63-(2) 927 0971 E-mail: [email protected]

SAMOA Dr Tony Aiolupo Senior Meat Inspector Ministry of Agriculture and Fisheries PO Box 1874 Apia Tel.: +685 21052 Fax: +685 26532 E-mail: [email protected]

SRI LANKA Dr Weligodage K. de Silva Director General Department of Animal Production & Health Peradeniya 20400 Tel.: +94-(081) 2388 195 Fax: +94-(081) 2388 619 E-mail: [email protected]

SRI LANKA Dr Tikiri Wijayathilaka Assistant Director (Veterinary Public Health) Animal Health Division Department of Animal Production & Health Peradeniya 20400 Tel.: +94-(081) 2386 270 E-mail: [email protected]

THAILAND Dr Pennapa Matayompong Veterinary Expert (Animal Products Inspection & Certification) Bureau of Livestock Standards & Certification Department of Livestock Development Phaya Thai Road, Bangkok 10400 Tel.: +66-(2) 653 4444 ext 3151 Fax: +66-(2) 653 4932 E-mail: [email protected], [email protected]

THAILAND Dr Sasi Jaroenpoj Senior Veterinary Officer Bureau of Livestock Standards & Certification Department of Livestock Development Phaya Thai Road, Bangkok 10400 Tel.: +66-(2) 653 4444 ext 3145 Fax: +66-(2) 653 4917 E-mail: [email protected]

Invited Experts

Dr Preeni Abeynayake Professor of Veterinary Pharmacology Department of Veterinary Public Health & Pharmacology Faculty of Veterinary Medicine and Animal Science University of Peradeniya Peradeniya 20400 SRI LANKA Tel.: +94-(81) 2395750 Fax: +94-(81) 2389136 E-mail: [email protected]

Dr Awa Aidara-Kane Coordinator Foodborne and Zoonotic Diseases Unit Department of Food Safety and Zoonoses World Health Organization 20, Avenue Appia 1211, Geneva 27 SWITZERLAND Tel.: +41-(22) 791 2403 Mobile: +41-79 500 65 87 Fax: +41-(22) 791 4807 E-mail: [email protected]












Invited Experts

Dr Loinda R. Baldrias Professor Department of Veterinary Paraclinical Sciences College of Veterinary Medicine University of the Philippines Los Banos 4031 College, Laguna PHILIPPINES Tel (Home): +63-(49) 5363563 Mobile: +63-9174733130 Fax: +63-(49) 5362730 E-mail: [email protected]; [email protected]

Dr Pennapa Matayompong Veterinary Expert (Animal Products Inspection & Certification) Bureau of Livestock Standards and Certification Department of Livestock Development Phaya Thai Road, Bangkok 10400 THAILAND Tel.: +66-(2) 653 4444 ext 3151 Fax: +66-(2) 653 4932 E-mail: [email protected], [email protected]

Dr Hnin T. Myint Regional Veterinary Officer OIE Regional Representation for Asia and the Pacific Food Science Building 5F The University of Tokyo 1-1-1 Yayoi Bunkyo-ku, Tokyo 113-8657 JAPAN Tel.: +81-(0)3-5805-1931 Fax: +81-(0)3-5805-1934 E-mail: [email protected]

Dr Patrick Otto Animal Health Officer Animal Production & Health Division Food and Agriculture Organisation Via delle terme di Caracalla 00153 Rome ITALY Tel.: +39-3458591011 Fax: E-mail: [email protected]

Dr Dirk U. Pfeiffer Prof of Veterinary Epidemiology Royal Veterinary College University of London Hawkshead Lane North Mymms, Hertfordshire AL9 7TA UNITED KINGDOM Tel.: +44-(1707) 666205 Fax: +44-(1707) 666574 E-mail: [email protected]

Dr Trung N. Vinh Scientist Centre for Tropical Medicine Oxford University Clinical Research Unit 764 Vo Van Kiet, W.1, Dist.5 Ho Chi Minh City VIETNAM Tel: +84-(8) 39241761 Fax: +84-(8) 39238904 E-mail: [email protected]











Invited Experts

Dr Jaap A. Wagenaar Professor Clinical Infectiology Department of Infectious Diseases and Immunology Faculty of Veterinary Medicine Utrecht University PO Box 80.165 3508 TD Utrecht THE NETHERLANDS Tel.: +31-(30)-2534376 Cell: +31-6-22204786 Fax: +31-(30)-2533199 E-mail: [email protected]

Observers

OIE Dr Kenji Sakurai Deputy Regional Representative OIE Asia Pacific Office Food Science Building 5F The University of Tokyo 1-1-1 Yayoi Bunkyo-ku, Tokyo 113-8657 JAPAN Tel.: +81-(3) 5805 1931 Fax: +81-(3) 5805 1934 E-mail: [email protected]

SRI LANKA Dr (Ms) P. Wijewantha - Additional Secretary, Ministry of Livestock and Rural Community Development Dr R.M. Ariyadasa - Provincial Director (Uva Province), Department of Animal Production and Health Dr A. Sivasothy - Director Animal Health, Dept of Animal Production and Health Dr W.A.J .Subasinghe - Deputy Provincial Director (North-western), Dept of Animal Production and Health Dr P.S. Fernando – Head, Bacteriology Division, Veterinary Research Institute

FAO Regional Office (Secretariat) Dr Vinod Ahuja Livestock Policy Officer FAO Regional Office for Asia and the Pacific Tel.: +66-(2) 6974308 Fax: +66-(2) 6974445 E-mail: [email protected]

Dr Carolyn Benigno Animal Health Officer FAO Regional Office for Asia and the Pacific Tel.: +66-(2) 6974330 Fax: +66-(2) 6974445 E-mail: [email protected]







FAO Regional Office (Secretariat) Dr Joachim Otte Senior Animal Health and Production Officer FAO Regional Office for Asia and the Pacific Tel.: +66-(2) 6974326 Fax: +66-(2) 6974445 E-mail: [email protected]

Dr Vishnu Songkitti Liaison Officer for APHCA FAO Regional Office for Asia and the Pacific Tel.: +66-(2) 6974256 Fax: +66-(2) 6974445 E-mail: [email protected]

Ms Yupaporn Simuangngam APHCA IT-Clerk FAO Regional Office for Asia and the Pacific Tel.: +66-(2) 6974368 Fax: +66-(2) 6974445 / 4433 E-mail: [email protected]




Minutes of the 72nd Executive Committee Meeting,cdn.aphca.org/dmdocuments/AMR WS...

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