National Antimicrobial Resistance (AMR) Surveillance Framework

NATIONAL ANTIMICROBIAL RESISTANCE SURVEILLANCE FRAMEWORK THE UNITED REPUBLIC OF TANZANIA AUGUST 2018 THE UNITED REPUBLIC OF TANZANIA NATIONAL ANTIMICROBIAL RESISTANCE SURVEILLANCE FRAMEWORK AUGUST, 2018 i TABLE OF CONTENT TABLE OF CONTENT......................................................................................................................i LIST OF FIGURES.........................................................................................................................iv LIST OF TABLES...........................................................................................................................iv LIST OF ACRONYMS AND ABBREVIATIONS..............................................................................v DEFINITION OF TERMS..............................................................................................................vii FOREWORD.............................................................................................................................viii ACKNOWLEDGEMENT...............................................................................................................ix EXECUTIVE SUMMARY................................................................................................................x CHAPTER ONE..........................................................................................................................1 INTRODUCTION.........................................................................................................................1 CHAPTER TWO..........................................................................................................................3 JUSTIFICATION FOR AMR SURVEILLANCE.................................................................................3 CHAPTER THREE........................................................................................................................4 SURVEILLANCE OF ANTIMICROBIAL RESISTANCE IN HUMAN.................................................4 3.1 SITUATIONAL ANALYSIS OF AMR IN HUMAN...................................................................4 3.2 GOAL AND OBJECTIVES..................................................................................................6 3.2.1 Goal of AMR Surveillance System............................................................................6 3.2.2 Strategic Objectives..................................................................................................6 3.3 SURVEILLANCE METHODS.................................................................................................6 3.3.1 Road Map for AMR Surveillance Implementation................................................6 3.3.2 Surveillance Roll-Out Site Preparation....................................................................7 3.4 DESCRIPTION OF SURVEILLANCE STRATEGY...................................................................9 3.4.1 Routine Clinical Surveillance Methodology...........................................................9 3.4.2 Priority Specimens, Organisms and Antibiotics......................................................9 3.5 SURVEILLANCE STANDARDS...........................................................................................12 3.5.1 Clinical Specimen Collection and Transport Standards.....................................12 3.5.2 Patient Sampling Standards...................................................................................13 3.5.3 Laboratory Standards.............................................................................................13 3.5.4 Quality Control.........................................................................................................14 3.5.5 External Quality Assurance.....................................................................................15 3.5.6 Isolate Repository and Confirmatory Testing........................................................15 3.5.7 Procurement of essential reagents, supplies and equipment...........................16 3.5.8 Reporting Standards................................................................................................16 3.7 SURVEILLANCE OF ANTIMICROBIAL USE......................................................................19 3.7.1 MONITORING OF ANTIMICROBIAL.........................................................................20 3.7.2 MONITORING ANTIBIOTIC USE IN HOSPITALS.........................................................20 ii 3.8 MONITORING AND EVALUATION OF AMR SURVEILLANCE.........................................21 CHAPTER FOUR.......................................................................................................................22 SURVEILLANCE OF ANTIMICROBIAL RESISTANCE IN ANIMAL, AGRICULTURE AND ENVIRONMENT........................................................................................................................22 4.1 SITUATIONAL ANALYSIS IN ANIMAL, PLANTS AND ENVIRONMENT..............................22 4.1.1 SITUATIONAL ANALYSIS IN ANIMALS........................................................................22 4.1.2 SITUATIONAL ANALYSIS IN PLANTS .........................................................................23 4.1.3 SITUATIONAL ANALYSIS IN ENVIRONMENT..............................................................23 4.2 GOAL AND OBJECTIVES................................................................................................25 4.2.1 Goal.........................................................................................................................25 4.2.2 Strategic Objectives................................................................................................25 4.3 SURVEILLANCE METHODS...............................................................................................25 4.3.1 Target Production Systems for Food and Agriculture.........................................25 4.3.2 Target bacteria for AMR surveillance....................................................................26 4.3.3 Target Antimicrobial agents...................................................................................27 4.4 SURVEILLANCE CATEGORIES..........................................................................................28 4.4.1 Passive surveillance.................................................................................................28 4.4.2 Active surveillance..................................................................................................28 4.4.3 Participatory based surveillance...........................................................................29 4.5 SAMPLING PROTOCOL..................................................................................................29 4.5.1 Purpose.....................................................................................................................29 4.5.2 Users and Responsibility...........................................................................................29 4.5.3 Sampling Design......................................................................................................30 4.5.4 Sample Size..............................................................................................................30 4.5.5 Individual study sample size estimation................................................................30 4.5.6 Environmental sampling.........................................................................................31 4.6 LABORATORY STANDARDS.............................................................................................31 4.6.1 Sample Submission and coding............................................................................32 4.6.2 Sample Collection...................................................................................................32 4.6.3 Laboratory testing Standards.................................................................................33 4.6.4 Antimicrobial susceptibility testing........................................................................33 4.6.5 Laboratory supplies, reagents and equipment...................................................33 4.6.6 Quality Assurance....................................................................................................34 4.6.7 Isolate repository......................................................................................................35 4.7 DATA MANAGEMENT AND INFORMATION SHARING..................................................35 4.8 ANTIMICROBIAL USE SURVEILLANCE.............................................................................35 4.8.1 Source of Data for AMU....................................................................................36 4.8.2 Data Collection Procedures..............................................................................36 iii 4.8.3 Types of Data to be collected.............................................................................36 4.9 MONITORING AND EVALUATION OF AMR SURVEILLANCE......................................37 CHAPTER FIVE.........................................................................................................................38 ROLES AND RESPONSIBILITIES............................................................................................38 5.1 National Multisectoral Coordinating Committee......................................................38 5.2 National AMR Surveillance Technical Working Group..............................................38 5.3 International Stakeholders............................................................................................38 5.4 SPECIFIC ROLES AND RESPONSIBILITIES IN THE HUMAN SECTOR...............................39 5.4.1 AMR SURVEILLANCE SUB-TECHNICAL WORKING GROUP....................................39 5.4.2 National Reference Laboratory.............................................................................39 5.4.3 Data Manager / IT Specialist..................................................................................39 5.4.4 Logistics and Procurement Personnel...................................................................40 5.4.5 AMR Surveillance Sites (Hospitals/Clinics and Laboratories)..............................40 5.5 Specific Roles and Responsibilities in the Food, Agriculture and Environment sectors...............................................................................................................................42 5.5.1 AMR Sub-TWG for the Food, Agriculture and Environment sectors.....................42 5.5.2 National Reference Laboratory.............................................................................43 5.5.3 Surveillance sites and other collection sites............................................................44 5.5.4 Farmers Associations and AMR surveillance network.........................................44 CHAPTER SIX...........................................................................................................................45 LEGAL FRAMEWORK AND RESOURCE MOBILIZATION..........................................................45 6.1 LEGAL FRAMEWORK.......................................................................................................45 6.2 RESOURCE MOBILIZATION..............................................................................................45 REFERENCES............................................................................................................................46 APPENDIX...............................................................................................................................51 Appendix I: LIST OF EXPERTS WHO PARTICIPATED IN THE DEVELOPMENT OF THE NATIONAL AMR SURVEILLANCE FRAMEWORK..................................................................51 Appendix II: Road map for roll-out of the Tanzania Antimicrobial Resistance Surveillance System.............................................................................................................52 Appendix III: Laboratory Requisition Form........................................................................53 Appendix IV: Paper-Based Reporting Form.....................................................................54 APPENDIX V: ANTIBIOTICS TO BE TESTED FOR EACH PRIORITY ORGANISM FOR FOOD, AGRICULTURE AND ENVIRONMENT....................................................................................54 Appendix VI: Food, Agriculture and Environmental Sample Collection & Submission Form......................................................................................................................................55 iv LIST OF FIGURES Figure 1: Simplified diagram of AST data sharing and isolate/sample transmission in the Antimicrobial Resistance Surveillance System..................................................................................25 Figure 2: Data flow for AMR surveillance............................................................................................41 Figure 3: Flow chart of AMR coordination and the surveillance.....................................................73 LIST OF TABLES Table 1: List of proposed sites for AMR surveillance implementation.............................................21 Table 2: Steps and key activities during roll out AMR surveillance.................................................23 Table 3: Priority surveillance pathogens by specimen for Tanzania AMR surveillance................26 Table 4: Priority pathogens-antimicrobial combinations for Tanzania AMR surveillance............27 Table 5: Minimum requirements for laboratory participation as a surveillance site in the AMR Surveillance System..............................................................................................................................34 Table 6: Strengths, Weakness, Opportunity and Challenges (SWOC) Analysis.............................57 Table 7: Minimum requirements for laboratory participation as a surveillance site in the AMR Surveillance System..............................................................................................................................65 Table 8: Classification groups of terrestrial and aquatic animals and plants population for consideration within surveillance........................................................................................................67 Table 9: Antimicrobials targeted for surveillance..............................................................................68 Table 10: Sample size estimation at predefined level of precision level.......................................75 Table 11: Estimated sample size needed for documenting increasing AMR frequencies ..........76 Table 12: Samples from Animals..........................................................................................................78 Table 13: Food Crop and Environmental Samples...........................................................................78 v LIST OF ACRONYMS AND ABBREVIATIONS AMR Antimicrobial resistance AMU Antimicrobial Use AST Antimicrobial susceptibility testing BMC Bugando Medical Centre BSI Blood-stream infections CUHAS Catholic University of Health and Allied Sciences CDC Center for Disease Control CLSI Clinical and Laboratory Standard Institute DDD Daily Defined Dose DEC Diarrhea genic E.coli DVC Director of Veterinary Services EAC East African Community EDTA Ethylene diamine Tetra acetic Acid EQA External quality assurance ESBL Extended-spectrum beta-lactamases EUCAST European Committee on Antimicrobial Susceptibility Testing FAO Food and Agriculture Organization of the United Nation GARP Global Antibiotic Resistance Partnership GDP Gross Domestic Products GLASS Global Antimicrobial Resistance Surveillance System IPC Infection prevention and control MCC Multi-sectoral Coordination Committee MNH Muhimbili National Hospital MoHCDGEC Tanzania Ministry of Health, Community Development, Gender, Elderly and Children MoLF Ministry of Livestock and Fisheries MRSA Methicillin-resistant Staphylococcus aureus MUHAS Muhimbili University of Health and Allied Sciences NAP National Action Plan on antimicrobial resistance NCC National coordinating committee NHLQATC National Health Laboratory Quality Assurance and Training Centre vi NGO Non-Governmental Organization OHCEA One Health Central and East Africa OIE World Organization for Animal Health PC Pharmacy Council PMO Prime Minister’s Office PO-RALG President’s Office Regional Administration and Local Government PRA Participatory Rapid Appraisal PT Proficiency testing QMS Quality Management System SADC Southern African Development Community SOP Standard operational procedure SSI Surgical site infection STI Sexual transmitted infection SUA Sokoine University of Agriculture TFDA Tanzania Food and Drugs Authority TVLA Tanzania Veterinary Laboratory Agency TWG Technical Working Group USAID United States Agency for International Development URT United Republic of Tanzania UTI Urinary tract infection VMU Veterinary Medical Use VPO Vice President’s Office WB World Bank WHO World Health Organization vii DEFINITION OF TERMS Antimicrobials: An agent or substance, derived from any source that acts against any type of microorganism such as bacteria, mycobacteria, fungi, parasite, and viruses Antimicrobial resistance: The ability of microorganisms to multiply or persist in the presence of an increased level of an antimicrobial agent relative to the susceptible counterpart of the same species. Drug-resistant infections: Describes infections caused by organisms that are resistant to treatment, including those caused by bacteria that do not respond to antibiotics Surveillance of antimicrobial resistance: Collection, validation, analyses and reporting of relevant clinical, microbiological and epidemiological data on antimicrobial resistance in targeted pathogens from different sources (e.g. humans, animals, food, environment), and on relevant antimicrobial use in humans and animals, and then applying the results to slow down or halt the development of resistance. Veterinary medical use: Administration of an antimicrobial agent to an individual or a group of animals to treat control or prevent infectious disease. Treat: Administer an antimicrobial agent to an individual or a group of animals showing clinical signs of an infectious disease; Control: Administer an antimicrobial agent to a group of animals containing sick animals and healthy animals (presumed to be infected), to minimise or resolve clinical signs and to prevent further spread of the disease; Prevent: Administer an antimicrobial agent to an individual or a group of animals at risk of acquiring a specific infection or in a specific situation where infectious disease is likely to occur if the drug is not administered viii Prof. Elisante Ole Gabriel , PERMANENT SECRETARY, MINISTRY OF LIVESTOCK AND FISHERIES Dr. Mpoki Ulisubisya, PERMANENT SECRETARY, MINISTRY OF HEALTH, COMMUNITY DEVELOPMENT, GENDER, ELDERLY AND CHILDREN FOREWORD Over the recent years, Antimicrobial Resistance (AMR) has become an increasingly important aspect for both animal and human health. Bacterial resistance to antimicrobials has shown to have serious economic impact in such a way that potent drugs are becoming ineffective resulting in loss of life for humans and animals as well as loss in agricultural product within the food chain. Trend has shown an increase in usage of Antimicrobials in human health, animal health and production of aquaculture and other farming systems. Misuse and overuse of these antimicrobials directly impact on the environment with negative ecosystem health. In recognition of this problem, the Government of the United Republic of Tanzania realized the need to join global initiatives to combat AMR by ratifying different consensus as agreed at different global levels through multi-sectoral approach. Development of this AMR surveillance framework has been a collaborative effort from various partners and stakeholders and was spearheaded by the Ministries responsible for human and animal health (Ministry of Health, Community Development, Gender, Elderly and Children, and Ministry of Livestock and Fisheries) in close collaboration with other key stakeholders at local and international level. The framework will help to streamline AMR surveillance activities in human health, agriculture and environment sectors in the country. It is therefore anticipated that, this framework will be effectively implemented, monitored and reviewed regularly in response to the experiences gathered from its utilization. Besides, the sustainability of this framework depends on the extent to which new practices on antimicrobial use will be embedded in the whole society. ix ACKNOWLEDGEMENT The National Antimicrobial Resistance (AMR) Surveillance Framework marks an important milestone in addressing challenges associated with AMR and Antimicrobial Use (AMU) that are increasingly becoming a major concern within public health, agricultural, and environmental sectors. The processes of developing the AMR surveillance plan considered situation analysis reports regarding AMR in public health, and agricultural sectors. The National AMR Multi-sectoral Coordinating Committee (MCC) wishes to acknowledge technical contributions from the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDGEC), the Ministry of Livestock and Fisheries (MoLF), the Ministry of Agriculture (MoA), Vice President’s Office (VPO)-Environment, the Prime Minister’s Office (PMO) (One Health Coordination Desk) as well as the World Health Organization. The list of experts is attached as appendix I. In addition the MCC wishes to acknowledge the support from the American Society for Microbiology (ASM) and Food and Agriculture Organization (FAO) of the UN that enabled the AMR Surveillance and Research Technical Working Group to accomplish this AMR Surveillance framework. Prof. Muhammad Bakari Kambi CHIEF MEDICAL OFFICER AND CHAIRPERSON NATIONAL ANTIMICROBIAL RESISTANCE MULTI-SECTORAL COORDINATING COMMITTEE EXECUTIVE SUMMARY x Antimicrobial resistance (AMR) is a major global threat to human and animal health, and it endangers modern human and veterinary medicine. Whilst the direct use of antimicrobial agents in human health is recognized as a major contributor to antimicrobial resistance in human pathogens, there are circumstances where antimicrobials used in both food-producing and companion animals are key contributing factors. Surveillance and reporting of AMR and AMU is a global health priority. It is anticipated that, the National Antimicrobial Resistance Surveillance Framework in human, animals, crops, food and environment will comprehensively mitigate the AMR and antimicrobial misuse in these sectors. The purpose of this AMR surveillance framework is to comprehensively and in a systematic manner collect, collate and generate information that will mitigate the AMR and antimicrobial misuse (AMU) in the country through effective monitoring of pathogens, AMU, antimicrobial sensitivity testing, antimicrobial residues and enhancing the prudent use of antimicrobials through communication of outcomes to the public. The strategic objectives of this framework are aligned with the National AMR Action Plan based on national needs and priorities. The framework has highlighted strength, weakness, opportunity and challenges of the existing AMR/AMU governance system in the country. In this framework, priority pathogens and antimicrobial agents for surveillance purposes have been identified based on prevalence, incidence levels, zoonotic and food borne illness potential and pathogenicity. In addition, the identified priority organisms have shown the potential to develop or are known to have developed antimicrobial resistance that is of concern to human, animal, crop and environmental health. Methods for AMR data collection are clearly defined in this framework and it differs from sectors. Both passive and active surveillance will be used to collect and analyze AMR epidemiological data. In this framework, standardized laboratory methods will be employed in order to obtain valid AMR surveillance data in the country. In view of this, standardized AMR sampling protocol and laboratory testing methods are described. Data management and sharing system has been sought to ensure that AMR information is shared to a range of stakeholders for action. 1 CHAPTER ONE INTRODUCTION Antimicrobial agents are powerful and effective drugs in the fight against infectious disease caused by bacteria, viruses, fungi and parasites [1,2]. Since discovery in the nineteen forties, antibiotics have contributed to dramatic reduction in morbidity and mortality from bacterial infections. However, increased use of antibiotics worldwide has been associated with a global rise of Antimicrobial Resistance (AMR), which threatens the return to pre-antibiotics era, where a common bacterial infection may once again result in death. AMR develops when strains of micro-organisms evolve to survive exposure to antimicrobial agents. In many resource-limited settings including Tanzania, there is high burden of infectious diseases and antibiotics are widely used and save lives [3]. However, in these settings antimicrobial agents are inappropriately used which eventually leads to emerging of antibiotic resistance due to selection pressure. It is difficult to address irrational uses of antibiotics in resource-limited settings due to lack of diagnostic tools. In addition, antimicrobial substances are widely used in animals for growth promotions which further fuel existing AMR problem [4]. Coupled with irrational antibiotic uses; spurious, falsified, and counterfeit antimicrobial often slip into the drug supply chain [4]. Antimicrobials for Veterinary Medical Use (VMU) are intended for treating, controlling and preventing infectious diseases in chickens, cattle and to a lesser extent in pigs, sheep and goats. Emerging commercial aquaculture with eminent antimicrobial use in production may further exacerbate resistant microorganism’s selection. In addition to the presence of antimicrobial metabolites in organic fertilizers used for crops, these agents are used directly in horticulture and cashew production [5-7]. Similarly, low quality water with potential antimicrobials from waste-water treatment plants in urban areas is used for horticulture irrigation [9]. Furthermore, feed additives containing enzymes, growth promoters, antimicrobial agents and probiotics are used in livestock feeds. The VMU and misuse of antimicrobials in human, animal and crop sectors, and its metabolites in organic fertilizers directly impact on the environment with negative ecosystem health. Estimates of total annual global antibiotic consumption in agriculture vary considerably due to lack or existing weak surveillance and data collection systems in many countries and they range from around 63,000 tonnes to over 240,000 tonnes [10]. However, it is clear by any measure that antimicrobial use is widespread, on a scale at least equivalent to use in humans, and is projected to increase. Van Boeckel et al. estimated that global consumption of antimicrobials in agriculture will increase by 67 percent from 2010 to 2030, and consumption of antimicrobials amongst the Brazil, Russia, India, China and South Africa will increase by 99 percent in that same time period. [11] Globally, AMR will cause shortfall in Gross Domestic Products (GDP) ranging between US $1 - 3.4 trillion annually from the year 2030 with the current AMR trend [12]. It is estimated that approximately 10 million people will die annually by the year 2050 given the current scenario [13]. Similarly, the annual global GDP may be reduced by 2.5 - 3% in 2050 relative to a base-case scenario with no AMR effects. In Low-Income Countries (LICs), AMR frequently occurs in microorganisms that are likely to be transmitted in the community such as Mycobacterium, Neisseria gonorrhoea [14], Vibrio infections and Campylobacter [15]. 2 According to Food and Drug Administration (FDA) (2011), between 50 and 70 percent of medically important antimicrobials in humans are also used in livestock. Studies suggest that 75-90 percent of tested antimicrobials are excreted from animals un-metabolized and enter sewage systems and water sources thus contaminating the ecosystems. In this scenario, animal wastes can contain resistant bacteria and antimicrobials that could then foster the emergence of resistance in bacteria beyond those in animal guts – including bacteria that may pose a greater risk to humans and animals [10]. Manure from farm animals is often used on crops as a fertilizer which has been shown to create resistance. In the United Republic of Tanzania (URT), agriculture contributes to at least 30% of the national GDP and 67% of the total employment. The livestock industry contributed about 13%, to the Agricultural GDP and 7.9% to the National GDP in 2015. Despite low contribution of livestock sector to the regional agriculture GDP, the livestock population and distribution has been increasing steadily ranking first in the EAC and SADC. The scenario of antimicrobials usage in human and animal health in Tanzania is similar to other developing countries. 3 CHAPTER TWO JUSTIFICATION FOR AMR SURVEILLANCE The Joint External Evaluation (JEE) report of IHR core capacities conducted in the Tanzania Mainland in 2016 indicated a lack of capacity for AMR detection and surveillance of infectious caused by AMR pathogens. The FAO Assessment Tool for Laboratory and AMR Surveillance System (ATLASS) Progressive Indicator Pathway score for AMR surveillance system in the country indicated to be level 1, which is mostly due to a lack of standardized methods in laboratories practicing AST and data collection for the monitoring of indicators of AMR for animals, agriculture and environment. The findings of these independent and joint reports clearly indicated the country’s capability to manage AMR and their associated threats is below the global recommended levels, underscoring the need to address challenges related to AMR and hence the developments of this surveillance framework. Moreover, the framework is intended to compliment the requirements of the National Action Plan for AMR (2017-2022) that outlines AMR and AMU surveillance and monitoring activities as one of the key component to be addressed nationally. In the URT, legislations regulating antibiotic use as well as monitoring and control of their residues are not adequately enforced (Nonga et al., 2009). The inadequacy probably explains the reported high rates of antimicrobial resistance in human, animals and residues in animal products, crops and the environment. In Tanzania, there is no surveillance guideline governing the use of antimicrobials and their associated effects in human, food producing animals, plant and environment. Individual researchers and scientists from different institutions in Tanzania have been working on AMR, but their research findings are not well coordinated to influence policy. Therefore, the purpose of this AMR surveillance framework is to comprehensively and in a systematic manner collect, collate and generate information that will mitigate the AMR and antimicrobial misuse in these sectors through effective monitoring of pathogens, Antimicrobial use (AMU), antimicrobial sensitivity testing, antimicrobial residues and enhancing the prudent use of antimicrobials through communication of outcomes to the public. Laboratory based AMR surveillance is required for national action plan in the monitoring of emergency and spread of antimicrobial resistance. The generated data will be essential to inform and direct policy on AMR. The ultimate goal of this AMR surveillance Framework is to enable standardized, comparable and validated data on AMR to be collected, analyzed and shared, in order to inform decision-making, drive local and national action and provide the evidence base for action and advocacy. While recognizing the global importance of drug resistance among viruses, fungi and parasites, this framework focuses on common bacteria causing infections in Tanzania but, will also consider pathogens identified globally as priority organisms for the early implementation of AMR surveillance. It is anticipated that activities which improve the isolation, identification, susceptibility testing and reporting of these organisms will eventually support development of clinical diagnostics for other pathogens. 4 CHAPTER THREE SURVEILLANCE OF ANTIMICROBIAL RESISTANCE IN HUMAN 3.1 SITUATIONAL ANALYSIS OF AMR IN HUMAN The most important problem associated with infectious disease is the rapid development of AMR that threatens the effective treatment and prevention of an ever-increasing range of infections caused by bacteria. Developing countries including Tanzania that bear 95% of the global burden of infectious diseases rely on empirical antimicrobial treatment to counteract these infections [16]. Tied with burden of infectious diseases, in Tanzania very high rates of resistance have been observed in bacteria that cause common health-care and community acquired infections [17,18] and alternative options are very expensive to afford. Furthermore, infections due to these multi-drug resistant organisms are associated with increased mortality and morbidity [19]. Bacterial pneumonia, bloodstream infections (BSI), urinary tract infections (UTI), bacterial sexually transmitted infections, and healthcare-associated infections such as methicillin resistant Staphylococcus aureus (MRSA) are among the important bacterial infections requiring antibiotics prescription. Data generated from individual researches and scientists from different institutions, shows enormous burden of antimicrobial resistant pathogens causing these infections [20-22]. Despite availability of data from individuals’ researches, there is lack of unified standardized AMR surveillance system to determine the burden of AMR pathogens countrywide. Studies have often reported very serious BSI requiring immediate antibiotic treatment with prevalence/ incidence rate of 10% in children under 14 years; 13.9% in children under 7 years; 7.5% in children under three years; and 14% in both children and adults [20, 23-25]. Neonatal sepsis rate has been reported as high as 39% of neonates admitted in neonate unit [26]. Most of bacterial isolates reported were highly resistant to commonly prescribed antibiotics; overall 60-80% of all Gram-negative isolates were resistant to Cotrimoxazole; 62.7-100% resistant to ampicillin, up to 67% resistant to gentamicin, 49% resistant to third generation cephalosporin and 14-49% were Extended spectrum beta-lactamases (ESBL) producers [23, 26-28]. A recent study from Tanzania Island, reported that six of seven Salmonella typhi isolates from BSI were multidrug resistant [24]. In the North-Western part of Tanzania mainland, Salmonella spp. were sensitive to ceftriaxone and imipenem, while being 84%, 69.2%, 38%, and 8% resistant to chloramphenicol, ampicillin, sulfamethoxazole/trimethoprim and ciprofloxacin respectively [21]. High levels of resistance of Gram positive bacteria from BSI were observed in penicillin G (70.6% - 91%) [23] whereas other study reported 28% of MRSA[26]. UTI is the second most common site of infection after Acute Respiratory Infection (ARIs) in the community and incidence varies by age, gender and health status. The prevalence in Tanzania varies from 13.9% in pregnant women to 39.7% among under-fives [20, 29- 31]. In all in country previous studies, E. coli was the most common cause of UTI, followed by Klebsiella pneumoniae. More than 85% of all isolates were resistant to ampicillin, 77% to Cotrimoxazole, 14-51% to Ceftriaxone, 14-27% to Ciprofloxacin [20, 29-31]. Generally, there has been an increasing trend of bacteria to become resistant to most prescribed antibiotics. Among E. coli isolates from urine; amoxicillin-clavulanate resistance has been increasing from 31.4% in 2004 5 [32] to 69.6 % and 85.7% in 2010 and 2014, respectively [20, 33]. Resistance trend to gentamicin among E. coli isolated from urine specimens has been found to range from 8.6% in 2004 to more than 44% in 2011at Muhimbili National hospital (MNH) [20, 32]. Resistance rate of E. coli to ciprofloxacin an alternative empirical treatment of UTIs when resistance to Cotrimoxazole is over 20% was found to be between 8.1% and 30.4% at Bugando Medical center (BMC) and MNH respectively [20, 31]. The rate of resistance of E. coli to ceftriaxone at BMC was found to increase from 14% in 2009 to 29.4 % in 2011 [29, 31] while at MNH, 49.3% and 50% of E.coli were resistance to ceftazidime and cefotaxime, respectively [20]. Two studies at MNH on Enterobacteriaceae causing hospital and community UTI found 23.8 45.2% of all isolates were ESBL producers [17, 20]. Surgical site infection (SSI) is among the common hospital acquired infections in developing countries. In Tanzania, S. aureus, E.coli, K. pneumoniae, Acinetobacter spp and Pseudomonas aeruginosa are among the predominant pathogens causing SSI. Recent studies from referral and tertiary hospitals reported 18.8% and 44% of Staphylococcus aureus isolates respectively [22, 34-35]. Moreover 71% [35] and 79.3% [22] were ESBL producers. The majority of Acinetobacter baumannii isolates from SSI at MNH, were highly resistant (73% to 100%) to most antimicrobial agents and 60% appeared to be [37]moderately sensitive to imipenem [22]. Previous studies in Tanzania revealed multi-drug resistant bacteria in diarrheal disease etiologic agents with 38% of diarrheagenic E. coli (DEC) found to be multi-resistant [36-37] and Shigella isolates were resistant to several antimicrobial agents. A recent study in Dar es Salaam found DEC displayed high rates of resistance to Cotrimoxazole (90.6%) and ampicillin (96.9%) while 56.2% found moderately resistant to chloramphenicol. At the same time Shigella spp. showed high rate of resistance to Co-trimoxazole (93.3%) [38]. Another study from a health facility in North Western, Tanzania on susceptibility pattern of Shigella from patients with dysentery found highly resistant to tetracycline, Trimethoprim-Sulphamethoxazole, ampicillin and chloramphenicol [39]. Neisseria gonorrheae is often resistant to first-line antibiotics but data on antimicrobial resistance of Neisseria gonorrheae etiologic agent for gonorrhea are scarce. The study done in 2013, showed high resistance rates of N. gonorrhea to ciprofloxacin (77.7 % which had replaced Cotrimoxazole as first line [40]. Despite availability of these data on resistance patterns of different pathogenic bacteria, generalization of the findings is very difficult due unequal sample size representation and different study methodology. Therefore, having one systematic surveillance system across the country could shed light on the burden of antimicrobial resistance. Currently the laboratory capacity in Tanzania is depicted by the existence of policy for ensuring quality of laboratory diagnostic capacities. The national laboratory quality standards/guidelines have been established, some laboratories at referral level participate in international EQA schemes, staff at all levels (Regional, Zonal and Reference Laboratories) have been trained in laboratory practices for isolation, identification and antimicrobial susceptibility testing (AST) performance. To date five referral laboratories including NHLQATC, have been accredited by SADCAS under ISO 15189, however 3 of them the microbiology section was not included 6 for accreditation. There is a program involving regional, special and some of faith based laboratories on accreditation process through SLMTA of which 48 Laboratories are enrolled in the program. However, there is limited laboratory diagnostic capacity for culture and AST at regional and district level often due to supply chain and human resource issues. 3.2 GOAL AND OBJECTIVES Surveillance of AMR in human is critical for providing data on the extent and trends of the AMR problem. In Tanzania, there is no AMR surveillance in the context of a One Health approach which in turn limits national efforts to tackle AMR. Through the National Action Plan (NAP) on Antimicrobial Resistance 2017-2022, the national surveillance system for AMR will be established. Laboratory-based surveillance is required for national action in the monitoring of AMR and its spread. For reliable microbiological and AST, it is imperative to equip laboratories with equipment, reagents and human resource. Furthermore, a coordinated mechanism for AMR reporting will be established in order to share information in one health approach. 3.2.1 GOAL OF AMR SURVEILLANCE SYSTEM The primary goal of this AMR surveillance system in human is to generate evidence on the burden of AMR among priority pathogens isolated in hospitals from in-patients and outpatients who have been referred for laboratory testing 3.2.2 STRATEGIC OBJECTIVES The goal of antimicrobial resistance surveillance will be met through the following strategic objectives i. Conduct routine AST on pathogens isolated from specimens of inpatients and/or outpatients with clinical infections at surveillance hospitals ii. Establish monthly reporting of AST results and patient data from surveillance sites to National Health Laboratory Quality Assurance and Training Centre (NHLQATC) iii. Establish regular and systematic communication of AST results from testing laboratories to clinical providers, infection prevention and control (IPC) and stewardship committees as described in this document iv. Analyze, interpret, and publicly report annual AMR surveillance data in a written report at each surveillance site v. Participate in global AMR surveillance through reporting to WHO 3.3 SURVEILLANCE METHODS 3.3.1 ROAD MAP FOR AMR SURVEILLANCE IMPLEMENTATION The implementation period for the Tanzania AMR Surveillance System will be during 2018–2021. Five health facilities are proposed for phase I roll-out AMR surveillance with potential expansion to additional ten facilities in phase II and phase III during this period (2018 – 2021). Before initiation of AMR surveillance, laboratory assessment will be conducted to establish the capacities of facilities. This assessment will then give a true picture of which surveillance sites to be included in phase I, II and III from the list in table 1. Program success in initial phase will guide scaling-up of the surveillance sites. Extension of AMR surveillance to include other facilities will occur when 7 laboratories are functioning at acceptable capacity. After 6-months of surveillance activities, a formal program evaluation to assess challenges and program revision shall be performed with support from local and international stakeholders. This process will repeat every 12-months as additional sites are added (Appendix II)Table Table 1: List of proposed sites for AMR surveillance implementation S/N Surveillance site Region 1 Muhimbili National Hospital Dar es Salaam 2 Mbeya Referral Hospital Mbeya 3 Bugando Medical Centre Mwanza 4 Kilimanjaro Christian Medical centre Moshi 5 Ndanda Hospital Mtwara 6 Temeke Regional Referral Hospital Dar es Salaam 7 Kibong’oto Hospital Moshi 8 Amana Regional Referral Hospital Dar es Salaam 9 Maweni Regional Referral Hospital Kigoma 10 Mawenzi Regional Hospital Kilimanjaro 11 Mount Meru Regional Hospital Arusha 12 Musoma Regional Hospital Mara 13 Mbeya Regional Hospital Mbeya 14 Sekou Toure Regional Hospital Mwanza 15 Mnazi mmoja Referral Hospital Zanzibar 16 Sumbawanga Regional Hospital Rukwa 17 Morogoro Regional Hospital Morogoro 18 Dodoma Regional Hospital Dodoma 19 Mpanda Regional Hospital Katavi 20 Kitete Regional Hospital Tabora 21 Kagera Regional Hospital Kagera 22 Shinyanga Regional Hospital Shinyanga 23 Benjamini Mkapa Hospital Dodoma 24 MUHAS Academic Medical Centre Dar es Salaam 25 Ifakara Referral Hospitals Morogoro 3.3.2 SURVEILLANCE ROLL-OUT SITE PREPARATION Prior to participation in AMR surveillance, facility´s laboratory will be assessed using standardized laboratory assessment tool for AMR to assess Laboratory capacity in microbiology section including record keeping, organization, personnel, facility, equipment, purchasing /inventory, quality control (QC)/quality assurance (QA), basic bacteriology, human resources and information systems. There shall be training of trainer on AMR surveillance who will be used to provide mentorship to the laboratories participating in AMR surveillance. In preparation for the initiation of surveillance, extensive sensitization and training on the AMR surveillance strategy and procedures will be conducted for hospital administration and relevant clinical and laboratory personnel from selected sentinel sites. Hospital administrators will be requested to designate AMR site coordinators from both the clinical and laboratory departments and ensure that the program can be actively promoted. Laboratories will be trained on surveillance requirements and procedures for culture, identification, AST, quality control, external quality assurance, data reporting, and all relevant standard operating procedures (SOPs). 8 The AMR site coordinators will attend a sensitization workshop where the AMR surveillance system strategy, as defined in this document, will be described in detail. Additional on-site meetings and orientation will be held to familiarize clinicians with good specimen collection practices, increase awareness of the national AMR surveillance system, allow laboratorians to review the format and implications of AST results provided to clinicians, alert clinicians to the availability of hospital AMR data, and foster clinician-laboratory communication for discussion of AMR organisms in individual patients, the hospital system, and the region. In the initial implementation period, participating laboratories will be provided with guidance on surveillance and reporting requirements, laboratory methodology, and QA as outlined in standard operating procedures (SOPs) for specimen collection, laboratory culture, and AST. Participating hospitals will also be asked to provide data regarding the catchment population (e.g., number of patients seeking care, demographics). Key activities during roll-out of AMR surveillance are summarised in Table 2. A reverse EQA (confirmatory testing at NHLQATC) will be conducted quarterly in-addition to EQA panel provided by the external provider be conducted quarterly Table 2: Steps and key activities during roll out AMR surveillance S/N Key Activities 1 Conduct meeting to review/harmonize the proposed AMR surveillance plan draft, assessment tools, SOPs and other manuals 2 Develop standard operating procedures (SOPs) for AMR surveillance 3 Assessment of National Reference Laboratory for AMR surveillance implementation 4 Technical support of National Reference Laboratory for AMR surveillance implementation 5 Assessment of proposed AMR surveillance sites (labs and Hospitals) 6 Conduct workshop for proposed AMR surveillance sites 7 AMR training workshop for clinician 8 Disseminate the AMR surveillance, tools, SOPs, manuals, and forms 9 Establish an electronic system for AMR data repository 10 Equip the national laboratory with equipment for bio-bank/bio repository 11 On site train of AMR surveillance sites personnel on culture, identification and AST for priority pathogens 12 Develop the master list for the materials/reagents/items, required for AMR surveillance and supply mechanism to ensure constant availability 13 Initiate implementation of AMR surveillance at site level 14 Provide mentorship and supportive supervision to facilities implementation of AMR surveillance 15 Train laboratory personnel, on AMR QA program 16 Institute EQA for AMR testing basing on the WHO guidelines and ISO standards to participating laboratories 17 Support implementation, of EQA AMR scheme for appointed laboratories 18 Report for AMR data to national and Global surveillance sites 9 3.4 DESCRIPTION OF SURVEILLANCE STRATEGY 3 .4.1 ROUTINE CLINICAL SURVEILLANCE METHODOLOGY In this surveillance, the primary method for surveillance of AMR organisms will be routine inpatient and out-patient collection of clinical specimens at participating hospitals. Specimens will be cultured and AST performed on all isolated pathogens. For all specimens positive for a priority organism(s), patient and laboratory data shall be reported into a laboratory information management system capable of facilitating reporting requirements (Figure 1). A standard data collection tool [Appendix II] will be used to record all surveillance data. AMR surveillance data will be entered into WHONET software and/or a computerized database at surveillance site level and also saved as hard copy at surveillance site. AST results will then be returned to clinicians, IPC and AMR teams. All isolates from each surveillance site will be stored at-70 °C for future studies. Collected data will then be submitted to NHLQATC, which will make it available to the AMR Unit in the Ministry of Health to generate reports and policy. Isolates with unusual, unexpected or indeterminate resistance patterns shall be sent to NHLQATC for confirmatory testing and AST. Every 10th isolate from each site shall be send to NHLQATC for QA. NHLQATC also will conduct aggregated data reporting to WHO completing the global component of the surveillance system. Figure 1: Simplified diagram of AST data sharing and isolate/sample transmission in the Antimicrobial Resistance Surveillance System 3.4.2 PRIORITY SPECIMENS, ORGANISMS AND ANTIBIOTICS Priority specimens for AMR surveillance in Tanzania include urine, blood, stool, cerebral spinal fluid (CSF), wound swabs/pus, and genital swabs (urethral and cervical). The first priority specimens for AMR surveillance for this surveillance plan shall be blood and urine cultures. This will then be followed up by other priority specimens once laboratories have been able to accurately report AST from urine and blood priority pathogens. The choice of priority specimens to follow may be revised during surveillance based on the capacity of laboratories to process the priority specimen and surveillance implementation. Priority pathogens to be considered for AMR surveillance in Tanzania include current GLASS list for global reporting and bacteria causing common infections in the country [table 3]. 10 AST will be conducted according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) and the NHLQATC will provide standard operating procedures (SOPs) to the sites or review and harmonize the SOPs currently in use at the participating laboratories. The priority organisms and antimicrobials for which susceptibility testing will be conducted are shown in table 4. However, the list of antibiotics is not exhaustive, facilities will be required to test all antibiotics highlighted in their SOP, but only listed on table 4 will be reported to Global Antimicrobial Resistance Surveillance System (GLASS). Principle for consideration of bacteria-antimicrobial drug combinations selection will be based on: compliance with GLASS manual, recommended first-line treatment or surrogate substances for AMR, and AST international guidelines. Table 3: Priority surveillance pathogens by specimen for Tanzania AMR surveillance Specimen Laboratory case definition Priority organisms for surveillance Blood Isolation of pathogen from blood E. coli, K pneumoniae, A. baumannii, S. aureus, S. pneumoniae, Salmonella spp. Urine Significant growth in urine specimena E. coli, K. pneumoniae Stool Isolation of Salmonellab or Shigella spp. from stool Salmonella spp, Shigella spp. Urethral and cervical swab Isolation of N. gonorrhoeae N. gonorrhoeae CSF Isolation of S. pneumoniae and N. meningitidis S. pneumoniae and N. meningitidis Wound swabs/pus Isolation of pathogens from swabs E. coli, K. pneumoniae, A. baumannii, S. aureus. Pseudomonas a Pure culture according to local laboratory practice. Catheter samples excluded. b Diarrhoeal surveillance is for non-typhoid salmonella species; for local clinical purposes, typhoid and paratyphoid should be included. Table 4: Priority pathogens-antimicrobial combinations for Tanzania AMR surveillance Pathogen Antibacterial class Antibacterial agents that may be used for ASTa,b Escherichia coli Sulfonamides and trimethoprim Co-trimoxazole Fluoroquinolones Ciprofloxacin or levofloxacin Third-generation cephalosporins Ceftriaxone or cefotaxime and ceftazidime Fourth-generation cephalosporins Cefepime Carbapenems Imipenem, meropenem, ertapenem or doripenem Polymyxins Colistin Penicillins Ampicillin 11 Klebsiella pneumoniae Sulfonamides and trimethoprim Co-trimoxazole Fluoroquinolones Ciprofloxacin or levofloxacin Third-generation cephalosporins Ceftriaxone or cefotaxime and ceftazidime Fourth-generation cephalosporins Cefepime Carbapenems Imipenem, meropenem Polymyxins Colistin Acinetobacter baumannii Tetracyclines Tigecycline or minocycline Aminoglycosides Gentamicin and amikacin Carbapenems Imipenem, meropenem Polymyxins Colistin Staphylococcus aureus Penicillinase-stable beta-lactams Cefoxitin Streptococcus pneumoniae Penicillins Oxacillin , Penicillin G Sulfonamides and trimethoprim Co-trimoxazole Third-generation cephalosporins Ceftriaxone or cefotaxime Salmonella spp. Fluoroquinolones Ciprofloxacin or levofloxacin Third-generation cephalosporins Ceftriaxone or cefotaxime and ceftazidime Carbapenems Imipenem, meropenem Shigella spp. Fluoroquinolones Ciprofloxacin or levofloxacin Third-generation cephalosporins Ceftriaxone or cefotaxime and ceftazidime Macrolides Azithromycin pseudomonas Tetracyclines Tigecycline or minocycline Aminoglycosides Gentamicin and amikacin Carbapenems Imipenem, meropenem Polymyxins Colistin Neisseria gonorrhoeae Third-generation cephalosporins Cefixime, Ceftriaxone Macrolides Azithromycin Aminocyclitols Spectinomycin Fluoroquinolones Ciprofloxacin Aminoglycoside Gentamicin Neisseria meningitidis Third-generation cephalosporins Ceftriaxone Macrolides Azithromycin Fluoroquinolones Ciprofloxacin Phenicols Chloramphenicol a Listed substances are priorities for resistance surveillance in each pathogen but might not be first-line treatment options. b One or more of the drugs listed may be tested. 12 3.5 SURVEILLANCE STANDARDS Minimum AMR surveillance laboratory capabilities are outlined in Table 5. Laboratory surveillance sites must meet the technical laboratory skill, QC, EQA, and data management minimum capabilities to participate in the AMR Surveillance System. A standardized assessment tool will be used to assess each proposed site. The assessment will be used to both determine eligibility to participate and to identify any deficient areas to be addressed prior to surveillance start. Table 5: Minimum requirements for laboratory participation as a surveillance site in the AMR Surveillance System Capacity Minimum Requirements Technical laboratory skills · Identify priority organisms and perform AST in accordance with EUCAST and/ or CLSI standards · Perform AST by using disc diffusion, semi-automated, or manual testing for minimum inhibitory concentration and gradient diffusion Quality control · Utilize a NHLQATC-approved QC system · Maintain QC data records for potential review by NHQATC External quality assurance · Participate in a recognized EQA program · Achieve acceptable performance reviews on periodic EQA dispatches Data management · Make commitment to collect and report good-quality data in accordance with reporting timelines · Employ staff trained in collecting, analyzing and reporting epidemiological, clinical and laboratory data · Dedicate time for staff member(s) to regularly input, analyze, and report data Hospitals’ clinical and laboratory departments · Willingness to participate · Adequate physical infrastructure and equipment · Adequate existing human resources · Microbiology expertise among laboratory staff · Patient populations - patient admissions and out-patient attendance) · Information Systems 3.5.1 CLINICAL SPECIMEN COLLECTION AND TRANSPORT STANDARDS As part of routine clinical care, clinicians at participating hospitals will send a sample(s) for culture and AST from inpatients and outpatients with suspected infection to the laboratory accompanied with standardized laboratory requisition form [Appendix III]. The laboratory requisition form includes the minimum patient data that shall be submitted with a clinical specimen including the following elements which are necessary for AMR surveillance data analysis: · Hospital / Facility Name · Patient Name · Unique Patient Identifier (e.g. Patient Medical Record Number) 13 · Date of Birth [or Age] · Sex · Inpatient / Outpatient · Patient Ward / Location · Admission Date · Specimen Type · Date of Specimen Collection For consistency quality specimen collection, AMR focal person at each hospital ensures that physician and other healthcare workers are provided with SOPs for specimen collection and transport. Laboratory will assess and accept submitted specimens based on acceptance criteria. It is the laboratory’s responsibility to ensure that clinicians have the appropriate containers and materials for priority specimen collection and that an adequate supply of these materials is maintained at all times. Laboratorians who suspect that specimen collection SOPs are not being followed (e.g., high level of specimen contamination with environmental organisms, hemolyzed samples) should meet directly with the clinical team to review collection procedures. 3.5.2 PATIENT SAMPLING STANDARDS The clinical sampling for AMR surveillance shall be guided by the syndromic diagnosis for which patient is being treated. This supports interpretation of the data to guide empiric therapies in the situation if only clinical treatment failures or the most seriously ill patients are investigated. Sentinel site laboratories will also process other samples; however, capacity building and data collection should initially focus on priority specimen as a core function. 3.5.3 LABORATORY STANDARDS 3.5.3.1 PATHOGEN ISOLATION AND IDENTIFICATION Specimen culture and testing for antimicrobial susceptibility will be done by sentinel site laboratories. Isolates with unusual susceptibility profiles, or of uncertain identification, shall be referred to the NRL for AMR as well as a proportion of all isolates for QC purposes. Reporting for AMR surveillance shall focus on the 10 national priority pathogens with the eight WHO priority pathogens included, as described in the GLASS manual and national priorities. These include: · Escherichia coli · Klebsiella pneumoniae · Acinetobacter baumannii · Staphylococcus aureus · Neisseria meningidis · Streptococcus pneumoniae · Salmonella spp. · Shigella spp. · Pseudomonas · Neisseria gonorrhoeae The pathogens shall be identified by using relevant biochemical and/or serological tests following SOPs 14 3.5.3.2 ANTIMICROBIAL SUSCEPTIBILITY TESTING AMR surveillance shall include the following bacteria-antimicrobial drug combinations in compliance with the GLASS manual (table 6). Antimicrobial susceptibility testing for priority pathogens shall be carried out in line with Clinical Laboratory Standards Institute (CLSI) guidelines, using the disc diffusion method. The laboratories shall document whether isolates are susceptible, intermediate or resistant (S/I/R) according to clinical breakpoints defined by CLSI together with the zone sizes (mm) to allow for retrospective adjustment if new breakpoints are set. As the laboratory performance becomes acceptable, minimum inhibitory concentrations (MICs) may be determined by broth dilution (manual or automated) or gradient diffusion tests such as E-Tests. MIC values shall be recorded. These shall happen after reviewing with the labs that will be part of this surveillance system to see if this is feasible. When a new drug is introduced into clinical practice, laboratories will routinely test susceptibility to the drug in order to identify emerging resistance. Laboratory staff will be trained to recognize unusual or unexpected findings in routine samples. They will also be instructed to inform NHLQATC when this happens and if needed request technical assistance. 3.5.4 QUALITY CONTROL Surveillance laboratories will be required to follow the guidelines for microbiology laboratory Quality Control (QC) as published by WHO (WHO 2003) or CLSI. Laboratories will review the components of their QC system with NHLQATC in the initial assessment. Internal quality control (IQC) is a routine procedure undertaken by laboratories to ensure quality of tests. IQC procedures shall be set up by laboratory management on regular periodic basis for tests they perform, and the results shall be recorded and discussed with all staff members. QC procedures must be practiced for each testing method used by the laboratory. Each test kit should have a set of positive and negative controls that are to be included in each test run. QC data sheets and summaries of corrective action shall be retained for documentation. · These are be reviewed and checked periodically by the NHLQATC. · Supervisory review shall be performed for out-of-range QC results and laboratories shall document corrective action that was taken on all QC failures. IQC should cover all steps of each diagnostic test from the collection of specimen to the transmission of the results, as well as media production and maintenance of equipment. IQC testing should be performed regularly with each laboratory determining the frequency depending on the load of specimens it receives for antimicrobial susceptibility testing. Ideally, each batch of AST should be accompanied by an IQC. Laboratory equipment should be assessed on a regular basis to ensure maintenance and quality. The use of reference bacterial strains as recommended by standard guidelines on AST such as CLSI and will contribute to the monitoring of the accuracy of the results. If the results for the control strain are accurate, i.e. all antimicrobial agents are in the control range, the procedure is assumed to be accurate and so AST may be performed on significant isolates. If the zones produced by the QC strains are out of the expected ranges, the technical personnel should try to determine the possible sources of the error and should troubleshoot the causes. If additional assistance is needed the sites will request assistance if they are unable to resolve the error on 15 their own from NHLQATC. IQC must be performed prior to initiating AST on the isolates. The control strains for the laboratories will be purchased from the American Type Culture Collection (ATCC) and the National Collection of Type Cultures (NCTC). 3.5.5 EXTERNAL QUALITY ASSURANCE EQA is a system for validating laboratory performance using an external, objective agency. All laboratories participating in AMR surveillance shall participate in a formal EQA scheme for all tests performed. Proficiency testing (PT), re-testing (rechecking) and on site evaluation shall be used as EQA methods where laboratories process samples/isolates using the normal testing methods by staff who routinely handle such samples. PT results must be reported according to instructions and submitted within required deadlines to agency implementing EQA, which provides feedback and allows comparison with results from other laboratories. Laboratories will also undergo an in-person visit by NLQATC at least twice yearly to review EQA and QC performance, assess all aspects of laboratory testing required to isolate and identify priority organisms and to detect resistance, assess data management quality, and answer questions that the laboratory might have. Each laboratory manager or head of laboratory must deal with unacceptable PT results, and corrective action must be taken and documented. The lab manager shall review EQA results and conduct root cause analysis and correction when corrective action failure occurs. In retesting and rechecking EQA, every 10th isolate from each surveillance sites will be send to NHLQATC for rechecking, and feedback will be provided for corrective action. In addition, during onsite evaluation visit, stored isolated will be picked randomly and retested for QA. For sustainability of EQA program during surveillance period, capacity need be built at NQLATC to ensure consistent supply of PT materials to participating laboratories. At the beginning of the surveillance, PT will be conducted twice a year, retesting of isolates at NQLATC from surveillance site will be performed quarterly. On site visit evaluation retesting will depend on the number of visits to the surveillance sites. 3.5.6 ISOLATE REPOSITORY AND CONFIRMATORY TESTING Zonal laboratories will serve as repository for priority AMR isolates from all participating laboratories in that zone. Once a month, sites will send AMR priority isolates to the zonal laboratories for isolate repository. Prior to and during transport, isolates will be stored, in accordance with SOPs at -20°C or -80°C. The repositories will be equipped with ultra-low freezers, generator and a robust electronic specimen tracking system with bar-coding to allow for retrieval of bacterial isolates overseen by a freezer manager. This resource will be a key asset in promoting nationally relevant research as it will house isolates and sources in the AMR surveillance network. Once a quarter, every 10% isolate found to have a priority AMR organism sent for repositories will undergo confirmatory testing. The zonal laboratories will investigate any discrepant results for correction. 16 3.5.7 PROCUREMENT OF ESSENTIAL REAGENTS, SUPPLIES AND EQUIPMENT Participating laboratories are responsible for ensuring appropriate inventory management of all necessary reagents, supplies and equipment for isolation, identification and AST of priority pathogens. Laboratories are also responsible for adhering to and keeping records of proper equipment maintenance. Participating laboratories will require training on inventory management, supply chain management system, and equipment maintenance. In addition, NHLQATC will maintain a listing of quality supplies and suppliers. The laboratory will follow ISO guidelines for total quality system implementation to monitor the consumption of reagents and supplies and to restock these in sufficient time so that regular activities are not interrupted and MOHCDGEC will ensure timely repair and preventive maintenance of equipment. 3.5.8 REPORTING STANDARDS Reporting of results requires efficient data management at both surveillance sites and national levels. QC will be incorporated at every stage, with automated data validity checks and rules, as well as audit to check data consistency, completeness and accuracy. Confidentiality will be protected and data security measures should be in place. The site coordinator ensures individual case-level anonymized data are submitted to the NHLQATC with health facility data. These include the total number of patient episodes and the total number of samples processed in the laboratory. The NHLQATC should feedback sentinel site data at least quarterly to healthcare administration, clinical and laboratory staff, to support continued engagement with AMR surveillance. Figure 2: Data flow for AMR surveillance 17 3.5.8.1 DATA STANDARDS The validity and efficiency of data collection, transmission, and analysis is a principle concern of any surveillance program. Prior to transmitting the monthly data files to the NHLQATC the data will be reviewed by the laboratory manager at the surveillance site to ensure that data is complete, valid, and in line with AMR surveillance system reporting requirements. AS Per the SOP for Data Management, data files shall be submitted using a uniform filename format that includes laboratory code that has been designated for each laboratory, month, and year. Participating surveillance sites shall enter patient and laboratory data into data management software and shall report AST results specifically linked to patient infections and reported with some clinical data. This reporting standard is referred as patient-based surveillance. Under patient-based surveillance, AST results shall not be reported if they are from a duplicate specimen or if multiple specimens are submitted for culture during the course of a single patient infection. Patient-based surveillance strives to count the AST profile of each individual infection only once. For example, if patient with sepsis had blood cultures drawn at two separate times throughout the course of their infection, and E. coli was isolated from both of their blood cultures, the results of both the first and second E.coli-positive blood cultures would be returned to the clinicians, but only the results of the first E.coli-positive blood culture would be reported into the AMR surveillance system. If the same patient has a subsequent blood culture positive for a different organism (e.g., K. pneumoniae), or if the original organism is later found in another specimen type (e.g., E. coli in urine), both these incidents would be counted as separate infections and each reported to the AMR surveillance system. To ensure repeat culture and AST results from a duplicate or subsequent specimen are removed from the AMR surveillance system, de duplication of non-unique infections will be performed annually by the data manager at the NHLQATC. Each laboratory must also save all electronic files on a local computer or data server as a back-up. 3.5.8.2 SURVEILLANCE SITE REPORTING In addition to the prompt entry of laboratory results into the record system [e.g. laboratory logbook, laboratory information management system (LIMS)) and return of all routine laboratory culture and AST results to clinical teams, laboratories will transfer the results of all priority AMR organisms from the record system in to WHONET. Although laboratory data alone (e.g. organism and AST of all isolates) could be reported to the AMR surveillance system in what is referred to as laboratory-based or isolate-based surveillance, it is more informative to include some clinical data which is specifically linked to a patient’s infection. This is referred to here as patient-based surveillance. The following patient and laboratory data elements should be reported for each priority organism isolated from priority specimens of patients in the outpatient / inpatient / both outpatient and inpatient departments: • Hospital / Facility Name • Unique Patient Identifier (e.g. Patient Medical Record Number) • Patient Date of Birth (or Age) 18 • Patient Sex • Inpatient / Outpatient • Patient Ward / Location • Admission Date (for inpatients) • Date of Specimen Collection • Specimen Type • Pathogen Identification • Gram Stain • AST line-listed data (e.g. minimum inhibitory concentration and/or inhibition zone diameter) for each antibiotic tested • AST interpretation: Susceptible (S), Intermediate (I), and Resistant (R) classification AMR data will be entered into WHONET. The data manager at the NHLQATC will assist laboratories in data management setup and training. The NHLQATC will also provide sites with a paper-based standard reporting tool [Appendix IV] to capture results prior to electronic entry into WHONET. Laboratory technicians should also use the paper-based tool when technical problems arise with WHONET. Procedures for data entry, storage, and export/transfer are provided in the SOP for Data Management. On a monthly basis, the raw, line-listed data in the WHONET will be transmitted electronically to the data manager at the NHLQATC. The following should also be reported monthly in order to calculate denominators: • Total number of specimens processed for each priority specimen type • Total number of culture-negative specimens for each priority specimen type Once a year, surveillance laboratories will be asked to provide updated estimates of hospital and population data, including: • Number and demographics of patients seeking care (separately for inpatient and outpatient) • Size and demographics of population served by hospital 3.5.8.3 ANTIBIOGRAM CREATION The laboratory shall create individualized hospital reports, such as antibiograms, to assist in the overall understanding of AMR organisms in that hospital and community. On annually, each surveillance laboratory will use their own AMR data to create their hospital’s antibiogram. The antibiogram shall be shared with the relevant clinical departments and hospital committees at the hospital in order to increase understanding of AMR organisms prevalent in that hospital and community, to impact treatment policies at the health facility, and to encourage continued participation in the surveillance system. Guidance on how to create hospital AMR report will be provided to each laboratory by the data manager at the NHLQATC. 19 3.5.8.4 NATIONAL AND GLOBAL REPORTING AMR data from surveillance sites will be centrally stored and managed at NHLQATC which will be responsible for conducting data quality checks and data analysis, generating official AMR reports, and providing long-term data storage. Data files received from surveillance laboratories will be reviewed for data quality and will undergo any necessary cleaning and de-duplication prior to importation into the nationwide database. The nationwide database will be backed up bi-weekly by the data manager at the NRL. Reporting of aggregate national and regional AMR data may be used to efficiently prioritize resources and inform policies directed at control of antimicrobial resistance. The following aggregated data will be included in the reports for each priority specimen type (i.e., blood, urine, stool, etc.): • Total number of submissions of that specimen type • Number of culture-negative submissions of that specimen type • Number of submissions positive for each priority pathogen, by: Pathogen type Patient age group Patient sex Time in hospital at time of specimen collection (< 2 days OR > 2 days) • All AST results for each priority organism-specimen combination, by: Patient age group Patient sex Time in hospital at time of specimen collection (< 2 days OR > 2 days) Reports will be published and distributed by MCC at least once yearly, and if indicated, special interim reports or focused analyses will be published. Every 12 months, data from all sites will be aggregated at NHLQATC and reported to WHO in accordance with the WHO Global Antimicrobial Surveillance System protocol 3.7 SURVEILLANCE OF ANTIMICROBIAL USE One of the major activities in the AMR National Action Plan is the surveillance of the use of antimicrobials. Data on the use and consumption of antimicrobials have a number of uses, including: • To relate exposure to antimicrobials to the development of antimicrobial resistance • To identify and provide early warning of problems relating to changes in exposure and utilization and to develop interventions to address problems identified • Monitoring the outcomes of interventions aimed at changing exposure • Assessing quality of prescribing against practice guidelines • Raising awareness in health professionals, consumers and policy makers about the issues of antimicrobial resistance and the contribution of inappropriate use of antimicrobials in humans 20 3.7.1 MONITORING OF ANTIMICROBIAL CONSUMPTIONS WHO methodologies for the monitoring of antimicrobial consumption will be used both at the national and facility levels. At the national level, data collection will be done mainly using the import data. Hence, the antimicrobial consumption data at national level will be collected periodically at: • TFDA - as most of the legal imports are recorded by TFDA including individual imports. The data base will provide the data for all antimicrobial imports to the private sector • MSD - as a Public Procurement Agency is likely to have reasonable documentation of purchases of antimicrobials distributed to public health facilities and Faith Based Organization • Local Manufacturers – to provide data on the produced antimicrobial which have been sold locally in a specified period of time and which are excluded from TFDA and MSD systems. This methodology will provide antimicrobial consumption data at product level which would accordingly provide consumption in terms of packages. The number of grams contained in each package of the given product can be determined as per WHO guidelines which can be divided by the DDD value in grams to get the total number of Daily Defined Dose (DDDs) for that product. To get the estimate of the country consumption for each of the selected products, the collected data on packages converted into DDDs will be further converted into the DDDs/1000inhabitants/day (DID). Core Set of Antimicrobial under Surveillance The WHO surveillance program focuses only on antimicrobials for systemic use. Topical antimicrobials are excluded.. Therefore the following group of antibacterials as per the Anatomical Therapeutic Chemical (ATC) classification system are included in the consumption surveillance. Antimicrobial WHO Classifications Antibacterials Antibiotics for alimentary tract Nitroimidazole derivatives for protozoal diseases J01 A07AA P01AB 3.7.2 MONITORING ANTIBIOTIC USE IN HOSPITALS Monitoring antibiotic consumption and use at the facility level, the WHO Methodology for Point Prevalence Survey on Antibiotic Use in Hospitals will be used. The tool was piloted in Mwananyamala Regional Hospital and Muhimbili National Hospital in April, 2018. The WHO methodology collects basic information on all hospitalized patients that are of relevance for treatment and management of infectious diseases. The methodology includes core and optional indicators including: · Indication for antibiotic prescribed · Antibiotic prescribed to patient (non-proprietary names, dose, duration, indication etc.) · Type of prescriber 21 · If antibiotic is in National Essential Medicines List · If sample has been taken for microbiology diagnostics · Type of specimen for microbiology diagnostics · Isolated organism · Resistance phenotype etc. The data obtained will be used to estimate the antibiotic use in hospitals, assess the implementation of standard treatment guidelines, evaluate the impact of stewardship programmes and inform on antibiotic prescribing trends. The information will support Policy Makers, managers, hospital therapeutic committees and Practitioners to raise awareness on prescribing practices in health professionals and design interventions on improving antibiotic use. 3.8 MONITORING AND EVALUATION OF AMR SURVEILLANCE Monitoring and evaluation of the Country AMR Surveillance System will be established. The evaluation team will be identified (local and external evaluator), with representation from the MCC, NHLQATC, Universities, development partners and some participating laboratories. Evaluation of the program will be guided by the objectives and surveillance system structure. The evaluation team will work together to design an evaluation that will be used to describe and improve program performance and determine the effect of the program. Surveillance system evaluation will be conducted by using an established framework for program evaluation, such as those available from CDC (CDC 1999). Results of the evaluation will be published by the MCC in a special report, and decision makers will use the findings to make adjustments to the Country AMR Surveillance System. Key Performance Indicators Key Performance Indicators (KPIs) are used to monitor progress and identify significant problems at sentinel sites where more detailed investigations are needed to understand why the indicators are not being met. The purpose of this investigation is to support sentinel sites to achieve the KPIs. List of key performance indicators for evaluation and monitoring [Box 1] Box 1: Indicators for a well-functioning sentinel surveillance site Ø >80% of all patients admitted with an infectious syndrome are correctly sampled Ø >95% of all samples sent for investigation include the physician’s clinical diagnosis Ø <10% of samples culture an organisms which is not clinically significant (a contaminant) Ø >95% of priority pathogens are correctly identified by the sentinel site laboratory (tested against the gold-standard of the coordinating AMR laboratory or by EQA assessment) Ø >95% of the resistance profiles are correctly identified by the sentinel site laboratory (tested against the gold-standard of the coordinating AMR laboratory or by EQA assessment) Ø <3 month lag time for reporting all AMR data to the NCC 22 CHAPTER FOUR SURVEILLANCE OF ANTIMICROBIAL RESISTANCE IN ANIMAL, AGRICULTURE 4.1 SITUATIONAL ANALYSIS IN ANIMAL, PLANTS AND ENVIRONMENT 4.1.1 SITUATIONAL ANALYSIS IN ANIMAL Domestic animals suffer from high burden of infectious disease such as bacterial, protozoan, fungi and viral. The most common bacterial diseases are Contagious Bovine Pleuropneumonia in cattle, Contagious Caprine Pleuropneumonia in goats and major tick-borne protozoan diseases of cattle namely; East Coast Fever and Anaplasmosis which are treatable with antimicrobials. Also, Salmonellosis, Colibacillosis, Mycoplasmosis, Infectious Coryza and Coccidiosis in chickens are common infections. These, in addition to non-specific infections and preventive management require use of antimicrobials [41]. Studies have reported drug residues in beef, eggs and milk. Antimicrobial use in veterinary services may be grouped into therapeutic, metaphylactic (timely mass medication), prophylactic and for growth promotion. Farmers may use antimicrobials in animals to compensate for poor farm management practices, lack of formal veterinary services, lack of regulatory capability and because of the prevalent animal diseases. Under these practices, it is likely that farmers are unaware of potential negative effects of antibiotic overuse in animals [7, 42-44]. Commercial chicken and cattle production accounts for most of the veterinary drug use in the URT including antimicrobials. The most common antimicrobials used are oxytetracycline, amprolium, sulphonamides, chlortetracyclines, doxycycline, flumequine, penicillins, neoxyvital, trimazine and tylosin [7,45-46]. In aquaculture, resistance to tetracycline, trimethoprim, amoxicillin, streptomycin, chloramphenicol, and erythromycin have been reported [47]. Information from few researches conducted in Tanzania, showed a considerable number of multidrug resistant bacteria known to cause mastitis in lactating cows [48]. High levels of resistance have been reported to penicillin G, chloramphenicol, streptomycin and oxytetracycline among Staph. hyicus, Staph. intermedius and Staph. aureus. Similar resistance results to amoxicillin and clavulanic acid combination, sulpha-methoxazole and neomycin have been found in poultry products contaminated with E. coli isolates [49]. An increasing trend is the incidence of antimicrobial resistance in multidrug resistant E. coli, Klebsiella pneumoniae, Staph. aureus and Salmonella in food animals in Tanzania [50]. The same authors indicated an increase in methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) in the food animal sector in Tanzania. Similarly, high prevalence of antimicrobial resistance of E. coli and Campylobacter spp isolates from animals have been reported in Tanzania for ampicillin, Amoxicillin + Clavulanic acid, gentamicin co-trimoxazole, tetracycline, amoxicillin, erythromycin, cefuroxime, norfloxacin and ciprofloxacin [50]. Antimicrobial resistant Campylobacter in food animals in Tanzania was reported from isolates in pigs, dairy, and beef cattle with specific resistance to ampicillin, gentamicin, streptomycin, erythromycin, tetracycline, ciprofloxacin, nalidixic acid, azithromycin, chloramphenicol, and tylosin [51]. Resistance of Campylobacter isolates from ducks in Morogoro on cefuroxime sodium, tetracycline, Ampicillin, erythromycin, gentamicin, 23 cloxacillin and amoxicillin have been reported [49]. In 2014, other studies revealed a high number of resistant E. coli and Enterococci isolates from wildlife and cattle in Tanzanian wildlife ecosystems [52]. Antimicrobial resistance has also been reported in isolates from fish and aquatic environment. 4.1.2 SITUATIONAL ANALYSIS in PLANTS Bacterial diseases of plants are less prevalent than diseases caused by fungi and viruses. Antimicrobial agents for prophylactic treatment of bacterial diseases of plants are limited in availability, use and efficacy, and the therapeutic use is largely ineffective. Where studies have been conducted, the most applications have been by spray treatment with tetracycline and streptomycin been the most commonly used antimicrobial agents. In Tanzania, however, the most commonly used antimicrobial agents are Sulphur preparations and specifically in horticulture and in cashew nuts (orchards) [6-7, 9]. 4.1.3 SITUATIONAL ANALYSIS in ENVIRONMENT Antibiotic resistant bacteria are found in animals that have traditionally not been given antimicrobials, such as wild-caught animals, fish and crops. However, bacteria in the environment may carry resistance genes. Some may have natural resistance because of genetic diversity, but some may be because of selection from antibiotic residues washed as effluent into water bodies through rain [53]. Antimicrobials may be released into the environment from human, animals and crop sources, through excretion, disposal of unused or expired compounds, medical wastes, effluents from pharmaceutical industries, discharge from wastewater treatment facilities, leakage from septic systems and agriculture. Other pathways for dissemination are via land application of human and animal wastes, surface runoff and unsaturated zone transport. Once in the environment, like any other organic chemicals, their efficacy depends on their physicochemical properties, prevailing climatic conditions, soil types and variety of other environmental factors. If antimicrobials in the environment are not efficiently degraded, the residues may contribute in development of antimicrobial resistant in microbial populations [54]. Studies on antibiotic residues in the environment have been conducted mostly in high-income countries and relatively little is known of the situation in developing countries. In aquaculture, there is a variable extent of resistance of up to 70% and the resistance observed was mainly due to environmental contamination. The origins of the pathogens were anthropogenic through human and animal wastes and urine with resistant genes for drugs and their residues. This contributes to emergence of resistance bacteria in aquaculture. In areas where integrated aquaculture is implemented the challenge may be more evident. Prominent genes encoding resistance to tetracycline, trimethoprim, amoxicillin, streptomycin, chloramphenicol, and erythromycin were identified in integrated fish farming systems [47]. Strength, weakness, opportunities and challenges facing management of VMU of anti-microbial are shown in details in Table 6 24 Table 6: Strengths, Weakness, Opportunity and Challenges (SWOC) Analysis STRENGTHS Existence of legislation for regulation of quality, safety and efficacy of antimicrobial agents (Acts, Regulations and Guidelines) Existence of regulatory bodies for medical products and professional conduct (TFDA, TBS, VCT, Department of Veterinary Services, Department of Preventive Services, Plant Health Services and other departments) Systems in place for quality control of antimicrobial agents and supply chain Existence of policy guidelines for management and optimal use of antimicrobial agents Political will, supportive government policies and structure. Establishment of multi-disciplinary structure for antimicrobial stewardship and existence of OH strategic Plan, National Action Plan for Public Health Security (NAPHS) and AMR National Action Plan (NAP). Existence of infrastructure (Laboratories and human resource skills) to monitor bacterial resistance and antimicrobial residue patterns Existence of interested professional bodies, associations and civil Societies in the country Training of clinicians, veterinarians and other professionals on improving antibiotic prescription in the human health, food and agriculture sectors. WEAKNESS Absence of a formal and specific regulatory framework for preservation of new antimicrobials Weak enforcement of laws and professional ethics that govern management and use of antimicrobial agents in public health, animal health, agriculture and environment Inadequate policies providing for governance of antimicrobial agents in food, agriculture and environment sectors. Improper handling and storage of antimicrobials leading to sub-effectiveness of these drugs. Inadequate access to data on antimicrobial use and resistance from primary to tertiary level. Lack of a system for control of prescriptions including post prescriptions review. Absence of national veterinary formulary Absence of national disease treatment/ protocol in food and agriculture sectors Absence of health insurance schemes in food and agriculture sectors Poor coordination among stakeholders in antimicrobial use. OPPORTUNITIES Existence of professional bodies and associations The growing bodies of stakeholders (donors, International Partners and agencies) interested in AMR The growing bodies of AMR network at regional and global levels Existence of internationally accepted Tools/data sharing systems for AMR/AMU monitoring/surveillance (GLASS, ATLASS, WHONET) CHALLENGES Wide spread and uncontrollable use of antimicrobial agents in the society Dispensing of antimicrobial agents done by non-professional individuals Erosion of ethical conduct by professionals. Mushrooming of unregistered premises that stock and sale medicines including antimicrobial agents in food and agriculture sectors 25 4.2 GOAL AND OBJECTIVES 4.2.1 GOAL The goal is to contribute to combating and reducing the burden of antimicrobial resistant bacteria in food, agriculture and the environment in the URT through effective monitoring of pathogens and antimicrobial sensitivity testing. The end desire is to enhance the prudent use of antimicrobials through communication of outcomes to the public with an ultimate aim of preserving valuable antimicrobials. 4.2.2 STRATEGIC OBJECTIVES i. Establish profiles of priority resistant pathogens against antimicrobial agents and monitor AMU and AMR in the food producing animals and their products to inform control interventions ii. Establish AMR baseline data from wastewaters, soil and other water sources in the environment iii. Generate AMR data, from animals, food, crops and environment for policy, control and future research guidance iv. Develop an early warning notification system for emergence of novel resistant strains/ pathogens and aid in rapid identification and control of outbreaks 4.3 SURVEILLANCE METHODS AMR Surveillance shall intend to collect, analyze and interpret AMR data for early detection of resistant strains and sharing of necessary information for appropriate action. Different surveillance methods will be employed in this surveillance plan in order to obtain relevant and reliable AMR data to allow interventions to reduce antimicrobial resistance burden in the food and agriculture sectors to be implemented in the country. Depending on the type of information required and availability of resources, both passive and active surveillance types will be implemented in order to track infections and resistant strains. It is also expected that both clinical and microbiological AMR data will be captured and analyzed in order to have valid and accurate AMR data. The surveillance methods in this framework will mainly focus on AMR and antimicrobial usage for the purpose of monitoring the trend of antimicrobial use in the food and agriculture sectors depending on circumstances. Surveillance of antimicrobial resistance or monitoring of prevalence of resistant bacteria of animal, food, environmental and human origin at regular intervals will be undertaken aimed at limiting the spread of antimicrobial resistance and optimizing the choice and use of antimicrobials. 4.3.1 TARGET PRODUCTION SYSTEMS FOR FOOD AND AGRICULTURE AMR surveillance will target the broad sectors of interest, types, roles or end user and production environments in which terrestrial and aquatic animals, plants would be found (Table 8). 26 Table 7: Classification groups of terrestrial and aquatic animals and plants population for consideration within surveillance Production system Environment Animal/ Plant type Major commodities (source of samples) Extensive and intensive ruminant production Grazing (pastoral and agro-pastoral), feedlots Cattle, goats, sheep Meat, milk, manure Pasture based and semi/zero-grazing Cattle (graded/ improved) Milk, meat and manure Commercial, semi intensive and extensive Poultry production cages, poultry houses and backyard Indigenous (chicken, ducks, guinea fowls), broilers and layers Meat, eggs, manure Extensive(free range) and intensive pig production Pig houses and backyard Local and Improved breeds of pigs Meat, manure Companions animals (Stray and housed) houses and backyard Dogs, cats Faecal Aquaculture and mariculture Cages, Recirculation Aquaculture System, pond and Happas Finfish and Crustaceans Freshwater and marine foods Intensive and extensive crop production farm land Vegetables, Fruit trees, Sunflower, cashew-nuts Fresh fruits and vegetables Honey production Bee hives Bee Honey Processed/ semi processed food/ environment Processing plants, transportation and storage facilities Meat, milk, fish, canned food Swabs, wall, effluent, workers 4.3.2 TARGET BACTERIA FOR AMR SURVEILLANCE Bacteria have coexisted with humans, animals and plants for millennia and many are essential to life, while others coexist without causing harm. Some may exist as part of the ‘normal flora’ of a human or animal in good health, but can cause disease when introduced to “normally” sterile parts of the body, such as when the host’s immune system is compromised and in cases of septicemia. There are varieties of bacteria that can be considered in the context of food, agriculture and environment health. In order for a bacterium to be considered sufficient enough for inclusion as an indicator pathogen for surveillance, they should be representative, of high incidence/ prevalence, have zoonotic potential, cause food-borne illnesses and of relatively high pathogenicity. In addition, such organism should have the potential to develop or is known to have developed antimicrobial resistance that is of concern to human, animal, crop and environmental health. These are E. coli. Enterococcus spp, Salmonella spp, Streptococcus, Staphylococcus aureus and Pseudomonas aeruginosa. 27 4.3.3 TARGET ANTIMICROBIAL AGENTS For the purpose of this surveillance, selection of antimicrobials of interest was based on expert opinion and available literatures regarding their availability, accessibility to farmers, spectrum and efficacy, and misuse or abuse. Others include related classes of antimicrobial of public health importance [5] Table 8: Antimicrobials Targeted for Surveillance Classes Principal use in humans Principal use in animals 1 Tetracyclines (Chlortetracycline, oxytetracycline, tetracycline, doxycycline) Used for treatment of infections of the urinary tract, respiratory tract, and the intestines and are also used in the treatment of chlamydia, especially in patients allergic to β-lactams and macrolides Major broad-spectrum primary agent for systemic infections in animals 2 Cephalosporins Treatment of infections in penicillin allergic patients. Prophylaxis in orthopaedic and other surgery and respiratory infections Intramammary treatment of mastitis due to staphylococci and streptococci in dairy cattle/ intrauterine treatment for metritis in cattle 3 Aminoglycosides (Gentamycin and Neomycin) Topical agent for skin infection and gut suppression Primary agent for enteric infections in livestock (oral form); broad spectrum primary agent for a range of systemic infections in livestock. Primary agent for E. coli and Salmonella infections in calves, pigs and broilers 4 Sulfonamides (Trimethoprim/ sulphonamide, Sulfadiazine, Sulfadoxine) Primary agents for broad-spectrum infections in livestock, horses and dogs including enteritis and pneumonia (oral and injectable), Oral sulfonamides (without Trimethoprim) are also used for coccidiosis in poultry and aquatic Used for treating and preventing powdery mildew in cashew-nuts 5 Macrolides (Erythromycin, and Azithromycin, Tylosin) Treatment of minor Gram positive, Chlamydia and Mycoplasma infections. Livestock for respiratory infections and other serious systemic infections including mastitis. Respiratory disease in broilers *(Source: modified from surveillance and reporting of AMR and AMU in animals and Agriculture in Australia, 2014) 28 4.4 SURVEILLANCE CATEGORIES Based on World Organization for Animal Health (OIE) Terrestrial Animal Health Code’ (OIE, 2013c) and ‘OIE Aquatic Animal Health Code’ (OIE, 2013b), AMR surveillance should help to answer the following key questions: a. How do you sample? b. Which sample origin/animal species? c. Which bacterial species? d. Which antibiotics are tested? e. How do you interpret the data? Furthermore, a code identifies the monitoring of AMR in terrestrial and aquatic animals to be necessary in order to: a. establish baseline data on the prevalence of antimicrobial resistant microorganisms and determinants; b. assess and determine the trends and sources of antimicrobial resistance in bacteria; c. detect the emergence of new antimicrobial resistance mechanisms; d. provide the data necessary for conducting risk analyses as relevant to animal and human health; e. provide a basis for policy recommendations for animal and human health; f. provide information for evaluating and guiding antimicrobial prescribing practices and for prudent use recommendations; and g. Explore the potential relationship between antimicrobial resistance in aquatic animal microorganisms and the use of antimicrobial agents. Methods/ Types of AMR surveillance will vary according to situation, and this may include needs and resources availability among others. There will be a well- coordinated three types of surveillance; passive, active and participatory AMR surveillance (figure 3). 4.4.1 PASSIVE SURVEILLANCE Passive surveillance system will target collecting data and samples that have been submitted to diagnostic laboratories for clinical purposes during routine activities. Diagnostic laboratories involved are zonal centers, wildlife and academic/research institution and private laboratories where appropriate. Electronic based system will be used to capture data. 4.4.2 ACTIVE SURVEILLANCE Active surveillance will be planned to target gathering information to guide prudent use of antimicrobials. Longitudinal, cross sectional or purposive surveillance will be used to establish changes in trends over time of resistance prevalence and the emergence of resistant priority pathogens. Surveillance sites will be selected based on the identified production systems and priority species as indicated in table 8. 29 Laboratories Outlets Processing Facilities Routine Samples Slaughter facilities Animal, Fish and plant Farms Fo od o f A ni m al O rig in An im al Fe ed s Te rre st ia l, Aq ua tic a nd P la nt Food processing Milk, eggs, meat etc Re gi on al a nd Zo na l A M R su rv ei lla nc e La bs Ac ad em ic an d Re se ar ch In st itu te s Reference Laboratory El ec tro ni c D at a M an ag em en t U ni t Veterinary Practices Figure 3: Flow chart of AMR coordination and the surveillance 4.4.3 PARTICIPATORY BASED SURVEILLANCE This is the application of Participatory Rural Appraisal (PRA) methods for the collection of epidemiological information to inform decision-making and action where by this method can be used in AMR surveillance at public and community level. The information to be captured during Participatory Surveillance will include knowledge, attitude, practices and perceptions on AMR and AMU. Tools to be used in the Participatory Surveillance will include Focus Group Discussion (FGD), semi structured questionnaire, check list, scoring, ranking, proportional piling and matrix scoring to characterize consumer and suppliers perceived relative preferences and risk factors (drivers) for AMU and AMR. 4.5 SAMPLING PROTOCOL Sampling protocol describes sampling purpose, design and operating procedure. 4.5.1 PURPOSE The purpose of this surveillance protocol is to describe sampling design, type of data to be collected, procedures for collecting, handling, transportation and storage of samples (quality specimen) for AMR laboratory analysis so as to ensure reliable laboratory test results as well as laboratory analyses. 4.5.2 USERS AND RESPONSIBILITY This protocol is intended to be used by all institutions/parties participating in AMR surveillance in Tanzania. It is the responsibility of the sample collectors and analyst to follow this procedure while collecting and handling samples from field to laboratories. Laboratory personnel should ensure that samples submitted meet the sample acceptance criteria for the laboratory testing. 30 4.5.3 SAMPLING DESIGN Longitudinal, cross sectional or purposive surveillance design will be used to establish changes in trends over time of resistance prevalence and the emergence of resistant of priority pathogens. 4.5.4 SAMPLE SIZE The sample size will vary depending on survey methodology to be employed, level of precision, animal species, and type of samples to be collected. For large animals sample size is calculated with the expected minimum disease prevalence of 1% and 95% level of confidence, the population being considered infinite in each sampling location. The sample size will be calculated using the standard formula for estimation of proportion: n = z2 x P (1 - P)/ d2, Where: n = the required sample size; P = estimated prevalence = 0.01; z = level of confidence as 1.96 and d = Desired precision level = 0.05. Sample size in Poultry and eggs is calculated as a Function of Population Size and Minimum Probability of Detection as shown in (Table 10) Table 7: Sample size estimation at predefined level of precision level Number of birds in flock 95% CI #50 #100 #500 #100 #10,000 E st im a te d P re v a le n c e 1% 48 96 225 258 29 5% 31 45 56 59 59 10% 22 25 28 29 29 99% CI E st im a te d P re v a le n c e 1% 50 99 300 68 448 5% 39 59 83 86 90 10% 29 36 42 43 44 CI = Confidence Interval, # =Number: Adopted from: USDA, APHIS, VS, NVSL, Ames, Iowa 50010 – World Reference Lab. 4.5.5 INDIVIDUAL STUDY SAMPLE SIZE ESTIMATION Surveillance standards for antimicrobial resistance adopted from the WHO will be used to guide sample size collection (Table 11). This standardized guide provides the relationship between sample numbers, and the sensitivity of a surveillance system to detect increases in resistance. For example, if a sample size of 200 yields a resistance rate of 5 per cent to a particular antibiotic, the resistance level measured in a second sample of the same size would need to rise above 11 per cent before it can be stated that the level of resistance in the population has increased. However, the sensitivity of the system can be improved by increasing the number of samples. To avoid effect of non-random distribution (clustering) of resistance isolates and recognizing the fact that resistance is randomly distributed throughout the population of isolates (assumption of statistical independence), the sample size requirement will need to be valid and much higher. 31 Table 10: Estimated sample size needed for documenting increasing AMR frequencies Resistance detected in original sample (%) Level of Resistance that would indicate significant increase in AMR frequency (%) Sample size(100) Sample size(200) Sample size(300) Sample size(400) Sample size(500) 2 9 7 5 4 3 5 14 11 9 8 7 10 21 17 15 14 12 25 39 35 32 31 28 50 65 60 58 56 52 Source: (World Health Organization, 2002) 4.5.6 ENVIRONMENTAL SAMPLING For environmental (soil, water and plants) samples, abstract transect can be used to determine the sampling frame and subset of sample population to be considered and the locations. The sample size shall be determined using randomization to select predetermined numbers as shall be informed by anecdotal evidence in the absence of adequate data on sample population. The active sampling shall be quarterly from selected sites 4.6 LABORATORY STANDARDS Table 11: Minimum requirements for laboratory participation as a surveillance site in the AMR Surveillance System Capacity Minimum Requirements Technical laboratory skills · Identify priority organisms and perform AST in accordance with WHO or CLSI standards · Perform AST by using disc diffusion, semi-automated, or manual testing for minimum inhibitory concentration and gradient diffusion Quality control · Utilize a CVL-approved QC system · Maintain QC data records for potential review by CVL External quality assurance · Participate in a recognized EQA program · Achieve acceptable performance reviews on periodic EQA dispatches Data management · Make commitment to collect and report good-quality data in accordance with reporting timelines · Employ staff trained in collecting, analyzing and reporting epidemiological, clinical and laboratory data · Dedicate time for staff member(s) to regularly input, analyze, and report data Site and Laboratory Staff · Willingness to participate · Adequate physical infrastructure and equipment · Adequate existing human resources · Microbiology expertise among laboratory staff · Information Systems To avoid challenges associated with results variability and in order for AMR data to be broadly comparable, laboratory methods must be standardized and harmonized, and AMR data be reported quantitatively. 32 4.6.1 SAMPLE SUBMISSION AND CODING All samples submitted to the laboratory for AMR Surveillance should be accompanied by a completed sample submission form where information regarding Sample (animal/fish spp, breed, animal/fish Identification, age, sex and collection date), farming system, location and owner and indicated (see information on submission form). On the other hand for food and feed samples: information contained in the form will include location, premise, sampling date, owner of the premise, food type, date of manufacturing, manufacturer and storage condition. For environmental samples: location, premise, sampling date, premise neighboring activities, and sample type information should be included. 4.6.2 SAMPLE COLLECTION Types of samples to be collected in relation to priority organisms are indicated in the table 12 and 13. Standard procedures for sample collection, preservation, transportation and storage should be adhered Table 8: Samples from Animals Priority organisms for screening Type of Samples Salmonella spp Swabs eg. Surface, Faecal sample GIT, etc Staphylococcus spp Swab samples from food producing animals (Faecal, nasal, choanal, cloacal and septic wound) E. coli Faecal sample, GIT swabs, body swab, water Enterococcus spp Faecal sample Campylobacter spp Faecal sample Table 9: Food Crop and Environmental Samples Priority organisms Type of Samples Streptococcus spp · Milk from cows with mastitis · Tissue samples, Plant tissue · Water sample Staphylococcus spp · Milk from cows with mastitis · Eggs, Plant tissue · Tissue samples, Plant tissue · Water sample Salmonella spp · Eggs, Plant tissue · Water sample E. coli · Eggs, Plant tissue · Water sample 33 4.6.3 LABORATORY TESTING STANDARDS All AMR testing should follow approved Tanzania Standards. During laboratory analysis for detection and isolation of particular bacteria, respective tests method should be used. Tanzania Standards methods will be given first preference. Where the Tanzania Standards are not available ISO standards will be opted. To determine the susceptibility of the isolate, ISO 20776 shall be used. There shall be specific SOPs for each priority pathogen identification namely: Salmonella, E. coli, Staphylococcus aureus, Aeronomonas, Enterococcus and Klebsiella. Antimicrobial Susceptibility Testing (AST) will be performed for the following antimicrobial groups namely: Tetracycline, Penicillin, Sulfonamides, Cephalosporins, Aminoglycosides and Macrolides. Quantitative results (disc diffusion, zone diameters or minimum inhibitory concentration values) will be performed in accordance to CLSI standards. The confirmation of isolates should be done using recommended techniques such as serotyping (salmonella spp), Polymerase Chain Reaction (E.coli and S.aureus) and E kits specific for ESBL Chromogenic media and other biochemical tests. For some species it will be necessary to identify pathogen to the type level (e.g. serotypes) 4.6.4 ANTIMICROBIAL SUSCEPTIBILITY TESTING Antimicrobial susceptibility testing for priority pathogens shall be carried out in line with Clinical Laboratory Standards Institute (CLSI) guidelines, using the disc diffusion method. The laboratories shall document whether isolates are susceptible (S), intermediate (I) or resistant (R) according to clinical breakpoints defined by CLSI together with the zone sizes (mm) to allow for retrospective adjustment if new breakpoints are set. As the laboratory performance becomes acceptable, minimum inhibitory concentrations (MICs) may be determined by broth dilution (manual or automated) or gradient diffusion tests such as E-Tests. MIC values shall be recorded. These shall happen after reviewing with the labs that will be part of this surveillance system to see if this is feasible. When a new drug is introduced into clinical practice, laboratories will routinely test susceptibility to the drug in order to identify emerging resistance. Laboratory staff will be trained to recognize unusual or unexpected findings in routine samples. They will also be instructed to inform CVL when this happens and if needed request technical assistance 4.6.5 LABORATORY SUPPLIES, REAGENTS AND EQUIPMENT Bacteriological media and reagents to be used in isolation, characterization and susceptibility testing should be as per respective test method standards and described in the respective SOPs. When selective media used is not described in the standards manufactures instruction shall be incorporated in SOP, operations of the equipment in the entire testing sequence should be described in the equipment operation SOP but the test condition will be as per respective test methods (Standard) or SOP. The laboratory involved in the implementation of this plan should ensure availability of all necessary supplies. 34 4.6.6 QUALITY ASSURANCE To assure the quality of results, the laboratory shall ensure the availability of competent technical personnel, implementation of Quality Management System (QMS), participation in intra and inter laboratory comparison testing. Internal and external quality audit and implementation of the non-conformance identified during audit should be part and parcel of each participating laboratory. Standards reference materials for each priority pathogens will be made available at all laboratory testing to minimize user errors and incorrect identifications. Each test kit should have a set of positive and negative controls that are to be included in each test run. QC data sheets and summaries of corrective action shall be retained for documentation. · These will be reviewed and checked periodically by the CVL. · Supervisory review shall be performed for out-of-range QC results and laboratories shall document corrective action that was taken on all QC failures. 4.6.6.1 INTERNAL QUALITY CONTROL Inter-laboratory Comparison test panel will be prepared and supervised by CVL to cover for IQC. It should cover all steps of each diagnostic test from the collection of specimen to the transmission of the results, as well as media production and maintenance of equipment. IQC testing should be performed regularly with each laboratory determining the frequency depending on the load of specimens it receives for antimicrobial susceptibility testing. Ideally, each batch of AST should be accompanied by an IQC. Laboratory equipment should be assessed on a regular basis to ensure maintenance and quality. The use of reference bacterial strains as recommended by CLSI standard guidelines will contribute to the monitoring of the accuracy of the results. If the results for the control strain are accurate, i.e. all antimicrobial agents are in the control range, the procedure is assumed to be accurate and so AST may be performed on significant isolates. If the zones produced by the QC strains are out of the expected ranges, the technical personnel should try to determine the possible sources of the error and should troubleshoot the causes. If additional assistance is needed the sites will request assistance if they are unable to resolve the error on their own from CVL. IQC must be performed prior to initiating AST on the isolates. The control strains for the laboratories will be purchased from the American Type Culture Collection (ATCC) and the National Collection of Type Cultures (NCTC). In retesting and rechecking IQC, positive isolate (including few negative) from each surveillance sites will be send to CVL for rechecking, and feedback will be provided for corrective action. In addition, during onsite evaluation visit, stored isolated will be picked randomly and retested for QA. For sustainability of ILC program during surveillance period, capacity need will be built at CVL to ensure consistent supply of panel materials to participating laboratories. At the beginning of the surveillance, ILC will be conducted twice a year, retesting of isolates at CVL from surveillance site will be performed quarterly. On site visit evaluation retesting will depend on the number of visits to the surveillance sites. 35 4.6.6.2 EXTERNAL QUALITY ASSURANCE (EQA) CVL will be participating into Proficiency testing (PT), re-testing (rechecking) and on-site evaluation organized by international and reference lab for AMR to cover for EQA. PT results must be reported according to instructions and submitted within required deadlines to agency implementing EQA, which provides feedback and allows comparison with results from other laboratories. CVL may conduct yearly and whenever possible twice per year in EQA and QC performance. 4.6.7 ISOLATE REPOSITORY All banked cultures should have a repository at National reference AMR laboratories (CVL). Once a month, surveillance sample collection sites will send AMR priority isolates to the national reference laboratory for isolate repository. Prior to and during transport, isolates will be stored, in accordance with SOPs at -20°C or -80°C. The repositories will be equipped with ultra-low freezers, generator and a robust electronic specimen tracking system with bar-coding to allow for retrieval of bacterial isolates overseen by a freezer manager. This resource will be a key asset in promoting nationally relevant research as it will house isolates and sources in the AMR surveillance network. Once a quarter, every 10% isolate found to have a priority AMR organism sent for repositories will undergo confirmatory testing. CVL will investigate any discrepant results for correction. 4.7 DATA MANAGEMENT AND INFORMATION SHARING Social, Field and laboratory data collected via surveillance will be handled and managed centrally at designated appropriate competent authorities. Screening analysis will be performed to generate information to inform level of resistance per microbial agents, resistant pathogen and likely risk areas along the broad chain of microbial agent’s distribution for consumption among different stakeholders. A principal element of AMR surveillance systems is the detection and demonstration of significant differences in proportion of resistant isolates from year to year and significant trends over periods of three or more years. Data analysis software will be done by using Laboratory Information Management System (LIMS) and other electronic software (e.g. Epicollect). They shall be used for flexible exploration and reporting of antimicrobial resistance. Data and any other information recorded in the LIMS will be used for generation of respective reports for implementation or subsequent intervention. Sharing of the information will be done depending on the requirements. Some of the stakeholders in the implementation of the plan will be linked directly to LIMS. National Reference Laboratory will host and manage the database server. 4.8 ANTIMICROBIAL USE SURVEILLANCE Monitoring of bacteria and Antibiotic residue from products of animal origin intended for human consumption collected at different steps of the food chain, including processing, packing and retailing, will be part of surveillance of antimicrobial use (AMU). 36 Monitoring of AMU involves collection of quantitative information by animal species, antimicrobial agent or class of agent, user (i.e. farmers) perception (access, storage, use, and handling), type of use, including therapeutic and non-therapeutic, and route of administration. The collection and analysis of such information is intended to support planning and risk analysis, and to address the problem systematically. Publication of these data will promote transparency and allow interested parties to assess trends and contribute to risk assessment and risk communication. World Health Organization recommends the following steps and factors to be considered in monitoring antimicrobial usage. i. Describe the system of distribution of antimicrobial agents in the country and identify sales points outside the mainstream regulatory system, for example, internet sales, import of medicated animal feeds and movement of antimicrobial agents across borders ii. Identify the antimicrobial agents in commercial circulation. iii. Identify potential points of data collection iv. Assess what each data source represents v. Set parameters for precision and completeness of the surveillance system 4.8.1 SOURCE OF DATA FOR AMU It is expected that the source of data for AMU will include but not limited to customs, import and export data, manufacturing and sales data. Others include from veterinary medicinal product registration authorities, wholesalers, retailers, pharmacists, veterinarians, feed stores, feed mills and pharmaceutical industry associations. Various tools including comprehensive designed data collection form to fill in data, registries will be used at defined periodic intervals. 4.8.2 DATA COLLECTION PROCEDURES To be able to monitor use of antimicrobial agents different data types and collection procedures will be employed as described below; i. Collect appropriate information of the pharmaceutical manufacturers and the regulatory authority (TFDA), targeting types of drugs, importers, volumes, labelling and packaging and distribution channels. ii. Non-conventional sources including Internet sales data related to antimicrobial agents could be collected where available iii. Collect information from the end-user (veterinarians and food animal producers) Collection, storage and processing of data from end-use sources should be carefully designed, well managed and have the capability to produce accurate and targeted information. 4.8.3 TYPES OF DATA TO BE COLLECTED i. Quantity of the active ingredient of the antimicrobial (s) used in food-producing animals per year. ii. Estimate of total usage: i.e. sales data, prescribing data, manufacturing data, clients, drugs usage records(type, amount, sources, storage, administration), import and export data or any combination of these 37 iii. Information on dosage regimens (dose, dosing interval and duration of the treatment) and route of administration are elements to include when estimating antimicrobial usage in food-producing animals. iv. Total number of food-producing animals by species, type of production and their weight in kilograms for food production per year; and v. Types of drugs, importers, volumes, labelling and packaging and distribution channels vi. Disposal of expired products? Responsible authorities? From government, private, institution? 4.9 MONITORING AND EVALUATION OF AMR SURVEILLANCE Monitoring and evaluation are dedicated to the assessment of overall performance of the AMR Surveillance system. Monitoring and evaluation of the AMR Surveillance System in the food, agriculture and environment sectors will begin in 2018. Prior to that time, an evaluation team will be identified (local and external evaluator), with representation from the NMCC, Universities, development partners and some participating laboratories to evaluate the capacity of the existing laboratories in the food, agriculture and environment sectors. Performance Indicators Indicators a. Proportion (%) of Institutions incorporated the AMR surveillance into their work plans. b. Proportion (%) of targeted resistant pathogens profiles established annually. c. Proportion (%) of surveillance sites covered in AMR surveillance annually. d. Proportion (%) of surveillance reports generated and shared quarterly, bi-annually and annually. e. Number of sites participating in ILC and EQA f. Number of policy documents developed g. Proportion (%) of early warning notifications resulted from emergency of novel resistant pathogen 38 CHAPTER FIVE ROLES AND RESPONSIBILITIES 5.1 NATIONAL MULTISECTORAL COORDINATING COMMITTEE The country has developed organizational structures for AMR surveillance with defined terms of reference. The National Multi-sectoral Coordinating Committee (MCC) on AMR is the central National steering body to oversee and coordinate all AMR related activities in all sectors. The AMR action plan operations shall be managed and implemented by different ministries and institutions but monitored through the MCC under the chairmanship of the Chief Medical Officer. The role of MCC is to advice, receive and approve surveillance plan and reports after being pre reviewed and recommended by AMR TWG responsible for surveillance and Research. Additional roles of MCC is oversee, coordinate and evaluate all AMR surveillance related activities in the food and agriculture sectors in the country; mobilize the needed resources and convene or organize scientific meetings, seminars and serve as national scientific platform for AMR surveillance in the food, agriculture and environment sectors The MCC has the National AMR Secretariat (with national AMR focal persons for the human and animal sectors) with responsibility among others to coordinate national activities for establishment of AMR surveillance system and report on the prevalence and trends in AMR to GLASS. 5.2 NATIONAL AMR SURVEILLANCE TECHNICAL WORKING GROUP The technical working group for AMR Knowledge, Surveillance, Research and sustainable investments shall provide technical support during implementation of AMR surveillance as per the NAP. The TWG is comprised of relevant technical specialties including experts from infectious diseases, microbiology, epidemiology, laboratory, animal health, infection prevention and control, pharmaceuticals. It is mandated with specific tasks including: • Support the development of a national surveillance system for antimicrobial resistance • Monitor the collection and reporting of data on use of antimicrobial agents in human and animal health and agriculture so that trends can be monitored and the impact of action plans assessed. • Oversee and support implementation of public health research agenda on antimicrobial resistance, including: research to promote responsible use of antimicrobial medicines; defining improved practices for preventing infection in human and animal health and agricultural practice; and encouraging development of novel diagnostic tools and antimicrobial medicines 5.3 INTERNATIONAL STAKEHOLDERS • Support in building laboratory capacity to identifying and report AMR organisms • Provide technical (e.g. trainings, mentorship, assessments) and material (e.g. reagents, equipment) support towards implementation of AMR surveillance • In consultation with the MCC, include the country AMR data in global reporting of AMR burden 39 5.4 SPECIFIC ROLES AND RESPONSIBILITIES IN THE HUMAN SECTOR 5.4.1 AMR SURVEILLANCE SUB-TECHNICAL WORKING GROUP • Providing technical input and support to NHLQATC • Planning human public health strategic priorities for AMR surveillance • Working close with NHLQATC on ensuring AMR surveillance is conducted • To assist NHLQATC for quantification of equipment, reagents and supplies • Reviewing and scrutinizing AMR data before submission to AMR TWG and Ministry of Health, Community development, Gender, Elderly and Children. 5.4.2 NATIONAL REFERENCE LABORATORY National Health Laboratory Quality Assurance and Training Centre (NHLQATC) is designated as the National Reference Laboratory (NRL) and this will include AMR. The roles and responsibilities of NRL include: • To provide guidance and technical support in AST and quality management to surveillance network laboratories • To provide a reference service for core organism/antimicrobial combinations as a minimum, for borderline isolates or isolates with unexpected or unusual resistance profiles • To confirm unusual or new resistance patterns before they are reported to the relevant national authority • To participate in EQA through appropriate international schemes • To liaise with the MCC in standardizing and verifying microbiological results • Receiving and managing surveillance data from all participating laboratories • To provide EQA across sentinel site laboratories and providing feedback • To assist sentinel site laboratories to procure equipment, reagents and supplies • To conduct or support research studies on AMR in collaboration with MCC and share findings with national and international stakeholders. • To maintain a bio-repository for bacterial isolates 5.4.3 DATA MANAGER / IT SPECIALIST • Assist surveillance site laboratories in data management setup, training, and troubleshooting Ensure electronic laboratory data base software is installed at sites Train on data entry, transmission, and manipulation (e.g. how to compile AST results and antibiograms) Assist sites with troubleshooting electronic database • Provide sites with guidance on how to create internal hospital aggregated reports • Maintain the national AMR surveillance database 40 • Ensure sites send raw, line-listed data monthly • Work with AMR surveillance sites to enforce data quality standards and proper data collection policies and procedures • Review AMR data and ensure that data reported meets AMR surveillance system requirements • Perform data cleaning and de-duplication prior to compilation of national AMR data and long-term storage • Maintain data back-ups • Perform data analyses and prepare annual regional and national AMR reports • Conduct periodic data verification visits which will compare source data and system data • Conduct periodic evaluation of data from facilities 5.4.4 LOGISTICS AND PROCUREMENT PERSONNEL • To coordinate procurement of supplies and reagents and ensure a sustainable supply chain system for the laboratories participating in the AMR surveillance system • Coordinate distribution of standardized reagents and supplies across participating laboratories. • Maintain a list of quality supplies and suppliers • Manage stocks to prevent interruptions in testing and increase accountability for items procured • Ensure that the sites request their annual supply needs • Negotiate service contracts across county and reference laboratories 5.4.5 AMR SURVEILLANCE SITES (HOSPITALS/CLINICS AND LABORATORIES) 5.4.5.1 HOSPITAL ADMINISTRATION • Ensure that there are adequate staff and physical infrastructure in place to perform surveillance activities • Assign a clinical focal person, with a commitment to AMR • Ensure clinicians have appropriate containers and specimen collection materials • Provide staff with specimen collection SOPs and laboratory requisition forms • Ensure frequent communication between the clinical focal personnel and laboratory • Provide MCC with annually updated estimates of hospital and population data • Review and disseminate surveillance reports at the facility level. • Establish hospital AMR Committee consisting of clinicians, laboratory technologists, pharmacists and IPC nurses to meets quarterly 41 5.4.5.2 HOSPITAL AMR COMMITTEE Each participating site shall have an AMR site committee; their members will be selected from hospital therapeutic committee which includes relevant representatives, for example: site coordinator, hospital administrator, data manager, laboratory manager, clinical microbiologist, physician, pediatrician, infection control manager, pharmacist and public health specialist. The role of the Hospital AMR Committee, led by the site coordinator, includes: • Working with the national technical team to facilitate a situational analysis of current capacity and sustainability at the site • Planning strategic priorities at the site • Liaise between hospital clinical and laboratory teams • Convene quarterly to discuss how to address challenges associated with specimen collection, specimen transport, results, reporting • Provide feedback on system and individual performance to the members of the surveillance system at the hospital • Review reports and make recommendations to the hospital administration • Share data and recommendations with additional committees and staff members • Ensure specimens are collected according to the SOPs • Ensure QC measures and regular audit for all AMR surveillance processes • Work with the national technical team to establish internal QA assessment, progressing to EQA assessment • Ensure effective lines of communication are in place for feedback of AMR results to clinicians and feedback of summarized AMR data to stakeholders (administration, clinical, IPC, laboratory and data staff) 5.4.5.3 CLINICIANS (DOCTORS, CLINICAL OFFICERS AND NURSES) • Request the necessary laboratory tests based on the symptomatic and clinical diagnosis • Submit and transport priority specimens per approved specimen collection SOP • Complete laboratory requisition forms [Appendix II] consistently and correctly with the required clinical data 5.4.5.4 LABORATORY TECHNOLOGISTS • Identify the pathogen accurately and perform the AST according to the SOP • Return routine culture results to the requesting hospital/clinicians in a timely manner • Track and keep records of rate of specimen rejection and rates of contamination • Maintain proficiency testing standards and conduct root cause analysis and correction when failure occurs • Manage inventory of all necessary reagents • Adhere to and keep records of proper equipment maintenance 42 5.4.5.5 LABORATORY MANAGER • Assign a laboratory focal person, with a commitment to AMR • Liaise between hospital clinical and laboratory teams • Ensure adherence to SOPs in the bacteriology laboratory • Review all positive culture results prior to returning to hospitals/ordering clinicians • Review and approve monthly submissions of AMR data to NRL • Perform supervisory review for out-of-range QC results and document corrective action that was taken on all QC failures • Review EQA results and conduct root cause analysis and correction when failure occurs • Share hospital antibiogram with the relevant clinical departments and hospital committees • Ensure appropriate inventory management of all necessary reagents and supplies such that isolation, identification, and AST of priority pathogens can be conducted at all times. • Quantify and forecast annual laboratory supply needs • Ensure equipment are in good working order, schedule maintenance and repairs, and replace equipment when needed • Manage major microbiology equipment service contracts for laboratory 5.4.5.6 LABORATORY FOCAL PERSON FOR AMR This shall be typically a laboratory technologist trained on electronic laboratory database eg. WHONET Input data into electronic AMR database e.g. WHONET • Submit line-listed data monthly to NHQATC • Send identified AMR priory pathogen isolates to the NHQATC as outlined in SOPs • With assistance from NHLQATC data manager use electronic AMR database e.g. WHONET to produce antibiogram for hospital • Train new staff on AMR surveillance system, data reporting, and AMR specific SOPs when necessary 5.5 SPECIFIC ROLES AND RESPONSIBILITIES IN THE FOOD, AGRICULTURE AND ENVIRONMENT SECTORS 5.5.1 AMR SUB-TWG FOR THE FOOD, AGRICULTURE AND ENVIRONMENT SECTORS There shall be a sector specific TWG on AMR surveillance in the food, agriculture and environment sectors. Members of this AMR sub-TWG will comprise relevant technical experts from TFDA, VPO- environment division, PMO-One Health Coordination desk, MLF (livestock and aquaculture) Animal (terrestrial/aquatic) health, TVLA and Ministry of Agriculture (plant health division). It may also constitute experts from NEMC, academic and research institution like SUA and FAO country office based AMR focal point. Role and responsibilities of the sub- AMR TWG shall include: 43 • Reporting to NAP TWG (Surveillance and Research) on the progress and the implementation of the AMR surveillance plan in the food, agriculture and environment • Operationalizing the National AMR surveillance plan in the food and agriculture and environment sectors; • Providing technical input, conducting situational analyses in these sectors; • Preparing annual work plans in the food, agriculture and environment as per National AMR Action Plan; • Reporting to NMCC • Providing updates on ongoing activities and provide technical advice to the NMCC • Prepare annual AMR surveillance work plan in the food, agriculture and environment • Map AMR surveillance activities in the food and agriculture and environment sectors; • Prepare budget for AMR surveillance • Prepare consolidate report for AMR surveillance in the food, agriculture and environment sectors. 5.5.2 NATIONAL REFERENCE LABORATORY The roles and responsibilities of CVL will include the following: • To provide technical support and guidance in AST testing and quality management to surveillance network laboratories • To provide bio-repository service for core organism/antimicrobial combinations as a minimum, for borderline isolates or isolates with unexpected or unusual resistance profiles; • Host and manage AMR surveillance database and share AMR information to the stakeholders • To confirm/characterize unusual or new resistance patterns before they are reported to the relevant national authority • To participate in external quality assurance through appropriate international schemes • To liaise with the MCC in standardizing and verifying microbiological results; • To provide external quality assurance across sentinel site laboratories and providing feedback • To assist sentinel site laboratories to procure equipment, reagents and supplies • To conduct or support research studies on AMR in collaboration with MCC and share findings with national and international stakeholders. Note: Operation of AMR surveillance framework for food, agriculture and environment sectors shall be managed and implemented through the MLF under the Tanzania Veterinary Laboratory Agency (TVLA). 44 5.5.3 SURVEILLANCE SITES AND OTHER COLLECTION SITES • Receive/collect samples/specimen and perform AST as per protocol • Transportation of samples/ pathogen isolates to the NRL for confirmation • Perform initial /descriptive AMR data analysis • Share AMR data with National Reference Laboratory for confirmation and analysis • Ensure that there are adequate staff and physical infrastructure in place to perform surveillance activities • Assign a clinical focal person, with a commitment to AMR • Ensure clinicians have appropriate containers and specimen collection materials • Provide staff with specimen collection SOPs and laboratory requisition forms • Ensure frequent communication between the AMR focal personnel and laboratory • Provide CVL with annually updated estimates of samples collected and population data • Review and disseminate surveillance reports at the facility level • Establish center AMR Committee consisting of Veterinarians, laboratory technologists, and field officers to meets quarterly 5.5.4 FARMERS ASSOCIATIONS AND AMR SURVEILLANCE NETWORK • Facilitate availability of AMR surveillance data • Facilitate dissemination of feedback information • Holders of AMR surveillance data – for policy and control advice • Obligatory mandate – sharing AMR data with RECs, AU-IBAR and OIE • Provide policy and future research direction for AMR • Facilitate importation/ exportation( paper work, logistics) of material/ supplies related to AMR 45 CHAPTER SIX LEGAL FRAMEWORK AND RESOURCE MOBILIZATION 6.1 LEGAL FRAMEWORK The implementation of the AMR Surveillance Framework requires a strong and sound managerial capability of ensuring an optimal coordination. A legislative framework must be strengthened in order to enforce implementation of the Framework. This Antimicrobial Resistance surveillance framework is fully aligned with the National Action Plan on AMR (2017-2022) and provisions for its regulation exists in different policies and legislations governing food, agriculture and environment sectors. These policies and legislations but not exhaustive include: i. National Health Policy, 2007 (Current in review) ii. National Livestock Policy of 2006 iii. The Animal Disease Act No. 17 of 2003 iv. The Veterinary Act No. 16 of 2003 v. Tanzania Food, Drugs and Cosmetics Act No. 1 of 2003 vi. Fisheries Act No. 20 of 2003 vii. Tanzania Plant Protection Act of 1997 viii. Tanzania Pesticides and Research Institute Act No. of 1979 ix. The National Environment Management Act No. of 1983. Other plans/ strategies that are closely linked to this include Tanzania Development Vision 2025 (Vision 2025), One Health Strategic Plan 2015 -2020, Health Policy 2007, Livestock Development Strategic Plan (2010-2015) and Tanzania Action Plan for Health Security (2017 2012). Furthermore, the framework is closely linked with other existing treaties and agreements addressing AMR at regional and global levels. These include: The East African Community Sanitary and Phytosanitary, FAO, OIE, WTO and WHO protocols/plans prescribing prudent use of antimicrobials specifically WHO Global AMR Action and the FAO Action Plan on AMR (2016 2020). 6.2 RESOURCE MOBILIZATION The costs of AMR surveillance are high, and involve considerable resources. Financial resources to implement AMR surveillance activities in the country will come from both external and domestic sources. It is expected that the Government of the united Republic of Tanzania through the respective ministries will allocate funds to implement and sustain AMR surveillance activities in the country. Private Institutions and other interested private, domestic and international stakeholders/ partners with capacity to finance AMR surveillance activities in the country. International organizations such as FAO, WHO, OIE, WB, UNDP through global, continental, regional and country programmes may be potential sources of funding for AMR surveillance activities in Tanzania. Other Global partners like Mott McDonald, The Fleming Fund, GARP, ReAct, Bilateral partners such as USAID, DFID and OHCEA can also provide financial support to implement AMR activities in Tanzania. 46 REFERENCES 1. Paterson DL: The role of antimicrobial management programs in optimizing antibiotic prescribing within hospitals. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2006, 42 Suppl 2:S90-95. 2. The United Republic of Tanzania Ministry of Health, Community Development Gender Elderly and Children (MoH), 2017. The National Action Plan on Antimicrobial Resistance, 2017-2022. 3. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY et al: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet (London, England) 2012, 380(9859):2095-2128. 4. Kluytmans JA: Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency? Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2010, 16(1):11-15. 5. Almuzaini T, Choonara I, Sammons H: Substandard and counterfeit medicines: a systematic review of the literature. BMJ Open 2013, 3(8):e002923. 6. Ngowi, AVF, Mbise, T.J., Ijani, A.S.M., London,L. and Ajayi O. C. (2007).Pesticides use by smallholder farmers in vegetable production in Northern Tanzania. Crop Prot. 2007 Nov; 26(11): 1617–1624. doi: 10.1016/j.cropro.2007.01.008 7. Mdegela RH, Mosha RD, Ngowi HA, Nonga H. (2013). Environmental and Health Impacts Associated with Usage of Agrochemicals in Mindu Dam Catchment Area, Morogoro, Tanzania. HURIA: Journal of the Open University of Tanzania, 15: 18-33. 8. Nonga, H. E., Simon, C., Karimuribo, E. D. and Mdegela, R. H. (2010) Assessment of antimicrobial usage and residues in commercial chicken eggs from smallholder poultry keepers in Morogoro municipality, Tanzania. Zoonoses Public Health, 57, 339-44 9. Mhongole, J. O.; Mdegela, R. H.; Kusiluka, L. J. M.; Forslund, Anita; Dalsgaard, A. (2016). Removal of Escherichia coli in treated wastewater used for food production in Morogoro, Tanzania. African Journal of Microbiology Research, DOI:10.5897/AJMR2016.8156 10. O’Neill J. Antimicrobials in Agriculture and the environment: Reducing unnecessary use and waste. London: Review on Antimicrobial Resistance. 2015. Available from:https:// amr-review.org/sites/default/files/Antimicrobials.pdf. 11. Van Boeckel TP, Brower C, Gilbert M, Global trends in antimicrobial use in food animals. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112 (18) 5649–54. doi:10.1073/pnas.1503141112. 47 12. World Bank. 2017. “Drug-Resistant Infections: A Threat to Our Economic Future.” Washington, DC: World Bank. License: Creative Commons Attribution CC BY 3.0 IGO. Available from:http://www.worldbank.org/en/topic/health/publication/drug-resistant infections-a-threat-to-our-economic-future. 13. O’Neill J. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. London: Review on Antimicrobial Resistance. 2014. Available from: https://amr-review. org/sites/default/files/AMR.pdf. 14. Unemo M, Shafer WM. (2014). Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev. 2014 Jul;27(3):587-613. doi: 10.1128/CMR.00010-14. 15. Nonga, H.E and Muhairwa, A.P. (2010) Prevalence and antibiotic susceptibility of thermophilic Campylobacter isolates from free range domestic duck (Cairina moschata) in Morogoro municipality, Tanzania. Trop Anim Health Prod 42: 165-172. 16. Hart CA, Kariuki S: Antimicrobial resistance in developing countries. BMJ 1998, 317(7159):647-650. 17. Manyahi J, Moyo SJ, Tellevik MG, Ndugulile F, Urassa W, Blomberg B, Langeland N: Detection of CTX-M-15 beta-lactamases in Enterobacteriaceae causing hospital- and community-acquired urinary tract infections as early as 2004, in Dar es Salaam, Tanzania. BMC infectious diseases 2017, 17(1):282 18. Mshana SE, Matee M, Rweyemamu M: Antimicrobial resistance in human and animal pathogens in Zambia, Democratic Republic of Congo, Mozambique and Tanzania: an urgent need of a sustainable surveillance system. Ann Clin Microbiol Antimicrob 2013, 12:28. 19. Blomberg B, Manji KP, Urassa WK, Tamim BS, Mwakagile DS, Jureen R, Msangi V, Tellevik MG, Holberg-Petersen M, Harthug S et al: Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study. BMC infectious diseases 2007, 7:43. 20. Moyo SJ, Aboud S, Kasubi M, Lyamuya EF, Maselle SY: Antimicrobial resistance among producers and non-producers of extended spectrum beta-lactamases in urinary isolates at a tertiary Hospital in Tanzania. BMC research notes 2010, 3:348. 21. Meremo A, Mshana SE, Kidenya BR, Kabangila R, Peck R, Kataraihya JB: High prevalence of Non-typhoid salmonella bacteraemia among febrile HIV adult patients admitted at a tertiary Hospital, North-Western Tanzania. International archives of medicine 2012, 5(1):28. 22. Manyahi J, Matee MI, Majigo M, Moyo S, Mshana SE, Lyamuya EF: Predominance of multi drug resistant bacterial pathogens causing surgical site infections in Muhimbili National Hospital, Tanzania. BMC research notes 2014, 7:500. 48 23. Moyo S, Aboud S, Kasubi M, Maselle SY: Bacteria isolated from bloodstream infections at a tertiary hospital in Dar es Salaam, Tanzania--antimicrobial resistance of isolates. S Afr Med J 2010, 100(12):835-838. 24. Onken A, Said AK, Jorstad M, Jenum PA, Blomberg B: Prevalence and Antimicrobial Resistance of Microbes Causing Bloodstream Infections in Unguja, Zanzibar. PloS one 2015, 10(12):e0145632. 25. Mtove G, Amos B, Nadjm B, Hendriksen IC, Dondorp AM, Mwambuli A, Kim DR, Ochiai RL, Clemens JD, von Seidlein L et al: Decreasing incidence of severe malaria and community acquired bacteraemia among hospitalized children in Muheza, north-eastern Tanzania, 2006-2010. Malar J 2011, 10:320. 26. Kayange N, Kamugisha E, Mwizamholya DL, Jeremiah S, Mshana SE: Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza-Tanzania. BMC pediatrics 2010, 10:39. 27. Blomberg B, Jureen R, Manji KP, Tamim BS, Mwakagile DS, Urassa WK, Fataki M, Msangi V, Tellevik MG, Maselle SY et al: High rate of fatal cases of pediatric septicemia caused by gram-negative bacteria with extended-spectrum beta-lactamases in Dar es Salaam, Tanzania. Journal of clinical microbiology 2005, 43(2):745-749. 28. Mshana SE, Gerwing L, Minde M, Hain T, Domann E, Lyamuya E, Chakraborty T, Imirzalioglu C: Outbreak of a novel Enterobacter sp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania. Int J Antimicrob Agents 2011, 38(3):265-269. 29. Masinde A, Gumodoka B, Kilonzo A, Mshana SE: Prevalence of urinary tract infection among pregnant women at Bugando Medical Centre, Mwanza, Tanzania. Tanzania journal of health research 2009, 11(3):154-159. 30. Msaki BP, Mshana SE, Hokororo A, Mazigo HD, Morona D: Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania. Archives of public health = Archives belges de sante publique 2012, 70(1):4. 31. Epaphura Festo BRK, Aldofina Hokororo, Stephen E. Mshana: Predictors of Urinary tract infection among febrile children attending at Bugando Medical Centre Northwestern, Tanzania. Archives of Clinical Microbiology 2011, 2 (5:2). 32. Blomberg B, Mwakagile DS, Urassa WK, Maselle SY, Mashurano M, Digranes A, Harthug S, Langeland N: Surveillance of antimicrobial resistance at a tertiary hospital in Tanzania. BMC public health 2004, 4:45. 33. Ahmed M, Moremi N, Mirambo MM, Hokororo A, Mushi MF, Seni J, Kamugisha E, Mshana SE: Multi-resistant gram negative enteric bacteria causing urinary tract infection among malnourished underfives admitted at a tertiary hospital, northwestern, Tanzania. Italian journal of pediatrics 2015, 41:44. 49 34. Eriksen HM, Chugulu S, Kondo S, Lingaas E: Surgical-site infections at Kilimanjaro Christian Medical Center. The Journal of hospital infection 2003, 55(1):14-20. 35. Mawalla B, Mshana SE, Chalya PL, Imirzalioglu C, Mahalu W: Predictors of surgical site infections among patients undergoing major surgery at Bugando Medical Centre in Northwestern Tanzania. BMC surgery 2011, 11:21. 36. Vila J, Vargas M, Casals C, Urassa H, Mshinda H, Schellemberg D, Gascon J: Antimicrobial resistance of diarrheagenic Escherichia coli isolated from children under the age of 5 years from Ifakara, Tanzania. Antimicrobial agents and chemotherapy 1999, 43(12):3022 3024. 37. Navia MM, Capitano L, Ruiz J, Vargas M, Urassa H, Schellemberg D, Gascon J, Vila J: Typing and characterization of mechanisms of resistance of Shigella spp. isolated from feces of children under 5 years of age from Ifakara, Tanzania. Journal of clinical microbiology 1999, 37(10):3113-3117. 38. Moyo SJ, Gro N, Matee MI, Kitundu J, Myrmel H, Mylvaganam H, Maselle SY, Langeland N: Age specific aetiological agents of diarrhoea in hospitalized children aged less than five years in Dar es Salaam, Tanzania. BMC pediatrics 2011, 11:19. 39. Temu MM, Kaatano GM, Miyaye ND, Buhalata SN, Shushu ML, Kishamawe C, Changalucha JM: Antimicrobial susceptibility of Shigella flexneri and S. dysenteriae isolated from stool specimens of patients with bloody diarrhoea in Mwanza, Tanzania. Tanzania health research bulletin 2007, 9(3):186-189. 40. Buhalata S, Kwesigabo, G., Sembuche, S. Aboud, S.: Genital tract infections in women attending sexually transmitted infection clinics in Mwanza , north-west Tanzania. South African Journal of Epidemiology Infection, 2013, 28(1):48–54. 41. Aboud S, Mdegela R (For the GARP Tanzania Working Group). (2015). Situation Analysis and Recommendations: Antibiotic use and resistance in Tanzania.The Center for Disease Dynamics, Economics and Policy, Washington, USA. 42. Kimera, Z. I., Mdegela, R. H., Mhaiki, C. J., Karimuribo, E. D., Mabiki, F., Nonga, H. E., and Mwesongo, J. (2015). Determination of oxytetracycline residues in cattle meat marketed in the Kilosa district, Tanzania. Onderstepoort Journal of Veterinary Research, 82(1), 01-05. 43. Mdegela, R. H., Kusiluka, L. J., Kapaga, A. M., Karimuribo, E. D., Turuka, F. M., Bundala, A., Kivaria, F., Kabula, B., Manjurano, A., Loken, T. and Kambarage, D. M. (2004) Prevalence and determinants of mastitis and milk-borne zoonoses in smallholder dairy farming sector in Kibaha and Morogoro districts in Eastern Tanzania. J Vet Med B Infect Dis Vet Public. 44. Mmbando LMG (2004). Investigation of oxytetracycline use and abuse: Determination of its residue in meat consumed in Dodoma and Morogoro. A thesis submitted for the award of a MVM Degree at Sokoine University of Agriculture, Morogoro, Tanzania, pp. 240 50 45. Karimuribo, E. D., Mdegela, R. H., Kusiluka, L. J. M., and Kambarage, D. M. (2005). Assessment of drug usage and antimicrobial residues in milk on smallholder farms in Morogoro, Tanzania Evaluation de l’utilisation des medicaments et determination des residus antimicrobiens dans le lait dans les petites exploitations agricoles a Morogoro en Tanzanie. Bulletin of Animal Health and Production in Africa, 53(4), 234-241. 46. Mubito E. P., Shahada F., Kimanya M. E. and Buza J. J (2014). Antimicrobial use in the poultry industry in Dar-es-Salaam, Tanzania and public health implications. American Journal of Research Communication, 2(4): 51-63 47. Shah SQ, Colquhoun DJ, Nikuli HL, Sørum H.(2012).Prevalence of antibiotic resistance genes in the bacterial flora of integrated fish farming environments of Pakistan and Tanzania Environ Sci Technol.;46(16):8672-9.doi: 10.1021/es3018607. Epub 2012 Aug 9. 48. Mdegela RH1, Ryoba R, Karimuribo ED, Phiri EJ, Løken T, Reksen O, Mtengeti E, Urio NA(2009).Prevalence of clinical and subclinical mastitis and quality of milk on smallholder dairy farms in Tanzania.J S Afr Vet Assoc.;80(3):163-8. 49. Nonga, H.E., Mariki, M., Karimuribo E.D., and Mdegela, R.H. 2009. Assessment of Antimicrobial Usage and Antimicrobial Residues in Broiler Chickens in Morogoro Municipality, Tanzania. Pakistan Journal of Nutrition, 8: 203-207. 50. Mshana, S. E., M. Matee, and M. Rweyemamu. 2013. Antimicrobial resistance in human and animal pathogens in Zambia, Democratic Republic of Congo, Mozambique and Tanzania: an urgent need of a sustainable surveillance system. Annals of Clinical Microbiology and Antimicrobials 12: 28. 51. Kashoma IP, Kassem II, Kumar A, Kessy BM, Gebreyes W, Kazwala RR, Rajashekara G(2015). Antimicrobial Resistance and Genotypic Diversity of Campylobacter Isolated from Pigs, Dairy, and Beef Cattle in Tanzania. Front Microbiol. 2015 Nov 12; 6:1240. doi: 10.3389/ fmicb.2015.01240. 52. Katakweba, A.A.S., Møller, K.S., Muumba, J., Muhairwa, A.P., Damborg, P., Rosenkrantz, J.T., Minga, U.M., Mtambo, M.M.A. and Olsen, J.E. (2015), Antimicrobial resistance in faecal samples from buffalo, wildebeest and zebra grazing together with and without cattle in Tanzania. J Appl Microbiol, 118: 966–975. doi:10.1111/jam.12738 53. Jiang, L., Hu, X., Xu, T., Zhang, H., Sheng, D., and Yin, D. (2013). Prevalence of antibiotic resistance genes and their relationship with antibiotics in the Huangpu River and the drinking water sources, Shanghai, China. Sci. Total Environ. 458–460, 267–272. doi: 10.1016/j. scitotenv.2013.04.038 54. Witte W (1998) Medical consequences of antibiotic use in agriculture. Science. 13; 279(5353):996-7 51 APPENDIX APPENDIX I: LIST OF EXPERTS WHO PARTICIPATED IN THE DEVELOPMENT OF THE NATIONAL AMR SURVEILLANCE FRAMEWORK S/N NAME POSITION/ PROFESSION ORGANIZATION 1. Dr Mtebe Majigo Microbiologist MUHAS 2. Dr. Charles Masambu Assistant Director Diagnostics MoHCDGEC 3. Prof. Stephen Mshana Department of Microbiology CUHAS 4. Dr. Joseph Masambu Principal Veterinary Research Officer Tanzania Veterinary Laboratory Agency 5. Dr. Rogath Kishimba Field epidemiologist MoHCDGEC 6. Ms. Siana Mapunjo AMR Focal Point MoHCDGEC 7. Optatus Maleo Laboratory Scientist CDC 8. Dr. Bachana Rubegwa National AMR Coordinator/One Health Epidemiologist Food and Agriculture Organization of the UN 9. Dr. Anthony A. Nsojo Clinical Microbiologist Lab Manager Mbeya Zonal Referral Hospital 10. Dr. Tumain Nagu Infectious Disease Specialist MUHAS 11. Dr. Mabula Kasubi Microbiologist MNH 12. Mr. Victor Mchunguzi Lab Scientist NHLQATC 13. Dr. Joel Manyahi Microbiologist MUHAS 14. Mr. Salum Said Alli Lab Scientist Mnazi Mmoja Hospital-Zanzibar 15. Dr. Emmanuel Swai Veterinary Epidemiologist Ministry of Livestock and Fisheries 16. Dr. Zachariah Makondo Centrol Vet Laboratory - Manager Tanzania Veterinary Laboratory Agency 17. Dr. Nyambura Moremi Microbiologist CUHAS 18. Dr. Gibonce Kayuni AMR Focal Point Ministry of Livestock and Fisheries 19. Dr. Justin Assenga Veterinary Epidemiologist One Health Coordination Desk Prime Minister’s Office 20. Dr.Sero Hassan Luwongo Pharmacologist/Principal Veterinary Officer Ministry of Livestock and Fisheries 21. Dr.Hamis Nikuli Principal Veterinary Officer Ministry of Livestock and Fisheries 22. Dr. Deusdedit Tinuga Veterinary Epidemiologist Ministry of Livestock and Fisheries 23. Dr.Adelard Mtenga Head of Food Safety Department Tanzania Food and Drugs Authority 24. Prof.Amandus Muhairwa Head, Department of Medicine and Public Health Sokoine University of Agriculture 25. Mr Joseph Tarimo Food Safety expert Tanzania Bureau of Standards 52 26. Ms. Kimambo Environmental Expert Vice President’s Office 27. Dr.Khadija Noor Omary Head, Central Veterinary Laboratory Ministry of Agriculture, Natural Resources, Livestock and Fisheries, Zanzibar 28. Prof.Fasina Folorunso Country Team Leader Food and Agriculture Organization of the UN 29. Dr.Niwael J. Mtui - Malamsha Veterinary Epidemiologist Food and Agriculture Organization of the UN 30. Dr. Raphael Sallu National Laboratory Expert Food and Agriculture Organization of the UN APPENDIX II: ROAD MAP FOR ROLL-OUT OF THE TANZANIA ANTIMICROBIAL RESISTANCE SURVEILLANCE SYSTEM 2017 2018 2019 2020 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 AMR Strategic Planning AMR Strategic Surveillance Plan ratified Phase I lab Prep for surveillance activities Surveillance activities First (6-month) surveillance evaluation First AMR report phase II lab Prep for surveillance activities Surveillance activities Second surveillance evaluation Second AMR report Phase III laboratory Prep for surveillance activities Surveillance activities Third AMR report 53 APPENDIX III: LABORATORY REQUISITION FORM Hospital / Facility: Ordering Physician: Telephone: Patient Name: Patient Medical Record Number: Date of Birth (dd/mm/yyyy): / / Gender: Male Female In-Patient Ward / Department: Out-Patient Date of Admission (dd/mm/yyyy): / / Out-Patient Specimen Type: Blood Urine Stool Wound Sputum CSF Other: Specimen Collection Date (dd/mm/yyyy): / / Time: AM/PM Specimen Collected By: - - - - - - - - - - - - - - - - - - - - - - - TO BE FILLED OUT BY LABORATORY - - - - - - - - - - - - - Specimen Receive Date (dd/mm/yyyy): / / Time: AM/ PM Specimen Received By: Specimen accession number: Notes: 54 APPENDIX IV: PAPER-BASED REPORTING FORM Laboratory Facility Name: Corresponding Hospital (if applicable): # Patient Medical Record Number Date of Birth (or Age) Gender (F/M) Inpatient / Outpatient (IP/ OP) Patient Ward (inpatient only) Admi ssion Date (inpa tients only) Date of Speci men Colle ction Speci men Type Gram Stain Patho gen Iden tified Ami kacin Ampi cillin Etc. 1 Zone Diameter Interpretation (S, I, R) 2 Zone Diameter Interpretation (S, I, R) APPENDIX V: ANTIBIOTICS TO BE TESTED FOR EACH PRIORITY ORGANISM FOR FOOD, AGRICULTURE AND ENVIRONMENT Priority pathogens Antimicrobial E.coli S. aureus Pseudo monas Klebsiella Salmonella Shigella spp S. pneumoniae Acineto bacter Sulfonamides/ trimethoprim Cotrimoxazole X X X X Fluoroquinolones Ciprofloxacin/ levofloxacin X X X X X 3” cephalosporins Ceftriaxone / Cefotaxime X X X X X Ceftazidime X X 4” cephalosporins Cefepime X X Carbapenems Imipenem/ Meropenem X X X X X Polymxins Colistin X X X Penicillins Oxacillin X Penicillin G X Ampicillin X X Penicillinase stable beta lactams Cefoxitin / Oxacillin Amoxicillin clavulanic X X Macrolides Azithromycin X X Aminocyclitols Spectinomycin Aminoglycosides Gentamicin X X Amikacin X Tetracyclines Tigecycline /minocycline X X 55 APPENDIX VI: FOOD, AGRICULTURE AND ENVIRONMENTAL SAMPLE COLLECTION AND SUBMISSION FORM ZONE REGION DISTRICT WORK STATION VILLAGE/SITE GRID REFERENCE: LATITUDE LONGITUDE IDENTIFICATION YES NO D A TE O F SA M P LI N G SP E C IE S SOURCE/TYPE OF SAMPLES (TICK) Meat Blood Milk Eggs Feacal Manure Fruits Fish Water Vegetables Additional Information: PRODUCTION SYSTEM Sample Packaging Info Sample Storage Condition TYPE TICK (Describe packaging of samples) TYPE TICK Ice Red meat production 2-8 C Dairy production -20 C Poultry production -80 C Pork production Liquid Nitrogen Companions animals Room Temperature Aquaculture Horticulture Processed / semi processed food Laboratory test requested Note: Provide any information on treatment (livestock) or cultural practices (crops) .................. ................................................................................................................................................................... ............................................................................. Full Name: ………………………………………………………… Signature...................Title:...................................................