POPM*4230 Lecture 1 General Principles of Disease PDF

POPM*4230 Lecture 1 General Principles of Disease 13  Lecture 1 - Objectives 1. Describe health and disease in terms of livestock animals and production, using appropriate disease terminology 2. Understand and describe the different classifications of disea...

POPM*4230 Lecture 1 General Principles of Disease 13  Lecture 1 - Objectives 1. Describe health and disease in terms of livestock animals and production, using appropriate disease terminology 2. Understand and describe the different classifications of disease 3. Understand disease transmission, determinants of disease, and role of animal health management 4. Describe the interactions between agent, host and environment factors and how that influences overall animal health 15  Animal Health 1. What is HEALTH? Inconsistent definitions: False negative tests – Absence of disease – simple – Y/N (dichotomous) Normality Genetic diseases – normal = healthy Susceptible Resistant – abnormal = diseased Homeostasis Where do we stop? – ‘mind and body in harmony with environment’ Where are the gaps in each? 16 1. What is HEALTH? WHO definition (human) Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity http://www.who.int/en/ Health is more than just the absence of disease! 17 1. What is HEALTH? With livestock we also need to reference: 1. Welfare ‘the provision of a complete diet, an environment that is optimal for the animal's physiological needs, comfortable to the animal's senses, in which the animal is secure and free from fear, and with no undue challenge by pathogenic micro-organisms or predators’ Sansbury – “positive health” 18 1. What is HEALTH? With livestock we also need to reference: 2. Production Given proper nutrition and environment - should reach maximum/optimum production? - If not – unhealthy? 3. Reproduction Given proper nutrition and environment - should reach maximum/optimum reproduction? - If not – unhealthy? 19  What is HEALTH? Conclusion: Obtaining a clear, agreed upon definition is difficult Health spectrum: more than just the absence of disease Reproduction Production Maintenance Susceptible Resistant Suboptimal/ below-potential production Sub-clinical disease The conceptualisation of health and Clinical disease disease in veterinary medicine Death Gunnarsson, 2006 20  2. What is DISEASE? Traditionally defined as a finite abnormality of structure or function with an identifiable pathological basis and recognizable clinical signs Now broadened to include: a. subclinical disease b. suboptimal production c. welfare Taken from Balliere’s Comprehensive Veterinary Dictionary Example of animal disease? 21  Definitions: Subclinical disease – Not visible, but measurable in some way Examples: Clinical disease – Overt, visible signs Examples: 22  Definitions: Sub-optimal production – Below what is expected for that breed, genetic line, industry …there is a strong relationship between disease management and production management…. 23  Welfare In livestock production systems welfare is often evaluated in the context of five freedoms: 1. Freedom from hunger and thirst; 2. Freedom from discomfort; 3. Freedom from pain, injury and disease; 4. Freedom to express normal behaviour; 5. Freedom from fear and distress. WOAH: Terrestrial Animal Health Code (Section 7) “Good animal welfare requires disease prevention…….” 24  Classification of Disease D Degenerative A Anomalous M Metabolic N Neoplastic I Infectious T Traumatic or Toxic Acronym to remember classification of disease 25  D.A.M.N. I.T. DEGENERATIVE Structure is altered by age, use or disuse or biochemical changes Example: arthritis 26  D.A.M.N. I.T. ANOMALOUS Abnormal structure or function - “congenital” (present at birth) May be genetic Example: cleft palate, atresia ani 27  D.A.M.N. I.T. METABOLIC Due to nutrition, toxins or hormonal activity that alters normal metabolism Examples: milk fever 28  D.A.M.N. I.T. NEOPLASM Abnormal growth of cells at the expense of normal tissue structure and function Examples: lymphosarcoma, cancer eye 29  D.A.M.N. I.T. INFECTIOUS Caused by microorganisms that invade the body and damage normal structure and function Example: Mycoplasma hyopneumonia causing pneumonia in pigs 30  D.A.M.N. I.T. TRAUMA Mechanical injury Examples: broken bone, ruptured muscle 31  D.A.M.N. I.T. TOXIC Caused by an exogenous substance that gains access to the system and damages normal structure, causing dysfunction Examples: Lead toxicity 32 BREAK! 33  Disease terminology Pathogen: Any disease-producing microorganism or material Bacterium, virus, fungus that can cause infection and/or disease D.A.M.N. I.T. Etiology: The study of the causes of disease Etiologic agent = causative agent of disease ≠ “the cause” 34 How do we know the cause of disease? Does it satisfy Koch’s Postulates Sick animal Isolate a Pathogen Re-isolate the Cause the same Infect a healthy animal same pathogen disease in this with this pathogen animal 35  Definitions: Infection: Invasion and multiplication of microorganisms in body tissues, especially causing local cellular injury due to competitive metabolism, toxins, replication, antigen-antibody response. An infectious disease Pathogenesis: The development of disease, the disease process The process by which a pathogen produces disease Taken from Balliere’s Comprehensive Veterinary Dictionary 36 Infectious Causes of Disease BACTERIA VIRUSES PRIONS MYCOTIC PARASITES 37  Infectious Causes of Disease Bacteria Viruses More like cells, non- Contain some form of pathogenic vs opportunistic nucleic acid (DNA or RNA) vs pathogenic Can replicate outside the Require host cell to host replicate Mostly responsive to Not responsive to antimicrobials but can traditional antimicrobial develop resistance agents Relative size ~ football FIELD Relative size ~ basketball 38  Infectious Causes of Disease PRIONS Abnormal form of PrP protein – genetic vs. infectious disease Resistant to proteases Somewhat host specific Cause of Transmissible Spongiform Sheep with Scrapie Encephalopathies (TSE) What is a commonly known name for BSE? 39  Infectious Causes of Disease Mycotic = fungal (e.g. Ringworm) Parasites Intracellular (e.g. coccidia; Neospora) Internal (e.g. intestinal “worms”) External (e.g. lice and mange mites) 40  Disease Transmission Disease transmission can be described as: How the pathogen is exchanged between hosts Which populations the pathogen is exchanged between 41  Contagious vs. Infectious Contagious: capable of being transmitted from animal to animal by contact or close proximity All contagious diseases are infectious but not all infectious diseases are contagious Example of an infectious disease that is…. a. Contagious b. Not contagious 42  Disease Transmission – How? 1. Direct contact between animals 2. Fomites Inanimate objects (shovel, boots) Object which is alive but organism doesn’t infect – passive carrier (e.g. human hands) Vehicle – food or water 3. Vector Invertebrate animal required for agent life cycle and transmission (e.g. flies for bluetongue or anaplasmosis) 43  Disease Transmission – How? 4. Infectious secretions or excretions Respiratory droplets, Eg: Infectious Bovine Rhinotracheitis virus Saliva, Eg: Bovine Viral Diarrhea virus Purulent exudate, Eg: caseous lymphadenitis of sheep & goats (CLA) Feces, Eg: parasite eggs, Salmonella Urine, Eg: Leptospira bacteria 44  Disease Transmission – Who? Horizontal transmission Vertical transmission Between animals of the Between animals of one same generation generation to a Infectious succeeding generation Contagious Dam → offspring In utero Eg: PRRSV (pigs) via nose-to- Eg: PRRSV (pigs) in utero nose contact, respiratory 45 droplets  Disease terminology Epidemiology: Study of patterns of disease that exist under field conditions, specifically…. Frequency Distribution Determinants of health & disease …in a population Analogous to pathogenesis in an individual NOT JUST DISEASE…… PRODUCTIVITY 46  Determinants of Health & Disease The Epidemiologic Triad Host Koch only had part of the picture… Agent Environment … just because we have an infectious agent present does not necessarily mean an animal becomes diseased…47  Determinants of Disease 1. Host factors – predisposing or protective Immune status Innate – genetic in origin? Acquired – colostrum, vaccinated, natural exposure? Depends on nature of agent, challenge and environment Herd immunity – upcoming lecture Age Physiologic effect = changes in cell or organ function that happen inevitably with the passage of time Associated with changes in production level, immune status, and/or physiologic state 48  Determinants of Disease 1. Host factors cont’d… Genetic – Simple – Holstein LDA – Phenotypic – white pigmentation/cancer eye – Genotype – pigs E coli resistance Physiologic state (pregnant/lactating) Production level Nutritional status Why does production level effect the host? 49  Determinants of Disease 2. Agent factors Virulence determinants Virulence = Degree of pathogenicity, includes severity, “fitness” of pathogen E.g. only some strains of E. coli are pathogenic - depends on cell surface and metabolic properties Pathogen challenge The amount of pathogen is important Critical load depends on host status Environment affects pathogen growth 50  Determinants of Disease 3. Environment factors Temperature Humidity Affects pathogen load Stocking density Affects host response Stall design Bedding / flooring Feeder design How can environment affect pathogen “growth”? 51 Epidemiologic Triad Host Agent Environment Pathogen load 52  “Epidemiologic Swamp” Bottom line: Disease occurrence involves a complex interaction 53 between the agent, host, and environment  Disease terminology Sufficient cause Factors working together to produce disease Alone, one factor may not be sufficient but in various combinations, disease occurs e.g. colostrum intake + colostrum quality + age of Disease is almost piglet + environmental always temperature + presence & multifactorial dose of infecting E coli 54  Sufficient causes: Alone, one factor may not be sufficient but in various combinations, disease occurs Presence of pathogenic E. coli bacteria A A A x Enteric colibacillosis x Enteric colibacillosis x Enteric colibacillosis 55  Sufficient causes: Alone, one factor may not be sufficient but in various combinations, disease occurs Volume of colostrum intake, quality of colostrum A B A B A C x Enteric colibacillosis x Enteric colibacillosis x Enteric colibacillosis 56  Sufficient causes: Alone, one factor may not be sufficient but in various combinations, disease occurs Cleanliness, temperature/humidity A D B E D A B A C ✓Enteric colibacillosis ✓Enteric colibacillosis ✓Enteric colibacillosis 57  Disease terminology Necessary cause Without this factor, disease cannot occur e.g. E. coli necessary to cause Colibacillosis But presence of a disease agent may or may not be sufficient to cause disease 58  Other important terms for describing disease Carrier state No clinical disease but potential to transmit an infectious agent – May remain asymptomatic (never diseased) – Incubating the disease (eventually or intermittently affected) – Convalescing from the disease e.g. Salmonella 59  Other important terms for describing disease Morbidity The condition of being diseased The amount of disease (frequency) Mortality The number of deaths (death as a statistic) Case Fatality (rate) Proportion of animals with a specific disease that die from it 60  Describing Disease Occurrence Endemic disease The usual frequency of occurrence of a disease in a population Expected The constant presence of a disease in a population Epidemic disease An occurrence of an infectious or non-infectious disease to a level in excess of the expected Sporadic disease Disease occurs infrequently and not readily predictable 61 Measures of Disease Occurrence Prevalence of disease At a point in time, the number of animals that are diseased / number of animals in the population – E.g. seroprevalence = % of animals with antibodies to a disease at the time of sampling 20 10 % of animals 0 affected 1 2 3 4 If measured on day 3 62 Prevalence = 10% Measures of Disease Occurrence Incidence of disease Number of new cases of disease in a specified time period or risk period / by number at risk Implies at least 2 observations or measurements To be included in denominator, must have been at risk Not at risk if already diseased or infected, or can’t experience the outcome of interest e.g., only pregnant animals can abort; bulls don’t get mastitis 63  Host Management Agent Environment At a given time point within a group, each individual may experience a different disease challenge and resistance to it. Over time, the role of each of the factors may change. 64  “Tipping Point” concept Health Disease Protective Risk factors factors Host Management Agent Environment 65 The “Iceberg” Concept J.M. Gay 66  Lecture 1 Summary Terms to know: Health Pathogen Carrier state Disease (subclinical, clinical) Etiology Morbidity, Mortality, Case fatality Clinical signs Infection Endemic, Epidemic, Sporadic Production (sub-optimal, optimal) Pathogenesis Necessary cause, Sufficient cause Welfare (sub-optimal, optimal) Epidemiology Prevalence, Incidence DAMNIT(T) classification of disease Disease transmission: Infectious causes Contagious vs infectious Transmission (how & between who)? Epidemiologic triad (A, H, E factors) 67  Last class: Principles of Disease Terms to know: Health Pathogen Carrier state Disease (subclinical, clinical) Etiology Morbidity, Mortality, Case fatality Clinical signs Infection Endemic, Epidemic, Sporadic Production (sub-optimal, optimal) Pathogenesis Necessary cause, Sufficient cause Welfare (sub-optimal, optimal) Epidemiology Prevalence, Incidence DAMNIT(T) classification of disease Disease transmission: Infectious causes Contagious vs infectious Transmission (how & between who)? Epidemiologic triad (A, H, E factors) 1 POPM*4230 Lecture 1 (cont’d) General Principles of Disease 2  Other important terms for describing disease Morbidity The condition of being diseased The amount of disease (frequency) Mortality The number of deaths (death as a statistic) Case Fatality (rate) Proportion of animals with a specific disease that die from it 3  Describing Disease Occurrence Endemic disease The usual frequency of occurrence of a disease in a population Expected The constant presence of a disease in a population Epidemic disease An occurrence of an infectious or non-infectious disease to a level in excess of the expected Sporadic disease Disease occurs infrequently and not readily predictable 4 Measures of Disease Occurrence Prevalence of disease At a point in time, the number of animals that are diseased / number of animals in the population – E.g. seroprevalence = % of animals with antibodies to a disease at the time of sampling 20 10 % of animals 0 affected 1 2 3 4 If measured on day 3 5 Prevalence = 10% Measures of Disease Occurrence Incidence of disease Number of new cases of disease in a specified time period or risk period / by number at risk Implies at least 2 observations or measurements To be included in denominator, must have been at risk Not at risk if already diseased or infected, or can’t experience the outcome of interest e.g., only pregnant animals can abort; bulls don’t get mastitis 6  Host Management Agent Environment At a given time point within a group, each individual may experience a different disease challenge and resistance to it. Over time, the role of each of the factors may change. 7  “Tipping Point” concept Health Disease Protective Risk factors factors Host Management Agent Environment 8 The “Iceberg” Concept J.M. Gay 9  Lecture 1 Unclear Items Infectious vs contagious – Infectious diseases: Caused by microorganisms capable of gaining access to the animal's system by some means (e.g. fomites, vectors, secretions, direct contact) – Contagious diseases: Capable of being transmitted from animal to animal by contact or close proximity. Contagious Infectious 10  POPM*4230 Lecture 2 Health Management Anne Deckert, DVM MS PhD 11 Slides adapted from lecture content provided by Dr. Terri O’Sullivan and Dr. Hannah Golightly  Lecture 2 - Objectives 1. List the approaches to disease control and describe the components and considerations of each approach 2. Define and understand basic epidemiology terms 3. Describe the health management approach and cycle 12 Approaches to Disease Control 1. Eradication 2. Prevention and Exclusion 3. Immunization 4. Disease Management 13 Approaches to disease control 1. DISEASE ERADICATION Objective is extinction of a species of infectious agent from a population Global National or Regional Farm level (E.g. Rinderpest) (E.g. Brucellosis, tuberculosis) (E.g. PRRSV) 14 Review: Infectious Agents BACTERIA VIRUSES PRIONS MYCOTIC PARASITES 15 Approaches to disease control 1a. GLOBAL Disease Eradication Very difficult to achieve To-date: Smallpox – 1980, humans Rinderpest – 2011, cattle Effective vaccination** 16 Approaches to disease control 1a. GLOBAL Disease Eradication Characteristics of an eradicable disease: 1. No carrier state 2. No subclinical infection/short incubation period Carrier state: No clinical disease but potential to transmit an infectious agent. Subclinical infection: Not visible, but measurable in some way. Incubation period: The period of time between when infection and signs of disease (or immunity) develop. 17 Approaches to disease control 1a. GLOBAL Disease Eradication Characteristics of an eradicable disease: 1. No carrier state 2. No subclinical infection/short incubation period 3. Limited to one species or family (e.g. ruminants) 4. Available intervention – good quality vaccine or test https://scienceleftuntitled.wordpress.com/2012/09/13 /the-tribe-that-eradicated-rinderpest/ 18 Approaches to disease control 1b. NATIONAL Disease Eradication Similar difficulties to global eradication Canada – free from: 1. Brucellosis – cattle, pigs 2. “TB free status” – except for Manitoba Mainly due to test and cull 19 Approaches to disease control 1c. FARM-LEVEL Disease Eradication Methods include depopulation & selective removal Depopulation Large proportion or entire population of herd is removed Depending on disease – determine what is done and where E.g. TB: Selective herd depopulation E.g. Foot and mouth disease: Entire herd depopulation euthanized on the farm 20 Approaches to disease control 1c. FARM-LEVEL Disease Eradication Selective Removal Deliberate euthanasia or removal of a minority of infected animals to protect the well majority Need a screening or diagnostic test to be able to detect disease Test must either: a. Detect the disease agent b. Test for evidence of an immune response to agent Example: PRRSV, TB, BVD 21  Test uses Screening Test Applied to healthy animals Usually before clinical disease evident Diagnostic Test Confirm or classify disease (may be follow up to positive screening test) Applied to “abnormal” or “unhealthy” animals 22 Approaches to disease control 1c. FARM-LEVEL Disease Eradication Selective Removal We want to use a diagnostic test that we trust the results from (i.e., an accurate diagnostic test) = high sensitivity and specificity – The sensitivity and specificity of a test tell us how well the test is able to correctly identify diseased and healthy animals No diagnostic test performs perfectly well - there will always be some misclassification of disease Approaches to disease control 1c. FARM-LEVEL Disease Eradication Test characteristics ** No test is perfect ** SENSITIVITY = the ability of a test to identify truly diseased/ infected animals = the proportion of truly diseased individuals that the test diagnoses as diseased in the population If sensitivity is poor/low, then the test will miss finding diseased animals (↑ false negatives) If sensitivity is high, there will be few false negatives 25 Testing for presence of disease TRUE STATE OF NATURE D+ d- TEST RESULT T+ a b a+b t- c d c+d a+c b+d N SENSITIVITY = p(T+|D+) or a/a+c False negative = p (t-|D+) or c/a+c 26 Approaches to disease control 1c. FARM-LEVEL Disease Eradication Test characteristics ** No test is perfect ** SPECIFICITY = the ability of a test to identify truly healthy or non-diseased animals = the proportion of truly healthy animals that the test calls non-diseased If specificity is poor, then the test will call healthy animals, diseased (↑ false positives) If specificity is high, there will be few false positives 27 Testing for presence of disease TRUE STATE OF NATURE D+ d- T+ a b a+b TEST RESULT t- c d c+d a+c b+d N SENSITIVITY = p(T+|D+) or a/a+c False negative = p (t-|D+) or c/a+c SPECIFICITY = p(t-|d-) or d/b+d False positive = p (T+|d-) or b/b+d 28 Example - Testing for presence of disease TRUE STATE OF NATURE D+ d- a b a+b T+ 90 45 135 TEST RESULT c d c+d t- 10 855 865 a+c b+d N 100 900 1000 SENSITIVITY = a/a+c = 90/100 = 90% False negative = c/a+c = 10/100 = 10% SPECIFICITY = d/b+d = 855/900 = 95% False positive = b/b+d = 45/900 = 5% 29  Predictive value of a test If a test is performed with the intent of deciding which animals are diseased & which are healthy, we need to know the predictive value of that test This depends upon 1: Characteristics of the test 2: Prevalence of disease test sensitivity in the population test specificity 30  Predictive value of a test If an animal has a (+) test, what is the probability it is truly (+)? = Positive Predictive Value (PPV)= p(D+|T+) or a/a+b TRUE STATE OF NATURE D+ d- TEST RESULT T+ a b a+b t- c d c+d a+c b+d N If an animal has a (-) test, what is the probability it is truly (-)? = Negative Predictive Value (NPV)= p(d-|t-) or d/c+d 31  Example #1– prevalence =15% True prevalence of disease = (150/1000) =15% Test sensitivity = 90% Test specificity = 95% Apparent prevalence of disease = (177/1000)=17.7% D+ d- T+ 135 42 177 PPV=135/177 = 76% t- 15 808 823 NPV=808/823 = 98% 150 850 1000 Not too bad but what if prevalence of disease changes? 32  Example #2 – prevalence = 5% Sensitivity = 90% & specificity = 95% True prevalence = 5% but apparent prevalence = 9.2% D+ d- T+ 45 47 92 PPV = (45/92) = 48.9% NPV= (903/908) =99.5% t- 5 903 908 50 950 1000 If the disease is present at low levels, will have a large % of test positive misclassified (over half in this case) 33  Summary terminology re: testing for disease Screening Test: Applied to healthy animals; usually before clinical disease evident Diagnostic Test: Confirm or classify disease; applied to “abnormal” or “unhealthy” animals Test sensitivity: P(T+|D+) TEST CHARACTERISTIC Test specificity: P(t-|d-) Positive predictive value: P(D+|T+) DEPENDS ON TEST & Negative predictive value: P(d-|t-) DZ PREVALENCE 34 BREAK! 35 Approaches to Disease Control 1. Eradication 2. Prevention and Exclusion 3. Immunization 4. Disease Management 36 Approaches to disease control 2. DISEASE PREVENTION/EXCLUSION All measures to exclude disease from an unaffected population of animals Exclude disease from a Protect a given population geographic area within a geographic area 37 Approaches to disease control 2. DISEASE PREVENTION/EXCLUSION a. Exclude disease from a geographic area E.g. at border crossings All animals (e.g. BSE cattle) Test negative animals (e.g. bluetongue, anaplasmosis, brucellosis) Only vaccinated animals (e.g. rabies) 38 Approaches to disease control 2. DISEASE PREVENTION/EXCLUSION b. Protect a given population within a geographic area Disease accreditation schemes Minimum disease swine herds Closed herds/flocks Vaccination without exposure to disease agent 39 Approaches to disease control 3. IMMUNIZATION Next Lecture https://scienceleftuntitled.wordpress.com/2012/09/13 /the-tribe-that-eradicated-rinderpest/ 40 Approaches to disease control 4. DISEASE MANAGEMENT All measures used to decrease the frequency of disease already present in a population of animals by decreasing or eliminating causes of the disease to a level of little or no consequence Methods: a. Quarantine b. Prophylactic treatment c. Mass immunization d. Environmental control 41 Approaches to disease control 4. DISEASE MANAGEMENT Disease management methods a. Quarantine Physical separation of sick or potentially exposed animals from the healthy population E.g. rabies suspect, PRRSV Very important with contagious diseases 42 Approaches to disease control 4. DISEASE MANAGEMENT Disease management methods b. Prophylactic Treatment Treat all animals within a population or geographic zone prophylactically at time of known risk E.g. deworming for parasites, antibiotics in feedlot for pneumonia All animals treated whether diseased or not, but based on informed risk assessment 43 Approaches to disease control 4. DISEASE MANAGEMENT Disease management methods c. Mass immunization All animals at risk within a population are vaccinated Agent is present in population or likely to be present Goal is to decrease clinical disease incidence or severity E.g. Porcine circovirus 44 Approaches to disease control 4. DISEASE MANAGEMENT Disease management methods d. Environmental control Ventilation Decrease pathogen load through cleanliness Swine: All in/All out Stocking density 45 Approaches to disease control Summary 1. Eradication Global, national, farm-level 2. Prevention and Exclusion Stop disease from entering unaffected geographic areas; protect unaffected populations 3. Immunization 4. Disease Management Quarantine, prophylactic treatment, immunization, environmental control 46  What is Health Management (HM)? Health management is the promotion of health and prevention of disease in animals within the economic/business framework of the animal owner/industry, while recognizing the issues of: animal welfare human safety environmental impact 47  How is HM delivered? Health management is a dynamic process in which selected management areas of importance to the industry, animal, and animal owner are identified and monitored. Examples: Milk production, pregnancy rate 48  How is HM delivered? Health management is a dynamic process in which selected management areas of importance to the industry, animal, and animal owner are identified and monitored. Health Management Cycle: Decisions are made and plans are developed and implemented. The outcomes are measured and evaluated. New decisions are made and new plans developed Continuous process! 49 Principles of HM Defining a HM Problem 1. No Problem Problem – Misperception 2. Old Problem Problem – A known previously seen problem or a repeated presentation 3. New Problem Problem 50 Principles of HM 1. Promote Optimal Health Focus is advising people on animal management Groups of animals (herds, flocks) Can be at the local, regional or national level 51 Principles of HM 2. Accommodate Business / Economic Realities Companion animals Level of disposable income Food animals Economically viable businesses 52 Principles of HM 3. Promote Animal Welfare Set current standards that are acceptable to animals, owner, society Code of Practice for the care and handling of…..pigs, cattle, horses. 53 Principles of HM 4. Promote Human & Food Safety Antibiotic residues Antibiotic resistance Zoonotic disease 54 Principles of HM 5. Consider Potential Environmental Impact Manure management Environmental farm plans Disposal 55 Principles of HM Summary 1. Promote Optimal Health 2. Accommodate Business/Economic Realities 3. Promote Animal Welfare 4. Promote Human and Food Safety 5. Consider potential environmental impact 56 The Health Management Cycle Set Goals Monitor and Assess Current Status Performance Make Decisions Outcomes Develop Plans Take Actions Effects of Other Factors 57  Setting SMART Goals Specific Measurable Achievable Results oriented Time framed 58  Setting SMART Goals Specific – A discrete aspect of management – Tied to an action 59  Setting SMART Goals Specific Measurable – Requires records 60  Setting SMART Goals Specific Measurable Achievable – Constraints of people, animals and their environment 61  Setting SMART Goals Specific Measurable Achievable Results oriented – Requires a “to do” list 62  Setting SMART Goals Specific Measurable Achievable Results oriented Time framed – When do you evaluate success/failure? 63  Lecture 2 Summary Terms to know: Epidemiology Screening test, diagnostic test Selective removal Sensitivity, Specificity Depopulation Disease management Predictive value (+,-) Eradication Health management SMART goal Approaches to disease control (eradication, prevention & exclusion, immunization, disease management) Principles of Health Management (HM) & HM Cycle SMART goals 64 https://scienceleftuntitled.wordpress.com/2012/09/13 /the-tribe-that-eradicated-rinderpest/  FYI: Office hours  Will begin week of Sept 23rd Time and Location TBD – will post to Courselink 65 Questions? 66  Last class… Terms to know: Epidemiology Screening test, diagnostic test Selective removal Sensitivity, Specificity Depopulation Disease management Predictive value (+,-) Eradication Health management SMART goal Approaches to disease control (eradication, prevention & exclusion, immunization, disease management) Principles of Health Management (HM) & HM Cycle SMART goals 1 The Health Management Cycle Set Goals Monitor and Assess Current Status Performance Make Decisions Outcomes Develop Plans Take Actions Effects of Other Factors 2  Setting SMART Goals Specific Measurable Achievable Results oriented Time framed 3  Setting SMART Goals Specific – A discrete aspect of management – Tied to an action 4  Setting SMART Goals Specific Measurable – Requires records 5  Setting SMART Goals Specific Measurable Achievable – Constraints of people, animals and their environment 6  Setting SMART Goals Specific Measurable Achievable Results oriented – Requires a “to do” list 7  Setting SMART Goals Specific Measurable Achievable Results oriented Time framed – When do you evaluate success/failure? 8  L2 Unclear Items 1. Calculations (SN, SP, FN, FP, PPV, NPV) Example question and answer for calculating SN, SP, FN and FP will be posted on CourseLink – give it a try! Focus on defining and understanding these terms – how they relate to each other and, why they are important with respect to disease control! 9  Example - Testing for presence of disease TRUE STATE OF NATURE D+ d- a b a+b T+ 90 45 135 TEST RESULT c d c+d t- 10 855 865 a+c b+d N 100 900 1000 SENSITIVITY = a/a+c = 90/100 = 90% False negative = c/a+c = 10/100 = 10% SPECIFICITY = d/b+d = 855/900 = 95% False positive = b/b+d = 45/900 = 5% 10 This  The Health Management Cycle The HMC is how we approach problems related to animal health and production. Problems can be classified as new, old (repeated or lingering), or one that is misperceived as not a problem at all. To increase your likelihood of We then set goals Set Goals success at addressing this related to the problem, your goal should be: identified problem. Specific, Measurable, Achievable, Results oriented, Time framed Monitor & assess current status Performance Make decisions, outcomes develop plans, take actions We follow the ” principles of HM” when making Effects of decisions/plans/actions: other factors promote optimal health & animal welfare & human/ food safety + accommodate economic realities.  POPM*4230 Lecture 3 Immunology & Vaccination Anne Deckert DVM MSc PhD Slides adapted from lecture content provided by Dr. Terri O’Sullivan and Dr. Hannah Golightly  Lecture 3 - Objectives Recognize the significance of the immune system in combating infection & disease Distinguish between non-specific (innate) & specific (adaptive) immune systems Summarize the roles of neutrophils, macrophages, T & B lymphocytes, & immunoglobulins 13  Lecture 3 - Objectives Describe the strengths and limitations of killed & modified live vaccines In combination with other lectures: – Outline and explain cattle herd & swine herd vaccination plan(s) for common diseases – List common diseases of cattle & swine for which vaccines are commercially available 14  INTRODUCTION TO IMMUNITY A multi-faceted system for the body recognize and protect itself from non-self – Ability to recognize self from non-self – Does not operate in isolation Antigen (Ag)- A part of an organism or substance that is recognized by the immune system as non-self – Often a cell-surface protein or sugar An organism molecule can have many antigens of variable “antigenicity” 15 16  Passive Immunity Pre-formed antibody acquired from an outside source – Colostrum – Hyper-immune serum (medical treatment) Half life ~ 21 days Maternal antibodies – Considered gone by 6 months old in calves – Variable in piglets O’Sullivan, 2012 Protection vs. interference with vaccination 17  Passive Immunity Protection vs. interference with vaccination O’Sullivan, 2012 18 19  Active Immune System Innate Adaptive (non-specific) (specific) Physical barriers Phagocytes Humoral Cell-mediated Neutrophils Antibodies Cell lysis Macrophages B lymphocytes T lymphocytes Complement system (humoral) 20 NK cells Active immune system: Innate/NS Innate (non-specific) Immunity Anatomical defences Skin/hoof/hair; mucous membranes – Protects from trauma, pressure, heat & cold – Skin is essentially first line of defence Mucus (respiratory, reproductive tracts) – Mechanical trapping of particles; facilitates removal Cilia (small hairs) – In trachea and bronchi – carry particles outward from airways Lacrimal secretions – Washes irritants & foreign objects from eyes 21 Active immune system: Innate/NS Non-specific Immunity: Humoral defences - Complement System Humoral reactions play a role in inflammation Complement system Circulating family of immune molecules (serum proteins) The major humoral, non-specific defense mechanism Once activated complement can lead to increased vascular permeability, recruitment of phagocytic cells, and lysis and opsonization of bacteria 22 Active immune system: Innate/NS Non-specific Immunity: Humoral defences - Complement System Three roles: – Complement fixation- binding to & destroying foreign cell membrane – Opsonization- “tagging” of foreign cells for stimulation of phagocytosis – Trigger inflammatory reaction that “walls off” damaged tissue Very destructive & are regulated to prevent unnecessary cell damage 23 Active immune system: Innate/NS Non-specific Immunity: Other Humoral defences Cytokines “Communication molecules” – e.g., Interleukin-1 (Il-1) induces fever and the production of acute phase proteins, some of which are antimicrobial because they can opsonize bacteria. Lysozyme (found in tears) breaks down the cell wall of bacteria. 24 Active immune system: Innate/NS Non-specific Immunity - Cellular defenses: White blood cells Phagocytes – Neutrophils (PMN’s) & Macrophages – Non-specifically engulf and digest foreign particles – Lack memory – Contribute to inflammatory response – Monocytes & macrophages (not PMN’s) work as Ag-presenting cells (APC) to the specific immune system 25 Active immune system: Innate/NS Cellular defenses con’t: Circulating WBCs - Neutrophils AKA Polymorphonuclear granulocytes (PMN’s) Most common – 55-70% of WBC Ingest and digest foreign particles (phagocytosis) – Digestion by lysozymes Neutrophil containing bacteria 26 Active immune system: Innate/NS neutrophils Cellular defenses con’t: Circulating WBCs - Neutrophils Attracted to sites of infection or inflammation by chemotaxis (chemical signaling e.g., cytokines, interleukins) When activated, neutrophils become “sticky” – Marginate in circulation – Squeeze through endothelial junctions (= diapedesis) – Migrate to the site of infection or tissue damage In addition to phagocytosis, neutrophils release cytokines to initiate specific immune cell response Especially important in mammary gland and uterus 27 Active immune system: Innate/NS Neutrophil migration to infected tissue Bacterium White blood Cells-PMN J.L. Burton Dept. Animal Science Michigan State University28 Active immune system: Innate/NS 1 Neutrophil in milk with 3 Staph. Aureus bacteria, one being engulfed by a pseudopod (“NET”) @ 20,000 X 29 Paape et al J. Mamm. Gl. Biol. Neoplasia 2002 Active immune system: Innate/NS monocyte Cellular defenses con’t: Circulating WBCs - Monocytes Largest cell; 5 to 8% of total WBC Cytoplasm contains lysosomes Eventually leave circulation to become macrophages in tissue Functions: – Non-specific removal of bacteria, fungi, necrotic debris – Act as Antigen presenting cell (APC) to T lymphocytes 30 Active immune system: Innate/NS Cellular defenses con’t: Tissue cells - Macrophages Monocytes migrate to tissue or reside in specific locations (E.g., liver, lung, spleen), then differentiate into macrophages Activated by phagocytosis of certain antigens, secretions of T cells & bacteria cell walls Migrate to sites of infection/inflammation (chemotaxis) Functions: – APC’s – Activate Helper T cells 31 Active immune system: Innate/NS antigen Innate immune system summary tissue damage vasoactive factors chemotactic factors ↑ Blood flow to affected area and ↑ vessel Chemical signals to activate and permeability to allow immune cells and attract immune cells molecules out complement phagocytic (antibodies) cells opsonization, phagocytosis antigen destruction 32  Active Immune System Overview Non-specific Immunity Specific Immunity (innate) (adaptive) Response is antigen- Response is antigen- independent dependent There is immediate maximal There is a lag time between response exposure and maximal response Not antigen-specific Antigen-specific Exposure results in no Exposure results in immunologic memory immunologic memory 33 34 Active immune system: Adaptive/Specific Overview of Specific Immune System B and T lymphocytes Each mature lymphocyte has the receptors to recognize specific antigens Has memory - greater and faster response to previously encountered antigens Surface antigen receptors on lymphocyte 35 Active immune system: Adaptive/Specific Overview of Specific Immune System Humoral Wing Cell Mediated Wing – B cells – (Macrophages) Plasma cells – T cells Memory cells Helper (CD4+) Suppressor (CD8+) – Production of Killer (cytotoxic, CD8+) specific antibodies – Cytokines IgM IgG – Destroy tumor cells and cells infected with IgA virus IgE 36 Active immune system: Adaptive/Specific Specific Immunity: Lymphocytes Lymphocytes – B cells from the bone marrow, mature in the bone marrow – humoral immunity Mostly nucleus, round – T cells from bone marrow, mature in the thymus – cell mediated immunity Stored in lymph nodes, lymphoid tissue (spleen). Lymphocyte 37 Active immune system: Adaptive/Specific B Lymphocytes: Antibody production “Naïve” lymphocytes scans for antigens – blood, lymph nodes The stimulated B cell divides repeatedly Forms a clone of antibody secreting plasma cells This large population of cells produces sufficient quantities of antibody to help WBC destroy the bacteria After the assault is over, some become memory B cells 38 Active immune system: Adaptive/Specific Antibody (Immunoglobins / Ig) Multiple types (IgA, IgM, IgG, IgE) – All are proteins produced by B cells (plasma cells) Antigen-antibody complexes stimulate additional production of antibody Function – Released into the intercellular fluid where they bind to the infecting antigen & flag it for destruction by phagocytes & the complement system – Coating may prevent attachment or invasion by bacteria or viruses – Bind toxins secreted by pathogens 39 Active immune system: Adaptive/Specific Types of Antibody IgA Found on mucosal surfaces – GI, respiratory, reproductive tracts Forms 10-15% of total IgA 40 Active immune system: Adaptive/Specific Types of Antibody IgM Circulates mainly in IgM blood, not tissue Generally produced most quickly in response to antigenic stimulation About 5-10% of total 41 Active immune system: Adaptive/Specific Types of Antibody IgG Most common (80%) IgG Found equally in circulation and tissue – i.e. migrates to sites of infection, crosses placenta Has the longest half-life of all the antibody types IgE Associated with parasites & allergies Least common 42 BREAK! 43 Active immune system: Adaptive/Specific Overview of Specific Immune System Humoral Wing Cell Mediated Wing – B cells – (Macrophages) Plasma cells – T cells Memory cells Helper (CD4+) Suppressor (CD8+) – Production of Killer (cytotoxic, CD8+) specific antibodies – Cytokines IgM IgG – Destroy tumor cells and cells infected with IgA virus IgE 44 Active immune system: Adaptive/Specific 45 Active immune system: Adaptive/Specific Cell Mediated Immunity Helper T Cells: When the Helper T cell “sees” the same antigens on both the T cell receptor macrophage & B cell, the T cell stimulates the B cell to start producing antibody by releasing interleukins After the assault has ended, some remain as memory helper T cells. 46 Active immune system: Adaptive/Specific Cell Mediated Immunity Cytotoxic (killer) T cells: Recognize infected cells bearing specific antigen complexes Destroy the cells by dissolving cell membranes Some remain as memory killer T cells Killer T cell destroying influenza virus infected cell 47 Active immune system: Adaptive/Specific Cell Mediated Immunity cytotoxic T cell infected cytokines cell cytolysis 48  Immune system overview Innate (non-specific) Adaptive (specific) Physical barriers Phagocytes Neutrophils Humoral Cell-mediated Macrophages Antibodies Cell lysis Complement B lymphocytes T lymphocytes system NK cells 49  Specific (active) Immune System Overview Non-specific Immunity Specific Immunity (innate) Response is antigen- Response is antigen- independent dependent There is immediate maximal There is a lag time between response exposure and maximal response Not antigen-specific Antigen-specific Exposure results in no Exposure results in immunologic memory immunologic memory 50  Nutrition & Immunity Overall running of the immune system is energy-demanding Antibodies are proteins (require dietary amino acids) Numerous vitamins and minerals are specific co-factors and enzyme components in phagocytic and cell lysis reactions 51  Nutrition & Immunity Protection of phagocytes from oxidative damage from radicals generated in digestion – Vitamins E and A, selenium, copper Iron Zinc 52  How can we exploit the immune system to prevent disease? Secondary or Primary Anamnestic Response Response Memory cells survive Logarithmic increase IgM Inductive period IgG ~ 14 days Baseline Negative phase (Ig consumed) Primary antigenic Secondary antigenic stimulation stimulation 53  VACCINATION ≠ IMMUNIZATION Vaccination = to administer a vaccine Immunize = to stimulate/confer a protective immune response “Strategic” vaccination = to administer a vaccine in such a way (usually meaning timing) as to maximize chances of protection against condition of interest 54  Immunization Strategies Modified Live Vaccines Lab-attenuated virus Produce a low-level, “true” infection Replicates in host Killed Virus Vaccines Completely inactivated No replication Adjuvants added to increase immune response 55  Immunization Strategies mRNA Vaccines mRNA vaccines include a short-lived synthetically created fragment of the RNA sequence of a virus mRNA fragments – phagocytosis by dendritic cells The dendritic cells read the mRNA and produce the viral antigens that the mRNA encodes  Cell-mediated response and development of immunity 56  Immune system overview Innate (non-specific) Adaptive Vaccine (specific) responsive Physical barriers Phagocytes Neutrophils Humoral Cell-mediated Macrophages Antibodies Cell lysis Complement B lymphocytes T lymphocytes system Killed vaccine  MLV NK cells MLV  mRNA mRNA 57  Killed Virus Vaccines Advantages – Generally stimulate good humoral response – More likely to be able to use during pregnancy – No risk of shedding – No risk of reversion to virulence – Properly stored a partial bottle can be used Greater stability – Less concern about stage of gestation at time of vaccination – Can incorporate new “strains” easier 58  Killed Virus Vaccines Disadvantages – Primer dose needs to be “boostered” in 2-4 weeks (1º series) = $$$ – Ability to stimulate CMI = ? – Antibodies alone not protective for many diseases – Antibodies only produced against strains in the vaccine – More expensive – High levels of antibody for approximately 4-6 months – when boostered 59  8 Schematic antibody 7 response to killed Total Ig 6 vaccine Antibody level 5 IgG 4 3 Total Ig Memory IgM IgG 2 IgM 1 0 0 10 20 30 40 Time (days) 60  Modified Live Vaccines (MLV) Advantages – Stimulate cell mediated and humoral sides of immune system – Single dose will usually provide protection – Are less expensive per dose – More rapid immune response – Longer lasting protection 61  Modified Live Vaccines (MLV) Disadvantages – (Historically) cannot be given to pregnant animals There are now exceptions – Need to be reconstituted prior to use – Can be inactivated by heat, sunlight, chemical residues in syringe – Must be used within hours. Partial bottles can not be stored 62 Schematic antibody response to MLV Level of antibodies 0 1 2 3 4 5 6 IgM IgG Total 0 10 20 30 40 Time (days) NB: antibody response ≠ protection 63  mRNA vaccines Advantages – Stimulate cell mediated and humoral sides of immune system – Can be designed and updated more easily and rapidly – Cannot cause disease – Are less expensive per dose – Small volumes of vaccine required 64  mRNA vaccines Disadvantages – Usually require 2 doses and possibly boosters – May require specialized storage conditions 65 To vaccinate or not to vaccinate… Is the vaccine: – Efficacious: can it work? (lab) – Effective: does it work? (field trials) – Efficient: is it worthwhile? (economics) 66  Apparent Vaccine Failure correct incorrect administration administration inappropriate passive death of route of injection immunity live vaccine animal responds animal fails to respond animal already different strain nonprotective infected or organism antigens passive animal biological inadequate immunization immunosuppressed variation vaccine nutrition genetics 67  Storage and handling “That vaccine you sold me doesn’t work…” 68  Setting expectations and setting up for success Protection from disease is a function of both host resistance and pathogen challenge – Onset of immunity is typically 2-4 weeks after vaccination – Nutrition (antioxidants, energy, protein, BCS) must be adequate to support immune response – In a population, 100% of animals may not mount a protective response to 1 round of vaccination Compliance is critical – Storage and transportation – Mixing, usage, maintenance of sterility – Correct route of administration – Accurate records to vaccinate all animals at correct times – Testing and vaccination of purchased animals 69  What does success look like? A well designed and implemented vaccination program, as part of a larger infectious disease program looks like…”nothing” “Grateful patients are few in preventive medicine, where success is marked by a non-event” “Poor management will overcome good immunology” 70  Lecture 3 Summary Terms to know: Antigen Active immunity Innate (non-specific) immunity Antigenicity Passive immunity Adaptive (specific) immunity Vaccination Colostrum Memory Immunize Strategic vaccination MLV Antibody Neutrophils Killed vaccine Macrophages Lymphocytes Immunoglobulin Components, roles & mechanisms of the active (innate & adaptive) and passive immune system branches in combating infection and disease MLV vs killed vaccines Factors critical for a successful vaccination program 71 Questions? 72  Lecture 3 Summary Terms to know: Antigen Active immunity Innate (non-specific) immunity Antigenicity Passive immunity Adaptive (specific) immunity Vaccination Colostrum Memory Immunize Strategic vaccination MLV Antibody Neutrophils Killed vaccine Macrophages Lymphocytes Immunoglobulin Components, roles & mechanisms of the active (innate & adaptive) and passive immune system branches in combating infection and disease MLV vs killed vs mRNA vaccines Factors critical for a successful vaccination program 1  To vaccinate or not to vaccinate… Is the vaccine: – Efficacious: can it work? (lab) – Effective: does it work? (field trials) – Efficient: is it worthwhile? (economics) 2  Apparent Vaccine Failure correct incorrect administration administration inappropriate passive death of route of injection immunity live vaccine animal responds animal fails to respond animal already different strain nonprotective infected or organism antigens passive animal biological inadequate immunization immunosuppressed variation vaccine nutrition genetics 3  Storage and handling “That vaccine you sold me doesn’t work…” 4  Setting expectations and setting up for success Protection from disease is a function of both host resistance and pathogen challenge – Onset of immunity is typically 2-4 weeks after vaccination – Nutrition (antioxidants, energy, protein, BCS) must be adequate to support immune response – In a population, 100% of animals may not mount a protective response to 1 round of vaccination Compliance is critical – Storage and transportation – Mixing, usage, maintenance of sterility – Correct route of administration – Accurate records to vaccinate all animals at correct times – Testing and vaccination of purchased animals 5  What does success look like? A well designed and implemented vaccination program, as part of a larger infectious disease program looks like…”nothing” “Grateful patients are few in preventive medicine, where success is marked by a non-event” “Poor management will overcome good immunology” 6  POPM*4230 Lecture 4 Drug/Antimicrobial Use and Antimicrobial Resistance in Food-producing Animals Anne Deckert DVM MSc PhD Slides adapted from lecture content provided by Dr. Terri O’Sullivan and Dr. Hannah Golightly  Lecture 4 - Objectives Understand regulations for the use of drugs in food-producing animals Understand the difference between antimicrobial resistance and antimicrobial residues Describe how antimicrobial use in food- producing animals can impact human health through resistance and residues List strategies to prevent antimicrobial resistance and residues related to livestock production and health 8 What types of drugs are used in animals?aused in animals? Antimicrobials Hormones Anti-inflammatories Fluids/electrolytes Analgesics Vaccines Anthelmintics Regulation of Veterinary Drugs in Canada 3 classes of drugs for veterinary use exist…. 1. Over-the-counter (OTC) 2. Prescription (Rx) 3. Medicated feeds Regulation of drugs occurs at different levels: Provincial National Practice of Veterinary Medicine Veterinary Drugs Directorate, Regulation of OTC drugs Health Canada Licensing and Labelling 10 Regulation of Veterinary Drugs in Canada Extra-label drug use (ELDU) – Any use of a drug not specifically listed on the label E.g., Changes in dose, route, frequency, indication, amount injected per site, withdrawal time, animal species Certain drugs, and families of drugs, are prohibited for extra-label drug use – E.g. Chloramphenicol, Clenbuterol, Diethylstilbesterol 11 Antimicrobial (AM) vs Antibiotic Antimicrobial & Antibiotic: kills or inhibits microbial growth yet results in minimal or no damage to the host Antimicrobial: kills or inhibits microorganisms (e.g., bacteria, viruses, protozoa…) Antibiotic: kills or inhibits bacteria 12  AM use in Vet Med & Food Animal Production Health, welfare, production, food safety To prevent disease – During times of stress (e.g. weaning, after transportation) Treatment of disease – Outbreaks in populations or illness in individual animals To control disease – E.g. to reduce disease spread after initial infection of some animals in the herd/flock To promote growth – As of December 2018 - removal of production enhancement or growth promotion claims from all medically important antimicrobials used in human medicine 13  Antimicrobial distribution Prescription - All Medically Important Antimicrobials (MIA) Sold only through veterinarians - Veterinary-patient- client-relationship (VCPR) needed Pharmacy, feed, direct sales May be administered by producers Over the Counter (OTC) – Category IV AM only Limited number of “low-risk” products Typically ‘older’ antimicrobials 14  Antimicrobial Classification System Drugs of Human Medicine Importance Antimicrobials (MIA) Medically Important Category I: Very High Importance (e.g. amoxicillin-clavulanic acid, ciprofloxacin, ceftiofur) Category II: High Importance (e.g. amikacin, gentamicin, nalidixic acid, ampicillin) Category III: Medium Importance (e.g. chloramphenicol, sulfisoxazole, tetracycline) Category IV: Low Importance (e.g. ionophores, colistin) “Consider importance to human medicine” Antimicrobial Classification System Drugs of Human Health Importance – The Veterinary Drugs Directorate Classification System (2009) Rationale for Classification: Spectrum of activity of antimicrobials Mode of action Mechanism of resistance Availability of alternative antimicrobial therapy Potential for transfer of resistance  Why do we care how antimicrobials are used in animals? Antibiotic Antimicrobial residues resistance Human health Environmental contamination Exports Animal Health 17  ANTIMICROBIAL RESIDUES A violative drug residue occurs when an edible animal product has drug residues in excess of the maximum allowable limit (MRL) 18 Antimicrobial RESIDUES Antimicrobial / Drug Residues Why do we care? Direct pharmacological effect on human – e.g. allergic Consumer perception Export / trade 19 Antimicrobial RESIDUES Antimicrobial / Drug Residues Commonly cited causes of violative meat residues: Not following label directions for treatment Not following label directions for withdrawal Treatment not recorded Poor animal identification ELDU and not providing a new withdrawal period Canada: ✓ Very low rate of violations ✓ Long term maintenance of important export markets 20 Antimicrobial RESIDUES Withdrawal Times The primary parameter used by veterinarians to prevent violative residues is the length of the withdrawal time Withdrawal time: the interval between the last treatment with a compound and the time when the animal can be marketed (slaughter or milked) Withdrawal Metabolism Toxicology Depletion Time 21 Antimicrobial RESIDUES Avoiding Antimicrobial / Drug Residues 1. Record keeping Animal ID and treatment records 2. Label directions or veterinary prescribed protocol (Extra-label drug use) Dose, route of administration, length and frequency of treatment, withdrawal period 3. Quality Assurance Programs Protocols, rules, audits eg. Canadian Pork Excellence – PigSafe (Swine) 22 Antimicrobial RESIDUES Avoiding Antimicrobial / Drug Residues 4. Food Animal Residue Avoidance Databank (CgFARAD) 5. Systematic and random testing of products Every tanker of raw milk and monthly random farm tests Random and targeted abattoir tests Significant penalties for violations 23  ANTIMICROBIAL RESISTANCE (AMR) Established when normally susceptible bacteria grow in the presence of medication given at levels intended to kill them or inhibit growth. 24 Antimicrobial RESISTANCE AMR: Normally susceptible bacterium grow in presence of antimicrobial(s) at levels which normally suppress growth or kill the bacterium. Assessed via Minimum Inhibitory Concentration (MIC): The MIC is the lowest concentration of antimicrobial at which the bacteria is inhibited from growing. E.g., 1 Susceptible bacteria 0.25 μ/ml 0.5 μ/ml 1.0 μ/ml 2.0 μ/ml 4.0 μ/ml 8.0 μ/ml E.g., 2 Resistant bacteria 0.25 μ/ml 0.5 μ/ml 1.0 μ/ml 2.0 μ/ml 4.0 μ/ml 8.0 μ/ml Clinical break point 25 Antimicrobial RESISTANCE So, how do bacteria become resistant? Development of Resistant Bacteria Bacteria can become resistant to antimicrobials by: 1. Developing genes for resistance through mutation 2. Picking-up genes for resistance from other bacteria Genes responsible for resistance may cluster together and move between bacteria as a unit 26 Antimicrobial RESISTANCE Amx = antimicrobial AMR Example: Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” BACTERIA 27 Antimicrobial RESISTANCE Amx = antimicrobial Population exposed to AMx ”A” Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” 28 Antimicrobial RESISTANCE Resistant bacteria survive Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” 29 Antimicrobial RESISTANCE Bacteria population composition changes Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” 30 Antimicrobial RESISTANCE Population exposed to AMx ”B”… Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” 31 Antimicrobial RESISTANCE Resistant bacteria survive Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” 32 Antimicrobial RESISTANCE … New multi-drug resistant bacterial population Non-resistant Bacteria that acquired Bacteria that acquired bacteria resistance to AMx “A” resistance to AMx “A” & “B” Exposure to antimicrobials changes the bacteria population structure & can result in populations of drug-resistant bacteria. Exposure to antimicrobials does not induce resistance directly in individual bacteria. 33 Antimicrobial RESISTANCE What does this have to do with food animals? AMR = A “microbial hazard” Transmission of resistant bacteria/genes through the food supply (e.g. meat or milk of an animal) represents a food safety concern Reduces our ability to effectively treat bacterial infections in humans and animals 34 Antimicrobial RESISTANCE AMR and Food Safety Animals  Humans Potential for movement of bacteria containing resistance genes/elements from animals into food Implies: Potential exchange of Some contamination of food resistance genes from AND animal commensal Failure of cooking or hygiene BACTERIA to human with consumer pathogenic BACTERIA in human gut 35 Antimicrobial RESISTANCE AMR and Food Safety Animals  Humans Potential for movement of bacteria containing resistance genes/elements from animals into food Transfer of AMR via movement of bacteria – NOT consumption of drug (antimicrobial) residues by humans 36 Antimicrobial RESISTANCE AMR and Human Health Humans  Humans Antimicrobial use in people is also important due to other exchange pathways (person-to- person) Community-acquired Hospital-based (nosocomial) 37 Antimicrobial RESISTANCE Human & Animal Health Consequences Identified as a Public Health Issue by WHO, WOAH, CODEX and individual countries including Canada Few (no) new antimicrobials are being developed From Antimicrobial Therapy in Veterinary Medicine, 5th Ed 38 Antimicrobial RESISTANCE Human & Animal Health Consequences Identified as a Public Health Issue by WHO, WOAH, CODEX and individual countries including Canada Few (no) new antimicrobials are being developed ⇧ morbidity and mortality due to AMR Multi-drug resistance = can’t effectively treat diseases Alternative antimicrobials: ⇧ toxicity, ⇩ efficacy, ⇧ cost Increasing public concern 39 Antimicrobial RESISTANCE Antimicrobial Use & AMR Primarily associated with AM misuse in human populations Evidence of bacterial resistance associated with AM use in agri-food production Organisms resistant to one antimicrobial typically become resistant to multiple drugs AMR in one area will eventually appear in other areas, & once AMR appears, it is unlikely to decline spontaneously 40  AQUACULTURE Sea / Swimming Lakes Drinking Water Drinking Rivers and water Streams Industrial & Household Antibacterial SOIL Chemicals Farm Effluents and Manure Spreading Sewage WILDLIFE Dead Rendering Offal stock Vegetation, Seed Crops, Fruit SWINE HUMAN SHEEP CATTLE Commercial COMMUNITY Animal Handling FOOD Abattoirs / Meat HOSPITALIZED - URBAN Feeds Preparation VEAL ANIMALS Processing -RURAL Consumption CALVES POULTRY Plants OTHER EXTENDED FARMED CARE LIVESTOCK FACILITIES COMPANION Direct ANIMALS Contact after Linton AH (1977), modified by Irwin RJ 41 Antimicrobial RESISTANCE Human & Animal Health Consequences E.g. Resistance to ceftiofur Ceftiofur Labelled for use in cattle and swine NOT labelled for use in chicken in Canada – Used extra-label to control E. coli omphalitis in broilers Human Health concern Resistance to ceftiofur = resistance to ceftriaxone one of the drugs of choice for: – Salmonellosis in pregnant women and children – Community and health-care acquired pneumonia – Bacterial meningitis – Potentially septic febrile infants – STDs 42 Antimicrobial RESISTANCE Minimizing AMR: Prudent Use 5-R Approach to Antimicrobial Stewardship: Responsibility: Use the right drug, on the right animal, against the right condition, at the right dose, at the right time Reduce: Reduce antimicrobial use by establishing good management protocols to reduce disease risk Replace: Replace antimicrobial use with other medications when possible, or use vaccines to prevent disease Review: Review medication usage periodically to identify areas for improvement Refinement: Refine use by selecting the most appropriate medication 43 Antimicrobial RESISTANCE Minimizing AMR: Multi-pronged approach to disease prevention & control Biosecurity Assessment & monitoring Facility Disease improvements prevention Diagnostics & & control vaccination Good stockmanship Nutrition ✓ Preservation of antimicrobials for animal & human health ✓ Consumer confidence ✓ Maintenance of trade relationships 44 Antimicrobial RESISTANCE Minimizing AMR: Prudent Use Consider importance to human medicine! Antimicrobial Classification System Drugs of Human Medicine Importance Antimicrobials (MIA) Medically Important Category I: Very High Importance (e.g. amoxicillin-clavulanic acid, ciprofloxacin, ceftiofur) Category II: High Importance (e.g. amikacin, gentamicin, nalidixic acid, ampicillin) Category III: Medium Importance (e.g. chloramphenicol, sulfisoxazole, tetracycline) Category IV: Low Importance (e.g. ionophores, colistin) 45 Antimicrobial RESISTANCE Minimizing AMR Current status in Canada More recent concern - historically hasn’t been a focus of quality assurance No regulatory testing at slaughter Surveillance – Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) Contribution of agriculture to AMR issues in human health is not quantified… 46 Antimicrobial RESISTANCE 47 Antimicrobial RESISTANCE Minimizing AMR: Surveillance CIPARS is a national integrated surveillance program – Collects data about antimicrobial use in animals, humans & plants – Collects data about antimicrobial resistance in humans & animals – Brings all these different pieces of information together to better understand the ecology of AMR across Canada 48 Antimicrobial RESISTANCE AMR: Summary It’s complicated! Some antimicrobials are more important than others AMR has animal and human health implications Few (none) new antimicrobials are being developed Prudent use is important Surveillance and research provides valuable information 49 BREAK! 50  Impacts of Antimicrobial use Antibiotic Antimicrobial residues resistance Human health Environmental contamination Exports Animal Health 51  Lecture 4 Summary Antimicrobial Resistance ≠ Antimicrobial Residue Antimicrobial Resistance - Microbial hazard Detection of resistant bacteria/genes in the meat or milk of an animal – not susceptible to antimicrobials Dissemination of resistant bacteria/genes continues beyond the residue withdrawal period Antimicrobial Residue - Chemical hazard Detection of antimicrobial drug or metabolite in the meat or milk of an animal Withdrawal period: Antimicrobial molecule < MRL 52 Antimicrobial Resistance ≠ Antimicrobial Residue Antimicrobial Resistance Antimicrobial Residue Microbial hazard Chemical Hazard 53  Lecture 4 Summary Terms to know: Antimicrobial Antimicrobial resistance 5-R Approach Antibiotic Antimicrobial residue Prudent use ELDU MIA Withdrawal time VCPR Antimicrobial resistance – How bacteria become resistant to antimicrobials – How resistant bacteria in animals can affect human health – How we can prevent antimicrobial resistance in food animals Antimicrobial residues – How violative residues in animal food products occur – Potential impacts of violative antimicrobial residues – Mechanisms are in place to avoid violative residues 54 INFOGRAPHIC ASSIGNMENT 15% OF TOTAL MARK 55 Infographic Assignment Overall task: Design a quick visual reference guide or fact sheet in the form of an infographic. – Provide information portraying a specific area of food-animal health or a health management technique/theory – Target audience = producers (i.e. swine producer, dairy producer) and any staff members that they may employ to work on their production unit(s) Use them on farm to serve as an educational sheet or quick reference guide for themselves or any other farm employees 56 Infographic Assignment Topic – Target your infographic for a specific commodity (e.g. poultry, dairy, etc) Consider narrowing it down further to a specific age or production class of a specific commodity (e.g. nursery pigs, dairy calves, etc). – List of suggestions