PHLT 2 Veterinary Epidemiology Session 4 Causation PDF

Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____...

Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ Lesson title: Concept of Disease in Causation Materials: - Paper and Pen Lesson Objectives: - Desktop Computer or Smart Phone with At the end of this period, the students are expected to: internet access 1. explain what is meant by the term causation. - pdf file copy of 2. explain the interaction between the components of reference book the epidemiologic triad of disease. 3. describe factors that influence the presence of disease References: in an individual animal and the population. 1. Thrusfield, Michael (1995). 1. Veterinary Epidemiology. Third edition. Oxford: Blackwell Science Ltd. 2. Martin, Meek, Willeberg (1987). Veterinary Epidemiology Principles and Methods, Ames: Iowa State University Press. Productivity Tip: Discover something fascinating about science. A. LESSON PREVIEW/REVIEW 1) Introduction (2 mins) This session will define and discuss cause of events more generally, as a necessary background to the investigation of the cause of disease. The epidemiological investigations aim to identify causal relationships and potential risk factors. Among the purposes of studying cause and effect is to generate knowledge to prevent and control disease. As you may recall, one important use of epidemiology is to identify the factors that place some animals in a population at greater risk to a disease than others. Causes of disease in individual animals may not necessarily be demonstrable causes of disease in populations and vice versa. Different diseases require different balances and interactions of various factors. The factors further interrelate in a variety of complex ways to produce disease. Development of appropriate, practical, and effective measures to control or prevent disease usually requires assessment of all identified factors and their interactions. FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ 2) Activity 1: What I Know Chart, part 1 (3 mins) Consider the following questions on the table below. On the first column briefly write in bullet points what you know about the question. Meanwhile, leave the third column blank until you have completed going through the whole lesson. What I Know Questions: What I Learned (Activity 4) 1. Defend the statement that “disease does not occur in random fashion.” 2. What is your concept on the cause of disease? 3. How are models of causation useful in epidemiologic investigation? B.MAIN LESSON 1) Activity 2: Content Notes (20 mins) Concept of Causation Most epidemiological investigation is based on assumption that disease and other health events does not normally occur in a random fashion. Diseases are more likely to occur in some members of the population than others which is attributed to risk factors that may not be distributed randomly in the population. Knowledge on the cause of the disease can help predict the outcome of an intervention and help treat disease. Hippocrates said, "To know the causes of a disease and to understand the use of the various methods by which the disease may be prevented amounts to the same thing as being able to cure the disease" Merriam-Webster Dictionary defined cause as “something that brings about a result especially a person or thing that is the agent of bringing something about.” Similarly, Rothman stated that cause is an event, condition, or characteristic without which the FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ disease would not have occurred. However, how do we know when something makes a difference? Because thunder follows lightning does not mean thunder is caused by lightning. Another example is demonstrated in this statement: “If the rooster crows at the break of dawn, then the rooster caused the sun to rise.” Association is not the same as causation. The crowing of the rooster is associated with the break of dawn, but the rooster is not the cause of the sunrise. The foremost characteristic of a cause is that the event must precede the effect for it to be a cause. Cause can come in just a short period before the effect or it can happen a long time before the effect. Meanwhile according to Mill (1862), cause refers to “the sum total of the conditions positive and negative taken together; the whole of the contingencies of every description, which being realized, the consequent invariable follows,”. Following this definition, infection with Actinobacillus lignieresii is not solely responsible for the wooden tongue disease in cattle. The organism must enter tissues of the mouth through epithelial damage associated with rough fodder e.g. containing sharp stems or thorns. Models of disease and injury facilitate our understanding of their etiology or causes. Etiology is the science of causation. Some causation models are the following: 1. The Epidemiology Triangle - Agent-host-environment model illustrates diseases based on the causative agent, affected hosts and the environment where it occurred. (this will be discussed further below in this session) 2. Wheel model - The Wheel of Causation (Mausner & Kramer, 1985) de-emphasizes the agent as the sole cause of disease, while emphasizing the interplay of physical, biological and social environments. It also brings genetics into the mix. 3. Web of Causation - Effects develop from chains of causation, each link has a complex genealogy of antecedents. This model provides for multifactoral causes that traverse various pathways. Mirroring reality, these causal webs can be highly intricate and complex. This is discussed further by Thrusfield, (1995). FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ 4. Nested Boxes Set of boxes graduated in size so that each fit into the next larger one Integrates factors at many levels of organization 5. Causal Pie - Each pie is a Sufficient Cause (each complete pie represents an animal that developed disease, and hence was sufficient). Each piece is a Component Cause. A component cause (piece) that is part of every sufficient cause (pie) (i.e., A) is a Necessary Cause. This is discussed further by Thrusfield, (1995). 6. Bradford Hill's Guidelines (1965) Sir Austin Bradford Hill provided nine considerations for assessing whether an observed association involved a causal component or not. Hill’s “guidelines” are useful for: ▪ Remembering distinctions between association and causation in epidemiologic research or investigation; ▪ Designing epidemiologic studies; and ▪ Critically reading and interpreting the results epidemiologic studies. The following are Hill’s considerations: a) Strength of Association = A strong association is more likely to have a causal component than is a modest association b) Consistency = A relationship is observed repeatedly c) Specificity = A factor influences specifically a particular outcome or population d) Temporality = The factor must precede the outcome it is assumed to affect e) Biological gradient = The outcome increases monotonically with increasing dose of exposure or according to a function predicted by a substantive theory f) Plausibility = The observed association can be plausibly explained by substantive matter (e.g. biological) explanations g) Coherence = A causal conclusion should not fundamentally contradict present substantive knowledge h) Experiment = Causation is more likely if evidence is based on randomised experiments i) Analogy = For analogous exposures and outcomes an effect has already been shown Significant considerations are discussed further by Thrusfield, (1995). FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ The Epidemiologic Triad of Disease Different authors of epidemiology propose various models on the cause of disease. The epidemiologic triad or triangle is perhaps the simplest as a traditional model for infectious disease. The triad consists of an external agent, a susceptible host, and an environment that brings the host and agent together. Agent refers to an infectious microorganism or pathogen such as virus, bacterium, protozoan, fungi, parasite, or other living microbes. Presence of the agent however is not enough to cause disease. Variety of factors may influence whether exposure to an organism will result in disease, including the organism’s pathogenicity (ability to cause disease) and dose. In epidemiological terms, the “agent” also includes chemical (i.e poison), physical (i.e. trauma), and nutritional (lack, excess) causes of disease or injury. Host refers to the animal affected with the disease. Variety of host factors (sometimes called risk factors) can influence exposure, susceptibility, or response of an animal to a causative agent. Environment refers to extrinsic factors to both agent and host. Environment affects the agent and provides opportunity for exposure of the host. Environmental factors include physical factors such as climate and geography, biologic factors such as insects that transmit the agent, and farm management factors such as housing and confinement. Disease results from the interaction between the agent and the susceptible host in an environment that supports transmission of the agent from a source to that host. Two ways of depicting this model are shown in the figure on the right. The first model in the figure, shows agent, host, and environment as having equal influence. In the other model the epidemiological triad is designed to be shaped like a seesaw with the environment being the base, the host being on one side and the agent being on the other. Here, the agent and host as variables that are dependent on each other and on the environment. Different diseases require different balances and interactions of these three components. When the seesaw is balanced it is known as the equilibrium state, this state signifies that everything is healthy. In a scenario where there is an infectious disease, the seesaw would be weighted towards one side. FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ Imbalances towards the Agent, Host, and Environment If the imbalance is towards the agent, it is considered as the agent having more of an ability to cause a disease on the animal or agent’s ability to transmit the disease overwhelms the host’s response. When the imbalance is towards the host, the host in this case outweighs the agent. Factors affecting susceptibility of the animal to a disease is increased. This ultimately increases the proportion of animals in the population vulnerable to the disease. The environment likewise plays vital role in how the agent and host are affected by a disease. Just like the host and the agent, the environment has direct correlation to the other factors when spreading a disease. The environment plays a role in where the disease is most likely to spread and where it is currently located. In the first diagram on the right, the environment favors the agent. Here, changes in the environment facilitates spread of the disease. The environment can affect the agent to either be more susceptible or less susceptible in the host, depending on the disease. When the environment is biased towards the host, environmental change alters susceptibility of the host. For instance, in certain times of the year, in specific environments the host may not have a high susceptibility to certain diseases but may be susceptible to others. With the use of the epidemiologic triad, it is easier for epidemiologists to correlate the connections the environment, host, and agent have with one another to spread a disease. The mission of an epidemiologist is thereby to break at least one of the sides of the triangle, disrupting the connection between the environment, the host, and the agent, and stopping the continuation of the disease. The disease continues to spread in the population when any part of the triangle is not broken; and in such scenarios, the disease agents still maintains high morbidity and/or mortality in the affected host population – with the prevailing environmental conditions encouraging the disease proliferation and spread. FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ Read full discussions on the topics below in the following sources: Thrusfield, Michael (1995). Veterinary Epidemiology Third Edition, Chap 3 p34-45 Martin, Meek, Willeberg (1987). Veterinary Epidemiology Principles and Methods Chap 5 p121 - 147 Methods of Acceptance of Hypothesis When field investigation suggest that certain factors may be causally associated with a disease, then the association must be assessed by formulating a causal hypothesis. One may accept (or reject) a causal hypothesis by four methods (Cohen and Nagel, 1934): 1. tenacity; 2. authority; 3. intuition; and 4. scientific inquiry. Koch’s Postulates In 1890 the German physician and bacteriologist Robert Koch set out his celebrated criteria for judging whether a given organism is the cause of a given disease. The Koch's postulates rendered some much-needed scientific clarity on criteria for testing causal associations regarding infectious diseases. Essentially, Koch's postulates consist of the following: 1) The organism must be present in every case of the disease. 2) The organism must be isolated from the host with the disease and grown in pure culture. 3) The specific disease must be reproduced when a pure culture of the organism is inoculated into a healthy susceptible host. 4) The organism must be recovered from the experimentally infected host. Image source: https://microdok.com/robert-koch-postulates/ The Koch’s postulates brought necessary degree of order and discipline into the study of infectious disease. However, Koch's postulates have their limitations which include the following: a) Some organism, when grown in laboratory media, dissociate to such an extend that the lose their virulence; b) Many pathogens do not grow in nutrient medium culture (i.e. viruses, mycoplasma) c) Some nonliving agents can produce transmissible disease in healthy animals (prions). FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ d) Some organisms are pathogenic only when present with other organisms. Example, Pasteurella multocida and Bordetella bronchiseptica causing atrophic rhinitis in pigs. e) Disregarded the influence of environment factors in causing disease. Evans' Rules Alfred Evans (I 976) has produced a set of rules that are consistent with modern concepts of causality: 1. The proportion of individuals with the disease should be significantly higher in those exposed to the supposed cause than in those who are not; 2. Exposure to the supposed cause should be present more commonly in those with than those without the disease, when all other risk factors are held constant; 3. The number of new cases of disease should be significantly higher in those exposed to the supposed cause than in those not so exposed, as shown in prospective studies; 4. Temporarily, the disease should follow exposure to the supposed cause with a distribution of incubation periods on a bell-shaped curve; 5. A spectrum of host response, from mild to severe should follow exposure to the supposed cause along a logical gradient; 6. A measurable host response (e.g. antibody, cancer cells) should appear regularly following exposure to the supposed cause in those lacking this response before exposure, or should increase in magnitude if present before exposure; this pattern should not occur in individuals not so exposed; 7. Experimental reproduction of the disease should occur with greater frequency in animals or man appropriately exposed to the supposed cause than in those not so exposed; this exposure may be deliberate in volunteers, experimentally induced in the laboratory, or demonstrated in a controlled regulation of natural exposure; 8. Elimination (e.g. removal of a specific infectious agent) or modification (e.g. alteration of a deficient diet) of the supposed cause should decrease the frequency of occurrence of the disease; 9. Prevention or modification of the host’s response (e.g. by immunization or use of specific lymphocyte transfer factor in cancer) should decrease or eliminate the disease that normally occurs on exposure to the supposed cause; 10. All relationships and associations should be biologically and epidemiologically credible. Causation vs Association Causation: Causation means that the exposure produces the effect. It implies that there is a true mechanism that leads from exposure to disease. Exposure must precede disease Association: Association is a statistical relationship between two variables. Also describe as the degree of dependence or independence between two variables. Finding an association does not make it causal. If a relationship is causal, four types of causal relationships are possible: FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  Necessary and Sufficient  Necessary, but not Sufficient  Sufficient, but not Necessary  Neither Sufficient nor Necessary Types of Association 1. non-statistical association  An association between a disease and hypothesized causal factor that arises by chance; that is, the frequency of joint occurrence of the disease and factor is no greater than would be expected by chance. 2. statistical association Variables are positively statistically associated when they occur together more frequently than would be expected by chance. Variables are negatively statistically associated when they occur together less frequently than would be expected by chance. Methods of Formulating Causal Hypothesis o Method of Difference. If the circumstances where a disease occurs are similar to those where the disease does not occur, with the exception of one factor, this one factor or its absence may be the cause of the disease. o Method of Agreement. If a disease occurs under a variety of circumstances but there is a common factor, this factor may be the cause of the disease. o Method of Concomitant Variation. If a factor and disease have a dose response relationship, the factor may be a cause of the disease. o Method of Analogy. If the distribution of a disease is sufficiently similar to that of another well understood disease, the disease of concern may share common causes with the other disease. o Martin, Meek, Willeberg (1987) included Method of Residue 2) Activity 3: Skill-building Activities You can earn total of ten (10) points in answering the following items. A. Epidemiologic Triad of Disease Read the Fact Sheet sent through google classroom, then answer the questions below. Describe its causation in terms of agent, host, and environment.  Agent:  Host:  Environment: FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ B. Upon observation, it was noted that pigs in a grower pen are excessively scratching their body on the walls. Red patched lesions are further seen on the skin. Identify factors associated with the above condition. Draw a diagram to show the causal association of the factors. Wait for further instructions on the submission of your work to claim your points. 3) Activity 4: What I Know Chart, part 2 (2 mins) You are about to complete the lesson at this point. To refresh what you have learned, review back the questions in the What I Know Chart from Activity 1 and write your answers to the questions based on what you now know in the third column of the chart. 4) Activity 5: Check for Understanding (5 mins) Take Quiz Uploaded in Google Classroom C. LESSON WRAP-UP 1) Activity 6: Thinking about Learning (5 mins) You are done with this session! Let’s track your progress. Shade the session numbers you have completed. P1 P2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ 2) My learning targets: Complete the table below. Record your scores, learning experience for the session and deliberately plan for the next session. Date Learning Target/Topic Scores Action Plan What session# did you do? What were the What were What contributed to the quality of your performance What’s the date learning targets? What activities did you your scores in today? What will you do next session to maintain today? do? the activities? your performance or improve it? FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH  Course Code: PHLT 2 Veterinary Epidemiology Student’s Activity sheet for Session #4 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ FAQs Does the Epi triad have limitation? While the epidemiologic triad serves as a useful model for many diseases, it has proven inadequate for human cardiovascular disease, cancer, and other diseases that appear to have multiple contributing causes without a single necessary one. FLM 1.0 Prepared by Daniel C. Ventura, Jr., DVM, PhD., DipVPH