Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand Sunpetch Angkititrakul, DVM, MSc, PhD Department of Veterinary Public Health Faculty of Veterinary Medicine, Khon Kaen University Introduction of Epidemiology Public health is primarily concerned with the prevention of disease in human populations, and epidemiology is the branch of public health which attempts to discover the causes of disease in order to make disease prevention possible. It thus differs from clinical medicine both in its emphasis on prevention (rather than treatment) and in its focus on populations (rather than individual patients). Thus, the epidemiological approach to a particular disease is intended to identify high-risk subgroups within the population, to determine the causes of such excess risks, and to determine the effectiveness of subsequent preventive measures. Although the epidemiological approach has been used for more than a century for the study of communicable diseases, epidemiology has considerably grown in scope and sophistication in the last few decades as it has been increasingly applied to the study of non-communicable diseases. At the st beginning of the 21 century, the field of epidemiology is changing rapidly, not only with regards to its basic methods, but also with regards to the hypotheses which these methods are used to investigate. In particular, in recent years there has been a revival in public health applications of epidemiology, not only at the national level, but also at the international level, as epidemiologists tackle global problems such as climate change. This text does not attempt to review the more complex methods used to study such issues. However, it does provide a coherent and systematic summary of the basic methods in the field, which can be used as a logical base for the teaching and development of research into these more complex issues. What is epidemiology? The word epidemiology comes from the Greek words epi, meaning “on or upon,” demos, meaning “people,” and logos, meaning “the study of.” Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to control of health problems. This definition of epidemiology includes several terms which reflect some of the important principles of the discipline. As you study this definition, refer to the description of these terms below. Study: Epidemiology is a scientific discipline, sometimes called “the basic science of public health.” It has, at its foundation, sound methods of scientific inquiry. Distribution: Epidemiology is concerned with the frequency and pattern of health events in a population. Frequency includes not only the number of such events in a population, but also the rate or risk of disease in the population. The rate (number of 1 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand events divided by size of the population) is critical to epidemiologists because it allows valid comparisons across different populations. Pattern refers to the occurrence of health-related events by time, place, and personal characteristics. Time characteristics include annual occurrence, seasonal occurrence, and daily or even hourly occurrence during an epidemic. Place characteristics include geographic variation, urban-rural differences, and location of worksites or schools. Personal characteristics include demographic factors such as age, race, sex, marital status, and socioeconomic status, as well as behaviors and environmental exposures. This characterization of the distribution of health-related states or events is one broad aspect of epidemiology called descriptive epidemiology. Descriptive epidemiology provides the What, Who, When, and Where of health-related events. Determinants: Epidemiology is also used to search for causes and other factors that influence the occurrence of health-related events. Analytic epidemiology attempts to provide the Why and How of such events by comparing groups with different rates of disease occurrence and with differences in demographic characteristics, genetic or immunologic make-up, behaviors, environmental exposures, and other so-called potential risk factors. Under ideal circumstances, epidemiologic findings provide sufficient evidence to direct swift and effective public health control and prevention measures. It is useful to distinguish epidemiological from clinical approaches to disease management. The clinical approach to disease management is focused on individual animals and is aimed at diagnosing a disease and treating it. It involves physical examination and generation of a list of differential diagnoses. Further examinations, laboratory tests and possibly response to treatment are then used to narrow the list of differential diagnoses to a single diagnosis. In an ideal world this will always be the correct diagnosis. The success of this approach depends on two conditions: • That the true diagnosis is on the list of differential diagnoses; and • Clinical signs arise from a single (disease process in the individual. The epidemiological approach The epidemiological approach to disease management is conceptually different in that there is no dependency on being able to precisely define the etiological agent. It is based on observing differences and similarities between diseased and non-diseased animals in order to try and understand what factors may be increasing or reducing the risk of disease. In practice, clinicians unwittingly use a combination of clinical and epidemiological approaches in their day-to-day work. If the problem is relatively clearcut then an epidemiological approach plays a very minor role. If the condition is new or 2 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand more complex then the epidemiological approach is preferred since it will provide a better understanding of what makes individuals susceptible to disease and once these factors are known the measures required to control the disease become better defined. Field epidemiology Field epidemiology is really a type of applied field research since we are trying to uncover what exists in an uncontrolled situation. The field epidemiologist attempts to gather and organize data to bring order and meaning to it when there is an urgent need for it. Field epidemiology can be applied to disease outbreaks, situation assessments and policy evaluation. Field epidemiology relies on a systematic approach to gather and organize data in a way that will support a better understanding of a disease situation. Once a disease agent(s) is/are identified a positive “case” is defined by establishing “case definition”. Even if the agent is not yet identified the following basic disease methods of disease control methods can be effectively to control the disease: Movement controls Stamping out Applying bio-exclusion and biosecurity principles Risk communication Vaccination may not likely be used for a new disease agent Learning from history is important. While control measures can be taken in the short term to control the disease, the field epidemiologist’s job is not only to help control the disease but to understand the how the disease occurred in order to prevent it from happening again in the future. This is a challenging task that uses both information and data. Obtaining information from animal owners is the process that provides data. For data to be useful, it must be collected, organized, summarized and reported in a systematic way. What data needs to be collected? Three initial questions need to be asked by the field epidemiologist so that the appropriate data is collected: 1. How large is the disease problem? Where does it exist and where does it not exist? First we seek and describe what we observe. Case finding and surveillance are key activities. 2. How did the situation arise and what led to its presence? A thorough investigation is required followed by preliminary analysis. 3. What can we do to better prevent and control the disease in the future? Further analysis of the findings of investigations and studies is needed. Health and Disease Epidemiology is used to assess both the health and disease status of a population. Epidemiology can be used to maximize the health of animals in order to increase milk, meat or egg production which will benefit human health as well. Alternatively, 3 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand epidemiology is commonly used to prevention and control animal diseases affecting either animals or humans requiring close collaboration between government and animal producers. At the population level disease can occur at different levels including sporadic, epidemic or endemic patterns. These patterns may suggest some possible types of sources of the disease to investigate more fully. The Epidemiologic Triangle (Triad): Disease is the result of complex interactions (some would say imbalance) between the triad of the agent (toxic or infectious), the host and the environment. The components of this interaction differ depending upon the specific circumstances of each group of affected animals. Particularly for agricultural animals, this triad is strongly influenced by husbandry and management factors, which are often the most important. For vector-borne diseases, vector factors are also linked to the other factors. Recognizing the different components of this triad is important because they are the source of opportunities to reduce disease at multiple points in the transmission cycle. A common mistake is to focus on only one aspect of the triad for disease control or prevention and to overlook the others. 4 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand The host is the animal (or human) that may contract a disease. Age, genetic makeup, level of exposure, and state of health all influence a host’s susceptibility to developing disease. The agent is the factor that causes the disease (bacteria, virus, parasite, fungus, chemical poison, nutritional deficiency etc) one or more agents may be involved. The environment includes surroundings and conditions either within the host or external to it that cause or allow disease transmission to occur. The environment may weaken the host and increase its susceptibility to disease or provide conditions that flavor the survival of the agent. Agent Factor Examples: Dose Environmental hardiness Virulence (microbial) Infectivity (microbial) Toxicity (poisons) Host Factor Examples: Innate resistance (e.g. gastric barrier, mucocilliary transport mechanism) Previous exposure Passive immune status (neonates) Vaccination status and response Age Gender Behavior (e.g. mutual grooming, dominance, pica) Production status (e.g., lactating vs. non-lactating) Reproductive status (e.g., pregnant vs. non-pregnant, sterile vs. intact) Genetics Environmental Factor Examples: Animal stocking density Animal movement between groups Housing (e.g. ventilation, sanitation) Environmental conditions (e.g. temperature, humidity, wind velocity, precipitation) Nutrition (protein, energy and macromineral and micromineral adequacy) The Spectrum of Disease Severity Because each group member is affected by one or more of the epidemiologic triad factors differently, disease in a group is often manifested as a spectrum that can range from inapparent to subclinical to clinical to fatal. 5 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand Subclinical means that signs of the disease cannot be detected without special tests. Clinical means that the signs of the disease can be detected during a normal clinical exam. Because the individual's body reacts to the disease, disease severity changes over time. During disease progression in a herd, individuals exposed at different points in time will be at different points in the natural history of the disease. Status and Spectrum of Disease Severity Exposure Status Unexposed Infection Status Exposed Uninfected Infected Subclinical (Inapparent) Disease Status Recovered Clinical Disease (Apparent) Morbidity (Sickness) Mild Mortality Severe Fatal Step in the disease process 1. Agent source Environment – land, water, air; Live Animals – infected tissue (skin) and contaminated secretions (tears) and discharges (oozing wounds, cuts); Dead animals – carcasses; Feed and Water; Animal products – milk, meat, eggs, other; Animal by-products – manure, feces, litter, offal (slaughter waste); Introduced through human intervention (Iatrogenic); Reservoir – includes wild animals, insects and other living sources of disease agents for the population at risk prior to exposure; Fomites – inanimate objects (clothing, equipment, vehicles) contaminated with disease agents; Vectors – insects and other living organisms can transmit disease agents either mechanically or biologically where the agent replicates within the vector. 6 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand 2. Exposure Initial introduction into the population Transmission within the population (individual to flock/herd to larger population) Direct transmission between infected host and susceptible host within the same population or among different populations Horizontal Vertical e.g. Brucellosis, tuberculosis Indirect transmission through contaminated clothing, equipment and vehicles Marketing systems Exposure dose of disease agent Route of exposure (oral-fecal versus venereal) within host population Animal density increases chances for secondary transmission in the PAR Survival time of the disease agent in the environment and host Frequency of exposure Critical periods for apparent infections when clinical signs are observed: Incubation period related to introduction of new animals or other contacts The shedding period is developed through experimental studies The period of clinical signs and recovery period can be observed visually when evident; sometimes animals die very suddenly without observing previous clinical signs Carrier state can be assessed through sampling at time intervals 3. Host susceptibility Species, breed, strain Age Sex Genetics Animal management and husbandry 4. Outcome (clinical / subclinical) It is important to measure disease outcomes using practical, available data including existing records, conducting surveys and surveillance to determine the number of either incident or prevalent cases. The ability to define a case appropriately will affect whether disease control or disease eradication is possible. Basic measures (indices) used to assess health and disease outcomes include productivity, morbidity and mortality. Important data that can be used in production systems include production records, treatment records, and mortality records. Outcomes can only be assessed if we collect these data. Modes of transmission After an agent exits its natural reservoir, it may be transmitted to a susceptible host in numerous ways. These modes of transmission are classified as: Direct o Direct contact o Droplet spread 7 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand Indirect o Air-borne o Vehicle-borne o Vector-borne Mechanical Biologic In direct transmission, there is essentially immediate transfer of the agent from a reservoir to a susceptible host by direct contact or droplet spread. Direct contact occurs through kissing, skin-to-skin contact, and sexual intercourse. Direct contact refers also to contact with soil or vegetation harboring infectious organisms. Thus, infectious mononucleosis (kissing disease) and gonorrhea are spread from person-to-person by direct contact. Hookworm is spread by direct contact with contaminated soil. Droplet spread refers to spray with relatively large, short-range aerosols produced by sneezing, coughing, or even talking. Droplet spread is classified as direct because transmission is by direct spray over a few feet, before the droplets fall to the ground. In indirect transmission, an agent is carried from a reservoir to a susceptible host by suspended air particles or by animate (vector) or inanimate (vehicle) intermediaries. Most vectors are arthropods such as mosquitoes, fleas, and ticks. These may carry the agent through purely mechanical means. For example, flies carry Shigella on appendages; fleas carry Yersinia pestis (agent that causes plague) in the gut and deposit the agent on the skin of a new host. In mechanical transmission, the agent does not multiply or undergo physiologic changes in the vector. This is in contrast to instances in which an agent undergoes part of its life cycle inside a vector before being transmitted to a new host. When the agent undergoes changes within the vector, the vector is serving as both an intermediate host and a mode of transmission. This type of indirect transmission is a biologic transmission. Causation The basis for most epidemiological investigations is the assumption that disease does not normally occur in a random fashion something causes it. As a result we can use epidemiological investigations to identify causal relationships and potential risk factors. Most scientific investigations are aimed at identifying cause-effect relationships. Webster’s dictionary defines a cause as ‘something that brings about an effect or a result.’ A cause of a disease is an event, condition, or characteristic which plays an essential role in producing an occurrence of the disease. Knowledge about cause-andeffect relationships underlies every therapeutic manoeuvre in clinical medicine. The situation is complicated if multiple causes are involved. Koch (1884) provided a framework for identifying causes of infectious disease. He specified that the following criteria (known as Koch’s postulates) had to be met before an agent could be considered as the cause of a disease: 8 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand • The agent has to be present in every case of the disease. • The agent has to be isolated and grown in pure culture. • The agent has to cause disease when inoculated into a susceptible animal and the agent must then be able to be recovered from that animal and identified. In the late nineteenth century Koch’s postulates brought a degree of order and discipline to the study of infectious diseases, although the key assumption of ‘one-agentone disease’ was highly restrictive (since it failed to take account of diseases with multiple etiologic factors, multiple effects of single causes, carrier states, and non-agent factors such as age and breed). Based on John Stuart Mill’s rules of inductive reasoning from 1856, Evan developed a unified concept of causation which is now the generally accepted means for identifying cause-effect relationships in modern epidemiology. Evan’s unified concept of causation includes the following criteria: • The proportion of individuals with disease should be higher in those exposed to the putative cause than in those not exposed. • Exposure to the putative cause should be more common in cases than in those without the disease. • The number of new cases should be higher in those exposed to the putative cause than in those not exposed, as shown in prospective studies. • Temporally, the disease should follow exposure to the putative cause. • There should be a measurable biologic spectrum of host responses. • The disease should be reproducible experimentally. • Preventing or modifying the host response should decrease or eliminate the expression of disease. • Elimination of the putative cause should result in lower incidence of disease. The "Iceberg" phenomenon In outbreaks of most disease in animal groups, both clinical cases (the tip of the iceberg) and subclinical cases (unobserved beneath the ocean surface) are present in the group. For many infectious agents, particularly those that are endemic, more of the infections in a group are subclinical (silent) than are clinical. For some exceptions, such as rabies, few if any subclinical infections occur and almost all if not all clinical infections end in death. This iceberg concept of severity distribution also holds for most induced, non-infectious diseases affecting a group, such as hypomagnesemia, ketosis and hypocalcemia. Disease in an individual is often evidence of a group phenomenon because the factors that caused the disease in that individual are usually affecting others adversely as well. 9 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand Measure of health One of the most fundamental tasks in epidemiological research is to quantify the occurrence of disease. This can be done by counting the number of affected individuals however, to compare levels of disease among groups of individuals, time frames and locations; we need to consider counts of cases in context of the size of the population from which those cases arose. A ratio defines the relative size of two quantities expressed by dividing one (numerator) by the other (denominator). Proportions, odds, and rates are ratios. Say we have a herd of 100 cattle and 58 are found to be diseased. The odds of disease in this herd are 58:42 or 1.4 to 1. A proportion is a fraction in which the numerator is included in the denominator. Say we have a herd of 100 cattle and 58 are found to be diseased. The proportion of diseased animals in this herd is 58 ÷ 100 = 0.58 = 58%. A rate is derived from three pieces of information: (1) a numerator: the number of individuals diseased or dead, (2) a denominator: the total number of animals (or animal time) in the study group and/or period; and (3) a specified time period. To continue the above example, we might say that the rate of disease in our herd over a 12-month period was 58 cases per 100 cattle. The term morbidity is used to refer to the extent of disease or disease frequency within a defined population. Two important measures of morbidity are prevalence and incidence. As epidemiologists we must take care to use these terms correctly. Prevalence Strictly speaking, prevalence refers to the number of cases of a given disease or attribute that exists in a population at a specified time. Prevalence risk is the proportion of 10 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand a population that has a specific disease or attribute at a specified point in time. Many authors use the term ‘prevalence’ when they really mean prevalence risk, and these notes will follow this convention. Prevalence can be interpreted as the probability of an individual from a population having a disease at a specified point in time. Two types of prevalence are reported in the epidemiological literature: (1) point prevalence equals the number of disease cases in a population at a single point in time (a snapshot), (2) period prevalence equals the point prevalence at the beginning of a study period plus the number of new cases that occurred during the remainder of the study period. Incidence Incidence measures how frequently initially susceptible individuals become disease cases as they are observed over time. An incident case occurs when an individual changes from being susceptible to being diseased. The count of incident cases is the number of such events that occur in a defined population during a specified time period. There are two ways to express incidence: incidence risk and incidence rate. 1. Incidence rate Incidence rate (also known as incidence density) is the number of new cases of disease that occur per unit of individual time at risk, during a defined time period. The denominator of incidence rate is measured in units of animal (or person) time. 2. Incidence risk Incidence risk (also known as cumulative incidence) is the proportion of initially susceptible individuals in a population who become new cases during a defined time period. 11 Introduction of Epidemiology Veterinary Field Epidemiology in Action 1-25 September 2009 Khon Kaen University, Thailand Study design A study generally begins with a research question. Once the research question has been specified the next step is to choose a study design. A study design is a plan for selecting study subjects and for obtaining data about them. Figure 10 shows the major types of epidemiological study designs. There are three main study types: (1) descriptive studies, (2) analytical studies, and (3) experimental studies. Descriptive studies are those undertaken without a specific hypothesis. They are often the earliest studies done on a new disease in order to characterise it, quantify its frequency, and determine how it varies in relation to individual, place and time. Analytical studies are undertaken to identify and test hypotheses about the association between an exposure of interest and a particular outcome. Experimental studies are also designed to test hypotheses between specific exposures and outcomes — the major difference is that in experimental studies the investigator has direct control over the study conditions. 12 Introduction of Epidemiology