Epidemiology Textbook PDF

INDEX S. Topic Pages No 1. Introduction to epidemiology 4-7 2. Sampling techniques 8-11 3. Components of epidemiology...

INDEX S. Topic Pages No 1. Introduction to epidemiology 4-7 2. Sampling techniques 8-11 3. Components of epidemiology 12-15 4. Describing disease occurrence 16-20 5. Determinants of disease 21-23 6. Transmission and maintenance of infection 24-27 7. Ecology of disease 28-30 8. Ecosystem 31-32 9. Patterns of disease 33-36 10. Investigation of epidemic 37-38 11. Disease control and eradication 39-41 12. International Organisations: Office International des Epizooties 42-45 13. Food and Agriculture Organization and World Health Organisation 46-47 14. Laws regulating animal diseases 48-50 15. Regulations regarding handling, import and export of biomaterials 51-53 16. Further readings and softwares 54  Chapter 1 Introduction to epidemiology The word epidemiology is based on Greek word i.e. epi- upon, demo- people, and logo- discoursing; it is ‘the study of that which is on people’ so Epidemiology is the study of disease in populations and of factors that determine its occurrence (Schwabe et al, 1977). The word epizootiology is based on Greek word i.e. zoo- animal, so relates to study of disease in animal populations. Objectives/Uses 1. To determine the origin of a disease whose cause is known. 2. To Investigate and control a disease whose cause is either unknown or poorly understood. 3. To acquire information on the ecology and natural history of disease. 4. To plan and monitor the disease control programmes. 5. To assess the economic effects of a disease and analyze the cost-benefit ratio of alternative control programmes. Types of Epidemiological investigations 1. Descriptive Epidemiology: It involves observing and recording diseases and possible causal factors. It is usually the 1st part of an investigation e.g. mastitis and associated factors. 2. Analytical Epidemiology: It is analysis of observations using suitable diagnostic and statistical tests e.g. whether mastitis is associated with hygiene. 3. Experimental Epidemiology: It involves observation and analysis of data from groups of animals in which factors associated with the groups can be selected and altered e.g. kaccha and pucca floors in relation to presence or absence of mastitis. 4. Theoretical Epidemiology: It is representation of disease using mathematical models that attempt to simulate natural patterns of disease occurrence. Epidemiological Sub disciplines 1. Clinical Epidemiology: It involves use of epidemiological principles, methods and findings in the care of individuals with particular reference to diagnosis and prognosis. 2. Computational Epidemiology: It involves application of computer science to epidemiological studies. It includes the representation of disease using mathematical models and use of expert systems. 3. Genetic Epidemiology: It is the study of the cause, distribution and control of disease in related individuals, and of inherited defects in populations. 4. Serological epidemiology: It involves application of serological tests for the investigation of various diseases. 5. Molecular Epidemiology: The application of new biochemical techniques like nuclear acid fingerprinting and hybridization, restriction enzyme analysis, PCR, monoclonal antibodies etc. to study small genetic and antigenic differences between micro organisms. 2  6. Predictive epidemiology: It deals with forecasting of possible diseases on the basis of ecological and environmental parameters. 7. Other Sub disciplines:  Chronic disease epidemiology is involved with the diseases of long duration.  Environmental epidemiology determines relationship between disease and environmental factors.  Nutritional epidemiology  Sub clinical epidemiology Concept of iceberg 3 The quantitative differences in manifestation of infectious disease within population can be described using the concept of iceberg. Animals that were exposed to infection and remain uninfected represent the base of the iceberg. These animals could be susceptible to infection in the future or had developed immunity as a result of previous exposure. The other group of animals may become infected but not develop the clinical disease. at some stage. The top of iceberg includes These animals may always remain in this animals with clinical disease- either mild or category or may develop clinical disease severe clinical disease or animals’ death. General Epidemiological Concepts Endemic (enzootic): Endemic is used in two senses to describe- the constant presence of disease in a population; or the usual frequency of occurrence of disease in a population. To describe an endemic disease, the affected population and its location should be specified e.g. anthrax is endemic in cattle in southern parts of India. When a disease is continuously present at high level in a population, it is called hyperendemic. Epidemic (epizootic): Epidemic was originally used to describe a sudden, usually unpredictable increase in number of cases of an infectious disease in a population. In modern epidemiology, an epidemic is an occurrence of an infectious or non-infectious disease to a level in excess of the expected (i.e. endemic) level. When an epidemic occurs, the population must have been subjected to one or more factors that were not present previously e.g. FMD or HS epidemics. To declare an epidemic, the endemic level of disease occurrence in a population must be known. Outbreak: Outbreak is occurrence of disease in a herd or any other identifiable group of animals. Outbreak is an epidemic limited to localized increase in incidence of a disease. For practical purposes, the term is synonymous with epidemic. Pandemic (panzootic): A widespread epidemic that usually affects a large proportion of population; may affect many countries or continents e.g. pandemic of FMD or earlier rinderpest in cattle, plague and smallpox in humans. Sporadic: A sporadic outbreak of a disease is one that occurs irregularly and haphazardly without any temporal or spatial clustering of cases (single case or cluster of cases which are not normally present in an area). This indicates that appropriate circumstances have occurred locally, producing small localized outbreaks. Exotic: The diseases that have entered a country from foreign lands are called exotic diseases and once these diseases start establishing itself in the new country termed as emerging diseases; To report any exotic disease in the country, the samples should be got tested from High Security Animal Disease Laboratory, Bhopal (MP) e.g. Bovine spongiform encephalopathy is not so far reported in the country so it is exotic disease whereas PPR is emerging disease. The diseases that have been eliminated/ eradicated from the country are called Exzootic diseases e.g. rinderpest. Zoonotic: The diseases and infections transmitted naturally between vertebrate animals and man. On the basis of patterns of disease and life cycle of infectious agents- Direct zoonoses (transmitted by direct or indirect contact between two vertebrate hosts e.g. rabies, brucellosis), Cyclozoonoses (require two species of vertebrates for perpetuation of infectious agent e.g. hydatid disease in dog-sheep cycle), Metazoonoses (the agent multiplies or/and develops in biological vector before being transmitted e.g. plague, schistosomiasis) and Saprozoonoses (cycle of infection involves inanimate objects e.g. botulism, fungal infections) Koch’s Postulates (Robert Koch, 1884): An agent is considered to be a cause of disease if- 1. It is present in all cases of the disease 2. It does not occur in another disease as a fortuitous and non-pathogenic organism. 3. It is isolated in pure culture from an animal, is repeatedly passaged, and induces the same disease in other animals. Koch’s postulates had the following assumptions which are impossible to fulfil. These require that a particular disease has only single cause and a particular agent should result in only one disease. These postulates have difficulty in dealing with multiple etiological causes, multiple effects of single agent, non infectious causes and host or other environmental factors into account. Evans Postulates (Evans, 1976): The proportion of individuals with the disease should be significantly higher in those exposed to the supposed cause than in those who are not; 1. The 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. 2. 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. 3. Temporally, the disease should follow exposure to the supposed cause with a distribution of incubation periods on a bell-shaped curve i.e. typical epidemic curve. 4. A spectrum of host responses, from mild to severe, should follow exposure to the supposed cause along a logical biological gradient (dose-response relationship). 5 5. 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. 6. The experimental reproduction of disease should occur with greater frequency in animals appropriately exposed to the supposed cause than in those not so exposed. 7. The elimination or modification of the supposed cause should decrease the frequency of occurrence of disease. 8. The prevention or modification of the host’s response (e.g. by immunization) should decrease or eliminate the disease that normally occurs on exposure to the supposed cause. 9. All relationships and associations should be biologically and epidemiologically credible. 6  Chapter 2 Sampling techniques Structure of animal populations Contiguous Populations: A population in which there is much contact between individuals in the population e.g. stray dog population. Separated Populations: These occur as discrete units such as herds and flocks. Separated populations can be closed with no movement of animals into or out of the unit e.g. dairy herd that raises its own replacements; or it can be open, with limited movement of individuals’ in and out e.g. dairy herds that receive replacements from other farms. Sentinel Herds: The herds that are reasonably representative of the population as a whole and which are tested at regular intervals for infectious disease to determine whether and to what extent the diseases are occurring in the population. Why do veterinary authorities need animal health information? The role of the national veterinary authorities is to control animal diseases, improve the health and productivity of the nation's livestock, and thereby, the well being of the people. To achieve the objective, the information is required to:  Identify what diseases exist in the country;  Determine the level and location of diseases;  Determine the importance of different diseases;  Set priorities for the use of resources for disease control activities;  Plan, implement and monitor disease control programs;  Meet reporting requirements of international organisations (e.g. OIE);  Demonstrate disease status to trading partners. Sources of data: The data is available from various sources. Some organisations record and store data routinely and therefore provide structured collection of data (data bases) to which reference can be made in epidemiological studies. Other organisations have data in registers or as reports. The data can be collected from Government veterinary organizations like Animal Husbandry departments in various states collect data on animal diseases from veterinary hospitals and dispensaries. An international bulletin of animal diseases is published by O.I.E. (Office International des Epizooties), which provides a statement of disease prevalence based on reports of member countries. Private veterinary practitioners are closely associated with large and small animals and are a good source of data on their diseases. Abattoirs process large number of animals and identify some diseases during meat inspection. The post-mortem results from Poultry packing plants may provide another source of information. In some countries animals, ill or dead animals (and are therefore unfit for human consumption) are sent for slaughter to premises other than abattoirs. These premises are called knacker yards. The stored collections of serum samples are called serum banks. These sera can also be used to provide information on other diseases using various serological tests. A registry is a reference list. In human medicine, registries of diseases (e.g. tumours) are maintained using hospital and death certificate data as numerators and census data as denominators. The sale records of pharmaceutical companies provide an indirect means of assessing the amount of diseases. Most Zoological gardens maintain detailed records of animals and their diseases. Many agricultural organisations record information on animal production which can be useful in epidemiological studies. The data can also be collected from various other sources such as Commercial livestock enterprises like large poultry farms, Non Veterinary Govt departments like economics and statistical departments, Farm records, Veterinary schools, Feral Animal organisations like Wildlife and animal conservation organisation and pest centres record data on feral animals, Pet food manufactures, Certification schemes, Pet shops and Breed Societies. Few terms Sample: The sample is a small group of units (animals, people, villages) that have been selected from the population. Each element in the sample is then examined to collect disease information. Target population: It is total population on which information is required and Study population is population from which a sample is drawn. Elementary units are population which cannot be divided further. Sampling frame: The members of population must be identified prior to sampling and list should be made and each member is sampling unit. Sampling fraction is ratio of sample size to study population size. Inference: Inference is process of assuming that the disease status of the population is similar to the disease status of the sample. Representative sample: A representative sample is one which is similar to the population. The inference is valid only when a representative sample is chosen. Sampling with and without replacement: The difference between the two techniques is that it is possible to select the same element twice when using sampling with replacement, but it is not possible when sampling without replacement. In epidemiological studies, we usually use sampling without replacement. When the population is large, the difference between the two techniques is unimportant. Probability proportional to size sampling: It is another probability sampling technique. Instead of the chance for selection of all units of interest being equal, in PPS sampling, the chance of a unit of interest being selected is proportional to some measure of the size of that unit of interest. Collecting animal health information: Passive surveillance: Passive surveillance is a system in which veterinary authorities make no active efforts to collect disease information; they just wait for disease reports to come to them. This method is currently used in India. The owner contacts the veterinary officer, when an animal become sick, 8 who may then treat and either submit a disease report or not. These reports and/or the results of examination of the specimens provide information on what diseases are present in the country. Passive surveillance data are often not able to provide information on amount of disease because of under-reporting. Passive-reporting systems usually cannot provide representative information on the level of disease in the population, or the geographical pattern of disease. More reports may come from one part of the population than another. The size of the population that the disease reports relate to is generally not known. This makes impossible the calculation of useful measures of disease, such as rates and proportions. Active surveillance: In active surveillance the main users of the information (usually the veterinary authorities) make active efforts to collect the information needed. As the users control the collection of information, it is possible to make sure that the information will be of appropriate quality. Retrospective studies: The information is collected from livestock owners (look backward over a period of time) about the diseases that have occurred earlier or even years before the studies. Prospective studies: The animals under study are observed and examined (look forward over a period of time) for a long time to collect information on the diseases. Sampling techniques: There are two methods of collecting samples- 1. Non probability Sampling: In this method probability of a member of the population being selected in the sample is not known and some groups are more likely to be selected than others. These techniques are unable to reliably select a representative sample. In epidemiological studies, we should not use non probability sampling techniques. There are various methods of non probability techniques: a. Convenience sampling: In this method samples are selected because they are easy, quick or inexpensive to collect. b. Purposive selection: In this elements in the sample are selected for some purpose. c. Haphazard Sampling: It is a technique where elements are selected for no particular reason at all and we usually do not follow any crieteria. 2. Probability Sampling: Probability or random sampling means that every element (unit of interest) in the population has the same probability of being selected in the sample. The random sampling is the only ways to reliabley select a representative sample. When random sampling is used, we can calculate how reliable an estimate is. The random samples can be selected using techniques of physical randomisation (coin, dice, playing cards, blank cards), random numbers (random number tables or computer generated random numbers) or software called survey toolbox. a. Simple random sampling: The sample is selected by drawing up a list of all the animals or herds in study population and then selecting sampling units randomly e.g. to select 10 pups from 100- prepare list of all- then select 10 pups using any random method. 9 b. Systematic random sampling: It involves selection of sampling units at equal intervals, the first animal being selected randomly e.g. to select 10 pups from 100- select first pup randomly- then every 10th pup (100/10=10) to be selected. c. Stratified sampling: It involves dividing the population into separate, exclusive groups (strata), and selecting a fixed number or percentage of sample from each group (stratum). If random sampling is used within each stratum, then it is known as stratified random sampling. Stratification can be based on any characteristic of the population. For a national seroprevalence survey, stratification by state provides quite useful picture of distribution of the disease e.g. to select 10 pup from 100 on sex basis- group pups into strata on sex basis (male and female) - select pups randomly from both sexes (proportional weighting i.e. if 60 pups male and 40 female then 6 male and 4 female pups to be selected randomly). d. Cluster sampling: Sometimes, the strata (clusters) are defined naturally (e.g. litters, herds etc.) or by geographical locations (e.g. countries, villages). The clusters can be selected by systematic, simple or stratified random methods; then all the individuals within the clusters have to be tested e.g. to select 10 pups from 20 bitches giving birth to 5 pups each (100 pups)- select 2 bitches (clusters) randomly- select all the pups from both clusters. e. Multistage sampling: It involves use of random sampling at different hierarchical levels of aggregated units of interest. It is most frequently applied as two-stage sampling, where herds are randomly selected as primary sampling units and within each of selected herds, the animals are selected randomly as secondary sampling units e.g. to select 10 pups from 20 bitches giving birth to 5 pups each (100 pups) - select 5 bitches randomly- then select 2 pups randomly from these 5 bitches. 10  Chapter 3 Components of epidemiology The first stage in any investigation is the collection of relevant data and then the investigations can be either qualitative or quantitative. 1. Qualitative Investigations: a. Natural History of Disease: The ecology of disease including mode of transmission, maintenance of infectious agents and patterns of disease occurrence. b. Causal Hypothesis testing: If field observations suggest that certain factors may be causally associated with a disease, then the association must be assessed by formulating a causal hypothesis. 2. Quantitative Investigations: Include followings: a. Surveys: Examination of an aggregate of units. A survey involves the examination of a small group (a sample) of elements (or units of interest) drawn from all the elements of interest (the population). A survey involves only a part of population. If survey examines the total animal population, it is called census. b. Monitoring: The on-going programmes directed at the detection of changes in the prevalence of disease in a given population and in its environment e.g. regular recording of milk yield or meat inspection findings. c. Surveillance: The investigation programmes (continuous) executed in a given population to detect the occurrence of disease for control purposes, which may involve testing of a part of the population. It is an intensive form of monitoring designed so that action can be taken to improve the health status of a population. The recording of tuberculous lesions at abattoir followed by tracing back of infected animals to their farm of origin is an example of surveillance. d. Studies: An investigation that involves the testing of causal hypothesis: 2 types:  Experimental Study: A study in which the investigator can allocate animals to different categories; thus the conditions of study are controlled by the investigator e.g. laboratory experiment or field trial.  Analytical observational Study: A study in which the investigator has no freedom or does not exercise his freedom to allocate the animals to different categories; disease is studied as it occurs naturally. It is of 3 sub types: 11  (1) Cross sectional studies: An observational study in which the animals are classified according to presence or absence of disease and presence or absence of exposure to hypothesized causal factors at a particular point of time (what is happening?). (2) Cohort studies: An observational study in which a group exposed to the factors is compared with a group not exposed to the factors with respect to the development of disease (what will happen?). (3) Case Control studies: An observational study in which a group of diseased animals (cases) is compared with a group of non-diseased animals (controls) with respect to exposure to a hypothesized causal factor (what happened?). e. Modelling: The representation of disease dynamics and effects of different control strategies using mathematical equations/models is modelling. Another type of modelling is biological simulation using experimental animals to simulate the pathogenesis of diseases that occur naturally in animals and man. Measures of association: It is desirable to provide more informative measure of the impact of a factor on disease occurrence. This can be expressed by absolute difference in disease occurrence between ‘exposed’ and ‘unexposed’ groups. Factor/Disease D+ D- Total F+ a b a+b F- c d c+d Total a+c b+d n = a+b+c+d Relative risk (RR) is the ratio of the incidence of disease in exposed animals to the incidence in unexposed animals. An RR of more than 1 indicates a positive statistical association between factor and disease.  RR= {a/(a+b)} / {c/(c+d)} Odds ratio (relative odds): It is calculated as the ratio between the odds of disease in exposed animals and the odds of disease in unexposed animals. Case-control study-  Exposure oddscases= a/c; Exposure oddscontrols= b/d  Exposure odds ratio= ad / bc Cohort study-  Disease oddsexposed= a/b; Disease oddsunexposed= c/d  Diseae odds ratio= ad /bc Cross sectional study-  Prevalence odds ratio= ad /bc 12 Attributable risk (AR): The attributable risk indicates to the extent to which the incidence of disease in exposed animals would be reduced if they had not been exposed to risk factor, assuming that the risk factor is causal.  AR= {a/(a+b)} - {c/(c+d)} Attributable fraction: It is amount of disease in the exposed animals due to some specific factor. AR RR-1 AF= ---------------------------------- = --------------------------- a/ (a+b) RR Variables: A variable is any observable event that can vary. Disease and causal factors are examples of variables. A study variable is any variable that is being considered in an investigation. A response (dependent) variable is one that is affected by explanatory (independent) variable e.g. if we want to study the effect of sex on occurrence of urolithiasis in dogs then sex is explanatory variable and urolithiasis is response variable. Association: Association is the degree of dependence or independence between two variables. It is of two types- Non statistical association is an association between a disease and hypothesized causal factor that arises by chance; whereas in Statistical association, variables are positively statistically associated and they occur more frequently than would be expected by chance. Confounding: (Latin confundere- to mix together) It is the effect of an extraneous variable that can wholly or partly account for an apparent association between variables. A variable that confounds is called confounding variable or confounder. A confounding variable must be  a risk factor for the disease that is being studied  associated with the explanatory variable. In a study, it was found that wearing of apron during milking resulted in leptospirosis in dairy farmers (response variable). Further studies showed that chances of contracting leptospirosis was associated with large herd size and it was observed that farmers having large herds wear apron more frequently than farmers with smaller herds. The basic cause of leptospirosis in dairy farmers is not due to wearing of apron but due to large size of herd. Formulating a causal hypothesis: Hypothesis is a proposition that can be tested formally; after which the hypothesis may be either supported or rejected. A description of time, place and population is useful initially.  Time: The association of disease or outbreak with year, season, month, day or even hour should be considered. Such details may provide information on climatic influences, incubation periods and source of infection e.g. HS outbreak may be associated with rainfall; the prevalence of hemoprotozoan diseases is increased during summer or rainfall.  Place: The geographical distribution of a disease may indicate an association with local geographical, managemental or ecological factors e.g. increased occurrence of fascioliasis in low lying areas. 13  Population: The type of animals affected is of considerable importance e.g. theileriosis is disease of crossbred and exotic cattle; canine parvo virus gastroenteritis is more common in Dobermans as compared to other breeds and pups more commonly affected than adults.  When the major facts have been established, alternative causal hypothesis can be formulated. There are four major methods of arriving at a hypothesis.  Method of difference: If the frequency of disease is different in two different circumstances and a factor is present in one circumstance but is absent from the other, then that factor may be suspected of being causal e.g. there was an increased incidence of stillbirths in sows in one of the three farrowing pens, the hypothesis was formulated that different type of burner caused the stillbirths, subsequently that burner was found to be defective producing large amounts of carbon monoxide and CO was assumed to be the cause of stillbirths. The defect in this method is that several different factors may be incriminated as possible causes. This method is the basis of ‘traditional experimental design’-namely keeping all factors constant except the one of interest.  Method of agreement: If a factor is common to a number of different circumstances in which the disease is present, the factor may the cause of the disease. This method is frequently used to identify possible causal factors in outbreak investigations e.g. salmonellosis was associated with a batch of meat and bone meal at different pig farms, and this was only circumstance in common, then the causal hypothesis- that the disease was caused by contamination of that batch of meat and bone meal is strengthened.  Method of concomitant variation: The method involves a search for a factor, the strength of which varies continuously with the frequency of disease in different situations e.g. occurrence of bovine hypomagnesemia and pasture levels of magnesium, association between smoking with lung cancer in man.  Method of analogy: This method involves comparison of the pattern of disease under study with that of the disease that is already understood, because the cause of disease that is understood may also be the cause of another poorly understood disease with a similar pattern e.g. some mammary tumours of mice have a viral origin therefore some mammary tumours of dogs may have a viral cause. When attempting to establish a causal hypothesis five principles should be considered:  Time sequence of events: The exposure to agent should precede actual occurrence of disease.  Strength of association: If a factor is causal, there will be a strong statistical association between the factor and the disease.  Biological gradient: If a dose-response relationship can be found between a factor and a disease, the possibility of a factor being causal is increased.  Consistency: If an association exists in a number of different circumstances, a causal relationship is probable. 14  Compatibility with the existing knowledge: Hypothesis should be compatible with the existing knowledge e.g. Smoking can be suggested as a likely cause of lung cancer because other chemical or environmental pollutants are known to have a carcinogenic effect on lab animals. 15  Chapter 4 Describing disease occurrence Few terms: Accuracy: It is an indication of the extent to which an investigation or measurement conforms to the truth. Thus if a set of scales records an animals weight at 15 kg and this is the actual weight of the animal, then the measurement is accurate. Refinement: The degree of detail in a datum is its refinement. Thus, 13 kg and 13.25 kg may both represent the accurate weight of an animal but second record is more refined than the first one. Precision: The term precision can be used in two senses- it can be used as a synonym for refinement or can be used statistically to indicate the consistency of a series of measurements. Thus repeated sampling of a population may allow estimation of a prevalence value of say 40% ± 5%. Alternatively, the value may be estimated as 40% ± 2%. The second estimate is more precise than the first. Reliability: A diagnostic technique is reliable if it produces similar results when it is repeated. Thus repeatability is a characteristic of a reliable technique. This is defined in terms of the degree of agreement between sets of observations made on the same animals by the same observer. This contrasts with reproducibility, which can be defined in terms of agreement between sets of observations made on the same animals by different observers. Validity: If a diagnostic technique measures what it purports to measure, it is valid. Validity is a long- term characteristic of a technique, of which sensitivity and specificity are indicators. Confidence interval: A confidence interval indicates how confident we are that the estimate is correct. We can be 95% sure that the true population value lies within a 95% confidence interval. Bias: It is any systematic (as opposed to random) error in the design, conduct or analysis of a study that renders the results invalid. Sensitivity and Specificity: Events may be recorded as being true when, actually they are not. Thus a dog may be misdiagnosed as having diabetes when it does not. This is false positive record. Alternatively, disease may not be diagnosed when it is actually present. This is false negative record. These errors lead to misclassification of diseased and non-diseased animals. These errors can be found by comparing results obtained by the diagnostic method with those obtained from an independent valid criterion. The sensitivity of a diagnostic method is the proportion of true positives that are detected by the method. Shivali The specificity of the method is the proportion of true negatives that are detected. True +ve True -ve Total Test +ve 20 (a) 10 (b) 30 Test -ve 5 (c) 30 (d) 35 Sensitivity = a/(a+c)= 20/25 = 0.80(80%) 16  Total 25 40 Specificity= d/ (b+d)=30/40= 0.75 (75%) Crude and specific measures Crude values are expression of the amount of disease and deaths in a population as a whole without taking into account the structure of the population affected. Specific measures of disease are those that describe disease occurrence in specific categories of the population related to host attributes such as age, sex, breed and method of husbandry etc. These are calculated in a similar manner to crude ones except that the numerator and denominator apply to one or more categories of a population with specific host attributes e.g. age specific incidence rate, breed specific prevalence etc. Morbidity and Mortality: The disease investigation in a population involves counting of the affected animals so that the amount of disease in the population can be described. This amount of disease in a population is the morbidity and in contrast the number of deaths in a population is mortality. These values help in assessing the extent of a problem in a population. The major reason for determining these values is to assess the extent of a problem in a population. This assessment is possible only when number of diseased animals is compared with the total number of animals in the population. e.g. if we say that 10 animals are suffering from mastitis, it does not indicate anything as these 10 may be out of only 10 animals i.e. all animals are affected or these may be out of 100 animals i.e. 10 per cent are affected. Measures of disease occurrence 1. Prevalence (P): It is the number of instances of disease or related attributes without distinction between old and new cases (e.g. infection or presence of antibodies) in a known population, at a designated time. It is also called Point Prevalence i.e. amount of disease in a population at a particular point of time. (There is another term i.e. Period Prevalence which refers to the number of cases that are known to have occurred during a specified period of time e.g. a year). It is calculated as: Number of individuals having disease at a particular point of time P= --------------------------------------------------------------------------------------------------------- Number of individuals in the population at risk at that point of time Example: If ten cows out of a herd of 200 are having mastitis on a particular day then the P = 10/200 = 0.05. So it represents the probability of an animal having a particular disease at a given time. It may take any value between 0 and 1 and is dimensionless. It can also be expressed as percentage e.g. in the above example P =.05×100 = 5%. Apparent prevalence (test or estimated prevalence, AP) is the number of animal tested positive for the disease divided by the number of total animals tested. True prevalence is estimate of the actual percentage population having the disease. It is calculated from the apparent prevalence, sensitivity and specificity of a test. 17  AP + (Sp -1) True prevalence= ---------------------------------------------------- Sp + (Se -1) 2. Incidence: It is the number of new cases that occur in a known population over a specified period of time. It has two measures- cumulative incidence and incidence rate. a. Cumulative Incidence (CI): It is the proportion of non-diseased individuals at the beginning of a period of study that become diseased during that period. Number of individuals that become diseased during a particular period CI = ------------------------------------------------------------------------------------------------------------- Number of healthy individuals in the population at the beginning of the period Similar to P it is also a proportion and can take values from 0 to 1 and is dimensionless b. Incidence Rate (I): It measures the rapidity with which new cases of disease develop over time: Number of new cases of disease that occur in a population during a particular period of time I = ------------------------------------------------------------------------------------------------------------------------- The sum, over all individuals, of the length of time at risk of developing disease The denominator is often measured as animal years at risk. It is sum of the periods of observation for each individual for which it is free from disease (i.e. is at risk) e.g. two animals remain free of disease for three years will be six animal years at risk. But it is mostly difficult to ascertain the period, for which the animal has remained free from disease. So for simplicity denominator can be taken as Average number of animals at risk × time period. So incidence rate can be calculated as: Number of new cases of disease that occur in a population during a particular period of time I = -------------------------------------------------------------------------------------------------------------------------------- (Number at risk at the start of the time period + number at risk at the end of the period/2) × time period Relationship between Incidence rate and Prevalence: Prevalence depends on duration D and incidence rate I of a disease: P α I × D. If the size of the population is not changing, and the level of disease stays about the same then we can estimate the prevalence, if we know incidence rate and the average duration of the disease: P = I× D 3. Attack Rate: When a population is at risk for a limited period of time then term attack rate is used to describe the proportion of animals that develop the disease. 4. Mortality: Mortality measures, similar to incidence measures, are of two types: a. Cumulative Mortality (CM): Similar to Cumulative incidence, but is the proportion of the individuals at the start of the study period that die in that period. Diseased animals present at the beginning of the period of study are included in the denominator. Number of individuals that die during a particular period CM = --------------------------------------------------------------------------------------------------------------------- Number of individuals in the population at the beginning of the period b. Mortality Rate (M): It is calculated similar to incidence rate. The numerator comprises the number of deaths. However, diseased animals are also included in the denominator. 18  Number of deaths due a disease that occur in a population during a particular period of time M = -------------------------------------------------------------------------------------------------------------------- The sum, over all individuals, of the length of time at risk of dying 5. Death rate: It is total mortality rate for all diseases in a population –rather than one specific disease. 6. Case Fatality (CF): The tendency for a condition to cause death of affected animals in a specified time is the case fatality. It is the proportion of the diseased animals that die. Number of deaths CF = ----------------------------------------------------------- Number of diseased animals 7. Survival (S): It is the probability of individuals with a specific disease remaining alive for a specific length of time. S = 1-CF Example1. : Suppose a veterinarian investigates a disease that runs a clinical course ending in either recovery or death, in a herd of cattle. On 1 st July 1999 the herd is investigated when the disease is already present. The herd is then observed for the following year, during which period there are no additions and all animals are followed up. Total herd size on 1st July 1999 = 600 Total animals clinically ill on 1 July 1999 st = 20 Total animals developing clinical disease between 1st July 1999 and 1st July 2000 = 80 Total animals dying from the disease between 1st July 1999 and 1st July 2000 = 30 Calculate P, CI, I, CM, M and CFR from above data. Analysis: Prevalence on 1st July 1999 = 20/600 =0.03 Cumulative incidence between 1 July 1999 and 1st July 2000 = 80/600-20 =80/580 =0.14 st Incidence Rate = 80/{(580+500)/2} =0.15 per animal year at risk. Cumulative Mortality between 1st July 1999 and 1st July 2000 = 30/600 =0.05 Mortality Rate = 30/{(600+570)/2} = 0.05 per animal year at risk. Case Fatality between 1 July 1999 and 1st July 2000 st = 30/100 = 0.30 Survival between 1st July 1999 and 1st July 2000 = 1-0.30 =0.70 Example 2. : A small intensive chicken farm with 2000 birds suffers an outbreak of Newcastle disease. The first birds start to get sick on the 3 March. By 5 March, many birds are dying. The owner contacts his local veterinary officer who visits the farm on 6 th March. On that day, the officer counts 56 birds showing signs of disease, and the owner reports that a further 143 have already died, and 28 birds had been sick but recovered. There are 1801 apparently healthy birds remaining. What is the prevalence of disease on the farm on 6 March? Also calculate other measures of disease (CI, I, CM, M and CFR). Analysis: 19 Prevalence on 6th march: = 56/(2000-143) = 56/1857 =3%. Incidence rate from 3rd March to 6th March (4 days) =227/(1886.5 at risk×4 days) =0.03cases per chicken per day= 21 cases per 100 chicken weeks at risk; =21 cases per 100 chicken per week  Total no of new cases of disease during these 4 days:  The 143 birds that died; Plus the 28 birds that got sick and recovered; Plus the 56 birds that were sick at the time of visit. Giving a total of 227 new cases of disease.  Average no of birds at risk: o No of birds at risk at the beginning = 2000 o No of birds at risk at the end = 2000-227 = 1773. o Average no at risk = (2000+1773)/2 = 1886.5 Cumulative incidence from 3rd March to 6th March (4 days) = 227/2000 = 0.1135 Cumulative Mortality from 3rd March to 6th March (4 days)= 143/2000 =0.0715 Mortality Rate =143/{(2000+1857)/2}*4 days = 143/1928.5*4 = 0.0185 per bird days at risk. Case Fatality from 3rd March to 6th March (4 days) = 143/227 = 0.629 Survival from 3rd March to 6th March (4 days) = 1-0.629 =0.371 Ratios, proportions and rates A ratio is a value obtained by dividing one quantity by another e.g. a male: female sex ratio might be 3:2 the upper figure being numerator and the lower figure the denominator. A proportion is a special case of a ratio in which the numerator consists of some of the individuals in the denominator e.g. the proportion of male to total population is 3:5. Thus prevalence, cumulative incidence, case fatality and survival are proportions. A rate is a ratio that expresses a change in one quantity (numerator) with respect to another quantity (denominator) e.g. velocity is a rate. 20  Chapter 5 Determinants of disease A determinant is any characteristic that affects the health of a population. Classification of Determinants 1. Primary and Secondary: Primary determinants are factors whose variation exerts a major effect in inducing disease. Frequently, these are the necessary causes e.g. viruses, bacteria, trauma etc. Secondary determinants correspond to predisposing, enabling and reinforcing determinants e.g. sex, age, location, climate, husbandry etc. 2. Intrinsic and Extrinsic: Determinants that are internal to the host are called intrinsic (endogenous) determinants e.g. genetic make up, species, breed, sex etc. Determinants that are external to the host are called extrinsic (exogenous) determinants e.g. transportation, location, infectious agents. 3. Determinants associated with Host, Agent and Environment: The epidemiological triad refers to the three components of epidemiological system- host, agent and environment. The determinants associated with host, agent or environment do not exert their effects in isolation, but interact to produce a disease. It refers to interdependent operation of factors to produce an effect. Host Determinants: 1. Species: Vary in their susceptibility and responses to different infectious agents e.g. FMD is disease of cloven footed animals; Glanders and strangles are diseases of equines. 2. Breed: Crossbred cattle are more prone to theileriosis, Jersey cows more prone to milk fever. 3. Age: Occurrence of many diseases shows a distinct association with age e.g. Collibacillosis and coccidiodis are diseases of young animals whereas tuberculosis and paratuberculosis mainly occur in adult animals. 4. Sex: Sexual differences in disease occurrence may be attributed to: a. Hormonal: Diabetes more in bitches. b. Occupational: Yoke gall formation in bullocks. 21  c. Social: Lung cancer more in men. d. Genetic:  Sex Linked inheritance: When DNA responsible for a disease is carried either on X or Y sex chromosomes e.g. Canine haemophilia A and B are associated with X chromosomes and are inherited recessively. So disease is more predominant in males.  Sex Limited inheritance: When DNA responsible for the disease is not in the sex chromosomes, but the disease is expressed only in one sex e.g. cryptorchidism in dogs.  Sex influenced inheritance: The expression of characteristic is lower in one sex than in other e.g. canine patent ductus arteriosis is inherited through several genes but more common in females.  Sex associated: Some diseases are apparently sex associated but are actually associated with other determinants related to sex. 5. Genotype: Genetic constitution of the host is its genotype. Some diseases have a genetic cause i.e. they are inherited by succeeding generations. 6. Size and Conformation: Hip dysplasia and osteosarcoma are more common in large breeds of dogs; dystocia more common in bulldogs. 7. Coat colour: White cats have high risk of developing cutaneous squamous cell carcinomas while canine melanomas are mainly in deeply pigmented breeds. Agent determinants 1. Infectivity, Virulence and Pathogenicity: Infectivity is ability of agent to establish itself in the host and represented as statistic ID 50. This refers to the individual dose or numbers of the agent required to infect 50% of a specified population of susceptible animals. Virulence can be defined as a measure of the severity of a disease caused by a specified agent and quantified by a statistic known as LD50 which refers to the individual dose or numbers of the agent which will kill 50% of a specified population of susceptible animals. Pathogenicity is an epidemiological term used to describe the ability of a particular disease agent of known virulence to produce disease in a range of hosts under a range of environmental conditions. 2. Antigenic variation: Some infectious agents seek to evade the hosts' defence mechanisms by altering their antigenic characteristics e.g. trypanosomiasis, FMD. The two main types of variation are- Antigenic shift, which involves a major change in antigenicity, so that previously infected individuals possess little or no immunity to the shifted agent e.g. influenza viruses. Antigenic drift, which involves only minor changes in antigenicity, so that hosts previously infected with the agent retain a certain degree of immunity to the drifted strain. 22 3. Gradient of Infection: It refers to variety of responses of an animal to challenge by an infectious agent, and so represents the combined effect of an agent’s pathogenicity and virulence and host characteristics such as susceptibility and immunity (concept of iceberg). 4. Outcome of infection:  Death: Usually removes an animal as a source of infection.  Recovery: May result in sterile immunity following an effective host response that removes all infectious agents from the body. No longer threat to susceptible population.  Carrier state: Carrier is used broadly to describe any animal that sheds an infectious agent without demonstrating clinical signs. May be either in apparently infected or sub clinically infected animal. Two types of carriers may exist i. Incubatory carriers: these excrete the infectious agent during the incubation period of disease. ii. Convalescent carriers: these shed the infectious agent during or after recovery from a disease e.g. FMD or rinderpest but not rabies.  Long standing chronic clinical infection: Potential source of infection.  Latent infection is one that persists in an animal without producing clinical signs. Environmental Determinants: 1. Location: Local geological formations, vegetation and climate affect spatial distribution of diseases. 2. Climate: Two types: a. Macroclimate: It comprises the normal components of weather to which the animals are exposed, i.e. Temperature, wind and rainfall, solar radiation, humidity, all of which affect health. Macroclimate also determines vegetation, distribution of hosts and vectors and so may affect spatial distribution of disease. Temperature may be the primary determinant e.g. low temperature causes hypothermia. Wind and rainfall increase heat loss from the animals and cold stress predisposes animals to disease. Macroclimate can also affect stability of agents e.g. association between cool damp weather and respiratory diseases may be due to stability of organisms in addition to reduction in host resistance. b. Microclimate: Climate that occurs in a small-defined space. This may be as small as within a few mm of an animal’s surface or as large as a calf house. 3. Husbandry: a. Housing: Ventilation, bedding material or structure of surfaces e.g. Hygroma of knee joint is more common in animals reared on pacca floor. 23  b. Diet: It has effects on the disease caused by energy, protein, vitamin and mineral deficiencies. Feeding regimes may also be determinant. c. Management: It determines stocking density and production policy. Increased density increases the microbial population that in turn increase various diseases. 4. Stress: It is the sum of biological reactions to any adverse physical, mental (and in man emotional) stimulus that tends to disturb homeostasis. Factors that are capable of producing stress are called stressors. 24  Chapter 6 Transmission and Maintenance of Infection The infectious diseases are the result of invasion of a host by pathogenic organisms. The continuous survival of infectious agents depends on: Start of Successful transmission to a host infection Life cycle or life history Shedding Replication of agent of agent Few terms Host: A plant, animal or arthropod that is capable of being infected with and therefore giving sustenance to an infectious agent. Replication and development of the agent usually occurs in the host. Definitive host: A parasitological term describing a host in which an organism undergoes its sexual phase of reproduction e.g. Taenia pisiformis in dog, Neospora caninum in dog. Intermediate host: An animal in which an infectious agent undergoes some development, frequently with asexual reproduction e.g. snails in fasciolosis and amphistomiasis. Paratenic Host: A host which mechanically transmit an agent without further development. The term used in helminthology -Same as mechanical vector. Primary Host (Natural host): An animal that maintains an infection in its endemic area e.g. dogs infected with CDV. It is also called maintenance host. Secondary Host: A species that is additionally involved in the life cycle of an agent, especially outside typical endemic area. Incubation Period: Period between infection and development of clinical signs. Prepatent period: The period between the infection of the host by the agent and the detection of the agent in the tissues or secretions of the host. Period of communicability: The time during which the infected host is capable of transmitting the agent. Vector: Invertebrate animals, usually arthropods that transmit infectious agent to vertebrates. Carrier: It is an infected animal that sheds pathogenic or potentially pathogenic organisms, and yet remains clinically normal. Reservoirs: If infection is maintained within the species population without requiring periodic re- introduction. Transmission 25 Vertical Transmission: Transmission of diseases from one generation to next by infection of embryo/ foetus. It can be:  Hereditary: When diseases are carried within the genome of either parent.  Congenital: Diseases acquired either in utero or in ovo. Methods: 1. Germinative transmission: It involves either the infection of the superficial layers of the ovary, or infection of the ovum itself e.g. avian leukosis viruses. 2. Transmission to the embryo: It occurs via the placenta (transplacental) or via the fetal circulation through the placenta to the foetus e.g. Toxocara canis, T. vitulorum 3. Ascending infection: Infection that is transmitted from the lower genital canal to the amnion and placenta. 4. Infection at parturition: Infection acquired from the lower genital canal at birth. Horizontal Transmission: Transmission of diseases from one segment of a population to other e.g. FMD from one cow to another. There are three types of Horizontal transmission: 1. Contact Transmission: Include direct and indirect means.  Direct: It denotes physical contact between the infected and susceptible individuals e.g. rabies and venereal diseases.  Indirect: It denotes contact between the infected and susceptible individuals by means of fresh secretions, excretions or exhalations e.g. leptospira organisms in urine or recently contaminated water mangers. 2. Vehicle Transmission: of infectious agents involves inanimate substances e.g. food, water, dust and fomites. It can be-  Mechanical: the vehicle simply acting as a physical transfer mechanism e.g. truck tires or veterinarian’s shoes contaminated with FMD virus or poultry feathers contaminated with Newcastle disease virus.  Biological: the multiplication or development of the agent takes place in the vehicle e.g. transmission of bacteria in milk. 3. Vector Transmission: Two types:  Mechanical: An animal, usually an arthropod that physically carries an infectious agent to primary or secondary host. The infectious agent neither develops nor multiplies in the mechanical vector e.g. Trypanosoma evansi in Tabanus fly.  Biological: A vector usually an arthropod in which an infectious agent undergoes either a necessary part of its life cycle or multiplication before transmission to the primary or secondary host. It can be: i) Developmental: when an essential phase of development occurs in the vector e.g. Dirofilaria immitis in mosquitoes. 26  ii) Propagative: When an agent multiplies in the vector e.g. louping ill virus in Ixodid ticks iii) Cyclopropagative: A combination of i) and ii) e.g. Babesia in ticks Transovarian/ Trans-stadial transmission (one, two, three host tick) Transovarian transmission enables an infectious agent to be maintained in a vector population through many generations without that population having to be reinfected, and, as such, the vector population remains a continuous source of risk. The best example is Boophilus microplus (one host tick- where entire parasitic development from larvae to adult takes place on one host) responsible for transmission of Babesia organisms. In this, engorged female tick after feeding on infected host falls on the ground and lays infected eggs, so larva are also infected; and transmit the infection to another host. In Trans-stadial transmission, one developmental stage becomes infected with the disease agent and the following stage transmits the disease (two host tick- where larvae and nymphs occur on one host and adults on another host e.g. Hyalomma anatolicum anatolicum.; three host tick- where each stage of development takes place on different hosts e.g. Rhipicephalus sanguineous). Routes of infection The site or sites by which an infectious agent gains entry to a host and by which it leaves the host, are the agents’ routes of infection. Different routes of infection include oral route, respiratory route, via skin (percutaneous), cornea and mucous membranes etc. Methods of transmission 1. Ingestion: This may occur via mechanical vehicle e.g. contaminated water, or by ingestion of intermediate hosts, such as cestode cysts in meat. Some ingested agents are usually excreted in faeces, producing faecal-oral transmission cycle. Other agents can be excreted by additional means like urine, breath etc., if they invade blood stream. 2. Aerial transmission: Airborne transmission of infectious agents via contaminated air. It is usual method of transmission with spores of fungi and some bacteria and pathogens of respiratory tract. Aerosole transmission is a type of airborne transmission involving transmission via an aerosole (any solution in the form of a fine spray in which the droplets approx. colloidal size (1- 100nm) 3. Contact: Transmission without transmission factors and without participation of an external medium. 4. Inoculation: It is the introduction of infectious agents into the body, by puncture of the skin or through a wound. 5. Iatrogenic transmission: Infection that is transferred during surgical and medical practice. Two main types:  Introduction of pathogens by dirty instruments. 27   Introduction of pathogens by contaminating prophylactic or therapeutic preparations. 6. Coitus: Infections transmitted sexually. In human medicine called STD- sexually transmitted diseases. Maintenance of Infection Transmission of infection involves some stages when the infectious agent is in the host and others when it is in the external environment or in a vector or in both. Both internal and external environments pose hazards to infectious agent.  Environment within the host: Natural defence mechanisms, surface active chemicals, specific reactive cells, phagocytes and humoral antibodies.  The External Environment: Desiccation and UV light. Agents avoid desiccation by being discharged in moist carriers such as faeces and urine or into favourable surroundings or in inanimate material. Maintenance strategies 1. Avoidance of a stage in external Environment:  By vertical transmission  By venereal transmission  By vector transmission  By transmission by sarcophagy (flesh eating) e.g. Trichinella spiralis from muscles of pig enters man. 2. Resistant Forms: The harmful affects of external environment can be reduced by surrounding the infectious agent with a shell that is resistant to heat and desiccation. Examples:  Spore production by : Clostridium and Bacillus organisms, fungi  Cyst production by: helminths and protozoa e.g. Toxoplasma gondii 3. ‘Rapidly-in’ and ‘rapidly-out’ strategy: Some agents enter the host, replicate and leave very quickly, before the host has time to mount an immune response or die e.g. some viruses of URT. Requires continuous supply of susceptible hosts. 4. Persistence within the host: Hosts defence mechanisms fail to eliminate agents as organisms adapt to hosts phagocytic cells or develop strategies to avoid hosts immune response e.g. immunosuppression (as in Mycobacteria), tolerance, antigenic variation, intracellular parasitism, multiplication at sites inaccessible to immune response etc. The persistence can be associated with a long incubation or prepatent period. 5. Extension of host range: Infectious agents may infect more than one host. It is facilitated by presence of various hosts in the same area. 28  Chapter 7 Ecology of disease  The study of animals and plants in relation to their habits and habitation is called Ecology. It is also called natural history of disease. Objectives:  Increase in understanding of pathogenesis, maintenance and transmission of disease.  Use of knowledge of disease ecology for forecasting of disease leading to development of suitable control techniques. Two major factors determine occurrence of diseases 1. Distribution of animal Population 2. Size of animal Population Distribution of animal populations  Earth is divided into discrete formations of vegetation -vegetational zones.  de Candolle said: Climate especially temperature dictated vegetation. He described deserts as formations of xerophiles, rain forests of megatherms and deciduous forests of mesotherms. Koppen used de Condolle’s classification as basis of the modern system: Koppen’s Climatic Division de Candolle’s Plant group A (Rainy with no winter): Megatherms B (Dry): Xerophiles C (Rainy with mild winters): Mesotherms D (Rainy climates with severe winters): Microtherms E (Polar climates with no warm season): Hekistotherms Few terms Biotope: Smallest spatial unit providing uniform conditions for life. An organism’s biotope therefore describes its location. Population: Individuals of any species at a place form its population. Biocenosis: Collection of living organisms including plants, animals and microorganisms in a biotope. Biotic community: Used synonymously with Biocenosis. Sometimes, it refers to large biocenosis. Biome: All the ecosystems taken together in a geographical area form a bigger unit called biomes. Biosphere: All the biomes world over taken together as a bigger unit constitute a single large self- sustained biological system called biosphere. 29 Biomes  Broad divisions of the earth are populated by similar animals  Theory of convergent evolution: Animals of different ancestral stock evolve similar features to suit their environment.  Zoologists classified different areas of the world according to the types of animals and plants present. These areas are called life zones or biomes e.g. tropical rain forests, savannah etc.  The distribution of infectious agents and their vectors (and therefore the diseases produced by the agents) are governed by environmental conditions of biomes e.g. some diseases are endemic in some biomes while others are absent there. Regulation of population size 1. The ‘balance of nature’: Populations grow, reach a certain size and then stop growing; so the population become stable and balanced with the rate of reproduction equaling the death rate. 2. Control of population by competition: Populations are brought into balance by competition for resources of the habitat, the most common of which is food. Competition, therefore, is density dependent. Gause conducted an experiment using one species of Paramecium with a constant supply of food. The growth curve for the protozoan is a sigmoid. 3. Dispersal: Population size is also controlled by climate in addition to competition for food. The drastic seasonal variations in climate may kill all the adults of a species in an area. Such species survive by dispersal to different climates. 4. Predation: Predators control populations e.g. predators of insects are efficient controller of populations but predators don’t have much effect on large animal populations. 5. Infectious Diseases: They can depress host population size when they occur as epidemics or pandemics with high CFR. 6. Home range: some animals have a natural restriction to area over which they roam-home range. It helps to control the population; moreover infected animals may transmit infection over their home range only and not further. 7. Territoriality: The part of animals’ home range that it defends aggressively from invaders is the animals’ territory. This behaviour response is territoriality e.g. stray dogs. The sizes of territories vary for different species. It can control the population size, as there is minimum size to a territory and a specific amount of space and, therefore, a finite number of animals that can exist in the territory. 8. Social dominance: In some species socially weaker animals are forced out when crowding occurs. It is also a population control mechanism. 30 9. Wynne-Edward’s Hypothesis: Population control is the main purpose of group behaviour. Crowding of rats result in associated fighting, cannibalism and reduced fertility. Niche Lotka-Volterra equations: Coexistence of two strongly competing species is impossible. Coexistence is possible only if competition is weak. Gause tested equations using two different species of Paramecium in a test tube culture: Either one or the other species survived depending upon the environment. It led to-  Principle of competitive exclusion: Competition excludes all but one species from particular position defined by animal feeding habits, physiology, mechanical abilities and behaviour. This position is an animal’s niche. [One species, one niche] e.g. Introduction of goats in Abington island to exclusion of Turtles due to competition for food. The snail- Biomphalaria glabrata- I/H for schistosomiasis replaced by more competitive snail Marisa cornuarietis (Biological control)  Avoidance of competition: by sympatric species i.e. species found in the same country or area e.g. Giraffes & wildebeests in East Africa. Gause experiment with two species of Paramecium when both survived.  Displacement more common than exclusion. Displacement is also a mechanism of increasing species diversity. Some examples of niches relating to diseases  Louse infestation: host species specific e.g. pig lice don’t live on man or dogs and vice versa. In humans’ also two types: head louse & body louse.  Intracellular parasitism: Intracellular parasites occupy a niche in cells e.g. all viruses, some bacteria (Brucella, Mycobacterium, rickettsiae) and some protozoa (Babesia). Advantageous- as safety from humoral antibodies and avoidance of competition with extracellular agents.  Epidemiological Interference: The presence of one type of respiratory adenovirus prevents infection with other types, as first one occupies niche (the lower respiratory tract), which therefore can’t be filled by other agents. This phenomenon is called epidemiological interference. Interference can affect the time of occurrence of disease e.g. epidemic caused by one agent may suppress epidemics caused by other similar agents. It can also affect the rate of natural immunization e.g. interference with other enteroviruses delays natural poliovirus immunization in man. 31  Chapter 8 Ecosystem The series of interconnected feeding relationships are called food chains. A simple food constitutes: Sun- grass/ producer- dear/ herbivore- lion/ carnivore. Different levels in food chain are called trophic levels. The energy, in the form of heat is lost at each trophic level, so chains do not normally have more than 4 or 5 trophic levels. Animals eat different types of food and some eat both plants and animals and therefore feed at more than one trophic level. Consequently, food chains combine into highly complex food chain. Animals at the higher levels have larger webs. Animals are generally of larger size and home ranges and so spread the disease over in lesser number when we move up the food larger areas than the small animals. Ecosystem  Relationship between animals linked by food chains determines the variety of animals in a particular area.  Similarly, Climate and vegetation govern the distribution of plants and therefore of animals in an area.  So areas are characterized by the animals and plants that occupy them and by their physical and climatic features. This unique interacting complex is called an ecosystem  The complex of living organisms, their physical environment, and all their interrelationships in a particular unit of space is ecosystem. Types of Ecosystem Autochthonous ecosystem: Coming from land itself e.g. deserts and tropical rain forests. 32 Anthropurgic ecosystem: Created by man e.g. cultivated pastures and towns. Synanthropic ecosystem: in contact with man. These facilitate the transmission of zoonotic infections. Ecological climax: An ecological climax is said to have occurred when plants, animals, microbes, soil and macroclimate have evolved to a stable, balanced relationship.  When infections are present, they too are stable and usually endemic.  Also, balance between host and parasite usually results in inapparent infections. Ecological Mosaics: It is a modified patch of vegetation created by man within a biome that has reached a climax. Ecological interfaces: It is junction of two ecosystems. Infectious agents can be transmitted across these interfaces. Landscape Epidemiology: It is the study of diseases in relation to the ecosystem in which they are found. Also called- Medical ecology, Horizontal epidemiology and Medical geography. Nidality: Many diseases are limited to distinct geographical areas. These natural homes of the diseases are called Nidi (Nidus = nest). This phenomenon is called nidality. Nosogenic Territory: It is an area that has ecological, social and environmental conditions that can support a disease. (Noso = disease; gen = to create). Nosoarea: It is a nosogenic territory in which a particular disease is present.e.g. Britain is Nosogenic territory for Rabies and FMD but is not a nosoarea for these diseases. Objectives of Landscape Epidemiology Landscape epidemiology is based on the concept that if the nidality of diseases is based on the ecological factors,then the study of ecosystems can help to predict the occurrence of diseases and to develop appropriate control strategies e.g.  Leptospirosis: It is known that prevalence of Leptospira serovar ballum in brown rat is density dependant. So an estimation of number of rats inhabiting an area enables prediction of the prevalence of serovar ballum infections. The number of rats can be estimated from the number of rat burrows. Thus if inspection of an area reveals a large number of rat burrows, the area may be reservoir of infection for the serovar ballum.  Tularaemia: In Sweden in 1967, an epidemic of Tularaemia occurred with more than 2000 human cases and a high mortality rate in hares. The epidemic was associated with the clearing of small areas of forest to create areas for grazing, which led to sudden increase in the population density of hares and rodents. Disease could have been transmitted either by handling dead hares or through bites of mosquitoes in these synanthropic ecosystems.  Kyassanur Forest Disease: The disease is caused by an arbovirus, which endemically and inapparently infects some small mammals, including rats in the Kyassanur forest. The virus is transmitted by several species of tick, one of which also infests man (Haemophysalis spinigera)- the usual host of the tick is cattle. When man created ecological mosaics for rice cultivation, his 33 cattle roamed into the surrounding forest and became infested with virus-infected ticks. The dense population of ticks then build up around villages which transmitted the infection to man. 34  Chapter 9 Patterns of disease Epidemic curve: The representation of the number of new cases of a disease by a graph with the calendar time on the horizontal axis and number of new cases on the vertical axis is the most common means of expressing disease occurrence and is called epidemic curve. Factors affecting shape of curve: 1. The infectivity of the agent 2. The incubation period of disease 3. The proportion of susceptible animals in the population. 4. The distance between animals (i.e. animal density) A highly infectious agent with a short incubation period infecting a population having large proportion of susceptible animals at high density produces a curve with a steep initial slope indicating rapid spread of infection among the population. Incidence rate Endemic occurrence Time Regression Accretion Progression Decrescence Egression  Gradation A minimum density of susceptible animals is required to allow a contact transmitted epidemic to commence. It is called threshold level e.g. it has been estimated that a minimum density of 12 dogs/km2 is required before a CPV epidemic can occur.  As an epidemic proceeds, the number of susceptible animals decreases (either due to death of infected animals or by increasing immunity following infection).  Thus, the epidemic can’t continue because there are insufficient susceptible animals available for infection (In above example, an epidemic stops when the density of susceptible dogs falls below 6 dogs/km2). 35   A period of time is then necessary to allow replacement of susceptible animals before another epidemic can commence---Cyclicity of epidemics. Common source and Propagating epidemics A common source epidemic is one in which all build up is suggestive of a propagated cases are infected from a common source. If epidemic. period of exposure is brief, then a common source epidemic is point source epidemic e.g. food poisoning outbreaks. An extremely rapid increase in the number of cases is suggestive No of new cases of a common source epidemic whereas a slow A propagating epidemic is an epidemic caused by an infectious agent in which initial (i.e. primary case- the individual that introduces disease into a herd; not necessarily the first diagnosed case in herd) cases excrete the agent, thus infect susceptible individuals, which constitute secondary cases and so on e.g. epidemics of FMD. One of the primary cases is an Index case (the first diagnosed case of an outbreak in a herd). The time intervals between peaks of successive temporal clusters of cases, separating the primary from the subsequent secondary cases, reflect the incubation period of the infection (Typically all cases of point source epidemic occur within one IP of the causal agent). Stop Kendall’s Waves Some epidemics occur as a series of outbreaks, which can be considered as a series of epidemic waves. Kendall identified 3 types of waves representing particular stage of epidemic -called Kendall’s Waves. There are 3 main differences between these waves: 1. Amplitude: Decreasing intensity from type1 to type 3. 2. Peakedness (concentration of cases): also decreasing from type1 to type 3. 3. Skewness: Noticeable in type1 but decreasing in succeeding types. Intensity Type 2 Type 3 Type 1 Time 36 Shape of each wave at a given time or place in a risk population of size S depends on:  rate of infection β and  rate of removal μ (removal occurs when infected animals die, isolated, recover or become immune) [μ /β = Sc (the relative removal rate)]  When S is much greater than Sc - type 1 wave occurs.  When S is only slightly greater than Sc- type 3 wave occurs. These waves are characterized by relatively lengthy outbreaks of low amplitude.  Type 2 outbreaks are intermediate to type 1 and 3. Trends in the temporal distribution of disease: 3 types  Short-term trends: Typical epidemics.  Cyclical trends (Including seasonal) are associated with regular, periodic fluctuations in the level of disease occurrence. These are due to periodic changes in the size of susceptible host population and/ or effective contact and may produce recurrent epidemics or endemic pulsations (regular, predictable cyclical fluctuations) e.g. 3-4 year cycle of bovine ephemeral fever or FMD. These may be probably due to the time taken by the susceptible population to reach the threshold level. Incidence rate Time  Seasonal Trends: It is a special case of cyclical trend, where the periodic fluctuations in disease incidence are related to particular season.  Fluctuations may be caused by change in host density, management practices, agent and environmental factors e.g. o Human brucellosis is more common in calving season due to increased risk of contracting disease from infected uterine discharges. o Leptospirosis more common in summer o TGE of pigs more common in winter.  Long term (secular) trends: Secular trends occur over a long period of time and represent a long- term interaction between host and parasite.  If a balance occurs, then a stable, endemic level of disease is maintained (1). 37   If the interaction is biased to the host, then there is gradual decrease in disease occurrence (2).  If the interaction is biased to the parasite, there is a gradual increase in disease occurrence (3). 3 Incidence rate 1 2 Time Spatial trends in disease occurrence  The spatial trends are typically the occurrence of environment factors in different locations. The epidemic not only represents clustering of cases over a period of time but also in a definite area.  An infectious disease results in a contagious spatial pattern in contrast to sporadic outbreaks that are distributed randomly.  Another pattern is regular spatial occurrence.  Identification of spatial clustering can also assist in identification of cause of the disease. Space Time Clustering: It is an interaction between the places of onset and the times of onset of disease-cases that are close in space tending to be close in time. 38  Chapter 10 Investigation of epidemic The Veterinarians are frequently called to investigate outbreaks/epidemics. In general, the major objectives of such investigations are  Halting the progress of disease  Determining the reasons for the outbreak  Instituting control measures, and  Recommending procedures to reduce the risk of future outbreaks. The outbreak can be controlled using traditional ‘clinical’ or the modern ‘epidemiological’ approach. The clinical approach focuses on diagnosis of diseased animals. In contrast, epidemiological approach focuses on comparison of subgroups or animals. The epidemiological approach in investigation of herd problems includes establishing a definitive or tentative diagnosis based on clinico-pathological examination, then establish the magnitude of problem, then temporal pattern is examined, then spatial pattern is examined. Although the methods used to accomplish these objectives will vary from situation to situation, there are two general approaches, depending upon the rate of spread of the problem. Outbreak can be 1. Slowly spreading propagative type or 2. Rapidly spreading common source type. Steps in investigating a propagating epidemic If the disease is IS IT PROPAGATED EPIDEMIC ------No ------ See point epidemic identified at any step; and animals that are Yes sources of infection are EXAMINE THE FIRST FEW ANIMALS THAT BECAME SICK found, then isolation, treatment or removal of (Does this explain the epidemic? Are they the source?) these animals should be If the source is not found done. Trace back to their EXAMINE RECENT ADDITIONS TO THE HERD/ FLOCKorigin may be essential if the disease is serious (Does this explain the epidemic? Are they the source?) and infectious. If the source is not found NOTE RECENT CHANGES IN MANAGEMENT, HOUSING, RATION ETC (Use the method of agreement or of difference) If the source is not found A MORE DETAILED STUDY INCLUDING LAB ANALYSIS OF APPROPRIATE SAMPLES IS REQUIRED When the source is found, one should institute trace back procedures to identify the origin of the problem and prevent further spread of the problem. 39  Steps in investigating a point epidemic IS IT A POINT EPIDEMIC -------NO--------- See propagated epidemic Yes IS IT AN EMERGENCY---------- NO--------Diagnosis? Yes No Yes OBTAIN A GENERAL HISTORY (Determine the animals involved, general setting and temporal aspects) Date of median case ONE SYNDROME? (Examine animals and collect samples.) Yes Incubation period Obtain specific details--------likely time of exposure Feed (e.g. composition) Water (e.g. sources) Environment (e.g. chemical spraying) INVESTIGATE ASSOCIATION OF FACTORS AND DISEASE Remove risk factors and obtain appropriate samples If no factors obvious, refine questions and begin again If solved, make appropriate recommendations and suggestions for future prevention  Most of time point epidemics are emergency situations and the vet must act quickly to find the source and prevent the exposure of more animals without wasting time at diagnosis.  However, if a diagnosis can be made, it may assist in identifying the source and nature of the problem, besides indicating the disease e.g. some agents have a strong association with specific sources (e.g. Salmonella with poultry feathers or milk). In addition average IP can be used to determine the most likely time of exposure. For this, mid point of epidemic, usually the median case is identified and then the average IP for the disease is subtracted from this to identify the most likely time and or the place of exposure. 40  Chapter 11 Disease control and eradication Prevention: The term is generally applied to measures designed to exclude the disease from an unaffected population e.g. by quarantine, vaccination etc. The prevention can be applied at individual or population level. The prevention can be achieved by primary prevention (preventing exposure to causal factor by quarantine or vaccination; vaccination although does not prevent exposure yet render animal immune to agent under field conditions), secondary (detect subclinical disease and treat before it becomes clinical e.g. somatic cell count to detect mastitis) or tertiary prevention (commonly known as therapeutics) Control: It describes efforts directed towards reducing the frequency of existing disease to a level biologically and/or economically justifiable. The control means reducing the morbidity and mortality from disease and can be achieved by treating diseased animals or by preventing disease. Eradication: The term eradication describes the efforts to eliminate selected causative agents from a defined area. It may be achieved by interfering in natural history of an infectious organism so as to make its survival unlikely, if not impossible. The eradication can be at local, national or global level e.g. rabies, glanders and pleuropneumonia has been eradicated from European countries. The disease to be selected for eradication-  The eradication should be economically justifiable.  Should have features that enhance easy case detection and surveillance.  and there should be atleast one tool that is effective in halting disease transmission. Preliminary steps to control an outbreak: In an outbreak, veterinarians have to provide fire brigade like service to diagnose the problem and to decrease its further spread. The strategies to control an outbreak vary according to the nature of problem, but the preliminary steps to be taken remain almost the same. Followings are the preliminary steps that can be taken in the face of any epidemic even before confirmation of disease: 1. Segregation: All diseased animals should be segregated from healthy animals so as to prevent the spread of the disease. Segregation should be complete i.e. all appliances (buckets, milking utensils etc) and grooming tools etc should be separate. Preferably attendants should be separate; if the same attendant has to attend diseased as well as healthy animals, he should first attend the healthy and then diseased animals. 2. Restrict movement of animals: Animals should not be taken out for grazing or drinking water or to cattle fair for sale and purchase so that spread of disease to other farms or areas is prevented. 3. Withdrawal of toxic feeds, fodder and water: Outbreak could be due to toxic feed, fodder, water or fodder contaminated with insecticides/pesticides. All such outbreaks can be controlled by withdrawal of toxic feed/fodder or poisonous drinking water. 41 4. Vaccination: In Indian conditions, slaughter policy cannot be followed so treatment and vaccination remains the only option. During the FMD outbreak, ring vaccination can be followed that means vaccination of animals in an area surrounding an infected region to provide a barrier against spread of infection. Hyper immune sera (passive immunization), if available can be used in susceptible animals to provide temporary resistance during the outbreaks. 5. Chemotherapy: Antibiotics, anthelmintics and other drugs can be used to treat sick animals for control of disease. 6. General improvement in hygiene: Although hygienic conditions are needed in normal conditions also to prevent the infectious diseases, but these procedures should be stepped up in the face of disease outbreaks. Thorough cleaning and disinfection of sheds in addition to proper disposal of dung and debris should be done. Entry of outsiders should be restricted as they tend to spread the disease if the disease is infectious or contagious in nature. A disinfectant dip should be provided at the entry of the shed. If some animal has died, after post-mortem examination, it should be buried deep in earth with thick lime or salt layer on it. 7. Reporting: Veterinarians should report the disease immediately to higher authorities. It will serve the following purposes:  Authorities will send the disease investigation experts or epidemiologists who can confirm or refute the charges.  It puts into operation various control measures such as quarantine, vaccination, ban on movement