SOME BASIC EPIDEMIOLOGY

CONCEPTS

IN

LEARNING OBJECTIVES:
At the end of the module, the student must be able to: 1.Discuss the importance of studying the causes of disease or health-related conditions 2.Explain and differentiate: 2.1 causal association 2.2 necessary cause from sufficient cause 3.Explain and discuss the following: 3.1 models that explain the biologic aspect of disease causation 3.2 statistical aspect of determining disease causation 4.Discuss the natural history of disease and its importance in prevention and control 5.Describe how diseases and disabilities are classified

SOME BASIC COMPONENTS IN EPIDEMIOLOGY DISEASE CAUSATION The Importance of Studying the Causes of Disease In Epidemiology, the establishment of disease condition is the ultimate goal such that once cause is established, prevention and control strategies may be formulated and directed towards the cause. Definition of cause - something that brings about an effect or a result ( Webster) Definition of Cause of disease an event, condition or characteristic that plays an essential role in producing an occurrence of the disease (Rothman) As a consequence, good health will be maintained for those who are not yet affected, prevention of disease among those who are at risk and management of the disease process among those who are already ill.

TYPES OF ASSOCIATION A. not statistically associated (independent) B. Statistically associated 1. Noncausally (secondarily associated) 2. Causally associated a. Indirectly associated b. Directly causal Statistical Association Definition of Statistical Association statistical dependence between two variables, i.e., the degree to which the disease rate in the exposed group is either higher or lower than the rate in the unexposed group If one category of event occurs in a certain proportion, x, of a group of persons and another proportion , y, the two types of events will occur together among some members of the group in a proportion, in fact , equal to the product of the separate proportions, xy. Statistical association means that the proportion of persons exhibiting both events is either significantly higher or significantly lower than the proportion predicted on the basis of simultaneous consideration of the separate frequencies of the two categories of events. Statistical associations are determined for categories and not for individual instances. Example: 100 persons vaccinated vs. 100 persons received placebo and not vaccinated against a particular disease (measles).

An epidemic occurred: 20 of the vaccinated persons and 50 of the unvaccinated contract the disease. Question: Is the difference due to chance? If you are not sure then do a test of hypothesis. If the difference is statistically significant then it is unlikely due to chance then we would say that a statistical association exists between vaccination and remaining free of the disease. QUESTION: Is it possible to say that vaccination caused any individual person in the vaccinated group to remain disease free? However, we cannot deny that information from a group experience may suggest the likelihood of causal association in an individual instance. The stronger the association between the two categories of events revealed by the group experience, the more likely is the assumption of causal association in a specific instance to be correct. Thus, if the disease frequency in the unvaccinated series had been 99 percent and that in the vaccinated series 1 percent, there would be a very high probability that the absence of disease in any one vaccinated individual was related to the vaccination, and the statement that the vaccination of any one individual was causally related to his freedom from disease would probably be correct. The validity of the previous statement would depend however, on the TOTAL experience and not any observation made on this one individual (other than that he was one of those who were vaccinated and remained free of the disease).

CAUSAL vs. NONCAUSAL ASSOCIATION Definition of Causal Association (of exposure and disease) is one in which a change in the frequency and quality of an exposure or characteristic results in a corresponding change in the frequency of the disease or outcome of interest. Causally associated requires that change in one party to the association alters the other. The large number of statistical associations which do not satisfy this requirement are sometimes referred to as (Noncausally) or secondary associations. Noncausal statistical associations usually result from association of both categories of events with a third category.

NONCAUSAL STATISTICAL ASSOCIATION- Example If Category A is causally associated with both Category B and Category C ( i.e. A precedes and influences B and C), B and C will also be associated statistically.

However, the association between B and C is noncausal, since there is no prospect of altering C by manipulating B or altering B by manipulating C. Injection of Neoarsphenamine (B) in outpatient clinics for venereal disease has been noted to be associated with jaundice-salvarsan icterus (C). For a long time the drug was regarded as the cause of the icterus, until it was discovered that the association was the result of causal association of both icterus and injection of neoarsphenamine with a third factor- treatment for syphilis (A).

Diagram A and Diagram B

C precedes both A & B and since an alteration in C will produce alterations in both A & B; factors A & B will also show statistical association with factor C. However, variations in A will never lead to resulting variations in B and vice versa. Hence, the statistical association you find between factors A & B which is statistically significant) will only be secondary to the association of both A & B to C. There is no way for icterus to affect neoarsphenamine or vice-versa. Hence, the two are secondarily associated through their individual associations with treatment for syphilis. CAUSAL ASSOCIATIONS :In the absence of experimental data, three types of consideration are useful in distinguishing between epidemiologic associations that are causal and those that are secondary: 1. Time sequence. For a relationship to be considered causal, the events that are considered causative must precede those thought to be effects. When the sequence of events cannot be determined precisely (a frequent situation in chronic disease), at least the possibility of such a sequence must exist. 2. Strength of the association. The stronger the association between two categories of events (for example, the higher the ratio of the incidence of B following A to the incidence of B without A), the more likely it is that the association is causal. If the suspected cause is a quantitative variable, the existence of a dose-response relationship that is, an association in which the frequency of the effect increases as the exposure to the cause increases is usually considered to favor a causal relationship, although even in a causal relationship, such an association may not exist over the entire range of exposures to the cause. 3. Consistency with existing knowledge. Here several considerations come into play: a. A causal hypothesis based on epidemiologic evidence is supported by knowledge of a cellular or subcellular mechanism that makes it reasonable in the light of existing knowledge in relevant sciences. In the absence of this support, there should at least be the belief that such mechanisms are possible.

b. Evidence that the distribution of the disease in populations follows the distribution of the supposed causal factor supports a causal hypothesis. Major discrepancies between the two patterns, not reconcilable in terms of other causal factors or explanations, tend to weaken a causal hypothesis. c. Evidence obtained through exclusion may be pertinent. The more extensive the efforts have been to identify non-causal explanations of an association, the more one is likely to believe, if these efforts have been unsuccessful, that the association is causal. DIRECT & INDIRECT CAUSAL ASSOCIATION Causal Associations may be direct and indirect: Direct Causal Association no third variable intermediate stage between cause and effect. Indirect Causal Association- a third intermediate stage between cause and effect. variable occupying an occupies an

Indirect Causal Association If A is causally related to D (A being the cause and D the effect) and D is causally related to B (D the cause and B the effect ), there will be a causal relationship between A & B, but the association is indirect. Diagram C Example: Treatment for syphilis is not for itself productive of icterus, but it is one of the factors associated with the use of unclean syringes. Further investigation of salvarsan icterus indicated that the unclean syringe component rather than the treatment of the syphilis was responsible for the icterus. However, since a certain number of cases of icterus would presumably be prevented by failure to treat syphilis, the association of syphilis treatment with icterus is a causal one , even though indirectly so.

Difference Between Direct and Indirect Causal Association The distinction between direct and indirect causal associations is a relative one. Apparent directness depends on the limitation of current knowledge. Example: The association of icterus with syphilis treatment was indirect, and that with the use of unclean syringes direct.Further investigation however revealed that the icterus was associated not with unclean syringes per se, but with injection of minute amounts of human serum that remained in unclean syringes after their previous use. This discovery resulted in a change of the name of the condition from Salvarsan Icterus to Serum Hepatitis. Still later, the icterus was found to be associated directly , not with serum, but with the presence in the serum of a specific virus.

Thus the association with the virus is currently considered the direct one and that with serum indirect.

Necessary and Sufficient Cause Answer to the Question what sector or component , as denoted by a letter, is common to all three circles? This is Sector A. In the above three diagrams, A may therefore be considered as a necessary cause since if one removes A , none of the circles or group of factors would be complete and would now be unable to cause the disease. What is interesting about the 3 diagrams is that you dont have to know all of the sectors or the contributing factors.By just eliminating one sector from the circle ( a sector already known to you) you will successfully eliminate those group of factors as a sufficient cause. For example removing D from the first circle, will render that group of factors inutile in causing the disease. Necessary Cause of disease a cause that must be present for the disease to occur i.e. , all cases are exposed to it. Sufficient Cause of disease a cause that inevitably results in disease, i.e., all exposed inevitably becomes cases For communicable diseases, the necessary cause is the organism causing the disease. Sufficient causes may involve an array of factors which contribute to the condition like like nutrition, compromised immune system, etc. Diagram D, E and F Concept of Sufficient Cause and Component Cause Sufficient Cause a set of minimal conditions and events that inevitably produce disease; minimal implies that none of the conditions and events is superfluous. In disease etiology, completion of a sufficient cause may be considered equivalent to the onset of disease. Example: Smoking is not a sufficient cause of lung cancer. Not everyone who are smokers, even heavy smokers, will develop the disease but only those who are susceptible to the effects of smoking. In other words there are other components of the causal constellation that act together with smoking to produce lung cancer.

Concept of Strength of Causes The apparent strength of a cause is determined by the relative prevalence of component causes. A rare factor becomes a strong cause if its complementary causes are common. The strength of a cause has little biologic significance in that the same causal mechanism is compatible with any of the component causes being strong or weak.

The identity of the constituent components of the cause is the biology of causation; the strength of a cause is a relative phenomenon that depends on the time-and place-specific distribution of component causes in a population.

Concept of Interaction Among Causes Two component causes in a single sufficient cause are considered to have a mutual biologic interaction. The degree of observable interaction depends on the actual mechanisms responsible for the disease. The extent of biologic interaction between two factors is a principle dependent on the relative prevalence of other factors.

The EPIDEMIOLOGIC TRIANGLE Like the epidemiologic lever this model is made up of three components. The three components are the Agent, Host and Environment. It implies that each component must be analyzed and understood for comprehension and prediction of the patterns of disease. A change in any of the components will alter an existing equilibrium and could decrease or increase the frequency of the disease.

THE WHEEL The wheel consists of a Hub (the host or man) which has genetic make-up as its core. Surrounding man is the environment, schematically divided into three sectors biological social physical The relative sizes of the components of the wheel depend upon the specific disease problem under consideration WEB OF CAUSATION Concept of Chain Mechanism.

WEB OF CAUSATION This maintains that effects never depend on single isolated cases but rather develop as the result of chains of causation in which each link itself is the result of a complex genealogy and antecedents. It discourages labelling any of the individual factors as the cause. Development of disease may be interrupted by cutting a link at any point. Knowledge of even one small component may allow significant degrees of prevention.

Judgement of a Cause-Effect Relationship HENLE-KOCHs POSTULATES (were used to determine if a specific living organism causes a particular disease ; however these were found to be inadequate not only for non-infectious disease but even with some infectious ones).

1. The organism must be found in every case of the disease under appropriate circumstances 2. It should occur in no other disease as a fortuitous and non-pathogenic parasites 3. It must be capable of reproducing the disease in experimental animals. 4. The agent must be recovered from the experimental disease produced Experimental Evidence Trials that are sufficiently large, randomized and carefully designed , conducted and analyzed can provide the strongest and most direct epidemiologic evidence on which to make a judgment about the existence of a cause-effect relationship.

Process of Causal Inference The process of determining whether the observed association is likely to be causal on the basis of epidemiologic data involves a chain of reasoning that addresses two major areas: 1) for any individual study, validity of observed association between an exposure and disease

2). For the totality of evidence, whether this totality of evidence taken from a number of sources supports the judgment of causality Process of Causal Inference Bradford Hills Criteria for making causal inferences:

1. Strength of Association the stronger the observed association between the exposure and disease, i.e., the larger the risk/rate ratio, the less likely due entirely to bias. 2. Dose-Response Gradient The observation that disease frequency increases or decreases monotonically with the dose or level of exposure usually lends support to a causal interpretation 3. Lack of temporal ambiguity It is important for the investigator to establish that the hypothesized cause preceded the occurrence of the disease. Establishing the temporal direction of the observed association, i.e,, ruling out temporal ambiguity is a necessary condition for making a causal inference. 4. Consistency of the findings If all studies dealing with a given relationship produce similar quantitative results, causal inference is enhanced. This criterion is particularly important if the studies involve different populations, methods, and/or time periods

5. Biological plausibility of the hypothesis if the hypothesized effect makes sense in the context of current biological theory and knowledge, we are more likely to accept a causal interpretation. 6. Coherence of the evidence If the findings do not seriously conflict with our understanding of the natural history of the disease or with other accepted facts about disease occurrence, a causal interpretation is strengthened. In essence, this criterion combines aspects of consistency and biological plausibility and is therefore similarly delineated as described for these two criteria. 7. Specificity of the association If a specific exposure is found to be associated with only one disease, or if the disease is found to be associated with only one exposure (after testing many possible associations in several studies), a causal interpretation is suggested. This criterion is not given much credibility or weight in contemporary epidemiology. THE NATURAL HISTORY OF THE DISEASE The natural history of the disease shows how interactions and interrelationships among agent, host and environment allow a disease to develop and progress. It comprises the body of knowledge about the agent, host and environmental factors relating to the disease process It includes the initial forces/factors which initiated the process in the environment or elsewhere thru the resulting changes which took place in man until continuing equilibrium is reached, or defect, disability and death ensues Advantages in Knowing the Natural History of a Disease:

1. It prepares the epidemiologist/MHOs to institute the control measures needed It helps in the analysis of his findings and guides him in the planning of control programmes Definitions: 1. Agent a factor whose presence or absence causes a disease. These maybe animate or inanimate. 2. Host the individual human in whom an agent produces disease. 3. Environment refers to all external conditions and influences affecting the life of living things; the host and the agent exist in the environment and the environment brings the host and agent into contact (or non contact) with each other.

PHASES of the Natural History of Diseases

1. Prepathogenesis this is the phase before man is involved. Thru the interaction of the agent, the host and environmental factors, the agent finally reaches man. Thus, it may be said that everyone is in the period of prepathogenesis of many diseases because disease agents are present in the environment where man lives. Pathogenesis this phase includes the successful invasion and establishment of the agent in the host. After a period of incubation, whereby the agent multiplies and develops, or gets absorbed and fixed in the tissues , sufficient tissue or physiologic changes may have taken place to produce detectable evidence of the disease process in man. This is the clinical horizon. This is the stage when diagnosis can usually be made. The disease process may never reach the clinical horizon , or it may proceed until t terminates in recovery, disability, or death, or until it is interrupted by treatment. The Process of Infection The Pathogenesis Period This is the Pathogenesis Period which is the phase of host agent interaction. In the case of infections there are 6 requirements:

1. Conditions in the environment must be favorable to the agent or the agent must be able to adopt to the environment 2. Suitable reservoirs must be present 3. A susceptible host must be present 4. Satisfactory portal of entry into the host 5. Accessible portal of exit from the host 6. Appropriate means of dissemination and transmission to a new host The host-agent relationship is reflected in the disease process itself. The signs and symptoms will vary according to such relationship. Such manifestations will depend on the following:

1. Characteristics and dosage of the agent 2. Reaction of the tissues of the host to the introduction of the agent; and 3. Portal of entry and tissues affected 4. When the host is infected, it mobilizes its defenses. The infectious agent on the other hand tries to multiply to overcome the hosts resistance, and may elaborate toxins. Four different reactions can happen: 1. The host successfully wards of the pathogen, by virtue of its natural resistance, acquired immunity, state of good health, etc. and by virtue of a weak agent or smaller dosage . Balanced Equilibrium In this condition, the forces of the agent and the forces of the host are equal so that both are not affected. This is a dangerous condition, the so called inapparent infection, because the host

becomes a healthy carrier who can readily and easily spread the disease to others and evade detection. Ex. Out of a mass srvey of 888 people in the barrios in Sumunul, Tawi-tawi in November, 1965, 112 were found positive in malarial parasites, 70% of which did not have any fever complaint I the past 4 weeks immediately preceding the survey. Subclinical Conditions- this refer to reactions which are very mild that they escape detection. This can also result in a carrier state. Full Blown Clinical cases these cases may may be typical or atypical

The Process of Infection The Pathogenesis Period

The Incubation Period (I.P.) When the infectious agent gains entry into the host, there is a certain lapse of time before the disease becomes manifest. This is the I.P. and represents the time required for the agent to establish itself, multiply and produce toxins. This point differentiates the action of preformed biological or chemical toxins or poisons which when ingested will cause almost immediate manifestations as compared with food infections which take some time. The I.P. , except in instances where the agent needs definite time periods to pass from one stage to another vary according to the following:

1. Virulence, dose and portal of entry. There is no question on the first two, but the portal of entry needs some clarification. Taking for example the epidemic of rabies in Tawi-tawi in 1964, the first four fatal cases were those bitten in the faces and the longest period observed was 35 days. In many reports of rabid dogs biting people in the leg, the I.P. Ranged from 60 days and above. . Previous experience of the host and the state of natural resistance . Previous experience affects the I.P. by the development of either immunity, tolerance or refractoriness to the disease. 3. the inherent character of the organism itself. Example is the strain of P.vivax with short I.P. and the P.vivax with protracted I.P.

LEVELS OF DISEASE PREVENTION-PRIMARY LEVEL Primary Level

This refers to the measures that may be applied in the prepathogenesis phases of the natural history. This consist of the following: 1. By measures designed to promote positive general health; development of good habits of health and hygiene, proper nutrition, proper attitude towards sickness, proper and prompt utilization of available health and medical facilities, etc.

2. Specific Protection By the use of measures against specific disease agents. This is the protection of man himself, or the establishment of barriers against agents in the environment. It consist of the following:

2.1 segregation of the reservoir or source of infection by isolation or quarantine 2.2 Control of means of spread such as vector control, sanitation of food, milk, water, and air, proper sewage disposal, proper disposal and or disinfection of excreta of sick people, eradication of animal reservoir, etc. 2.3 increasing the resistance of immunization both active and passive the prospective host by specific

LEVELS OF DISEASE PREVENTION-SECONDARY LEVEL This is applied in the pathogenesis period. This consist of early diagnosis and prompt treatment of the disease in order to arrest the disease and to prevent its spread to other people. It is necessary that all cases be discovered ASAP in order to attain said objective. It is however unfortunate that early detection is the exception rather than the rule in our experience with public health practice in the country. By treating the cases , we are actually eradicating the reservoir. In the case of animal reservoirs for fatal disease like rabies, no attempts are made in the treatment of these animals. Their immediate destruction is the rule. Ex. In the Tandubas experience (April-May 1964), since it was not possible to identify which dogs were infected by the rabid animals, all the dogs in the island were killed by the marines and concerned citizens.

LEVELS OF DISEASE PREVENTION-TERTIARY LEVEL This consist of the following:

1. Disability limitation - this indicates failure of prevention at an earlier level. It requires treatment of a more or less advanced disease process. 2. Rehabilitation this is applied with the objectives of returning the affected individual to a useful place in society and make maximum use of his remaining capacity. 3. Intensive, periodic follow-up and treatment. Done to prevent relapses in certain diseases; to effect complete cure in diseases which have relapse tendency. Attention is called to the fact that thus far, no mention has been made of health education as belonging to another level of prevention. Health

Education is of universal application, and is instrumental in accomplishment of all the measures proposed in all levels of prevention

the

With reference to specific protection, the points of attack depend on which of the three ecologic factors of disease/health are most vulnerable to corrective measures,. It is to be recognized, therefore that such measures to be applied effectively and efficiently, they need to be guided properly. For this reason, knowledge of surveillance and epidemiological investigation is necessary.

Classification of Disease and Disability Grouping of people which will allow the groups to be distinguished from one another is an important step in epidemiology. These grouping would provide guidance on how to treat the disease as well as how to prevent the disease from developing. There are two ways to classify the groups: 1. based on manifestational criteria meaning that you classify according to signs and symptoms being manifested. 2. by way of experiential criteria wherein people are grouped according to an experience they had in common prior to the development of the disease. One might say that they had some experience in common during prepathogenesis of the disease. Why is there sometimes poor correspondence between groupings based on manifestational and experiential criteria? 1. a single specified experience sometimes has many, varying effects (polymorphous) in many forms ( different effects or outcomes from a single experience) 2. a particular manifestation at time comes from diverse experiences (one manifestation from different experiences). How do epidemiological findings contribute towards classifying disease based on manifestations? One perfect example is about cancer of the uterus. Manifestations (as well as risk factors) for cancer of the cervix are very much different for those found for cancer of the corpus. Hence, it is now accepted that there are two separate disease entities regarding cancer of the cervix uteri and cancer of the corpus uteri. Regarding infections or communicable diseases, classification depends on internalization of the microorganism. This is an experiential criterion since the persons have to experience being exposed to the microorganism first and letting that microorganism gain hold in their bodies before the actual disease could develop and before they can be classified accordingly Two practical applications of being able to classify a disease based on common experience:

1. The group of ill individuals at hand have illnesses highly dependent on a common experience and the experience becomes a focus for special therapeutic intervention. 2. Means may be devised to prevent exposure to the microorganism or to limit the ill-effects of the microorganism.