PRINCIPLES OF EPIDEMIOLOGY ~ PART 1: SOURCES AND CONTAGIONS OF INFECTION

EPIDEMIOLOGY is one of the most important of all sciences related to the study of disease. This subject is thought by some to be related to communicable diseases only, and by others to consist merely of examining suspected cases. It is true that case examination is of basic importance in order that wrong or inaccurate diagnosis may be eliminated. This is only the beginning of a thorough epidemiologic study. The word "epidemiology" in its simplest sense can be defined as the science or study of epidemics. In the past this science was mainly concerned with the study of epidemics of disease. As both science and study were developed and improved, it became evident that this approach to the elucidation of disease could readily be applied to all forms of disease, epidemic, non-epidemic, and even non-infectious. Cancer is a non-infectious disease and has not appeared in epidemic form, yet it has a very definite epidemiology. The epidemiology of simple goiter has resulted in the finding of so-called goiter belts, and the control of the disease by iodine therapy. Lead poisoning and ergot poisoning have not infrequently occurred in epidemic form although they are not infectious. The discovery of their causes and source was definitely the result of epidemiologic study. Tuberculosis is a communicable disease but rarely and only under special conditions does it become epidemic. Nevertheless the epidemiology of tuberculosis is a vast and important study. Any disease may with value be studied from an epidemiologic standpoint and such diverse subjects as heart disease, endocrine disorders and congenital deformities can be offered as examples.

The purpose of epidemiology is to discover all the causes of any given disease as well as the factors associated with its occurrence. The basic sciences, bacteriology, chemistry, etc., are primarily concerned with the exciting or essential cause of disease. These processes of study represent laboratory procedures under controlled conditions. Epidemiology on the other hand concerns itself with the predisposing as well as the essential causes. These predisposing factors include the study of disease with relation to its history, its geographical distribution, its seasonal prevalence, its racial preference, the age, sex and economic condition of its victims, their dietary habits, their occupations, and in short, all of the things which go into the life and environment of man as they may be related to disease process. Epidemiology involves the study of all the links in the chain of circumstances leading to disease.

Epidemiologic studies often point the way to the discovery of the essential cause of disease. Long before bacteriology was established epidemiologists demonstrated that typhoid fever was closely associated with the contamination of water supplies by human excrement. In the nineteenth century Munich was known as a hot bed for typhoid fever. Fecal matter was deposited in shallow vaults and the drinking-water was taken from shallow wells. The whole city was honeycombed with privies and wells and the people were drinking strong infusions of their own excrement. Epidemiologic study revealed a definite relationship between typhoid fever and contaminated water supply. Pettenkoffer taught that fecal matter underwent a ripening process in the soil and thereby became the cause of typhoid fever. Responding to his teachings the people of Munich introduced a complete sewer system and brought a pure drinking water from a distant mountain lake. This resulted in a marked decrease of typhoid fever and Pettenkoffer’s theory was apparently justified by the result. Further studies and later with the development of bacteriology the causative organism was identified. Even though bacteriology finally demonstrated the causative organism of typhoid fever, and today that same science might find the organism in a water supply, it still remains the problem of the epidemiologist to prove any given case of typhoid fever due to that water supply, as well as to discover why and how the water supply is being contaminated. Finally the elimination of the cause of contamination must be accomplished or controlled.

When approaching a study of the predisposing causes of a disease, the history may assume great importance. That which is already known about a disease, and those theories which may have been advanced or which seem best to explain its epidemic or endemic character may indicate the particular details that need investigation. The geographic distribution of persons suffering with simple goiter led to the discovery that the lack of iodine was a most important etiologic factor. Age incidence may be of significance at times for example in the diseases of childhood as contrasted to those of senility. Why should measles be a disease acquired by most of its victims in childhood while cancer is definitely more prevalent in late adulthood? Does the economic condition of its victims effect the prevalence of any given disease? If so, how and why?

The general public in the past few years has become aware of this important phase of epidemiology. Welfare and various assistance boards might with advantage use such information. Closely linked with economic status is the dietary habits of people. The epidemiology of pellagra affords a most enlightening subject. Here too, may be added scurvy and ben-ben. The epidemiology of scurvy pointed to a food factor as an essential cause long before vitamin C was discovered. Those who have occasion to read or be connected with the industrial medicine readily appreciate the enormous problem of disease as related to occupation. The study of silicosis, once called miner’s consumption, is a monumental work in which epidemiologic methods played a leading role. Although once thought to be infectious, it was through careful study of all the predisposing factors that this disease was finally proved to be occupational and due to the inhalation of unabsorbable dusts. With this knowledge the control of the disease became a problem of prevention and such methods as the use of masks and various wetting processes were developed.

The field of epidemiology is so vast that reliance must be placed on the technical branches of science for skilled work. An epidemiologic study may suggest the bacterial origin of a disease. It is then the expert bacteriologist who by carefully controlled laboratory experiments proves or disproves such a working hypothesis. A contaminated water supply or an improper method of sewage disposal may be found to be a most important factor in the spread of a given disease. Now the highly trained sanitary engineer is needed to advise proper technical methods to correct the dangerous water supply or faulty sewer system. In spite of the fact that the epidemiologist needs the assistance of various technical branches of science, the basic decisions and plans of procedure still fall upon him. He must of necessity be well trained in medicine and especially in public health. He must realize and be able to appreciate the value and dangers of statistics. A working knowledge of the problems of bacteriology, pathology, chemistry, immunology, engineering, and economics is essential. Since epidemiology is the science of disease causation, it is essential that the epidemiologist should know the exciting causes of disease, the routes by which they are transmitted, the modes of entrance and exit of the infectious agent, its life history outside as well as inside the human body, the incubation periods of the infectious diseases, and their periods of infectiousness. He should know the history of disease, when, where, and under what circumstances it has occurred and should be acquainted with the details of numerous epidemiologic investigations of different classes of disease under differing circumstances. Since this is his specialty so to speak, his knowledge in this field should be unusually complete. It need hardly be said that he should have a thorough grounding in the subjects commonly taught as hygiene, public health, and preventive medicine.

Epidemiology, like the subject commonly taught as the "Practice of Medicine" draws from other sciences the knowledge it requires to solve its problems. The two have many things in common, such as the history of the disease under consideration, its predisposing causes, bacteriology, immunology, pathology, symptomatology, differential diagnosis, prognosis and treatment. But whereas medicine places the emphasis on the latter part of the foregoing series, epidemiology concerns itself primarily with those at the beginning of it.

The epidemiologist is not much concerned with the details of treatment but is very much interested in the etiology — both specific cause, and the predisposing causes or circumstances. Both he and the physician are interested in the diagnosis of a given case, but for different reasons. The question in the physician’s mind relates to prognosis and treatment; in the epidemiologist’s, it relates to those circumstances in the action and environment of the patient that may have a bearing on its cause. The physician may call the pathologist, the roentgenologist or the surgeon to his aid. The epidemiologist resorts to the bacteriologist, the statistician or the sanitary engineer for assistance. In essence, the physician is diagnosing and treating cases, while the epidemiologist is the one trying to diagnose and treat causes.

For a large number of communicable diseases, it is now held that a bacterium or ultra-filterable virus is the causative agent. Several still unanswered questions immediately present themselves, however. What causes that strain of pathogenic organism to become so virulent at a particular time that many people are affected simultaneously? And, conversely, why, when faced with the same dose of the microbe or virus, do some people succumb to it and become clinically ill, while others are able to fight off the attack?

Alterations in the virulence of bacteria may be due to various factors. Because of the practical character of finding the answer to this, much work has been done on the subject, but no general agreement has been reached. Changes in virulence may be accompanied by morphological changes in the bacterium, as when the capsule of the bacterium is lost, or smooth forms become rough ones, or clumps or chains of the bacteria suddenly occur. Since virulence is dependent upon the resistance of the host as much as on the properties of the bacterium itself, changes in the immunity of the host are important. For example, measles is a rapidly fatal disease among South Sea Islanders not previously exposed to it, while it is a mild disorder among Europeans who have built up their immunity by sub-clinical doses of it.

Changes in the host also cause changes in the virulence of a particular bacterium or virus. The classic example is smallpox in the human and cowpox in the cow. Generations of passage through a secondary host may bring about attenuation of virulence of some bacteria. Another change in the pathogenic power of a bacteria may be caused by drug-fastness, i.e., tolerance of the bacteria to a therapeutic agent (such as salversan, sulfonamides, or penicillin). The cause for this change is not clear. It may be a metabolic change, with the growth of alternative mechanisms, or the bacteria may produce more of something which combats the drug (e.g., increased output of p-aminobenzoic acid by staphylococcus aureus in the presence of sulfonamides). A new theory holds that sometimes non-drug resistant bacteria are killed off immediately, and only those mutants which can withstand the therapeutic agent are left alive to reproduce, while still another theory holds that a physiological variation in the ability to decompose proteins, ferment sugars, synthesize amino acids, and produce pigments is involved.

As stated above, disease is caused by two factors interacting upon one another. One is the power of the bacterium to cause the disease; the other is the ability of the host to withstand the attacks of the causative agent. The ability of the host to withstand infection is extremely complicated. The basic defence mechanisms of the body (such as antibodies, agglutinins, phagocytes, and the like) can be aided or hindered in their work by the nutritional state of the body of the host, natural immunity of the species, various physical and chemical agents, fatigue, and the addition from without of some agents which combat the infection. Since this is an individual factor, the question of how large numbers of people can reach clinical illness at the same time is an intriguing one. As Geddes Smith has put it: "These are the factors that normally shape disease prevalence. There must be first an infective agent, then a source or reservoir in which the agent is kept alive, then a vehicle by which it passes to new hosts, then a group of susceptible human beings so spaced that infection can spread from one to another. The causes of epidemics presumably lie within this set of variables or within their possible combinations".

The infective agent changes in virulence from time to time or over long periods of time; for certainly, scarlet fever as seen by Sydenham was a much more serious disease than it is today. The groups of susceptible human beings change as the four horsemen of the Apocalypse advance or retreat, and usually these changes have been without the conscious will of the people. Where man has stepped in most successfully to change epidemic incidence has been in the vehicle by which disease has passed to new hosts. Because milk is now pasteurized, and (under normal circumstances) people do not drink infected water, some modern epidemics have been forestalled.

Presumably the medieval epidemics followed the same laws; that is, there were reservoirs in which the infection was kept alive between epidemics, some means of conveying the infection to new hosts; and, finally, individuals spaced in such a fashion that the infection could travel from one to another group without burning itself out. In small valleys and other cul-de-sacs whose inhabitants did not travel widely, epidemics may have wiped out large sections of the endogenous population, but they were not conveyed to other groups outside the area. In these cases, the fuse for the train of gunpowder was missing, and no chain reaction was possible.

The city of Liverpool, England, has contributed much to the development of epidemiology and public health. The city was the first in the United Kingdom to have a Medical Officer of Health, William Henry Duncan, for whom both the annual Duncan Memorial Lecture and the Duncan Society (dedicated to the advancement of public health) are named. In 1931, one of Duncan’s successors, Clare Oswald Stallybrass, authored the earliest known epidemiology textbook, "Principles of Epidemiology and the Process of Infection". At 696 pages (649 pages of text, the rest indices), the book addressed its subject matter in considerable depth. What do we know of the author and his textbook?

Information regarding Stallybrass is difficult to obtain on this side of the Atlantic. The first printing of "Principles of Epidemiology and the Process of Infection" (1931) from Macmillan Publishers Ltd gives minimal biographic information. Library catalogs cite 1881 as Stallybrass’ birth year, but no year of death is given. An earlier book is listed also (Hope EW, Hanna W, and Stallybrass CO. Industrial hygiene and medicine. London: Balliere Tindall, 1923). This earlier book, which focused on occupational medicine, discussed its subject with considerable facility, including insightful discussions of both pneumoconiosis and cancer.

Intended for the Medical Officer of Health, the 16 chapters of Stallybrass’ book focus on infectious diseases. In the book’s preface, epidemiology is defined as the “science of infective diseases — their prime causes, propagation, and prevention. More especially it deals with their epidemic manifestations”. This focus was chosen because “[since] infective diseases still cause more than half of the deaths, and probably an ever higher proportion of the illnesses of men, it is hoped that a work treating of infection will pose of interest to others besides those officially engaged in preventive medicine”. The preface noted the eclectic nature of epidemiologic inquiry: “The basis of the science is the knowledge of the process of infection of the individual, and of the responses to infection of the individual and of the herd. So clinical medicine, pathology, bacteriology and immunology all bring grist to the epidemiologist’s mill”.

One might think that epidemiologists of this era, before non-infectious diseases became a focus of epidemiologic activity, were concerned about infectious diseases because non-infectious diseases were less prevalent. However, in 1923 Stallybrass recognized non-infectious diseases as amenable to epidemiologic consideration: “A very marked increase in the incidence of cancer has been an almost accompaniment of the rise of modern industry. This increase is still continuing and is remarkably regular”. Stallybrass then summarized a 1922 report by Collis and Greenwood on the use of mortality rates as a proxy for hygienic condition: ‘The rise in cancer incidence is greater than can be accounted for by more accurate diagnosis, and is much greater than can be explained by any increase in the expectation of life. Cancer is less frequent in rural than in urban communities due to the incidence of cancer at earlier ages in the towns. Apart from the special liability of females to cancer of the breast and generative organs, cancer is everywhere more frequent in males than in females. Cancer becomes progressively more prevalent in urban populations in the northern hemisphere the further these are removed from the equator”. The discussion concluded, “The cause of the great increase of cancer is to be found in some feature of industrial and urban life. A consideration of the various forms of industrial cancer throws much light on the etiology of cancer”. Cancer was clearly of concern in preventive medicine even in the 1920s. Perhaps it was not considered to be in the domain of the epidemiologist because it was more properly the province of the occupational physician. Such an explanation does not preclude non-infectious diseases from statistical epidemiologic inquiry, yet it accounts for the inattention to non-infectious diseases by epidemiologists of this era.

Some chapters (chapters 1 and 8) had been published previously. The first chapter, a history of the concept of contagion, is accurate and insightful. The second chapter discusses epidemiologic principles, focusing on the specificity of disease and the use of Koch’s postulates. Several concepts commonly taught in present-day introductory courses, such as the influence of age, gender, and season on disease incidence, are considered. Three factors are cited as key in the spread of disease: the host, the environment, and the reservoir. Interestingly, the concept of herd immunity is introduced. (Stallybrass asserts it developed in 1909.)

Chapter 3 considers statistical methods, including age adjustment, indirect standardization, and proportionate mortality, as well as correlation and regression.

In chapter 4, the characteristics of agents are considered, such as toxicity and lethality. Chapters 5-7 discuss host factors, such as immunity and factors affecting susceptibility. Herd immunity is described in chapter 8. In chapters 9-15, agent transmission is discussed, with a focus on the different routes used by various agents. The final chapter concentrates on prophylaxis and disease prevention, including the many means then understood to interrupt agent transmission.

Of what significance was Stallybrass’ book? This is a difficult question, insofar as most of its likely users are now deceased. In 1990, the late Morton L. Levin, a major figure in the development of modern cancer epidemiology, communicated that he had used Stallybrass as a textbook during Wade Hampton Frost’s introductory course in the 1930s. This is the only knowledge of a major figure in epidemiology using this particular textbook.

Stallybrass is less well known than his contemporary, Major Greenwood, who held Epidemiology Chair at the London School of Hygiene and Tropical Medicine and was author of "Epidemics and Crowd-Diseases: Introduction to the Study of Epidemiology. London: Williams and Norgate, 1935". Greenwood established the English tradition of randomized clinical trials that found fruition in Bradford Hill’s 1948 streptomycin trial and continued in the activities of Peto and Collins, among others. Major Greenwood began his statistical epidemiology career in the laboratory of Lord Hill, Bradford Hill’s father — a major English physiologist. Greenwood’s position afforded more visibility than might accrue to a Liverpool medical officer.

— "Greenwood, M. Epidemiology - historical and experimental. London: Oxford University Press, 1932";

— "Hamer, W. Epidemiology - old and new. London: Trubner & Co., 1928", although one might argue that this is an account of descriptive epidemiology and not really a textbook;

— "Vaughan, VC. Epidemiology and public health - Text and Reference book for physicians, medical students and health workers. St. Louis, MO: Mosby & Co., 1922";

Those differences should not, however, diminish the impact of Stallybrass’ text or deny him due recognition as the author of the first epidemiology textbook.

Addendum: Herewith, we continue our research on history of epidemiology in Bulgaria and bringing down more occasional notes on the life and works of Dr. Ivan Golosmanov. As already mentioned in some previous reports, there are wide discrepancies between the written agenda on epidemiology in Bulgaria from the first half of the 20th century — cf., "Georgiev, P (editor). Annals of Bulgarian Epidemiology in the 20th century. Sofia, 2000" and "Golosmanov, I. Professional Factors and Epidemiology of Tuberculosis. Sofia, 1937". De facto, it is large underwritten while the principal investigators are deliberately taken away from the scientific and academic stage.

For the case of Dr. I. Golosmanov we have concluded some further facts. Besides the book at hand, which is a precious acquisition for our booklist, we have tried to deduce some real stanzas on the professional way of this physician — achievable, on behalf the rich bibliography and index of the book "Principles of Epidemiology ~ Part 1: Sources and Contagions of Infection". As indicated by the title, its total preoccupation is with infectious disease. His previous book on tuberculosis, however, was devoted to principles of chronic disease and included material on secular trends, social class differences, the greater variation of disease incidence countywide. Tuberculosis thus is a communicable disease but rarely and only under special conditions does it become epidemic. We make those distinctions on a postulator basis and because it appears "thro hoc" that we are dealing here with personality of a scientist of the type of C. O. Stallybrass. Both were forgotten by the mass institutional public and have remained unreferenced. They are but very timely and first in their literary heritage that have to be studied by contemporary epidemiologic generations.

Dr. Ivan Golosmanov demonstrate a very erudite style in this particular book. He started his career as epidemiologist with his doctoral thesis from Lausanne, "Helminthes intestinaux de l'homme. Leur frequence dans le Canton de Vaud" (1905). His first scholarly report on the Sofia Railroad Construction Workers comes from the period 1910-1917. He next contributed with the publication "Golosmanov, Ivan. Les Services d'hygiène publique en Bulgarie. Genève, 1926". /in French and English/ — which, authoritatively becomes the first international record on health care administration in Bulgaria. Unfortunately, he couldn't write part 2 of this epidemiology textbook because he was already at advanced age and had retired from the post "Chief Inspector of Infectious Disease, Directorate of Public Health" in 1941. Besides, World War was still going on. If we look formally at the book, we should notice the wide array of French and German authors in citation. English and Russian authors are also present, with Stallybrass cited from a russian translation (1936). There are many bulgarian studies included as reference, some of them from well known sources (Prof. T. Petrov as hygienist; Prof. K. Markov as becteriologist, etc.), and others less unknown from circulation. We liked best here an original contribution on zoonotic plague carriers, "Arctomys bobac" and "Spermophilius citillus i musicus", denoted by the author with their plurality of bulgarian names — "Tarbagan", "Susel" and "Laluger", ditto.

(i). Number of anti-rabies vaccinations at the Bacteriological Institute, Sofia, 1920-1924 — stratified by contagions of infection (dogs, cats, bovine, pigs, horses, donkeys, wolves, human and others).