Dr. A. K. AVASARALA MBBS, M.D. PROFESSOR & HEAD DEPT OF COMMUNITY MEDICINE & EPIDEMIOLOGY PRATHIMA INSTITUTE OF MEDICAL SCIENCES, KARIMNAGAR, A.P. INDIA : +91505417 avasarala@yahoo.com ORIGIN, GROWTH & DEVELOPMENT OF EPIDEMIOLOGY

EPIDEMIOLOGY TREE ORIGIN (HIPPOCRATIC TIMES ) 463 BC GROWTH 1600-1905 (GRAUNT TO FLETCHER) DEVELOPMENT 1915 till to date

AD

EPIDEMIOLOGY TREEHas taken roots in Hippocratic timesStarted growing in 17th centuryLull in next two centuries due to microbial era dominationDeveloped and blossomed in 20th & 21st centuries.

SLIDES 4 TO 8ORIGIN

ORIGIN 2400 YEARS AGOHIPPOCRATES planted the seed & the tree of epidemiology has taken its roots in 463 BC, hence it is very old.

His treatise on the role of environment in causing the disease Airs,Waters and Places is the first vivid epidemiological description

Hence paradoxically, Epidemiology , is both very old and very young science as it has mostly developed recently.

HIPPOCRATES , THE FIRST EPIDEMIOLOGIST

AIRS,WATERS & PLACESOF HIPPOCRATESHe stated in his famous treatise On Airs, Waters, Places, that... Whoever wishes to investigate medicine properly should proceed thus: in the first place to consider the seasons of the year, and what effects each of them produces. Then the winds, the hot and the cold, especially such as are common to all countries and then such as are peculiar to each locality. In the same manner. When one comes into a city to which he is a stranger, he should consider its situation, how it lies as to the winds and the rising of the sun; for its influence is not the same whether it lies to the north or the south, to the rising or to the setting sun.

HIS KEEN OBSERVATION & APPLIED COMMONSENSE

HE ADVISED to search for factors causing disease in Air (hot &cold winds)Water (marshy, soft, hard, from rocky soil, unfit for cooking)places (naked without vegetation, deficient in water, well watered, elevated and cold) personal habits (drinking, excessive eating, fond of exercise, and labor)

GROWTH

SLIDES 9 TO 24

GROWTH NOURISHED BY GRAUNT, SNOW, LIND, FLETCER, DOLL, HILL, GOLDBERGER, ARR, JENNERWITH THEIRPHILOSOPHICAL GENIUSKEEN OBSERVATIONCOUNTING OF CASESEXPLOITING THE NATURAL DISTURBANCES OF HEALTH & DISEASEAPPLIED COMMONSENSE, CREATIVE THINKING,GENERALIZATION CONCEPT SCIENTIFIC REASONING & VALIDITYCOMPARABILITY AND ACCOUNTABILITY

EVOLUTIONARY PROCESS IT HAS GROWN FROM PURE OBSERVATIONS &ADVICES FROM HIPPOCRATES TO

COUNTING OF CASES &ANALYSIS BY GRAUNT & WILLIAM FARR NATURAL EXPERIMENTS BY JOHN SNOW

TRUE EXPERIMENTS BY LIND, JENNER, FLETCHER, DOLL & HILL & OTHER EPIDEMIOLOGISTS IN THE LAST TWO CENTURIES

FIVE PHAGES OF GROWTH

First phage:Investigation of specific diseases- efforts were concentrated to investigate cholera, pellagra, scurvy, beri beri, lung cancers ( e.g. Snows cholera, Fletchers beri beri, Linds scurvy experiments)Second phage (turning point): Introduction of randomization ,blinding and controlling to eliminate bias and enhance the quality of methods of investigation and make them systematic without errors. Credit of stimulus goes to DOLL & HILL experiments at this stage.

CONCEPT OF RANDOMIZATION &SMOKING AND LUNG CANCER EXPERIMENTSBRADFORD HILL. A1900MOSQUITO BORNE NATURE OF YELLOW FEVERFINLAY1881NATURAL EXPERIMENT ON LONDON CHOLERAJOHN SNOW 1849ANALYSIS OF VITAL STATISTICS & EFFECTS OF IMPRISONMENT IN PRISONERSWILLIAM FARR1889EXPLAINED INTERPLAY OF FACTORS CAUSING EPIDEMICSW.H .FROST1880TRIAL WITH COWPOX VACCINEEDWARD JENNER1796CITRUS FRUITS TO CURE SCURVY IN SAILORSJAMES LIND1747LONDON BILLS OF MORTALITY ANALYSISJOHN GRAUNT1600ADGROWTH 17TH TO 19TH CENTURIES

JOHN GRAUNTS CONTRIBUTION (1600AD) John Graunt in 17th century counted the mortality rates for 37 years in London from the Bills of mortality and found 1) constancy in the ratio from male to female in births and deaths.2) age specific mortality is higher among males than in females. 3) seasonal fluctuations in deaths from various causes. 4) measured the ebb and flow of various diseases and the host factors. 5) suggested quantitative methods to test the hypothesis of this variations.

JAMES LINDS CONTRIBUTION (1747) JAMES LIND (1747) of 18 th century made notable contributions to the growth of epidemiology. James Lind, a naval surgeon, conducted a true experiment on his 12 soldiers suffering from scurvy. He made them into six pairs and supplemented each pairs diet with 1) vinegar, 2) mixture of nutmeg, garlic, mustard and tamarind in barley water, 3) elixir vitriol, 4) sea water, 5) cider, and 6) two oranges and one lemon for six days. Limeys, the pair which has taken oranges and lemons showed improvement from Scurvy and it was a proved that fresh fruits relieved scurvy. This is a true experiment he carried out where in he deliberately modified the diets to get the desired information.

EDWARD JENNERS CONTRIBUTION (1796)EDWARD JENNER(1796), an English Physician, was the first person to immunize against smallpox with cowpox vaccine. He accidentally found that milkmaids infected with cowpox were immune to smallpox. Then he inoculated a boy of 10 years of age with mild live cowpox vaccine to immunize against smallpox and over the succeeding two years he successfully inoculated 22 more persons thus paved the way for preventive medicine and epidemiology.

WILLIAM FARRS CONTRIBUTION (1889)William Farr, a physician of the 19th century, working as the first in Registrar General office of England & Wales, analyzed the vital statistics for 40 years and made valuable observations with regard to the then health situation and recommended their application for public health improvement. He found high mortality in certain occupations like miners. He studied the health of prisoners and found, while 8 only died due to executions, 52 died of imprisonment. He also found that fluctuations in marriage rates depend upon price of bread, cholera, population movements and persons monetary value. His findings paved the way for proper health planning and policies and thus fostered epidemiology.

JOHN SNOWS CONTRIBUTION (1849)John Snow (1849) is a physician for Queen Victoria and great epidemiologist. He is a philosophical genius because he could control cholera in London even before the causative organism was discovered and found out how cholera spreads. His genius showed in his meticulous and scientific way of conducting the natural experiment to prove his hypothesis that contaminated water is the vehicle for the cholera spread. He thoughtfully considered all other causes that may confound his hypothesis and wisely neutralized them. He had seen that no difference whatever existed, either in the houses or the people receiving water supply of two water companies, or in any physical conditions with which they are surrendered.

SNOW S WORDS ABOUT HIS EXPERIMENT The intermixing of the water supply of the Southwark and Vauxhall Company with that of the Lamberth Company, over an extensive part of London, admitted of the subject being sifted in such a way as to yield the most incontrovertible proof on one side or the other. In the sub- districts enumerated in the above table [Table in this chapter] as being supplied by both Companies, the mixing of the supply is of the most intimate kind. The pipes of each Company go down all the streets, and into nearly all the courts and alleys. A few houses are supplied by one Company and a few by the other, according to the decision of the owner or occupier at that time when the Water Companies were in active competition.

GREATNESS OF SNOWS EXPERIMENTThe experiment, too, was on the grandest scale. No fewer than three hundred thousand people of both sexes, of every age and occupation, and of every rank and station, from gentlefolks down to the very poor were divided in to two groups without their choice, and, in most cases, without their knowledge; one group being supplied with water containing the sewage of London, and, amongst it, whatever might have come from the cholera patients, the other groups having water quite free from such impurity.

AUSTIN BRADFORD HILLS CONTRIBUTION (1900) AUSTIN BRADFORD HILL, in mid 1900, gifted to the concept of Randomization for the epidemiological growth. It enhanced the value of all the experiments that were carried in later years as it eliminates the biases (systematic errors) and neutralizes all the known and unknown confounders in the studies. In the present century, any scientific experiment, test, drug, method is accepted only after it is subjected to randomized controlled trials. All present clinical trials are randomized ones and as the randomization made the procedure more scientific, it is carried out first in any study. His experiments in 1954, to prove causal relationship between smoking and lung cancer really speeded up the growth of epidemiology.

FLETCHERS CONTRIBUTION (1905) FLETCHER(1905) studied Beriberi that occurred in lunatics in mental asylum in Kuala Lumpur (Malaysia) and proved that it is due to nutritional deficiency and not a place disease as suggested by Sir Patrick Manson. In this true experiment, he allocated the lunatics into two groups, one to receive parboiled rice and other to get Siamese rice (polished one). Siamese rice group had higher number of deaths when compared to cured parboiled rice group. He later changed the wards and found the same results thereby disproving that it is a place disease.

FLETCHER EXPERIMENT By June 20th many cases of beri-beri had occurred amongst the patients in the east ward who were eating uncured rice, whereas no cases had occurred in the west ward, the inmates of which were dieted on cured (Indian) rice.In view of the theory so strongly advocated by Sir Patrick Manson that beri-beri is a place disease, it was thought possible that the eastward was infected. Therefore on June 20th the patients were a, those on uncured rice being moved to the westward and those on cured (Indian) rice transferred to the east. From June 20th to Dec. 31st no beri -beri developed among the patients on cured rice although they were living in a ward where beri-beri had been rife amongst the lunatics who were fed on uncured (Siamese) rice.

GOLDBERGERS CONTRIBUTION (1915) GOLDBERGER JOSEPH (1915) proved that Pellagra is not an infectious disease as it was thought earlier, but a nutritional deficiency state. He induced pellagra experimentally by providing a diet deficient in Nicotinic acid and conducted studies in several rural communities and in institutions to demonstrate conclusively that pellagra was a dietary deficiency disease.

DEVELOPMENTSLIDES 25 TO 32

INTERNATIONAL CONTRIBUTION FOR DEVELOPMENTWORLD HEALTH ORGANIZATIONUNICEFUSAIDPRIVATE FUNDING AGENCIESGLOBAL NETWORK OF NON-GOVERNMENTAL ORGANIZATIONS WORLD WIDE WEB (INTERNET EPIDEMIOLOGY)

20 TH CENTURY DEVELOPMENT TO REDUCE CARDIOVASCULAR MORTALITYWHO CLOFIBRATE CLINICAL TRIAL,OSLO STUDY, NORTH KARELIA PROJECT, MRFIT(USA), STANFORD THREE COMMUNITY STUDY, BETA BLOCKERS IN MYOCARDIAL INFARCTION, ASPIRIN STUDY,20thcen-turyADENOCARCINOMA OF VAGINA IN YOUNG WOMENBoston Hospital Study1971ORAL CONTACEPTIVES & HEALTHDoll1969LEUKEMIA DUE TO IRRADIATION TREATMENT FOR ANKYLOSING SPONDYLITISBrown & Hill1955SMOKING & LUNG CANCERA.B. Hill1954SMOKING & LUNG CANCERDoll1952CORONARY HEART DISEASEFramingham Heart Study1948WHOOPING COUGH VACCINE TRIALMedical Research Council (UK) 1946OXYGEN THERAPY & RETROLENTAL FIBROPLASIAKinsley & Hemphill1942INDUCED PELLAGRA BY DIETARY MODIFICATIONSGold Berger & Wheeler1915PARBOILED RICE FOR TREATING BERIBERI IN LUNATICSFletcher1905

FEW 21ST CENTURY DEVELOPMENTAL STUDIES

21ST CENTURY DEVELOPMENTWORLD WIDE WEB (GLOBAL HEALTH NETWORK) SUPERCOURSE AIMED AT UNIVERSAL DISTRIBUTION OF EPIDEMIOLOGICAL INFORMATIONMULTICENTRIC TRIALS ARE FOLLOWED BY THE WORLD TO PROVE THE CONSITENCYCOLLOBORATIVE APPROACH IS ACCEPTED BY WORLD AS MOST FEASIBLE WAY OFDOING THINGS RANDOMIZED CONTROLLED TRIALS ACCEPTED BY WORLD AS SCIENTIFIC NECESSITY

SCOPE FOR FURTHER DEVELOPMENT VERY VAST BECAUSE EPIDEMIOLOGY ENGAGES THE MOST HONEST SERVINGMEN OF VON KIPPLING VERY WISELY.ANY ASPECT OF LIVES OF THE POPUPATION CAN BE QUESTIONED WITH WHY, WHAT, WHEN, WHERE, WHOM AND HOW. THERE IS NO RESTRICTION FOR ITS TRANSGRESSION FROM PAEDIATRICS TO GERIATRICS. INTERNATIONAL ACCEPTANCE AND DEPENDENCE ON EPIDEMIOLOGY TO MANAGE AND SOLVE HEALTH PROBLEMS MAKES ITS DEVELOPMENT MANDATORY NOW AND IN NEAR FUTURE. WORLD WIDE WEB (GLOBAL HEALTH NETWORK& SUPERCOURSE) WITH ITS EXTENSIVE NETWORK ENRICHES THE QUALITY AND QUANTITY OF EPIDEMIOLOGICAL INFORMATION TO THE PUBLIC WHO WILL IN TURN APPRECIATE, ACCEPT, GET BENIFITTED AND NATURALLY PROMOTE ITS GROWTH & DEVELOPMENT.

SUMMARY & CONCLUSIONS

NO ONE CAN CONCLUDE OR SUMMARISE AS EPIDEMIOLOGICAL GROWTH &DEVELOPMENT AS IT IS A PHILOSOPHICAL STUDY OF A HEALTH PROBLEM. HENCE WE CANNOT PUT A FULLSTOP ANYWHERE FOR EPIDEMIOLOGICAL GROWTH. IT WILL BE GROWING IN ALL DIRECTIONS AS LONG AS APPLIED COMMONSENSE IS PREVAILINGLE WITH EPIDEMIOLOGISTS AND PUBLIC. GREAT BEGINNING : HIPPOCRATES ADVISED, GRAUNT AND FARR COUNTED AND ANLYSED THE CASES, SNOW EXPLOITED & EXPERIMENTED THE NATURAL EVENT TO TKNOW HOW ITS SPREADS. LIND, FLETCHER AND OTHERS EXPERIMENTED AND HENCE THEY BECAME THE FORERUNNERS OF EPIDEMIOLOGY AND PAVED THE WAY FOR OTHERS AND TAUGHT OTHERS WHAT IS EPIDEMIOLOGY AND HOW IT SHOULD BE PRACTICED.

REFERENCESBrian Mac Mahan -Epidemiology-principles & methods Roger Detels, James Mc Even-Oxford Text Book of Public Health Maxcy-Rosenau-Last, Public Health &Preventive medicineBrett & Cassens - Public Health Medicine, National Student Series.

One should consider most attentively the waters which the inhabitants use, whether they be marshy and soft, or hard and running from elevated and rocky situations, and then if satisfy and unfit for cooking: and the ground, whether it be naked and deficient in water, or wooded and well watered, and whether it lies in a hollow, confined situation, or is elevated and cold; and the made in which the inhabitants live, and what are their pursuits, whether they are fond of drinking and eating to excess, and given to indolence, or fond of exercise and labor.

Third phage:- Extension to study risk factors Risk factor trials, both single and multiple, etiological and clinical , have followed (Framingham Heart study, MRFIT(USA) leading to immense development epidemiology. Fourth phage :- Extension to study and evaluate the health services their need, efficacy, impact and cost-effectiveness and their operational research. Fifth phage :- Stage of collaboration- public private sector mix, collaboration with funding agencies at national and international level (WHO,WORLD BANK, USAID etc)

Thus he became the forerunner of epidemiology in addition to the Father of Biostatistics, the science which helped and contributed to the growth as a twin brother to epidemiology. His counts and measurements proved to be more useful than mere observations to understand about the diseases prevalent then and thus he paved for epidemiological growth with objective measurements of health situation at that times.

He gave similar diet to all the six pairs and added different new foods and achieved the results by comparison.

In 1849, Londoners used to receive drinking water supplies from two private water companies, Lambeth and Southwark companies. These companies used to draw water from Thames river at a point named Battersea Fields where water is heavily contaminated with human sewage. Between 1845 and 1854 ,Lambeth company changed its source of water collection to a point higher in the Thames where there is less pollution while Southwark company continued to collect from source ,Battersea fields . After the source of collection was changed, remarkable difference in number of cholera deaths between the two companies (5/1000 population in Southwark users versus 0.9/1000 population in Lambeth users) was observed. He found decline in deaths in Lambeth customers while there is no fall in deaths of Southwark users which is still supplying contaminated water from same source.

Snow exploited this natural event and carried out house to house survey of about 300,000 users of both companies and confirmed his hypothesis that cholera deaths were due to the contaminated water supplied by Southwark company by comparing the death rates of both companies, by observing the reduction in mortality after changing the source by Lambeth company and by excluding other probable confounding factors. He prepared and used a spot map showing deaths and cases and found clustering of cases in Broad street. He removed the head of the tap and cases declined in that area. His experiment in his own words ----In many cases a single house has a supply different from that on either side. Each company supplies both rich and poor, both large houses and small; there is no difference either in the condition or occupation of the persons receiving the water of the different Companies. Now it must be evident that, if the diminution of cholera, in the districts partly supplied with the improved water, depended on this supply, the houses receiving it would be the houses enjoying the whole benefit of the diminution of the malady, whilst the houses supplied with the water from Battersea Fields would suffer the same mortality as they would if the improved supply did not exist at all. As there is no difference whatever, either in the houses or the people receiving the supply of the two Water Companies, or in any of the physical conditions with which they are surrounded , it is obvious that no experiment could have been devised which would more thoroughly test the effect of water supply on the progress of cholera than this, which circumstances placed ready made before the observer

Snows endeavor , though very exhaustive is not an experiment in strict terms as he did not manipulate the event deliberately (Lambeth company changed its source of collection by its own decision) Another limitation is lack of randomization. However these limitations will not reduce the greatness of his exploitation of a natural man made disaster to reveal the mode of transmission of cholera even before the cholera vibrio was discovered. Thus he became a great epidemiologist of all times.

Another major contribution is his check-list to judge the causality of association. which rightly helped several epidemiologists of later periods to decide about the causal association .

The lunatics were housed in two exactly similar buildings on opposite sides of a quadrangle surrounded by a high wall. On Dec. 5th (1905) all the lunatics at that time in the hospital were drawn up in the dining shed and numbered off from the left. The odd numbers were subsequently domiciled in the ward on the East Side of the courtyard and no alteration was made in their diet, they were still supplied with the same uncured (Siamese) rice as in 1905. The even numbers were quartered in the ward on the west of the quadrangle and received the same rations as the occupants of the other ward, with the exception that they were supplied with cured (Indian) rice.On Dec,5th there were 59 lunatics in the asylum; of these 29 were put on cured rice and 30 on Siamese rice. The next patient admitted to the asylum was admitted to the Bengal rice ward, and the one admitted after him to the uncured rice ward, the next to cured, and so on alternately to the end of the year(CONTD NEXT SLIDE)

In all, among the 120 patients eating uncured rice, there were 34 cases of beriberi and 18 deaths; among the 123 patients assigned to cured rice, there were no deaths and only 2 cases, both of which had been manifest at the time of admission to the asylum.

GOOD DEVELOPMENT :-BRADFORD HILL FLAVOURED THE EPIDEMIOLOGICAL METHODS WITH THE PERFUME OF RANDOMIZATION &CONTROLLING AND ENHANCED ITS QUALITY AND CONTROL MODERN EPIDEMIOLOGISTS APPLIED IT FOR RISK FACTORS , HEALTH SYSTEMS AND HEALTH SERVICES EXPLOITING THE PRIVATE SECTOR, INTERNATIONAL&NATIONAL BODIES

GOOD DIRECTION :-EPIDEMIOLOGY IS DEVELOPING IN RIGHT DIRECTION IMBIBING THE RULES &ETHICS OF SCIENTIFIC STRATEGIES, MULTICENTRIC AND COLOBORATIVE APPROACHES WITH COOPERATION AT LOCAL , NATIONAL,AND INTERNATIONAL LEVELS