Goldberger1 - 1. The Etiology of Pellagra. The...

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Unformatted text preview: 1. The Etiology of Pellagra. The Significance of Certain Epidemiological Observations with Respect Thereto1 JOSEPH GOLDBERGER The writer desires to invite attention to certain observations recorded in the literature of pellagrafi significance of which appears entirely to have escaped attention. . At the National Conference on Pellagra held in Columbia, 8. 0., November 3, 1909, Siler and Nichols in their paper on the “Aspects of the peliagra p‘r'oblem in Illinois" stated that certain facts “would seem to indicate that the exciting cause of the disease is present within the institution” (Peoria State Hospital), and add that “at the same time no nurses, attendants, or employees have shown the disease." ' Manning, medical superintendent of_ the asylum at Bridgetown, Barbados, on the same occasion, in arguing against the identity of a disease that he called psilosis pigmentosa, with pellagra, but which undoubtedly is this disease, states that he had never seen it develop in an attendant. At the same conference Mobley, from the Georgia State Sani- tarium, in the course of his discussion of the relation of pellagra to insanity, presents data showing that at the Georgia State Sanitarium a considerable proportion of the cases of pellagra develop in inmates who have been residents therein for considerable periods, mention- ing one casein an inmate after 10 years' residence. In this connection he remarks, what must have struck him, as it no doubt must have appealed to Siler and Nichols at the Illinois institution, as a curious fact, that “so far as can be ascertained there has never been a case of pellagra to develop among the nurses, white or colored, while employed as such in the Georgia State Sanitarium." Sambon (1910) in his “Progress report" states that in Italy “no precautions are ever taken to avoid propagation of the malady in any of the pellagrosari, locande sanitarie, hospitals, insane asylums, and other institutions in which very numerous pellagrins are col- lected every year. Long experience has taught that there is no danger 1 Public Health Rep, Vol. 29, No. 26 (June 26, 1914), 1683—86. 19 20 Preliminary Observations and Hypothesis whatever of transmission from the sick to the healthy in any collective dwelling within urban precincts." Sambon's statement is confirmed by Lavinder, who in a personal communication states that on careful inquiry while visiting a large pellagrosario near Venice, one in which some 300 to 500 pellagrms are constantly present and cared for by a large number of Sisters of Charity and other employees, he was assured that no employee had ever developed the disease while at the institution. ' The results of personal inquiry at some of our State asylums in which pelLagra occurs confirm the reported observations above Cited. Thus at the South Carolina State HospitaLfor the Insane, where Babcock (1910 Ann. Rept.) states that cases of pellagra develop in patients who have been there for years, no case so far as the wnter was able to ascertain has occurred in the nurses or attendants. It may be of interest to recall in this connection that in his annual report for 1913 Babcock states that a total of about 900 pellagrins had been admitted to his institution during the preceding six years. At the State hospital for the insane at jackson, Miss., there have been recorded 98 deaths from pellagra for the period between Qcto- her 1, 1909, and July 1, 1913. At this institution cases of institutional origin have occurred in inmates. Dr. C. Herrington, aSSistant physician and pathologist, told me at the time of my v_151t of a case in an inmate after 15 and in another after 20 years’ re51dence at the institution. N0 case, so far as I was able to learn, has developed in a nurse or attendant, although since January 1, 1909, there have been employed a total of 126 who have served for periods of from i to 5 years. I . _ In considering the significance of the foregoing observations it is to be recalled that at all of these institutions the ward personnel, nurses, and attendants spend a considerable proportion of the 24 hours, on day or night duty, in close association with the inmates; indeed at many of these institutions, for lack of a separate budding or special residence for the nurses, these live right in the ward With and of necessity under exactly the same conditions as the inmates. It is striking therefore that although many inmates develop pel- lagra after varying periods of institutional residence, some even after 10 to 20 years of institutional life, and therefore it seems permissible to infer, as the result of the operation within the institution of the exciting cause or causes, yet nurses and attendants living under identical conditions appear uniformly to be immune. If pellagra be a communicable disease, why should there be this exemption of the nurses and attendants? The Etiology of Pellagra 21 To the writer this peculiar exemption or immunity is inexplicable on the assumption that pellagra is compiunicable. Neither “contact” in any sense nor insect_ transmission is capable of explaining such a phenomenon, except on the assumption of an incubation or latent period efiending over _1_o to 20 years. In support of such an assump- tion there exists, so far as the writer is aware, no satisfactory evidence. The explanation of the peculiar exemption under discussion will be found in the opinion of the writer in a difference in the diet of the two groups of residents. At some of the institutions there is a manifest difference in this regard; in others none is apparent. The latter would seem to be a fatal objection to this explanation, but a moment’s consideration will show that such is not necessarily the case. The writer from personal observation has found that although the nurses and attendants may apparently receive the same food, there is nevertheless a difference in that the nurses have the privilege~which they exercise—of selecting the best and the greatest variety for themselves. Moreover, it must not be overlooked that nurses and attendants have opportunities for supplementing their institutional dietary that the inmates as a rule have not. In this connection brief reference must be made to two other epidemiological features of pellagra. It is universally agreed (1) that this disease is essentially rural, and (2) associated with poverty. Now there is plenty of poverty. and all its concomitants in ail—cities, and the question naturally arises why its greater predilection for rural poverty? What important difference is there between the elements of poverty in our slums and those of poverty in rural dwellers? It is not the writer’s intention to enter at this time into a detailed dis- cussion of these questions; he wishes to point out one difference only. This difference relates to the dietary. Studies g urban and rural dietaries (Wait—Office of Experirfi'ent Stations, Bull. 221, 1909) have shown that on the whole the very poor of cities have a more varied diet, than the poor in rural sectioryfi‘Except in extreme cases, the city poor . . . appear to be better nourished than the moun- taineers" of Tennessee. With regard to the question of just what in the dietary is respon- sible, the writer has no opinion to express. From a study of certain institutional dietaries, however, he has gained the impression that vegetables and cereals form a much greater pigsortion in them than they do in the dietaries oTwell-to-do people; t at is, people who are not, as a class, subject to pellagra. The writer is satisfied that the consumption of corn or corn prod- ucts is not essential to the production of pellagra, but this does not 22 Preliminary Observations and Hypothesis mean that com, the best of corn, or corn products, however nutritious and however high in caloric value they may be, are not objectionable when forming of themselves or in combination with other cereals and with vegetables, a large part of the diet of the individual. In view of the great uncertainty that exists as to the true cause of pellagra, it may not be amiss to suggest that pending the final solu- tion of this problem it may be well to attempt to prevent the disease by improving the dietary of those among whom it seems most preva- lent. In this direction I would urge the reduction in cereals, vege- tables, and canned foods that enter to so large an extent into the dietary of many of the people in the South and an increase in the fresh animal food component, such as fresh meats, eggs, and milk. It may be of interest to add that intensive studies along the lines so strongly suggested by the observations above considered are being prosecuted by several groups of workers of the United States Public Health Service. 2. The Cause and Prevention of Pellagm1 JOSEPH GOLDBERGER Because of the prevalence of pellagra throughout a considerable part of the United States, and the fact that this disease has so far baffled all attempts to ascertain its cause and means of prevention, the following letter from Surg. Joseph Goldberger, in charge of the Government's pellagra investigations, is of interest. Evidence seems to be accumulating to show that pellagra is due to the use of a dietary in which some essential element is reduced in amount or from which it is altogether absent, or to the use of a dietary in which some element is present in injurious amount. UNITED STATES PUBLIC HEALTH SERVICE Washington, September 4, 1914. The SURGEON GENERAL, Public Heglth Service. SIR: As indicated in my progress report of June 5, 1914, the primary object of the pellagra studies that are being conducted under my general direction is the determination of the essential cause of the disease. Although pellagra has been known and studied abroad for nearly two centuries, not only is its essential cause not known, but the broad question of whether it is to be classed either as a dietary or as a communicable (contagious or infectious) disease has never been satisfactorily determined. Abroad, the spoiled-maize theory of Lombroso has for many years been the dominating, one. Its adequacy, however, has on various grounds been repeatedly questioned. In the United States, with the progressive and alarming increase in the prevalence of the disease, there has developed both in the lay and in the medical mind the opinion that pellagra is an infegt-ious dis— ease; This opinion has received important support, first, from the Illinois Pellagra Commission and, second, from the Thompson- McFadden Commission (Siler, Garrison, and MacNeal). In planning 1 Public Health Rep” Vol. 29, No. 37, (September 11, 1914), 2354—57. 33 24 Preliminary Observations and Hypothesis our investigations, therefore, due consideration was given to these two distinct possibilities, and the problem was attacked from both points of View. From the point of view that we might be dealing with an infection, a comprehensive series of inoculations in the monkey was begun last fall by Drs. C. H. Lavinder and Edward Francis. Although every kind of tissue, secretion, and excretion from a considerable number of grave and fatal cases was obtained and inoculated in every con- ceivable way into over a hundred rhesus monkeys, the results have so far been negative. At my suggestion Dr. Francis is making a culture study of the blood, secretions, and excretions of pellagrins by the newer anaerobic methods. This has been in progress about six weeks, but has so far given only negative results. Epidemiologic studies were begun and have been in progress at the Georgia State Sanitarium in immediate charge of Dr. David G. Willets, and at an orphanage in Jackson, Miss., in immediate charge of Dr. C. H. Waring. These studies have brought out facts of the very greatest significance. In a paper published in the Public Health Reports of June 26, 1914, I called attention to certain observations which appear inex- plicable on any theory of communicability. These observations show that although in many asylums new cases of pellagra develop in inmates even after 10, 15, and 20 years’ residence, clearly indicating thereby that the cause of the disease exists and is operative in such asylums, yet at none has any one of the employees contracted the disease, though living under identical environmental conditions as the inmates, and many in most intimate association with them. In order to obtain precise data bearing on these observations, Dr. Willets is making a careful study of the records of the Georgia State Sanitarium. These show that of 996 patients admitted during 191o—excluding those that died, were discharged during their first year, or had pellagra on admission or within a year of admission— there remained at the institution after one year 418, and of this number 32, or 7.65 per cent, have developed pellagra since that time. Of the present employees of this asylum, 293 have been in more or less intimate association with pellagrins and have lived in substan- tially the same or in identical environment as the asylum inmates for at least one year. If pellagra had developed among these employees at the same rate as it has among the inmates, then 22 of them should have the disease. As a matter of fact not a single one has it. The Cause and Prevention of Pellag'ra 25 The studies at the orphanage at Jackson show that on July 1, 1914, of 21 1 orphans 68, or 32 per cent, had pellagra. The distribution of these cases with respect to age developed the remarkable fact that practically all of the cases were in children between the ages of 6 and 12 years, of whom in consequence over 52 per cent were afflicted. In the group of 25 children under 6 years of age there were 2 cases and in the group of 66 children over 12 years of age there was but 1 case. Inasmuch as all live under identical environmental conditions, the remarkable exemption of the group of younger and that of the older children is no more comprehen- sible on the basis of an infection than is the absolute immunity of the asylum employees. A minute investigation has been made at both institutions of all conceivable factors that might possibly explain the striking exemp- tion of the groups indicated. The only constant difference discover- able relates exclusively to the dietary. At both institutions those of the exempt group or groups were found to subsist on a better diet than those of the affected groups. In the diet of those developing pellagra there was noted a disproportionately small amount of meat or other animal protein food, and consequently the vegetable food component, in which corn and sirup were prominent and legumes relatively inconspicuous elements, forms a disproportionately large part of the ration. Although other than this gross defect no fault in the diet is appreciable, the evidence clearly incriminates it as the cause of the pellagra at these institutions. The inference may there— fore be safely drawn that pellagra is not an infection, but that it is a disease essentially of dietary origin; that is, that it is caused in some way such as, for example, by the absence from the diet of essen- tial vitamins, or possibly, as is suggested by Meyer and Voegtlin’s work, by the presence in the vegetable—food component of excessive amounts of a poison such as soluble aluminum salts. One-sided eccentric diets such as were consumed by the affected groups above referred to are in the main brought about by economic conditions. Poverty and the progressive rise in the cost of food oblige the individual, the family, and the institution to curtail the expen- sive elements—meat, milk, eggs, legumes—of the diet and to subsist more and more largely, especially in winter, on the cheaper cereal (corn), carbohydrate (sirup, molasses), and readily procurable vege- tables and fats (“sow belly"). In the well-to-do, more or less well- recognizable eccentricities of taste may cause the individual, without himself realizing it, to subsist on a one~sided or eccentric diet. Some- What similar eccentricities of taste are more or less common in the 26 Preliminary Observations and Hypothesis insane, some of whom, indeed (as the demented), because of apathy and indifference, will not eat at all. most part included in the “untidy” class, require speta'al The poorer the institution, the fewer and of lower grade to be its attendant personnel and therefore the greater the dam that these very trying and troublesome types of inmates will inadequate attention, and so be improperly (one-sidedly) fed. It has repeatedly been noted by observers that at insane asylums the “untidy” (the group in which my observations show scurvy and beriberi most likely to develop) were the most afflicted with pellagra. By some this supposed excessive susceptibility is explained as dependent on the untidiness which favors filth infection. The true explanation, however, is that both the untidiness and the supposed excessive susceptibility of these inmates are primarily dependent on the apathy and indifference typical of most of this group. The deteriorated mental condition causing apathy and indifference results not only in untidiness of person, but passively or actively in an eccentricity in the diet. I believe that in this, in conjunction with a diet admittedly low in the animal protein component we have the explanation of the excessive prevalence of the disease at the Peoria State Hospital, a hospital almost all of whose inmates in 1909 were of the “hopeless, untidy, incurable" class, drawn from the other Illinois institutions. While confident of the accuracy of our observations and of the justice of our inferences, there is nevertheless grave doubt in my mind as to their general acceptance without some practical test or demonstration of the correctness of the corollary, namely, that no pellagra develops in those who consume a mixed, well-balanced, and varied diet, such, for example, as the Navy ration, the Army garrison ration, or the ration prescribed for the Philippine Scouts. Respectfully, Jos. GOLDBERGER, Surgeon in Charge of Pellagra Investigations PART TWO Human Experiments - vmtmi‘w’v 3. The Prevention of Pellagm. A Test of Diet Among Institutional Inmates1 JOSEPH GOLDBERGER C. H. WARING DAVID G. WILLETS Introduction In a paper published June 26, 1914, attention was called to certain epidemiological observations relating to 'pellagra which appeared inexplicable on any theory of communicability. These observations showed that, at certain institutions at which pellagra was either epidemic or had long been endemic among the inmates, the nurses and attendants, drawn from the class economically and socially iden- tical with that most afilicted in the population at large, appeared uniformly to be immune, although living in the same environment and under the same conditions as did the inmates. Neither “contact” nor insect transmission seemed capable of explaining such a phe- nomenon. It was suggested that the explanation was to be found in a difierence, which was believed to exist, in the diet of the two groups of residents. From a study of the dietaries of certain institutions in which pellagra prevailed the impression has been gained that cereals and vegetables formed a much greater-proportion in them than they did in the dietaries of well-to-do people; that is, people who as a class are practically exempt from pellagra. It was suggested, therefore, that it might be well to attempt to prevent the disease by reducing the cereals, vegetables, and canned foods and increasing the fresh animal foods, such as fresh meats, eggs, and milk; in other words, by pro- viding those subject to pellagra with a diet such as that enjoyed by well-to-do people, who as a group are practically free from the disease. In planning the field studies for 1914 it was proposed, with the approval of the bureau and the department, to put this suggestion to a practical test. In accordance with the original plan to carry on the test for at least two years, the experiment is still in progress. The results so 1 Public Health Rep" Vol. 30, No. 43 (October 22, 1915). 3117—31. 29 30 Human Experiments far recorded are so striking, however, and of such profound practical importance that they are reported at this time. In planning the test of the preventive value of diet it was decided to take advantage of the universally recognized fact that “normally” pellagra tends to recur in the individual from year to year. In order to obtain significant and perhaps decisive results, it was decided to submit to the test as large a number of individuals as possible at some institution where the disease was endemic. After some search an orphanage with a high incidence of pellagra among its residents was found at Jackson, Miss. As a preliminary, a study was made of the epidemiology of the dis- ease at this institution, and the singular fact was very quickly dis- covered that the disease was practically exclusively confined to those between 6 and 12 years of age. After a detailed inquiry the only explanation that could be found for the remarkable restriction of the disease to this group was a difference in the diet of the resident groups. In the diet of the affected group, as contrasted with that of the exempt groups, there was noted a disproportionately small amount of lean meat or other animal protein food, so that the vegetable com- ponent, in which biscuits (wheat flour), grits, meal.(corn), and sirup were prominent and legumes relatively inconspicuous, formed a dis- proportionately large part of the ration. Inquiry at other institutions developed analogous conditions, and as a whole the findings, in the light of the recent advances in our knowledge of beriberi, very strongly suggested the idea that the disease was dependent upon a diet that was for some reason faulty and that this fault was in some way either prevented or corrected by including in the diet larger pro- portions of the fresh animal protein foods. These findings not only confirmed the writer’s previous tentative deductions but helped in defining these deductions more clearly, and moreover made it pos- sible more definitely to formulate plans, which were temporarily broadened to include a test of diet in the treatment as well as in the prevention of the disease. At the suggestion of the writer, Dr. W. F. Lorenz, special expert, United StatesPublic Health Service, who was at that time studying the psychiatric manifestations of pellagra at the Georgia State Sani- tarium, treated a series of 27 cases in the insane at that asylum exclu- sively by diet. Considering the class of cases with which he was deal- ing, his results, as well as those of Dr. D. G. Willets, who for a time continued the work begun by Lorenz, were notably favorable. When the various recent methods of treatment, each warmly advo- T he Prevention of Pellagra 31 cated by its author, are critically reviewed in the light of the test made by Lorenz and by Willets, one cannot fail to be struck by the fact that the one thing they all appear to have in common is the so—called “nutritious” diet, and it is difficult to escape the conclusion that it is to this single common factor that the marked success that is usually claimed for the “treatment” should properly be assigned. It is of much interest to note that fully 50 years ago Roussel (Roussel 1866, pp. 529-530), on the basis of long experience and from a critical review of the literature of his day, came to precisely the same conclusion. This is so much to the point that it is quoted here- with: “Without dietetic measures all remedies fail [italics are Rous- sel’s] . . . when drugs and good food are simultaneously employed it is to the latter that the curative action belongs, the former exercises simply an adjuvant action and is without proved efficacy except against secondary changes or accidental complications.” Important as the treatment of the individual case may be, it seemed to the writers of much more fundamental importance to apply their resources to the problem of prevention. Arrangements were therefore made to extend the preventive study to a second orphanage and later to two groups of insane at the Georgia State Sanitarium. Orphanage Study Both the orphanages at which the value of diet in the prevention of pellagra has been tested are located in Jackson, Miss. The first of these to be considered will be spoken of as orphanage “M. J.” Cases of pellagra have been recognized at this institution every spring for several years. During the spring and summer of 1914, up to September 15, 79 cases of the disease were observed in children at this orphanage. Although several of these were known to have had pellagra on admission or had developed it a short time after admission, a number appeared to have developed the disease for the first time after considerable periods of residence at this institu- tion. The factor or factors causing pellagra and favoring its recur- rence seemed, therefore, to be operative at this orphanage. The second of the orphanages, which will be referred to as orphan- age “B. J.," is located about half a mile east of orphanage “M. J." Here, as at “M. J.," cases of pellagra have been recognized every spring for several years. The writers are informed by the superin- tendent that a condition which he cannot distinguish from that now called pellagra has occurred every year among the children ever since his connection with the institution, a matter of some 12 to 13 years. 32 Human Experiments From his description it is believed that there can be but little doubt that pellagra has prevailed at this institution almost, if not quite, since its foundation in 1897. During the spring and summer of 1914, up to September 15, there were observed among the children at this institution 130 cases of pellagra. As at “M. J.," some of these were in recent admissions; a large proportion, however, occurred in long-time residents. There appears to be little if any reason to doubt that the factor or factors causing the disease and favoring its recurrence have been operative at this institution for many years. At both institutions the hygienic and sanitary conditions found left much to be desired. Both were much overcrowded. The drinking water at each is drawn from the public supply. One is equipped with a water carriage sewerage system connected with that of the city; the other has the unscreened surface privy type of sewage disposal and, incidentally, we found here a great deal of soil pollution. At the very outset it was requested that no change be made in hygienic and sanitary conditions, and it is believed that these have remained as they were found and as they have been for several years. Since about the middle of September, 1914, the diet at both orphanages has in certain respects been supplemented by the Public Health Service. At both institutions a very decided increase was made in the proportion of the fresh animal and of the leguminous protein foods. The milk supply was greatly increased. Provision was made to give every child under 12 years a cup of about 7 ounces of milk at least twice a day. Those under 6 years had it three times a day. Until the spring of 1915 the milk used was-all fresh sweet milk. In April of this year buttermilk was added to the diet. This was served at first only on alternate days to those over 12 years of age; later, when a sufficient supply became available, it was served daily at the midday meal to all. Eggs, except in cooking or for the sick, had previously not entered into the regular diet of these children. The writers prescribed at least one eg at the morning meal for every child under 12 years of age. It had been the custom to serve the children with fresh meat but once a week; under the writers’ direction it was increased to three or four times a week. Beans and peas, which had been conspicuous in the diet only during the summer and fall, were made an important part of nearly every midday meal at all seasons. The Prevention of Pellagra 33 The carbohydrate component of the institution diets was also modified. The breakfast cereal was changed from grits to oatmeal, partly because it was believed to be an advantage to reduce the corn element and in part because it was believed that the oatmeal would favor the increased consumption of milk. The corn element, though much reduced, was not wholly excluded. Corn bread was allowed all children once a week and grits to those over 12 years of age once or twice a week. Cane sirup or molasses, which it had been customary to serve freely at two or three meals each day, was for some weeks entirely excluded, and later allowed in small amounts at only three or four evening meals a week. The object in this was to reduce the proportion of the carbohydrate element. A more detailed idea of the character of the diet furnished may be obtained by reference to the menus herewith submitted. (See pp. 34—3 5.) Results Orphanage “M. ].”—Of the 79 cases of pellagra observed at “M. J.” during the spring and summer of 1914, not less than 67 completed at least the anniversary date of their attacks under the observation of the writers. Of these not less than 9 have had at least 2 annual attacks. In none of the 67, following the change in diet, has there been observed so far this year any recognizable evidence of a recur- rence, nor have the writers been able to detect any evidence justify- ing a diagnosis of pellagra in any of the nonpellagrin residents, numbering 99 children and adults, who have been continuously under observation for at least one year. In other words, barring recent admissions, there has been no pellagra at this institution this year. Orphanage “B. J.”—Of the 130 cases of pellagra observed in the children at “B. J.” during the summer of 1914, not less than 105 have completed at least the anniversary date of last year's attack under the writers’ observation. Not less than 14 of these have his- tories of at least 2 successive annual attacks. In only 1 of these 105 pellagrins, following the above change in diet, has there, so far this year, been recognized evidence justifying the diagnosis of a recur- rence. Of the residents of this orphanage that did not present any definite evidence of pellagra in 1914, 69 have remained continuously under observation for at least a year; none has thus far developed recog- nizable evidence of the disease this year. Recent admissions aside, there has been but one case of pellagra at this institution this year. 34 Human Experiments Orphanage, M. ].—January 1 to 7, 1915. BREAKFAST All ages: Oatmeal, with sugar and milk, biscuit with butter. daily. Frankfurters (boiled). one morning, in place of fried bacon or eggs. Matrons and “big” boys: Fried bacon on six mornings. All under 12 years: Milk (about 7 ounces) as a beverage, daily; one egg (scrambled. fried. or boiled). six mornings. DINNER January 1: January 4—Continued. All— Matrons— Vegetable soup (tomatoes, Irish pota- Corn bread. toes, corn, onions, rice). Hot biscuit. Baked sweet potatoes. Corn bread. Janual’Y 5: Light bread. A11- Matrons— Vegetable soup (tomatoes, rice, onions). Biscuit. Roast beef- Baked sweet potatoes. 1311;?“ 2‘ Boiled lima beans. Navy beans (boiled). Mi'ngm‘i Baked “We” P°m°e5- Biscuits. corn bread. Light bread. Pie (blackberry, peach). January 5; Matrons— An- Hot biscuit. Rout been Com mum Boiled navy beans. . Baked sweet potatoes. “KT 3' Blackberry pie (five tables). Roast beet Stewed pears (three tables). Lima beans (boiled). L'Eh‘ bread- Layer cake. Ma‘fonf“ Matrons— mmm' Baked sweet potatoes. 00'” mm Boiled rice custard. . Blackberry pruerves. J “11113:” 7' January 4: Vegetable soup (tomatoes, rice, onions). All— Boiled frankfurters Vegetable soup (tomatoes. rice, onions, Boiled lima beans. navy beans). Baked sweet potatoes. Hash for three tables. Light bread. Baked sweet potatoes. Matrons— Boiled navy beans. Biscuit. Light brad. Corn muffins. N. B.—Children under 6 years of age received about 7 ounces of mik each daily in addition to the above. The Prevention of Pellagra 35 SUPPER 135"“? 1: January 5: A{iii—erred runes or um k' An— in. . Light bread‘ P P Light bread. Over 12—- Simp‘ Boiled grits. Over 12— . Boiled grits. 13:31:? 2' Fried fresh pork. Sirup. . Light bread. Jam’m 6- Over 11— “If Boiled rice. Light bread. Fried bacon. Stew/ed apples. January 3: Over 12— All— Beef hash. Cakes. Boiled rice. Light bread. Milk. January 7: All— anua 4: 1 All-:7 Light bread. Stewed apples. Sirup. Light bread. Milk. 0"" 12— Over 12— Ffied bacon. Fried bacon. 30”“ “5°- Boiled rice. N. B.—All under 1: years received about 7 ounces of milk daily in addition to the bread and stewed fruit or sirup. The matrons and teachers were served with hot biscuits daily in addition to the other articlu noted. Asylum Study Through the courtesy and with the very helpful cooperation of the board of trustees, superintendent, clinical director, and staff of the Georgia State Sanitarium, two wards were turned over to the writers for a test of the value of diet in the prevention of pellagra. To this asylum, the largest in the South, there are admitted annually 3. con- siderable number of cases of pellagra. Besides this, cases of institu- tional origin are of frequent occurrence. This asylum must, therefore, be regarded as an endemic focus of the disease. Of the two wards placed at our disposal one is in the colored and the other in the white female service; the former was organized in October, the latter in December, 1914. Each ward has a capacity of about 50 beds. To each there were admitted about 40 adult pellagrins who had had attacks at one time or another during 1914. In organizing the wards and selecting our patients the list of female pellagrins that at that time were known to have had attacks in 1914 was practically exhausted. In selecting the 36 Human Experiments patients only one condition was observed, namely, that the patient should, if possible, be of such a mental type as would give the highest degree of probability of remaining under observation for at least a year. In consequence a very considerable proportion of them were of a much deteriorated, untidy class. There were, nevertheless, un- avoidably included several in whom the mental condition improved to such a degree that we felt obliged to permit them to go when a request for their discharge was made. Not all, therefore, of our origi- nal patients remained under observation long enough to be included in the present discussion. Very few of the patients presented active symptoms on admission to the writers’ wards, the object so far as this test was concerned being not a study of the treatment of active symptoms but the pre- vention of recurrences. A very considerable number of the patients, however, presented marked residuals of a recent attack. Many of the colored patients had been dieted by either Dr. Lorenz or Dr. W illets during the acute stage of their attacks in the same ward prior to its organization for the purpose under consideration. A number of the white females had been dieted during the acute stage by Dr. Y. A. Lyttle, of the asylum staff, and formed part of a series reported on by him at the meeting of the Southern Medical Association in Novem- ber, 1914. The writers are especially indebted to Dr. Lyttle for his courtesy in subordinating his own study and turning these patients over to them. The diet furnished the inmates of these two wards was prescribed by the writers, and instructions were given to the nurses to give more than ordinary care in supervising the feeding. As at the orphanages, a decided increase was made in the animal and leguminous protein foods. A cup of sweet milk, about 7 ounces, is furnished each patient for breakfast and one of buttermilk at both dinner and supper. About half a pound of fresh beef and 2 to 21/2 ounces of dried field peas or dried beans enter into the daily ration. Oatmeal has almost entirely replaced grits as the breakfast cereal; sirup has been entirely excluded. Corn products, though greatly reduced, have not been entirely eliminated. The menu that follows will serve to give a more detailed idea of the character of the diet furnished. (See p. 37.) Aside from the change in diet and the increased watchfulness over the individual feeding enjoined on the nurses and attendants, no change in the habitual routine of the corresponding services was made. The patients were permitted and encouraged to visit the yard The Prevention of Pellagra 37 Weekly menu for Ward 23. MONDAY Breakfast: Grits, sweet milk, sugar, broiled steak, hot rolls, biscuits, coffee. Dinner: Roast beef, gravy, peas, potatoes, rice, biscuits, buttermilk. Supper: Stewed apples, light bread, coffee, buttermilk, sugar. TUESDAY Breakfast: Oatmeal, sweet milk, sugar, Hamburg steak, biscuits, hot rolls, coffee. Dinner: Beef stew, potatoes, rice, bread, buttermilk. Supper: Baked beans, light bread, coffee. sugar, buttermilk. WEDNESDAY Breakfast: Oatmeal. sweet milk, sugar, beet hash, hot rolls, biscuits, coffee. Dinner: Pea soup, corn bread, gravy, potatoes, rice. bread. buttermilk. Supper: Stewed prunes, light bread, coffee, sugar, buttermilk. THURSDAY Breakfast: Oatmeal, sweet milk, sugar, fried steak, hot rolls, Dinner: Beef stew. peas, potatoes, rice, bread, buttermilk. Supper: Baked beans, bread, coffee, sugar, buttermilk. biscuits, coffee, FRIDAY Breakfast: Oatmeal, sweet milk, sugar, broiled beefsteak, hot rolls, biscuits. coffee. Dinner: Pea soup (puree). roast beef, potatoes, rice, bread, buttermilk. Supper: Light bread, coffee, sugar, buttermilk, apples, baked beans. SATURDAY Breakfast: Oatmeal, sweet milk, sugar, Hamburg steak. hot rolls, biscuits, coffee. Dinner: Beef stew, potatoes, rice, bread, buttermilk. Supper: Bread, baked beans, buttermilk, coffee, sugar. SUNDAY Breakfast: Oatmeal, sweet milk, sugar, mackerel, bread, coffee. Dinner: Loaf beef and gravy, peas, potatoes, rice, bread, buttermilk, pudding. Supper: Beef hash, bread, sugar, coffee, buttermilk. Non. I —Green vegetables in season at irregular intervals. diet, are ~ Milk and . as a ' 1 fumxshed those patients who may require them. eggs spec“ and take the air as fre weather permitted. ' Results.—Of the pellagrins admitted to the writers’ wards at the time of their organization, or shortly thereafter—that is, not later thanDecember 31, 1914—72 (36 colored and 36 white), have remained contmuously under observation up to October 1, 1915, or remained at least until after the anniversary date of their last year’s attack. Of the 36 colored patients, 8 have histories of at least 2 annual attacks; of the 36 white patients, 10 have histories of at least 2 attacks. None of this group of 72 patients has presented recognizable evrdence of a recurrence of pellagra. quently as their physical condition and the 38 Human Experiments Significance The significance of the results set forth naturally depends upon the rate of recurrence that may properly have been expected to.occur in the groups studied under “normal” conditions; that 15, Without interference of any kind. The ideal form of the experiment would have been, of course, to retain for purpose of comparison a control group at each of the 1n_st1- tutions. This was impracticable at the orphanages. In estlmatmg the significance of the results of the orphanage study, the writers are therefore obliged to depend on general observations and on expen- ence at other similar institutions. Satisfactory observations on the rate of recurrence either in children or adults are, so far as the writers are aware, not available in the accessible literature. There are to be found for the most part simply general statements that the disease tends as a rule to recur from year to year. Fortunately, Dr. H. W. Rice, of Columbia, S. C., has very kindly given a copy of his records of the cases of pellagra observed by him in children at an orphanage to which he has been attending physician. These records show that of 31 children who had pellagra in 1912, 18, or 58 per cent, had recur- rences in 1913; of the 21 who had it in 1913,, 16, or 76 per cent, had it in 1914; and of 75 who had the disease in 1914, 56, or 75 per cent, had it again in 1915. The rate of recurrence in children at this instr- tution seems to have varied, therefore, between 58 per cent and 76 per cent. These very valuable data enable one to form a definite conception of the frequency of recurrence that one m1ght expect from year to year in children at such institutions as those at wh1ch the writers have worked. Taking 50 per cent, a rate somewhat lower than the lowest of the above rates, as being fairly and conservatively representative and applying it to the orphanages at Jackson, it is found that 33 recur- rences at "M. J.” and 52 at “B. J." might reasonably have been expected this year, whereas, as already stated, there actually was none observed at the former and only one at the latter institution. Although not specifically so planned, conditions at the Georgia State Sanitarium have been such as to give a control group of pella- grins in both the colored and the white female service. This permits the making of a direct comparison of the results observed in the writers’ wards with those in other wards of the corresponding services at this institution. The control group of colored female pellagrins of 1914 consists of 17 who have remained under observation for a period comparable to The Prevention of Pellagra 39 that of the group on the special diet. Of these, 9, or 53 per cent, have already presented recurrences. The control group of white female pellagrins of 1914 consists of 15 individuals. Of these, 6, or 40 per cent, have had recurrences this year. Combined, the two control groups have thus far presented an average of 47 per cent of recurrences. Besides the recurrence rates in these control groups, the rates of recurrence in previous years in these services have been determined from a study of the records. It is found that in the colored female service the average rate for the four years 1911, 1912, 1913, and 1914 has been 52.5 per cent, the rate in different years having varied from 40 to 70 per cent. In the white female service the average recurrence rate for the same period has been 37.5 per cent, the rate having varied between 22 and 48 per cent. It must be quite evident, therefore, that on the basis of any of the foregoing rates a considerable number of recurrences in the groups of insane pellagrins subsisting on the modified diet might reasonably have been expected. On the basis of the average recurrence rate, 47 per cent, observed this year in the control groups, we might have expected some 34 recurrences, or on the basis of the average rate, 37.5 per cent, for four years, for the white female service, a rate lower than the average for the colored female service, we might have expected some 20 to 27 recurrences. As already stated, however, none has actually been observed. Viewing the foregoing results as a whole, bearing in mind that three different institutions in two widely separated localities are involved, each institution being an endemic focus of the disease, and bearing in mind, also, that the number of individuals considered is fairly large, it seems to the writers that the conclusion is justified that pellagra recurrences may be prevented and, in view of the con- ditions of the test, that they may be prevented without the interven- tion of any other factor than diet. In this connection the question arises whether the conclusion is justified that the development of pellagra, apart from its recurrence, may be prevented by diet. The character of the answer to the question will depend on the view held as to the nature of the pellagra recur- rence. Among the epidemiologic features of pellagra none is more striking than the tendency for the disease not only to develop in the spring or early summer, but to recur year after year at about the same sea- son. Various explanations of this singular phenomenon have been advanced. According to Sambon (1910, p. 49), “this peculiar peri- 4° Human Experiments odicity of symptoms can be explained only by the agency of a para- sitic organism presenting definite alternating periods of latency and activity." A somewhat similar conception appears to be held by the workers of the Thompson-McFadden Commission (Siler, Garrison, and MacNeal, Oct. 15, 1914), who distinguish between conditions favorable for the development of the disease, in the first place, and those that permit its subsequent recurrence. Why Sambon and many other observers should consider this periodicity of symptoms as explicable only by the agency of a parasitic organism or of a Virus or a toxin presenting definite alternating periods of latency and activity is rather hard to understand when it is recalled that in endemic scurvy (Lind, 1772, pp. 33, 84, 130, 306) and particularly in endemic beriberi, diseases of well-known dietary origin, a strikingly similar periodicity is present. The following description of the clini- cal course of beriberi taken from Scheube (1903, pp. 19972oo) well illustrates this point: “After developing the disease" [beriberi], says Scheube, “the condition of the patient may remain the same for months. Then, especially on the appearance of thecold'season, im- provement sets in and recovery ensues. The predisposmon is not extinguished by recovery from the disease; on the other hand, he who has once had beriberi is apt to be attacked again. The relapses are sometimes milder, sometimes more severe than the initial attack, and are repeated every year for shorter or longer periods, sometimes, 10, 20, or even 30 years. Sometimes the disease remains absent for one or several years, and then appears anew, Occasionally two or even three attacks occur during the course of one year." In the light of this striking analogy, it would seem entirely per- missible to invoke as an explanation of the periodic recurrence in pellagra, what undoubtedly is the explanation of the same phenom- enon in beriberi, namely, a modification or change in diet brought about by or incidental to the recurring seasons (Vedder, 1913, p.29). In accordance with this explanation the recurrence in pellagra is to be considered as in beriberi, etiologically, at least, essentially identi- cal with the initial attack; it would seem permissible to conclude, therefore, that the means found effective in the prevention of recur- rences will be found effective in the prevention of the initial attack. From the foregoing it will be observed that the writers' results are at variance with those of some other recent workers in this field, notably, the Thompson-McFadden Pellagra Commission. In a sum- mary of their second progress report (Siler, Garrison, and MacNeal, Sept. 26, 1914, p. 1093) this commission concludes that its efforts to discover the essential pellagra-producing food or the essential The Prevention of Pellagra 41 pellagra-preventing food have not been crowned with success, and that their evidence suggests that neither exists in the population studied by them. In the opinion of the writers this conclusion is due to the way in which they analyzed what is undoubtedly a very valuable mass of data. They assume that the relation of a particular food to pellagra can be determined by comparing the incidence of the disease in groups of families using this particular food with different degrees of frequency. This assumption, however, fails to take into account the possibility that more than one food having a relation to the disease may have been present in the dietaries of the families studied. Thus it seemed to them, and at first thought it no doubt would seem to others, that if meat, for instance, had any relation to pellagra, this would be revealed by a comparison of the incidence of the dis- ease in a group of families using this food daily with the incidence in a group using it rarely. As a matter of fact, however, although a comparison of the incidence of pellagra in different families grouped on the basis of the frequency of the use of fresh meat might result, let us say, in finding a greater relative incidence in families using it daily than in those using it rarely, it would not on that account be permissible to conclude that meat had no preventive value, for it may very well be that the families using meat rarely were protected by some other food or foods, such as milk, eggs, or peas, of which they may have been abundant consumers. In fact, it is believed by the writers that an analysis of the com- mission’s data from this point of view will show, for instance, that there does exist, or may exist, in a group of cotton-mill villages an inverse proportional relation betWeen degree of pellagra morbidity and the percentage of families using fresh meat and milk “daily” and “habitually.” In other words, the disagreement in our results from those of the commission is more apparent than real. It is beside the present purpose to enter into a discussion of the etiology of pellagra. In order that the position of the writers may be clear, however, it is pointed out that they are not to be under- stood as meaning that pellagra is necessarily due to a lack or defi- ciency of fresh animal or leguminous protein food. All that they wish to say at present is that the dietary "fault" upon which in their judgment the development of pellagra essentially depends is capable of being corrected or prevented by including in the diet a suitable proportion of these foods. Nor are they to be understood as meaning that the pellagra-causing “fault” is capable of correction or preven- tion in this way only. The possibility is not excluded that there may 42 Human Experiments be other foods capable of serving the same purpose. Indeed, there is some reason to justify at least a suspicion that barley, rye, and millet may have this power in some degree. Moreover, it may be, if Funk's suggestion that pellagra is a vita- min deficiency, brought about by the consumption of overmilled corn, is proven to be correct, that the use of undermilled corn will of itself correct the "fault" in a diet in which this cereal is the staple. For the present at least the point of chief. of fundamental, practical importance is the recognition of the fact that the pellagra-producing dietary “fault,” whatever its essential nature or however brought about, is capable of correction or prevention, as the results above presented seem to clearly indicate, by including in the diet suitable proportions of the fresh animal and leguminous foods. Summary and Conclusion 1. The diet at two orphanages, “M. J." and “B. J.,” for several years endemic foci of pellagra, was modified in accordance with the directions of the writers in September, 1914. Hygienic and sanitary conditions have remained unchanged. 2. The modification in the diet consisted principally of a marked increase in the fresh animal and the leguminous protein foods. 3. Since the change in diet at orphanage "M. J.” there has not been observed any recognizable evidence of a recurrence in any of the pellagrins of 1914, 67 of whom remained under observation until they had completed at least the anniversary date of their attacks. Nor have any new cases been observed among the nonpellagrin resi- dents of 1914, 99 of whom have been under observation for not less than a year. 4. Since the change in diet at orphanage “B. J.” there has been observed this year but a single individual with recognizable evidence of a recurrence among the pellagrins of 1914, 105 of whom remained under observation until they had completed at least the anniversary date of their attacks. Nor has any new case been observed among the nonpellagrin residents, 69 of whom have been under observation not less than a year. 5. At the Georgia State Sanitarium, an endemic focus of pellagra, a ward of pellagrins in the colored female service and one in the white female service was organized in October and December, 1914, respectively, for a test of diet in the prevention of pellagra, 6. The diet in these wards was modified on the same principle as that at the orphanages. The institution routine and the hygienic and sanitary conditions have remained unchanged. The Prevention of Pellagra 43 7. Since the change of diet and up to October 1, 1915, there has not been observed this year any recognizable evid _ . . ence of a re in anylof the pellagrins in these wards, 72 of whom (36 coloileldrzlifd 36 white females) have remained continuously under observation throughout this period or at least unt' ' _ 11 the corn lemon 0 ' versary date of their 1914 attacks. P f the amn- 8. During the corresponding period of observation not less than 15 (47 per Cent of 2 cont 1 - recurrences. ) 3 r0 female pellagrins have presented 9. The conclusion is drawn that appropriate diet without any altera or sanitary. pellagra may be prevented by an tion in the environment, hygienic Application The practical application of the foreg ' ‘ I oing to the problem of the prevention and erad1cation of pellagra seems so obvious that ex- tended discussmn is not called for in the present communication I particularly as a somewhat detailed outline of treatm _ I ent d - tion has already been published (Goldberger, Willets, 31:11:! 1914). At this time it is desired simply to submit for consideration In order that a suitable modification in the diet of the population chiefly affected may be brought about, the writer would recommend' I. An increase in the diet of fresh animal and l ' a v e particularly during the late winter and spring. gumlmms feeds, a. Ownership of a milk cow and increase in milk production for home consumption. 1:. Poultry and egg raising for home consumption c. Stock raising. . d. Diversification and the cultivation an adequate pea patch) in order t economic effects of a crop failure and more readily available. 6. Making these foods as accessible as possible in the more or less isolated industrial communities of food crops (including o minimize the disastrous and to make food cheaper 44 Human Experiments References Funk, C. Die Vitamine (Wiesbaden, 1914). _ _ . . “Prophylaxie und Therapie der Pellagra ins Lichte der Vitamin- lehre,” Munch. Med. Wchnschr. (1914), pp 698—199. f t In epi .oldber er, . “The Etiolo of Pellagra; t e signi cance o cer a1 - C demiogogiciil observationsgywith respect thereto,” Public Health Rep. (Washington, DC), June 26, 1914, pp. 1683—86. . . . “The Cause and Prevention of Pellagra,” zbzd. (September 11, 1914l.“Beans for Prevention of Pellagra,” I. Am. Med. Assn. Vol. 65 October 10, 1 1 , .1 1 . Gdldberger, J., Waging, ii, and Willets, D. G. "The Treatment and Prevention of Pellagra,” Public Health Rep. (Washington, DC), Octo- ber2,1 1 , .2821—2. .SRefin‘inFIl‘lo. 228 5from Public Health Rep. (Washington, D.C.), October 23, 1914. . . Reprint No. 228 from Public Health Rep. (Washington, DC), October 23, 1914; revised edition (January 15, 1915). Lind, A Treatise on the Scurvy (3d ed.; London, 1772). Lorenz, W. F. “The Treatment of Pellagra," Public Health Rep. (Wash- ington, D.C.), September 11, 1914. ‘ Lyttle, Y. A. “The Dietetic Treatment of Pellagra. With report of eleven cases,” Southern Med. ]. Vol. 8 (August, 1915), pp. ~65,9«62. Roussel, T. Traite' de la Pellagra et des Pseudo-Pellagres (Paris, 1866). ‘ Sambon, L. W. “Progress Report on the Investigation of Pellagra," Reprint from the J. Trop. Med. and Hyg. (London, 1910). Scheube, B. The Diseases of Warm Countries (London, 1903). Siler, J. F., Garrison, P. E., and MacNeal, W. J. “A Statistical Study of the Relation of Pellagra to Use of Certain Foods, etc.” Arch. Int. Med. (Chicago), Vol. 14 (September 15, 1914), pp. 292-373. I . “Further Studies of the Thompson-McFadden Pellagra Commis- sion. A summary of the second progress report," I. Am. Med. Assn. (Chicago), Vol. 63 (September 26, 1914), pp. 1090—93. . “The Relation of Methods of Disposal of Sewage to the Spread of Pellagra,” Arch. Int. Med, Vol. 14 (October 15, 1914), pp. 453-74. Vedder, E. B. Beriberi (New York, 1913). 4. Pellagra Prevention by Diet Among Institutional I nmates1 JOSEPH GOLDBERGER C. H. WARING W. F. TANNER’ In 1914, when the study herein reported was begun, American opinion as to the etiology and prophylaxis of pellagra may be said to have been very unsettled, if not chaotic. The spoiled-maize theory of the cause and as the basis for prevention, though stoutly held in some important quarters, was declining in favor; and the belief that the disease was an infection of some kind, supported as it was by such important studies as those of the Illinois and of the Thompson- McFadden pellagra commissions (Report of the Pellagra Commis- sion, 1912; Siler, Garrison, and MacNeal, 1914), was gaining a ready and rapidly widening acceptance. The state of mind, both lay and professional, is well indicated by the following from Lavinder (1909, pp. 1617-24) even though written five years earlier: There are several very good reasons just now why this question of com- municability should have arisen to much importance in this country. . . . In the first place, the disease has arisen and grown to large proportions, apparently like the proverbial mushroom, almost in a single night. It is something new, a malady with which we are not familiar, and in some of its manifestations is repulsive, if not actually loathsome; indeed, some of the older writers, evidently struck with this fact, applied to it the name “leprosy,” a term which, since the days of Moses, has been a synonym to mankind of all that is repulsive and loathsome in human disease. Then, too, it has been associated in our minds very frequently with mental aliena- tion, a state naturally abhorrent to all; and its reported death rate has been vety large indeed. Furthermore, the indefinite and pervasive character of its etiology, with the lack, not only of any specific treatment, but the apparent inefficacy of all treatment, has added further color to an already vivid picture. 1 Public Health Rep., Vol. 38, No. 41 (October 12, 1923), 2361—68. 2 During the first two years of the study at the Georgia State Sanitarium, Dr. David G. Willets, late assistant epidemiologist, United States Public Health Service, was associated with us. His premature separation was unhappin made necessary by the development in December, 1916, of what proved to be a fatal illness. 45 ...
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Goldberger1 - 1. The Etiology of Pellagra. The...

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