I need answers to the following 16 questions in the CDCcase study. Thank you.

Centers for Disease Control and Prevention Epidemiology Program Office Case Studies in Applied Epidemiology No. 471-600 An Epidemic Disease in South Carolina Student's Guide Learning Objectives After completing this case study, the participant should be able to: 1. Apply the principles of descriptive epidemiology (time, place, person) in the investigation of a disease outbreak; 2. Characterize the epidemiology of a disease with appropriate tables, graphs, and charts, and generate hypotheses related to etiology. This case study was written by Alexander Langmuir in 1947. Current version was updated by Richard Dicker in 2000 with review and suggestions from the EIS Summer Course instructors. Note to Participants One purpose of this case study is to demonstrate how much can be learned about a disease simply by looking at its descriptive epidemiology. Therefore, the identity of the disease and its clinical features have been intentionally withheld. If you are familiar with this epidemic from previous courses or reading, please do not reveal the identity or etiology of this disease to your colleagues. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service CDC / EIS Summer Course 2000: Epidemic Disease in S.C. - Student's Guide Page 3 PART I Over a period of years, physicians in the rural southeastern United States reported the occurrence of a disease that had not been recognized previously. Since reporting was required in only one state, and since medical services were limited, recording of the incidence of this disease was irregular. The disease in question, although easily diagnosed on clinical grounds, was of unknown etiology at the time. Pathogenesis, mode of spread, immunity, and the role of social and environmental factors were matters of controversy. Many theories concerning the nature of the disease were proposed. Question 1: In an effort to determine the extent of the disease, a questionnaire was mailed to all practicing physicians in eight states in the Southeast regarding the number of cases they had seen in the preceding 5 years. Only one-fourth of the physicians responded. They reported an increase from 622 to 7,017 cases over the 5-year interval. The following year, a U.S. Public Health Service epidemiologist was assigned to investigate the epidemic. After some preliminary observations, a field survey was conducted to determine the extent and the nature of the disease. Into what general etiologic categories might one divide diseases that can occur in epidemic form? The survey was conducted in a five-county region in northwestern South Carolina where the disease was prevalent. The survey area included 24 mill towns with populations from 500 to 1,500. These villages varied widely in their sanitary status. Some had public water supplies, some had sewage systems, some had both, and some had neither. The survey focused on families of a single racial group. Question 2: In each village, biweekly visits were made to each household over a period of 1 year to look for cases. The name, age, gender, and marital status of each member were recorded. The occurrence of the disease was determined by history and examination. Questionable cases were referred to one of the directors of the study who had considerable experience in diagnosing the disease. What categories of information would you want in order to characterize the epidemic? Table 1. Cases of The Disease by Month of Onset in 24 Villages Surveyed for One Year (Total Population = 22,653) Month January February March April May June July August September October November December * Number of cases 0 4 28 120 310 432 154 57 28 14 0 0 Adjusted to 31-day month. Note: In individual villages, incidence peaked in different months. Question 3a: Review and graph the data in Table 1. Rate per 1000* 0 0.2 1.2 5.5 13.7 19.7 6.8 2.5 1.3 0.6 0 0 Table 2. Incidence of The Disease by Age and Gender in 24 Villages Surveyed for One Year Males Age group (years) 70 200 164 106 80 5 9 4 6 25.0 53.6 37.7 75.0 228 153 105 114 6 3 2 2 26.3 19.6 19.1 17.5 10,812 483 44.7 11,238 664 59.1 Total * As enumerated between May 1 and July 15. Question 3b: Review and graph the data in Table 2. Question 4: Discuss the epidemiologic characteristics of the disease illustrated in your graphs. Table 3. Incidence of The Disease Among Women by Marital Status and by Age Married women Age group (years) Population Single women # Cases Cases per 1,000 pop. Population # Cases Cases per 1,000 pop. 16-29 1,905 89 46.7 1,487 16 10.7 30-49 1,684 98 58.2 141 4 28.4 50+ 387 4 10.3 26 0 0 Total 3,976 191 48.0 1,654 20 12.1 Question 5: Using the data in Table 3 , compare the rates of disease between married and single women. Table 4. Incidence of The Disease by Occupation, Age, and Gender Gender Mill worker? Age group (years) Ill Well Total Attack rate (%) Female Yes 55 0 2 4 2 0 0 0 330 194 93 9 5 0 332 198 95 9 5 0.6 2.0 2.1 0 0 Female No 55 28 5 12 16 4 1 577 200 204 220 91 92 605 205 216 236 95 93 4.6 2.4 5.6 6.8 4.2 1.1 Male Yes 55 0 3 1 3 0 1 0 355 361 318 93 51 0 358 362 321 93 52 0.8 0.3 0.9 0 1.9 Male No 55 23 4 1 0 1 4 629 161 12 10 14 26 652 165 13 10 15 30 3.5 2.4 7.7 0 6.7 13.3 Question 6: Using Table 4, calculate the overall attack rates for: a. Mill workers and non-mill workers (regardless of gender). b. Female mill and non-mill workers. c. Male mill and non-mill workers. Table 5. Population and Number of Households Affected by The Disease Over a 9-Month Period in 7 South Carolina Villages Total population Population in affected households Population in unaffected households 4,399 424 3,975 Total number of cases Number of first cases in affected households Number of additional cases in affected households (subsequent cases in a household after the first case) 115 77 38 Total number of households 798 Question 7a: Based on the data in Table 5, what is the overall attack rate for the disease in the community? Question 7b: What proportion of households are affected with the disease in the community? Question 7c: What is the risk that other individuals in a household that already has a case will also have the disease? Question 7d: What are the average household sizes for affected and for unaffected households? Question 7e: Interpret the above results. Table 6. Incidence of The Disease by Economic Status in 24 Villages* Surveyed for 1 Year Family socioeconomic status Stratum Stratum Stratum Stratum Stratum Stratum Stratum Total 1 (lowest) 2 3 4 5 6 7 (highest) Rate per 1,000 Cases Population 99 240 260 177 132 23 2 796 2,888 4,868 5,035 5,549 1,832 769 124.4 83.1 53.4 35.2 23.8 12.6 2.6 933 21,737 42.9 * Restricted to cases developing after 30 days of residence. Question 8a: Using the data in Table 6, describe the effect of socioeconomic status, if any, on the disease. Question 8b: In general, what factors related to low socioeconomic status might influence the occurrence of disease? The investigators also conducted sanitary surveys. Each village, as a unit, was rated for quality of general cleanliness, excreta disposal, and water supply. The figure below shows a scatter Question 9: diagram of incidence of disease and sanitary rating for 24 villages. (On scatter diagram, high sanitary rating means good sanitation.) Discuss the relationship between incidence of the disease and the sanitary rating. Question 10: Summarize the important epidemiologic characteristics of the disease determined at this point. In 1856, John Stuart Mills laid out a series of canons of inductive reasoning. Among them are: The Method of Difference - If two populations are similar except for one factor, then differences in disease may be hypothesized to be the result of the one difference. The Method of Agreement - If a number of populations share a common exposure to a factor, then occurrence of disease in all of these populations may be hypothesized to be the result of the common factor. The Method of Concomitant Variation - If amount of exposure and amount of disease vary proportionally, then disease may be hypothesized to be the result of the exposure (basically, dose-response or ecologic correlation). The Method of Residues - If exposures can be removed or abated, then the factor that is associated with the greatest reduction in disease may be hypothesized to be a causal factor. The Method of Analogy If the symptoms and mode of transmission of an unknown disease resemble those of a known disease, the causal factor(s) may be hypothesized to be similar. Question 11: Using the information you have about Disease X or another newly identified disease, give an example of each canon. Two different commissions studied the evidence related to this disease. The first commission ended its investigation with these conclusions: "(1) According to the weight of evidence (the) disease (is) due to infection with a living micro-organism of unknown nature; (2) A possible location for this infection is the intestinal tract; and (3) Deficient animal protein in the diet may constitute a predisposing factor in the contraction of the disease." Two years later, the second commission concluded that: "(1) The supposition that the ingestion of good or spoiled maize is the essential cause of (the disease) is not supported by our study; and (2) (The disease) is in all probability a specific infectious disease communicable from person to person by means at present unknown." A year later, the commission presented the following at the annual meeting of the American Medical Association: "In the group of incident cases most thoroughly studied, evidence of close association with a preexisting case was disclosed in more than 80 per cent. "A house-to-house canvass of the homes of over 5,000 people living in six endemic foci of (the disease) failed to disclose any definite relation of the disease to any element of the diet. "In these six villages new cases originated almost exclusively in a house in which a preexisting case was living, or next door to such a house, suggesting that the disease has spread from old cases as centers." Question 12: For each of the epidemiologic characteristics of time, place, and person, which etiologic hypothesis (infectious vs. dietary) is more compatible with the data? Question 13: How might you test the infectious or dietary hypothesis about the cause of the disease? PART II Many people postulated that an infectious agent was responsible for the disease. The epidemiologist carried out transmissibility studies that were described as follows: [The investigator] drew blood into a clean sterile syringe from the arm of a woman who was broken out and very sick with her first attack of [the disease] ... [He] shot a sixth of an ounce of the blood, still warm from the veins of the sick woman, under the skin of [his assistant's] left shoulder. [Then the assistant] shot a fifth of an ounce of the blood of the sick woman under the shoulder of [the investigator]. For two days the arms of these adventurers were stiff ... That was all. But [the investigator] was a glutton for proofs ... The [government] commission has said that [the disease] spread like typhoid fever, from the bowels of the suffering ones. On the 26th of April ... alone, he faced it... Here he stands, alone in this most grotesque of laboratories--the washroom of a Pullman car. Out of his pocket he takes a little vial. Into a pill mass with wheaten flour he makes up the Question 14: contents of this tube--the intestinal discharge of a woman very sick with a true case of [the disease]. He swallows this dose. "And maybe the scales of the skin rash are contagious, too," says [the investigator], who is a thorough man. So for good measure he makes himself a powder from flour and the scaled-off skin from two more people sick with [the disease]. He swallows this powder...[1] Using feces, urine, vomitus, and skin scales from patients, the investigator carried out additional similar experiments, called "filth parties," on himself and volunteers, including his wife and assistants. None of them came down with the disease. In studies at mental institutions and orphanages where the disease was rampant, the investigator observed that none of the nurses or other ward personnel, even those attendants who lived on the ward, came down with the disease. The investigator was convinced that this disease was not an infectious disease. Do you agree with the investigator? Why or why not? PART III To investigate the possible role of diet, the investigators did a survey of all households in seven villages to compare the average daily consumption of various foodstuffs. Table 8 shows the consumption pattern for four foods by presence or absence of the disease in these households. Table 8. Consumption patterns of various foods by presence or absence of disease in the households in seven villages Disease Present Question 15: Disease Absent Total Fresh meat high quantity low quantity TOTAL 9 52 61 208 472 680 217 524 741 Fresh milk high quantity low quantity TOTAL 6 50 56 275 396 671 281 446 727 Salt pork high quantity low quantity TOTAL 29 29 58 289 391 680 318 420 738 Syrup high quantity low quantity TOTAL 18 40 58 231 451 682 249 491 740 How would you analyze the data presented in Table 8? Question 16: Analyze the data in Table 8. Question 17: Interpret these results. PART IV - CONCLUSION The disease under investigation was pellagra. Pellagra was virtually unknown in the United States until 1907, although sporadic deaths were reported in 1889 and 1902. The first epidemic of pellagra occurred at the Mount Vernon (Alabama) Asylum for Negroes in 1906, with 85 cases and 53 deaths. Although pellagra was thought to be most prevalent in Georgia, North Carolina, South Carolina, Florida, Alabama, Mississippi, and Louisiana, these states did not participate in national mortality registration. Nonetheless, the number of reported deaths from participating states rose from none in 1904 to 1,015 in 1913. Dr. Joseph Goldberger was requested by the Surgeon General to investigate the pellagra problem in March 1914. At that time the Italians championed the hypothesis that the disease was caused by spoiled corn, while the Americans were convinced it was an infectious disease. Three observations made Goldberger suspect a nutritional disease: 1. Although the disease was endemic in asylums, attendants and professionals had never contracted a single case. 2. The disease was almost exclusively confined to the poor. 3. The disease was most common in rural areas. In June 1914, Goldberger published his first report on his observations at the asylum in Milledgeville, Georgia, noting that professionals and attendants did not get pellagra. He noted significant dietary differences in the habits of the patients and non-patients, especially with regard to consumption of meat and milk. In 1915, Goldberger instituted an enriched feeding program in two Mississippi orphanages that had a pellagra prevalence of 47%. As a result, no cases of pellagra occurred the following year among 103 patients. Also in 1915, Goldberger visited the Rankin State Penitentiary in Mississippi where no case of pellagra had ever been reported. He induced pellagra after 5 months among six out of 11 inmates by placing them on a diet containing no meat, milk, or fresh vegetables. In 1916, Goldberger began trials of pellagra transmission. Using himself, his wife, and 12 other volunteers, he injected blood from pellagrous patients into healthy people. He also consumed a mixture of feces, urine, vomitus, and skin scales from pellagrous patients. Neither he nor the other subjects developed pellagra. Later that year, he initiated his South Carolina mill-town study-- first in seven villages, later in 24 villages. From 1918 to 1926, Goldberger conducted studies to find pellagra-preventing (P-P) factor. He initially focused on amino acids. Tryptophan was shown to have some effect in preventing pellagra. He found that dried yeast had highest P-P activity. P-P appeared to be a watersoluble, heat-resistant substance, possibly a new B vitamin. Goldberger died in 1929. Eight years later, Elvehjem determined that the missing element in pellagrins' diets was niacin, a B vitamin, of which tryptophan is a precursor. Economic hypothesis concerning appearance of pellagra in United States In the early 1900s, many families in the rural South migrated from farms to small mill villages, and became dependent on wage earnings as a source of income. During the period 1900-1913, wages increased by less than 25%. During the economic depression from 1906-1911, wages actually decreased. At the same time, food prices increased dramatically. Average food prices increased Worldwide, sporadic cases of pellagra continue to occur in Egypt, India, and eastern and southern Africa, but epidemics have been 50% from 1900 to 1913. These price increases, coupled with a decrease in locally available food as wage earners left the farm, made certain foods difficult to obtain. In the United States, pellagra presented a significant public health problem as late as 1940 when 2,138 deaths were recorded. uncommon since World War II. However, a large outbreak of pellagra occurred among Mozambican refugees in southern Malawi in 1990. Among 286,000 refugees in 11 sites, 17,878 cases of pellagra were reported between February 1 and October 30, 1990 [2]. This outbreak was attributed to a disruption of supplies of groundnuts, an important source of niacin. Suggested Reading Schultz MG. Joseph Goldberger and pellagra. Am J Trop Med Hyg 1977;26(5):1088-92. References -- Goldberger J, et al.. A study of the endemic pellagra in some cotton-mill villages of South Carolina. Bull Hygienic Lab 1929;153;1-85. 1. DeKruif P. Hunger fighters. New York: Harcourt, Brace & Co. 1928:335-70. 2. CDC. Outbreak of pellagra among Mozambican refugees--Malawi, 1990. MMWR 1991;40(13):209213. Table 9. Factors accounting for the observed epidemiologic characteristics of The Disease (pellagra) Observed epidemiologic characteristic Explanation TIME Seasonal variation Summer peak Disease identified by rash; sunlight exacerbated rash (possible explanation). PERSON Age and gender distribution No case-patients 50 years of age Unlikely to get supplemental food since no longer working. Marital status Married women at increased risk Marriage, child-bearing (see above). Socioeconomic status Incidence inversely related to socioeconomic status Protective foods more expensive. Occupation Increased incidence among non-mill workers Mills provided supplemental food. PLACE Affected households Increased incidence among household members of a casepatient Similar diets