Jekel’s_Epidemiology,_Biostatistics,_Preventive_Medicine,_and_Public-19-30.pdf

Basic Epidemiologic Concepts 1 and Principles CHAPTER OUTLINE the data are reviewed in the Biostatistics section, Chapters 8 I. WHAT IS EPIDE...

Basic Epidemiologic Concepts 1 and Principles CHAPTER OUTLINE the data are reviewed in the Biostatistics section, Chapters 8 I. WHAT IS EPIDEMIOLOGY?â ‡ 3 to 13. The scientific study of disease can be approached at the II. ETIOLOGY AND NATURAL HISTORY OF DISEASEâ ‡ 4 following four levels: A. Stages of Diseaseâ ‡ 4 B. Mechanisms and Causes of Diseaseâ ‡ 4 1. Submolecular or molecular level (e.g., cell biology, genet- C. Host, Agent, Environment, and Vectorâ ‡ 4 ics, biochemistry, and immunology) D. Risk Factors and Preventable Causesâ ‡ 5 2. Tissue or organ level (e.g., anatomic pathology) 1. BEINGS Modelâ ‡ 5 3. Level of individual patients (e.g., clinical medicine) III. ECOLOGICAL ISSUES IN EPIDEMIOLOGYâ ‡ 8 4. Level of populations (e.g., epidemiology). A. Solution of Public Health Problems and Unintended Creation of Perspectives gained from these four levels are related, so New Problemsâ ‡ 8 the scientific understanding of disease can be maximized by 1. Vaccination and Patterns of Immunityâ ‡ 8 coordinating research among the various disciplines. 2.â ‡ Effects of Sanitationâ ‡ 10 Some people distinguish between classical epidemiology 3. Vector Control and Land Use Patternsâ ‡ 11 and clinical epidemiology. Classical epidemiology, which is 4. River Dam Construction and Patterns of Diseaseâ ‡ 11 population oriented, studies the community origins of B. Synergism of Factors Predisposing to Diseaseâ ‡ 11 health problems, particularly those related to infectious IV. CONTRIBUTIONS OF EPIDEMIOLOGISTSâ ‡ 11 agents; nutrition; the environment; human behavior; and A. Investigating Epidemics and New Diseasesâ ‡ 11 the psychological, social, economic, and spiritual state of a B. Studying the Biologic Spectrum of Diseaseâ ‡ 12 population. Classical epidemiologists are interested in dis- C. Surveillance of Community Health Interventionsâ ‡ 12 covering risk factors that might be altered in a population to D. Setting Disease Control Prioritiesâ ‡ 13 prevent or delay disease, injury, and death. E. Improving Diagnosis, Treatment, and Prognosis of Clinical Investigators involved in clinical epidemiology often use Diseaseâ ‡ 13 research designs and statistical tools similar to those used by F. Improving Health Services Researchâ ‡ 14 classical epidemiologists. However, clinical epidemiologists G. Providing Expert Testimony in Courts of Lawâ ‡ 14 study patients in health care settings rather than in the com- V. SUMMARYâ ‡ 14 munity at large. Their goal is to improve the prevention, early detection, diagnosis, treatment, prognosis, and care of REVIEW QUESTIONS, ANSWERS, AND EXPLANATIONSâ ‡ illness in individual patients who are at risk for, or already affected by, specific diseases.1 Many illustrations from classical epidemiology concern infectious diseases, because these were the original impetus I.â ‡ WHAT IS EPIDEMIOLOGY? for the development of epidemiology and have often been its focus. Nevertheless, classical methods of surveillance and Epidemiology is usually defined as the study of factors that outbreak investigation remain relevant even for such con- determine the occurrence and distribution of disease in a temporary concerns as bioterrorism, undergoing modifica- population. As a scientific term, epidemiology was intro- tion as they are marshaled against new challenges. One duced in the 19th century, derived from three Greek roots: example of such an adapted approach is syndromic epide- epi, meaning “upon”; demos, “people” or “population”; and miology, in which epidemiologists look for patterns of logos, “discussion” or “study.” Epidemiology deals with much signs and symptoms that might indicate an origin in more than the study of epidemics, in which a disease spreads bioterrorism. quickly or extensively, leading to more cases than normally Epidemiology can also be divided into infectious disease seen. epidemiology and chronic disease epidemiology. Histori- Epidemiology can best be understood as the basic science cally, infectious disease epidemiology has depended more of public health. It provides methods to study disease, injury, heavily on laboratory support (especially microbiology and and clinical practice. Whereas health care practitioners serology), whereas chronic disease epidemiology has collect data on a single patient, epidemiologists collect data depended on complex sampling and statistical methods. on an entire population. The scientific methods used to However, this distinction is becoming less significant with collect such data are described in the Epidemiology section the increasing use of molecular laboratory markers (genetic of this text, Chapters 1 to 7, and the methods used to analyze and other) in chronic disease epidemiology and complex 3 4 S e c t i o nâ … 1â … Epidemiology statistical analyses in infectious disease epidemiology. Many skin. However, irradiated ergosterol is an important source illnesses, including tuberculosis and acquired immunodefi- of D vitamins, which are necessary for growth. If a woman’s ciency syndrome (AIDS), may be regarded as both infectious diet is also deficient in vitamin D during the rapid growth and chronic. period of puberty, she may develop osteomalacia as a result The name of a given medical discipline indicates both a of insufficient calcium absorption. Osteomalacia can method of research into health and disease and the body of adversely affect future pregnancies by causing the pelvis to knowledge acquired by using that method. Pathology is a become distorted (more pear shaped), making the pelvic field of medical research with its own goals and methods, opening too small for the fetus to pass through. In this but investigators and clinicians also speak of the “pathology example, the social, nutritional, and environmental causes set of lung cancer.” Similarly, epidemiology refers to a field of in motion the biochemical and other biologic mechanisms of research that uses particular methods, but it can also be used osteomalacia, which may ultimately lead to maternal and to denote the resulting body of knowledge about the distri- infant mortality. bution and natural history of diseases—that is, the nutri- Likewise, excessive fat intake, smoking, and lack of exer- tional, behavioral, environmental, and genetic sources of cise are behavioral factors that contribute to the biologic disease as identified through epidemiologic studies. mechanisms of atherogenesis, such as elevated blood levels of low-density lipoprotein (LDL) cholesterol or reduced blood levels of high-density lipoprotein (HDL) cholesterol. These behavioral risk factors may have different effects, depending II.â ‡ ETIOLOGY AND NATURAL HISTORY on the genetic pattern of each individual and the interaction OF DISEASE of genes with the environment and other risk factors. Epidemiologists attempt to go as far back as possible to The term etiology is defined as the cause or origin of a discover the social and behavioral causes of disease, which disease or abnormal condition. The way a disease progresses offer clues to methods of prevention. Hypotheses introduced in the absence of medical or public health intervention is by epidemiologists frequently guide laboratory scientists as often called the natural history of the disease. Public health they seek biologic mechanisms of disease, which may suggest and medical personnel take advantage of available knowl- methods of treatment. edge about the stages, mechanisms, and causes of disease to determine how and when to intervene. The goal of interven- C.â ‡ Host, Agent, Environment, and Vector tion, whether preventive or therapeutic, is to alter the natural history of a disease in a favorable way. The causes of a disease are often considered in terms of a triad of factors: the host, the agent, and the environment. For A.â ‡ Stages of Disease many diseases, it is also useful to add a fourth factor, the vector (Fig. 1-1). In measles, the host is a human who is The development and expression of a disease occur over susceptible to measles infection, the agent is a highly infec- time and can be divided into three stages: predisease, latent, tious virus that can produce serious disease in humans, and and symptomatic. During the predisease stage, before the the environment is a population of unvaccinated individuals, disease process begins, early intervention may avert exposure which enables unvaccinated susceptible individuals to be to the agent of disease (e.g., lead, trans-fatty acids, microbes), exposed to others who are infectious. The vector in this case preventing the disease process from starting; this is called is relatively unimportant. In malaria, however, the host, primary prevention. During the latent stage, when the agent, and environment are all significant, but the vector, the disease process has already begun but is still asymptomatic, Anopheles mosquito, assumes paramount importance in the screening for the disease and providing appropriate treat- spread of disease. ment may prevent progression to symptomatic disease; this is called secondary prevention. During the symptomatic stage, when disease manifestations are evident, intervention may slow, arrest, or reverse the progression of disease; this is called tertiary prevention. These concepts are discussed in more detail in Chapters 15 to 17. Agent B.â ‡ Mechanisms and Causes of Disease When discussing the etiology of disease, epidemiologists dis- tinguish between the biologic mechanisms and the social, behavioral, and environmental causes of disease. For Vector example, osteomalacia is a bone disease that may have both social and biologic causes. Osteomalacia is a weakening of the bone, often through a deficiency of vitamin D. According to the custom of purdah, which is observed by many Muslims, women who have reached puberty avoid public observation by spending most of their time indoors, or by wearing cloth- Host Environment ing that covers virtually all of the body when they go out- doors. Because these practices block the action of the sun on bare skin, they prevent the irradiation of ergosterol in the Figure 1-1â ‡ Factors involved in natural history of disease.  C h a p t e râ … 1â … Basic Epidemiologic Concepts and Principl es 5 Host factors are responsible for the degree to which the D.â ‡ Risk Factors and Preventable Causes individual is able to adapt to the stressors produced by the agent. Host resistance is influenced by a person’s genotype Risk factors for disease and preventable causes of disease, (e.g., dark skin reduces sunburn), nutritional status and particularly life-threatening diseases such as cancer, have body mass index (e.g., obesity increases susceptibility to been the subject of much epidemiologic research. In 1964 a many diseases), immune system (e.g., compromised immu- World Health Organization (WHO) expert committee esti- nity reduces resistance to cancer as well as microbial disease), mated that the majority of cancer cases were potentially pre- and social behavior (e.g., physical exercise enhances resis- ventable and were caused by “extrinsic factors.” Also that tance to many diseases, including depression). Several factors year, the U.S. Surgeon General released a report indicating can work synergistically, such as nutrition and immune that the risk of death from lung cancer in smokers was status. Measles is seldom fatal in well-nourished children, almost 11 times that in nonsmokers.2 even in the absence of measles immunization and modern Advances in knowledge have consolidated the WHO find- medical care. By contrast, 25% of children with marasmus ings to the point where few, if any, researchers now question (starvation) or kwashiorkor (protein-calorie malnutrition its main conclusion.3 Indeed, some have gone further, sub- related to weaning) may die from complications of measles. stituting figures of 80% or even 90% as the proportion of Agents of disease or illness can be divided into several potentially preventable cancers, in place of WHO’s more categories. Biologic agents include allergens, infectious cautious estimate of the “majority.” Unfortunately, the phrase organisms (e.g., bacteria, viruses), biologic toxins (e.g., botu- “extrinsic factors” (or its near-synonym, “environmental linum toxin), and foods (e.g., high-fat diet). Chemical agents factors”) has often been misinterpreted to mean only man- include chemical toxins (e.g., lead) and dusts, which can made chemicals, which was certainly not the intent of the cause acute or chronic illness. Physical agents include kinetic WHO committee. In addition to man-made or naturally energy (e.g., involving bullet wounds, blunt trauma, and occurring carcinogens, the 1964 report included viral infec- crash injuries), radiation, heat, cold, and noise. Epidemiolo- tions, nutritional deficiencies or excesses, reproductive activ- gists now are studying the extent to which social and psy- ities, and a variety of other factors determined “wholly or chological stressors can be considered agents in the partly by personal behavior.” development of health problems. The WHO conclusions are based on research using a The environment influences the probability and circum- variety of epidemiologic methods. Given the many different stances of contact between the host and the agent. Poor types of cancer cells, and the large number of causal factors restaurant sanitation increases the probability that patrons to be considered, how do epidemiologists estimate the per- will be exposed to Salmonella infections. Poor roads and centage of deaths caused by preventable risk factors in a adverse weather conditions increase the number of automo- country such as the United States? bile collisions and airplane crashes. The environment also One method looks at each type of cancer and determines includes social, political, and economic factors. Crowded (from epidemiologic studies) the percentage of individuals homes and schools make exposure to infectious diseases in the country who have identifiable, preventable causes of more likely, and the political structure and economic health that cancer. These percentages are added up in a weighted of a society influence the nutritional and vaccine status of manner to determine the total percentage of all cancers its members. having identifiable causes. Vectors of disease include insects (e.g., mosquitoes asso- A second method examines annual age-specific and ciated with spread of malaria), arachnids (e.g., ticks associ- gender-specific cancer incidence rates in countries that have ated with Lyme disease), and mammals (e.g., raccoons the lowest rates of a given type of cancer and maintain an associated with rabies in eastern U.S.). The concept of the effective infrastructure for disease detection. For a particular vector can be applied more widely, however, to include cancer type, the low rate in such a country presumably human groups (e.g., vendors of heroin, cocaine, and meth- results from a low prevalence of the risk factors for that amphetamine) and even inanimate objects that serve as cancer. Researchers calculate the number of cases of each vehicles to transmit disease (e.g., contaminated needles asso- type of cancer that would be expected to occur annually in ciated with hepatitis and AIDS). A vector may be considered each age and gender group in the United States, if the lowest part of the environment, or it may be treated separately (see observed rates had been true for the U.S. population. Next, Fig. 1-1). To be an effective transmitter of disease, the vector they add up the expected numbers for the various cancer must have a specific relationship to the agent, the environ- types in the U.S. They then compare the total number of ment, and the host. expected cases with the total number of cases actually diag- In the case of human malaria, the vector is a mosquito of nosed in the U.S. population. Using these methods, epide- the genus Anopheles, the agent is a parasitic organism of the miologists have estimated that the U.S. has about five times genus Plasmodium, the host is a human, and the environ- as many total cancer cases as would be expected, based on ment includes standing water that enables the mosquito to the lowest rates in the world. Presumably, the excess cancer breed and to come into contact with the host. Specifically, cases in the U.S. are caused by the prevalence of risk factors the plasmodium must complete part of its life cycle within for cancer, such as smoking. the mosquito; the climate must be relatively warm and provide a wet environment in which the mosquito can breed; 1.â ‡ BEINGS Model the mosquito must have the opportunity to bite humans (usually at night, in houses where sleeping people lack The acronym BEINGS can serve as a mnemonic device for screens and mosquito nets) and thereby spread the disease; the major categories of risk factors for disease, some of the host must be bitten by an infected mosquito; and the host which are easier to change or eliminate than others (Box must be susceptible to the disease. 1-1). Currently, genetic factors are among the most difficult 6 S e c t i o nâ … 1â … Epidemiology HIV infection can also result from unprotected vaginal inter- Box 1-1â … BEINGS Acronym for Categories of course, which is the predominant transmission route in Preventable Cause of Disease Africa and other parts of the world. Other behaviors that can lead to disease, injury, or premature death (before age 65) Biologic factors and Behavioral factors are excessive intake of alcohol, abuse of both legal and illegal Environmental factors Immunologic factors drugs, driving while intoxicated, and homicide and suicide Nutritional factors attempts. In each of these cases, as in cigarette smoking and Genetic factors HIV infection, changes in behavior could prevent the unto Services, Social factors, and Spiritual factors ward outcomes. Many efforts in health promotion depend heavily on modifying human behavior, as discussed in Chapter 15. to change, although this field is rapidly developing and “E”—ENVIRONMENTAL FACTORS becoming more important to epidemiology and prevention. Epidemiologists are frequently the first professionals to Immunologic factors are usually the easiest to change, if respond to an apparent outbreak of new health problems, effective vaccines are available. such as legionnaires’ disease and Lyme disease, which involve important environmental factors. In their investigations, epidemiologists describe the patterns of the disease in the “B”—BIOLOGIC AND BEHAVIORAL FACTORS affected population, develop and test hypotheses about The risk for particular diseases may be influenced by gender, causal factors, and introduce methods to prevent further age, weight, bone density, and other biologic factors. In addi- cases of disease. Chapter 3 describes the standard approach tion, human behavior is a central factor in health and disease. to investigating an epidemic. Cigarette smoking is an obvious example of a behavioral risk During an outbreak of severe pneumonia among indi- factor. It contributes to a variety of health problems, includ- viduals attending a 1976 American Legion conference in ing myocardial infarction (MI); lung, esophageal, and naso- Philadelphia, epidemiologists conducted studies suggesting pharyngeal cancer; and chronic obstructive pulmonary that the epidemic was caused by an infectious agent distrib- disease. Cigarettes seem to be responsible for about 50% of uted through the air-conditioning and ventilation systems of MI cases among smokers and about 90% of lung cancer the primary conference hotels. Only later, after the identifica- cases. Because there is a much higher probability of MI than tion of Legionella pneumophila, was it discovered that this lung cancer, cigarettes actually cause more cases of MI than small bacterium thrives in air-conditioning cooling towers lung cancer. and warm-water systems. It was also shown that respiratory Increasing attention has focused on the rapid increase in therapy equipment that is merely rinsed with water can overweight and obesity in the U.S. population over the past become a reservoir for Legionella, causing hospital-acquired two decades. The number of deaths per year that can be legionnaires’ disease. attributed to these factors is controversial. In 2004 the U.S. An illness first reported in 1975 in Old Lyme, Connecti- Centers for Disease Control and Prevention (CDC) esti- cut, was the subject of epidemiologic research suggesting mated that 400,000 deaths annually were caused by obesity that the arthritis, rash, and other symptoms of the illness and its major risk factors, inactivity and an unhealthy diet.4 were caused by infection with an organism transmitted by a In 2005, using newer survey data and controlling for more tick. This was enough information to enable preventive mea- potential confounders, other CDC investigators estimated sures to begin. By 1977 it was clear that the disease, then that the number of deaths attributable to obesity and its risk known as Lyme disease, was spread by Ixodes ticks, opening factors was only 112,000.5 Regardless, increasing rates of the way for more specific prevention and research. Not until obesity are found worldwide as part of a cultural transition 1982, however, was the causative agent, Borrelia burgdorferi, related to the increased availability of calorie-dense foods discovered and shown to be spread by the Ixodes tick. and a simultaneous decline in physical activity, resulting in part from mechanized transportation and sedentary lifestyles.6-11 “I”—IMMUNOLOGIC FACTORS Obesity and overweight have negative health effects, par- Smallpox is the first infectious disease known to have been ticularly by reducing the age at onset of, and increasing the eradicated from the globe (although samples of the causative prevalence of, type 2 diabetes. Obesity is established as a virus remain stored in U.S. and Russian laboratories). Small- major contributor to premature death in the United pox eradication was possible because vaccination against the States,12,13 although the exact magnitude of the association disease conferred individual immunity and produced herd remains controversial, resulting in part from the complexi- immunity. Herd immunity results when a vaccine dimin- ties of the causal pathway involved (i.e., obesity leads to ishes an immunized person’s ability to spread a disease, death indirectly, by contributing to the development of leading to reduced disease transmission. chronic disease). Most people now think of AIDS when they hear of a Multiple behavioral factors are associated with the spread deficiency of the immune system, but immunodeficiency of some diseases. In the case of AIDS, the spread of human also may be caused by genetic abnormalities and other immunodeficiency virus (HIV) can result from unprotected factors. Transient immune deficiency has been noted after sexual intercourse between men and from shared some infections (e.g., measles) and after the administration syringes among intravenous drug users, which are the two of certain vaccines (e.g., live measles vaccine). This result is predominant routes of transmission in the United States. potentially serious in malnourished children. The use of  C h a p t e râ … 1â … Basic Epidemiologic Concepts and Principl es 7 cancer chemotherapy and the long-term use of corticoste- promote or protect against a variety of illnesses, including roids also produce immunodeficiency, which may often be heart disease and cancer. As a result, genetic epidemiology severe. is a growing field of research that addresses, among other things, the distribution of normal and abnormal genes in a population, and whether or not these are in equilibrium. “N”—NUTRITIONAL FACTORS Considerable research examines the possible interaction of In the 1950s it was shown that Japanese Americans living in various genotypes with environmental, nutritional, and Hawaii had a much higher rate of MI than people of the behavioral factors, as well as with pharmaceutical treat- same age and gender in Japan, while Japanese Americans in ments. Ongoing research concerns the extent to which envi- California had a still higher rate of MI than similar individu- ronmental adaptations can reduce the burden of diseases als in Japan.14-16 The investigators believed that dietary varia- with a heavy genetic component. tions were the most important factors producing these Genetic disease now accounts for a higher proportion of differences in disease rates, as generally supported by subse- illness than in the past, not because the incidence of genetic quent research. The Japanese eat more fish, vegetables, and disease is increasing, but because the incidence of noninher- fruit in smaller portions. ited disease is decreasing and our ability to identify genetic Denis Burkitt, the physician after whom Burkitt’s lym- diseases has improved. Scriver18 illustrates this point as phoma was named, spent many years doing epidemiologic follows: research on the critical role played by dietary fiber in good health. From his cross-cultural studies, he made some stun- Heritability refers to the contribution of genes relative to all ning statements, including the following17: determinants of disease. Rickets, a genetic disease, recently showed an abrupt fall in incidence and an increase in heritabil- “By world standards, the entire United States is constipated.” ity in Quebec. The fall in incidence followed universal supple- “Don’t diagnose appendicitis in Africa unless the patient mentation of dairy milk with calciferol. The rise in heritability speaks English.” reflected the disappearance of a major environmental cause of “African medical students go through five years of training rickets (vitamin D deficiency) and the persistence of Mendelian without seeing coronary heart disease or appendicitis.” disorders of calcium and phosphate homeostasis, without any “Populations with large stools have small hospitals. Those change in their incidence. with small stools have large hospitals.” Based on cross-cultural studies, Burkitt observed that Genetic screening is important for identifying problems in many of the diseases commonly seen in the United States, newborns, such as phenylketonuria and congenital hypothy- such as diabetes and hypertension, were rarely encountered roidism, for which therapy can be extremely beneficial if in indigenous populations of tropical Africa (Box 1-2). This instituted early enough. Screening is also important for iden- observation was true even of areas with good medical care, tifying other genetic disorders for which counseling can be such as Kampala, Uganda, when Burkitt was there, indicating beneficial. In the future, the most important health benefits that such diseases were not being missed because of lack of from genetics may come from identifying individuals diagnosis. These differences could not be primarily genetic who are at high risk for specific problems, or who would in origin because African Americans in the United States respond particularly well (or poorly) to specific drugs. experience these diseases at about the same rate as other U.S. Examples might include individuals at high risk for MI; groups. Cross-cultural differences suggest that the current breast or ovarian cancer (e.g., carriers of BRCA1 and BRCA2 heavy burden of these diseases in the United States is not genetic mutations); environmental asthma; or reactions to inevitable. Burkitt suggested mechanisms by which a high certain foods, medicines, or behaviors. Screening for suscep- intake of dietary fiber might prevent these diseases or greatly tibility genes undoubtedly will increase in the future, but reduce their incidence. there are ethical concerns about potential problems, such as medical insurance carriers hesitating to insure individuals with known genetic risks. For more on the prevention of “G”—GENETIC FACTORS genetic disease, see Section 3, particularly Chapter 20. It is well established that the genetic inheritance of individu- als interacts with diet and environment in complex ways to “S”—SERVICES, SOCIAL FACTORS, AND SPIRITUAL FACTORS Medical care services may be beneficial to health but also Box 1-2â … Diseases that Have Been Rare in can be dangerous. One of the important tasks of epidemiolo- Indigenous Populations of Tropical gists is to determine the benefits and hazards of medical care Africa in different settings. Iatrogenic disease occurs when a disease is induced inadvertently by treatment or during a diagnostic Appendicitis Diverticulitis procedure. A U.S. Institute of Medicine report estimated that Breast cancer Gallstones 2.9% to 3.7% of hospitalized patients experience “adverse Colon cancer Hemorrhoids events” during their hospitalization. Of these events, about Coronary heart disease Hiatal hernia 19% are caused by medication errors and 14% by wound Diabetes mellitus Varicose veins infections.19 Based on 3.6 million hospital admissions cited in a 1997 study, this report estimated that about Data from Burkitt D: Lecture, Yale University School of Medicine, 44,000 deaths each year are associated with medical errors 1989. in hospital. Other medical care–related causes of illness include unnecessary or inappropriate diagnostic or surgical 8 S e c t i o nâ … 1â … Epidemiology procedures. For example, more than 50% of healthy women tremendous growth in world population, now more than 7 who undergo annual screening mammography over a billion, and rapid technologic developments, humans have 10-year period will have at least one mammogram inter- had a profound impact on the global environment, often preted as suspicious for breast cancer and will therefore be with deleterious effects. The existence of wide biodiversity, advised to undergo additional testing, even though they do which helps to provide the planet with greater adaptive not have cancer.20 capacity, has become increasingly threatened. Every action The effects of social and spiritual factors on disease and that affects the ecosystem, even an action intended to health have been less intensively studied than have other promote human health and well-being, produces a reaction causal factors. Evidence is accumulating, however, that per- in the system, and the result is not always positive. (See sonal beliefs concerning the meaning and purpose of life, http://www.cdc.gov and http://www.census.gov/main/www/ perspectives on access to forgiveness, and support received popclock.html.) from members of a social network are powerful influences on health. Studies have shown that experimental animals and humans are better able to resist noxious stressors when A.â ‡ Solution of Public Health Problems and they are receiving social support from other members of the Unintended Creation of New Problems same species. Social support may be achieved through the family, friendship networks, and membership in various One of the most important insights of ecological thinking is groups, such as clubs and churches. One study reviewed the that as people change one part of a system, they inevitably literature concerning the association of religious faith with change other parts. An epidemiologist is constantly alert for generally better health and found that strong religious faith possible negative side effects that a medical or health inter- was associated with better health and quality of life.21 The vention might produce. In the United States the reduced effects of meditation and massage on quality of life in mortality in infancy and childhood has increased the preva- patients with advanced disease (e.g., AIDS) have also been lence of chronic degenerative diseases because now most studied.22 people live past retirement age. Although nobody would Many investigators have explored factors related to health want to go back to the public health and medical care of 100 and disease in Mormons and Seventh-Day Adventists. Both years ago, the control of infectious diseases has nevertheless these religious groups have lower-than-average age-adjusted produced new sets of medical problems, many of them death rates from many common types of disease and specifi- chronic. Table 1-1 summarizes some of the new health and cally from heart disease, cancer, and respiratory disorders. societal problems introduced by the solution of earlier health Part of their protection undoubtedly arises from the behav- problems. iors proscribed or prescribed by these groups. Mormons prohibit the use of alcohol and tobacco. Seventh-Day Adven- 1.â ‡ Vaccination and Patterns of Immunity tists likewise tend to avoid alcohol and tobacco, and they strongly encourage (but do not require) a vegetarian diet. It Understanding herd immunity is essential to any discussion is unclear, however, that these behaviors are solely respon- of current ecological problems in immunization. A vaccine sible for the health differences. As one study noted, “It is provides herd immunity if it not only protects the immu- difficult … to separate the effects of health practices from nized individual, but also prevents that person from other aspects of lifestyle common among those belonging to such religions, for example, differing social stresses and network systems.”23 Another study showed that for all age cohorts, the greater one’s participation in churches or other groups and the stronger one’s social networks, the lower the Table 1-1â ‡ Examples of Unintended Consequences from observed mortality.24 Solution of Earlier Health Problems The work of the psychiatrist Victor Frankl also docu- Initial Health Unintended mented the importance of having a meaning and purpose in Problem Solution Consequences life, which can alleviate stress and improve coping.25 Such factors are increasingly being studied as important in under- Childhood Vaccination Decrease in the level of standing the web of causation for disease. infections immunity during adulthood, caused by a lack of repeated exposure to infection III.â ‡ ECOLOGICAL ISSUES IN EPIDEMIOLOGY High infant Improved Increase in the population mortality sanitation growth rate; appearance Classical epidemiologists have long regarded their field as rate of epidemic paralytic “human ecology,” “medical ecology,” or “geographic medi- poliomyelitis cine,” because an important characteristic of epidemiology Sleeping Control of tsetse Increase in the area of land sickness in fly (the disease subject to overgrazing is its ecological perspective.26 People are seen not only as cattle vector) and drought, caused by individual organisms, but also as members of communities, an increase in the cattle in a social context. The world is understood as a complex population ecosystem in which disease patterns vary greatly from one Malnutrition Erection of large Increase in rates of some and need river dams (e.g., infectious diseases, country to another. The types and rates of diseases in a for larger Aswan High caused by water system country are a form of “fingerprint” that indicates the stan- areas of Dam, Senegal changes that favor the dard of living, the lifestyle, the predominant occupations, tillable land River dams) vectors of disease and the climate, among other factors. Because of the  C h a p t e râ … 1â … Basic Epidemiologic Concepts and Principl es 9 A ABSENCE OF B PRESENCE OF 50% HERD IMMUNITY HERD IMMUNITY Initial case First disease generation Second disease generation Third disease generation Figure 1-2â ‡ Effect of herd immunity on spread of infection. Diagrams illustrate how an infectious disease, such as measles, could spread in a susceptible population if each infected person were exposed to two other persons. A, In the absence of herd immunity, the number of cases doubles each disease generation. B, In the presence of 50% herd immunity, the number of cases remains constant. The plus sign represents an infected person; the minus sign represents an uninfected person; and the circled minus sign represents an immune person who will not pass the infection to others. The arrows represent significant exposure with transmission of infection (if the first person is infectious) or equivalent close contact without transmission of infection (if the first person is not infectious). transmitting the disease to others. This causes the prevalence agent, and this exposure could result in a mild reinfection. of the disease organism in the population to decline. Herd The reinfection would produce a natural booster effect and immunity is illustrated in Figure 1-2, where it is assumed maintain a high level of immunity. As diphtheria became that each infected person comes into sufficient contact with less common because of immunization programs, fewer two other persons to expose both of them to the disease if people were exposed, resulting in fewer subclinical booster they are susceptible. Under this assumption, if there is no infections. herd immunity against the disease and everyone is suscep- In Russia, despite the wide availability of diphtheria tible, the number of cases doubles every disease generation vaccine, many adults who had not recently been in the mili- (Fig. 1-2, A). However, if there is 50% herd immunity against tary were found to be susceptible to Corynebacterium diph- the disease, the number of cases is small and remains approx- theriae. Beginning in 1990, a major epidemic of diphtheria imately constant (Fig. 1-2, B). In this model, if there is greater appeared in Russia. By 1992, about 72% of the reported cases than 50% herd immunity, as would be true in a well- were found among individuals older than 14 years. This was immunized population, the infection should die out eventu- not caused by lack of initial immunization, because more ally. The degree of immunity necessary to eliminate a disease than 90% of Russian adults had been fully immunized from a population varies depending on the type of infectious against diphtheria when they were children. The disease in organism, the time of year, and the density and social pat- older people was apparently caused by a decline in adult terns of the population. immunity levels. Before the epidemic was brought under Immunization may seem simple: immunize everybody in control, it produced more than 125,000 cases of diphtheria childhood, and there will be no problems from the targeted and caused 4000 deaths.27 An additional single vaccination diseases. Although there is some truth to this, in reality the is now recommended for adults to provide a booster. control of diseases by immunization is more complex. The examples of diphtheria, smallpox, and poliomyelitis are used here to illustrate issues concerning vaccination programs SMALLPOX and population immunity, and syphilis is used to illustrate As mentioned earlier, the goal of worldwide eradication of natural herd immunity to infection. smallpox has now been met by immunizing people against the disease. Early attempts at preventing smallpox included actions reportedly by a Buddhist nun who would grind scabs DIPHTHERIA from patients with the mild form and blow into the nose of Vaccine-produced immunity in humans tends to decrease nonimmune individuals; this was called variolation. The over time. This phenomenon has a different impact at term vaccination comes from vaca, or “cow”; epidemiologists present, when infectious diseases such as diphtheria are less noted that milkmaids developed the less severe form of common, than it did in the past. When diphtheria was a smallpox. more common disease, people who had been vaccinated Attempts at eradication included some potential risks. against it were exposed more frequently to the causative The dominant form of smallpox in the 1970s was variola 10 S e c t i o nâ … 1â … Epidemiology minor (alastrim). This was a relatively mild form of smallpox that, although often disfiguring, had a low mortality rate. SYPHILIS However, alastrim provided individual and herd immunity Syphilis is caused by infection with bacteria known as spiro- against the much more disfiguring and often fatal variola chetes and progresses in several stages. In the primary stage, major form of the disease (classical smallpox). To eliminate syphilis produces a highly infectious skin lesion known as a alastrim while increasing rates of variola major would have chancre, which is filled with spirochete organisms. This been a poor exchange. Fortunately, the smallpox vaccine was lesion subsides spontaneously. In the secondary stage, a rash effective against both forms of smallpox, and the immuniza- or other lesions may appear; these also subside spontane- tion program was successful in eradicating both variola ously. A latent period follows, after which a tertiary stage may minor and variola major. occur. Untreated infection typically results in immunity to future infection by the disease agent, but this immunity is not absolute. It does not protect individuals from progressive POLIOMYELITIS damage to their own body. It does provide some herd immu- The need for herd immunity was also shown by poliomyeli- nity, however, by making the infected individual unlikely to tis. The inactivated or killed polio vaccine (IPV), which develop a new infection if he or she is exposed to syphilis became available in 1955, provided protection to the again.31 Ironically, when penicillin came into general use, immunized individual, but did not produce much herd syphilis infections were killed so quickly that chancre immu- immunity. Although it stimulated the production of blood nity did not develop, and high-risk individuals continued to antibodies against the three types of poliovirus, it did not repeatedly reacquire and spread the disease. produce cell-mediated immunity in the intestine, where the polioviruses multiplied. For this reason, IPV did little to 2.â ‡ Effects of Sanitation interrupt viral replication in the intestine. Declining rates of paralytic poliomyelitis lulled many people into lack of In the 19th century, diarrheal diseases were the primary killer concern, and immunization rates for newborns decreased, of children, and tuberculosis was the leading cause of adult leading to periodic small epidemics of poliomyelitis in the mortality. The sanitary revolution, which began in England late 1950s and early 1960s because poliovirus was still about the middle of the century, was the most important present. factor in reducing infant mortality. However, the reduction The live, attenuated Sabin oral polio vaccine (OPV) was of infant mortality contributed in a major way to increasing approved in the early 1960s. OPV produced cell-mediated the effective birth rate and the overall rate of population immunity, preventing the poliovirus from replicating in the growth. The sanitary revolution was therefore one of the intestine, and it also provided herd immunity. After the causes of today’s worldwide population problem. The widespread use of OPV in the United States, the prevalence current world population (>7 billion) has a profound and of all three types of the wild poliovirus declined rapidly, as often unappreciated impact on the production of pollutants, monitored in waste sewage. Poliovirus now seems to have the global fish supply, the amount of land available for cul- been eradicated from the Western Hemisphere, where the tivation, worldwide forest cover, and climate. last known case of paralytic poliomyelitis caused by a wild Care must be taken to avoid oversimplifying the factors poliovirus was confirmed in Peru in 1991.28 that produce population growth, which continues even as It might seem from this information that OPV is always the global rate of growth seems to be slowing down. On the superior, but this is not true. When the health department one hand, a reduction in infant mortality temporarily helps for the Gaza Strip used only OPV in its polio immunization to produce a significant difference between the birth and efforts, many cases of paralytic poliomyelitis occurred among death rates in a population, resulting in rapid population Arab children. Because of inadequate sanitation, the children growth, the demographic gap. On the other hand, the often had other intestinal infections when they were given control of infant mortality seems to be necessary before spe- OPV, and these infections interfered with the OPV infection cific populations are willing to accept population control. in the gut. As a result, the oral vaccine often did not “take,” When the infant mortality rate is high, a family needs to have and many children remained unprotected.29 The health a large number of children to have reasonable confidence department subsequently switched to an immunization that one or two will survive to adulthood. This is not true program in which children were injected first with the inac- when the infant mortality rate is low. Although it may seem tivated vaccine to produce adequate blood immunity. Later, paradoxical, reduced infant mortality seems to be both a they were given OPV as a booster vaccine to achieve herd cause of the population problem and a requirement for immunity. population control. Now that OPV has succeeded in eradicating wild polio- In addition to affecting population growth, the sanitary virus from the Western Hemisphere, the only indigenous revolution of the 19th century affected disease patterns in cases of paralytic poliomyelitis occurring in the United States unanticipated ways. In fact, improvements in sanitation were since 1979 have been iatrogenic (vaccine-induced) polio a fundamental cause of the appearance of epidemic paralytic caused by the oral (live, attenuated) vaccine itself. Since 1999, poliomyelitis late in the 19th century. This may seem coun- to eliminate vaccine-caused cases, the CDC has recom- terintuitive, but it illustrates the importance of an ecological mended that infants be given the IPV instead of the OPV.30 perspective and offers an example of the so-called iceberg Some OPV is still held in reserve for outbreaks. phenomenon, discussed later. The three polioviruses are Polio was officially eradicated in 36 Western Pacific coun- enteric viruses transmitted by the fecal-oral route. People tries, including China and Australia in 2000. Europe was who have developed antibodies to all three types of poliovi- declared polio free in 2002. Polio remains endemic in only a rus are immune to their potentially paralytic effects and few countries. show no symptoms or signs of clinical disease if they are  C h a p t e râ … 1â … Basic Epidemiologic Concepts and Principl es 11 exposed. Newborns receive passive antibodies from their countries where HIV is usually spread through heterosexual mothers, and these maternal antibodies normally prevent activity. In addition, the compromised immunity caused by polioviruses from invading the central nervous system early AIDS permits the reactivation of previously latent infections, in an infant’s first year of life. As a result, exposure of a young such as tuberculosis, which is now resurging in many areas infant to polioviruses rarely leads to paralytic disease, but of the globe. instead produces a subclinical (largely asymptomatic) infec- The relationship between malnutrition and infection is tion, which causes infants to produce their own active anti- similarly complex. Not only does malnutrition make infec- bodies and cell-mediated immunity. tions worse, but infections make malnutrition worse as Although improved sanitation reduced the proportion of well. A malnourished child has more difficulty making anti- people who were infected with polioviruses, it also delayed bodies and repairing tissue damage, which makes the child the time when most infants and children were exposed to less resistant to infectious diseases and their complications. the polioviruses. Most were exposed after they were no This scenario is observed in the case of measles. In isolated longer protected by maternal immunity, with the result that societies without medical care or measles vaccine, less than a higher percentage developed the paralytic form of the 1% of well-nourished children may die from measles or its disease. Epidemic paralytic poliomyelitis can therefore be complications, whereas 25% of malnourished children may seen as an unwanted side effect of the sanitary revolution. die. Infection can worsen malnutrition for several reasons. Further, because members of the upper socioeconomic First, infection puts greater demands on the body, so the groups had the best sanitation, they were hit first and most relative deficiency of nutrients becomes greater. Second, severely, until the polio vaccine became available. infection tends to reduce the appetite, so intake is reduced. Third, in the presence of infection, the diet frequently is 3.â ‡ Vector Control and Land Use Patterns changed to emphasize bland foods, which often are deficient in proteins and vitamins. Fourth, in patients with gastroin- Sub-Saharan Africa provides a disturbing example of how testinal infection, food rushes through the irritated bowel at negative side effects from vectors of disease can result from a faster pace, causing diarrhea, and fewer nutrients are positive intentions of land use. A successful effort was made absorbed. to control the tsetse fly, which is the vector of African sleep- Ecological and genetic factors can also interact to produce ing sickness in cattle and sometimes in humans. Control of new strains of influenza virus. Many of the new, epidemic the vector enabled herders to keep larger numbers of cattle, strains of influenza virus have names that refer to China and this led to overgrazing. Overgrazed areas were subject to (e.g., Hong Kong flu, Beijing flu) because of agricultural frequent droughts, and some became dust bowls with little practices. In rural China, domesticated pigs are in close vegetation.32 The results were often famine and starvation for contact with ducks and people. The duck and the human cattle and humans. strains of influenza infect pigs, and the genetic material of the two influenza strains may mix in the pigs, producing a new variant of influenza. These new variants can then infect 4.â ‡ River Dam Construction and Patterns humans. If the genetic changes in the influenza virus are of Disease major, the result is called an antigenic shift, and the new virus may produce a pandemic, or widespread, outbreak of For a time, it was common for Western nations to build large influenza that could involve multiple continents. If the river dams in developing countries to produce electricity and genetic changes in the influenza virus are minor, the phe- increase the amount of available farmland by irrigation. nomenon is called an antigenic drift, but this still can During this period, the warnings of epidemiologists about produce major regional outbreaks of influenza. The avian potential negative effects of such dams went unheeded. The influenza (H5N1) virus from Southeast Asia differs greatly Aswan High Dam in Egypt provides a case in point. Directly from human strains, and it has caused mortality in most after the dam was erected, the incidence of schistosomiasis people who contract the infection from birds. Should this increased in the areas supplied by the dam, just as epidemi- strain of influenza acquire the capacity to spread from one ologists predicted. Similar results followed the construction human to another, the world is likely to see a global pan- of the main dam and tributary dams for the Senegal River demic (worldwide epidemic). Project in West Africa. Before the dams were erected, the sea The same principles apply to chronic diseases. Overnutri- would move far inland during the dry season and mix with tion and sedentary living interact so that each one worsens fresh river water, making the river water too salty to support the impact of the other. As another example, the coexistence the larvae of the blood flukes responsible for schistosomiasis of cigarette smoking and pneumoconiosis (especially in coal or the mosquitoes that transmit malaria, Rift Valley fever, workers) makes lung cancer more likely than a simple sum and dengue fever.33 Once the dams were built, the incidence of the individual risks. of these diseases increased until clean water, sanitation, and other health interventions were provided. IV.â ‡ CONTRIBUTIONS OF EPIDEMIOLOGISTS B.â ‡ Synergism of Factors Predisposing to Disease A.â ‡ Investigating Epidemics and New Diseases There may be a synergism between diseases or between factors predisposing to disease, such that each makes the Using the surveillance and investigative methods discussed other worse or more easily acquired. Sexually transmitted in detail in Chapter 3, epidemiologists often have provided diseases, especially those that produce open sores, facilitate the initial hypotheses about disease causation for other the spread of HIV. This is thought to be a major factor in scientists to test in the laboratory. Over the past 40 years, 12 S e c t i o nâ … 1â … Epidemiology Table 1-2â ‡ Early Hypotheses by Epidemiologists on Natural History and Prevention Methods for More Recent Diseases Epidemiologic Hypotheses Disease Date of Appearance Agent and Route of Spread Methods of Prevention Lyme disease 1975 Infectious agent, spread by ticks Avoid ticks Legionnaires’ disease 1976 Small infectious agent, spread via air- Treat water in air-conditioning systems conditioning systems Toxic shock 1980 Staphylococcal toxin, associated with use of Avoid using long-lasting tampons syndrome tampons (especially Rely brand) Acquired 1981 Viral agent, spread via sexual activity, especially Use condoms immunodeficiency male homosexual activity, and via sharing of Avoid sharing needles syndrome (AIDS) needles and exchange of blood and blood Institute programs to exchange needles products during intravenous drug use and and screen blood transfusions Eosinophilia-myalgia 1989 Toxic contaminant, associated with use of dietary Change methods of product syndrome supplements of L-tryptophan manufacturing Hantavirus 1993 Hantavirus, spread via contact with Avoid contact with excreta of deer mice pulmonary contaminated droppings of deer mice syndrome New-variant 1996 Prions, spread via ingestion of beef infected with Avoid eating infected beef Creutzfeldt-Jakob bovine spongiform encephalopathy Avoid feeding animal remains to cattle disease Severe acute 2003 Animal coronavirus transferred to humans by Avoid handling, killing, and eating respiratory handling and eating unusual food animals nonstandard food animals syndrome (SARS) epidemiologic methods have suggested the probable type of asymptomatic and mild cases of disease. An outbreak of agent and modes of transmission for the diseases listed in diphtheria illustrates this point. When James F. Jekel worked Table 1-2 and others, usually within months of their recogni- with the CDC early in his career, he was assigned to investi- tion as new or emergent diseases. Knowledge of the modes gate an epidemic of diphtheria in an Alabama county. The of transmission led epidemiologists to suggest ways to diphtheria outbreak caused two deaths; symptoms of clinical prevent each of these diseases before the causative agents illness in 12 children who recovered; and asymptomatic were determined or extensive laboratory results were avail- infection in 32 children, some of whom had even been able. Laboratory work to identify the causal agents, clarify immunized against diphtheria. The 32 cases of asymptom- the pathogenesis, and develop vaccines or treatments for atic infection were discovered by extensive culturing of the most of these diseases still continues many years after this throats of the school-age children in the outbreak area. In basic epidemiologic work was done. this iceberg (Fig. 1-3), 14 infections were visible, but the 32 Concern about the many, more recently discovered and asymptomatic carriers would have remained invisible resurgent diseases34 is currently at a peak, both because of a without extensive epidemiologic surveillance.37 The iceberg variety of newly emerging disease problems and because of phenomenon is paramount to epidemiology, because study- the threat of bioterrorism.35 The rapid growth in world pop- ing only symptomatic individuals may produce a misleading ulation; increased travel and contact with new ecosystems, picture of the disease pattern and severity.38 The biologic such as rain forests; declining effectiveness of antibiotics and spectrum also applies to viral disease.39 insecticides; and many other factors encourage the develop- ment of new diseases or the resurgence of previous disorders. In addition, global climate change may extend the range of C.â ‡ Surveillance of Community some diseases or help to create others. Health Interventions B.â ‡ Studying the Biologic Spectrum of Disease Randomized trials of preventive measures in the field (field trials) are an important phase of evaluating a new vaccine The first identified cases of a new disease are often fatal or before it is given to the community at large. Field trials, severe, leading observers to conclude that the disease is however, are only one phase in the evaluation of immuniza- always severe. As more becomes known about the disease, tion programs. After a vaccine is introduced, ongoing sur- however, less severe (and even asymptomatic) cases usually veillance of the disease and vaccine side effects is essential to are discovered. With infectious diseases, asymptomatic ensure the vaccine’s continued safety and effectiveness. infection may be uncovered either by finding elevated anti- The importance of continued surveillance can be illus- body titers to the organism in clinically well people or by trated in the case of immunization against poliomyelitis. In culturing the organism from such people. 1954, large-scale field trials of the Salk inactivated polio This variation in the severity of a disease process is known vaccine were done, confirming the value and safety of the as the biologic spectrum of disease, or the iceberg phenom- vaccine.40 In 1955, however, the polio surveillance program enon.36 The latter term is appropriate because most of an of the CDC discovered an outbreak of vaccine-associated iceberg remains unseen, below the surface, analogous to poliomyelitis, which was linked to vaccine from one specific  C h a p t e râ … 1â … Basic Epidemiologic Concepts and Principl es 13 identify not only changes in disease occurrence, but also 2 increases in potentially suspicious symptom patterns. Death VISIBLE CASES 12 Clinical illness D.â ‡ Setting Disease Control Priorities Disease control priorities should be based not only on the INVISIBLE currently existing size of the problem, but also on the poten- CASES Asymptomatic 32 infection tial of a disease to spread to others; its likelihood of causing (i.e., “carriers”) death and disability; and its cost to individuals, families, and the community. U.S. legislatures often fund disease control efforts inappropriately, by considering only the number of cases reported. In the 1950s, a sharp drop in reported syphilis rates quickly led to declining support for syphilis control in the United States, which contributed to its subsequent rebound.24 Sometimes health funding is influenced when powerful individuals lobby for more money for research or Figure 1-3â ‡ Iceberg phenomenon, as illustrated by a diphtheria control efforts for a particular disease or injury. epidemic in Alabama. In epidemics, the number of people with severe Although relatively few people in the United States were forms of the disease (part of iceberg above water) may be much smaller infected with HIV in the early 1980s, epidemiologists recog- than the number of people with mild or asymptomatic clinical disease (part nized that the potential threat to society posed by AIDS was of iceberg below water). (Data from Jekel JF etâ ¯al: Public Health Rep 85:310, far greater than the absolute numbers of infected individuals 1970.) and associated costs suggested at that time. Accordingly, a much larger proportion of national resources was allocated to the study and control of AIDS than to efforts focused on other diseases affecting similar numbers of people. Special laboratory.41 Ultimately, 79 vaccinated individuals and 105 concerns with AIDS included the rapid increase in incidence of their family members were found to have developed over a very brief period, the high case fatality ratio during poliomyelitis. Apparently, a slight change from the recom- the initial outbreak and before therapy was developed and mended procedure for producing the vaccine had allowed available, the substantial medical and social costs, the ready clumping of the poliovirus to occur, which shielded some of transmissibility of the disease, and known methods of pre- the virus particles in the center of the clumps so that they vention not being well applied. were not killed by formaldehyde during vaccine production. In the 21st century, a degree of control has been achieved As a result, some people received a vaccine containing live over AIDS through antiretroviral drugs. However, new virus. It was only through the vaccine surveillance program trends in other diseases have emerged. Most importantly, that the problem was detected quickly and the dangerous increased caloric intake and sedentary living have produced vaccine removed from use. a rapid increase in overweight and obesity, leading to an Likewise, ongoing surveillance programs were responsi- increase in type 2 diabetes. In addition, new respiratory dis- ble for detecting outbreaks of measles that occurred in 1971, eases have appeared in Asia. The first, severe acute respiratory 1977, and 1990, after impressive initial progress in vaccina- syndrome (SARS), appeared in China in 2003 and was caused tion against the disease. Epidemiologists were able to show by an animal coronavirus traced to unusual food animals. If that much of the unexpected disease occurred in college the new form of avian influenza (H5N1) spreads worldwide, students and others who had received measles vaccine before it likely would move to the top of the priority list until it was 12 months of age without a later booster dose. The timing controlled. of the vaccine was important, because if given while mater- nal antibodies against measles persisted in the infants, the antigenicity of the vaccine was reduced.42 Such findings have E.â ‡ Improving Diagnosis, Treatment, and Prognosis led to the current recommendations to provide measles of Clinical Disease vaccine initially at 15 months of age and to give a booster dose at 4 to 6 years of age.30 The application of epidemiologic methods to clinical ques- Routine smallpox vaccination among the entire American tions helps us to improve clinical medicine, particularly in population stopped in 1972 after the eradication of the the diagnosis, therapy, and prognosis of disease. This is the disease was announced. However, after the terrorist attacks domain of clinical epidemiology. on September 11, 2001, the United States developed a small- Diagnosis is the process of identifying the nature and pox response plan in case of future bioterrorism events. Sur- cause of a disease through evaluation of the clinical history, veillance of the small number of persons vaccinated against review of symptoms, examination or testing. Epidemiologic smallpox since 2000 then revealed cases of vaccine-associated methods are used to improve disease diagnosis through the cardiomyopathy, and this outcome encouraged the CDC to selection of the best diagnostic tests, the determination of curtail a large-scale vaccination program. As part of its the best cutoff points for such tests, and the development of response plan, the U.S. now has a stockpile of smallpox vac- strategies to use in screening for disease. These issues are cines sufficient to vaccinate everyone in the country in the discussed in Chapters 7 and 8, as well as in the preventive event of a smallpox emergency. Epidemiologists are thus medicine section of this book. contributing to national security by helping to establish new The methods of clinical epidemiology frequently are used approaches to surveillance (syndromic surveillance) that to determine the most effective treatment in a given 14 S e c t i o nâ … 1â … Epidemiology situation. One study used a randomized controlled clinical Epidemiologists generally describe the causes of a disease trial in many U.S. centers to test the hypothesis that phar- in terms of the host, agent, and environment, sometimes maceutical therapy with methylprednisolone reduced spinal adding the vector as a fourth factor for consideration. cord damage and improved residual motor function after In exploring the means to prevent a given disease, they acute spinal cord injury. The hypothesis was confirmed.43 look for possible behavioral, genetic, and immunologic Epidemiologic methods also help improve our under- causes in the host. They also look for biologic and nutri- standing of a patient’s prognosis, or probable course and tional causes, which are usually considered agents. Epide outcome of a disease.44 Patients and families want to know miologists consider the physical, chemical, and social the likely course of their illness, and investigators need accu- environment in which the disease occurs. Epidemiology is rate prognoses to stratify patients into groups with similar concerned with human ecology, particularly the impact of disease severity in research to evaluate treatments. health interventions on disease patterns and on the environ- Epidemiologic methods permit risk estimation. These ment. Knowing that the solution of one problem may create are perhaps best developed in various cardiac risk estimators new problems, epidemiologists also evaluate possible unin- using data from the Framingham Heart Study (see www. tended consequences of medical and public health framinghamheartstudy.org/risk/index.html) and in the interventions. Gail model for breast cancer risk (see http://www. Contributions of epidemiologists to medical science cancer.gov/search/results). include the following: n Investigating epidemics and new diseases F.â ‡ Improving Health Services Research n Studying the biologic spectrum of disease n Instituting surveillance of community health inter The principles and methods of epidemiology are used in ventions planning and evaluating medical care. In health planning, n Suggesting disease control priorities epidemiologic measures are employed to determine present n Improving the diagnosis, treatment, and prognosis of and future community health needs. Demographic projec- clinical disease tion techniques can estimate the future size of different age n Improving health services research groups. Analyses of patterns of disease frequency and use of n Providing expert testimony in courts of law services can estimate future service needs.45 Additional epi- demiologic methods can be used to determine the effects of medical care in health program evaluation as well as in the broader field of cost-benefit analysis (see Chapter 29). References 1. Haynes RB, Sackett DL, Guyatt GH, et al: Clinical epidemiology, G.â ‡ Providing Expert Testimony in Courts of Law ed 3, Boston, 2006, Little, Brown. 2. US Surgeon General: Smoking and health, Public Health Service Increasingly, epidemiologists are being called on to testify Pub No 1103, Washington, DC, 1964, US Government Printing regarding the state of knowledge about such topics as product Office. hazards and the probable risks and effects of various envi- 3. Doll R, Peto R: The causes of cancer, Oxford, 1981, Oxford ronmental exposures or medications. The many types of University Press. lawsuits that may rely on epidemiologic data include those 4. Mokdad AH, Marks JS, Stroup DF, et al: Actual causes of death in the United States, 2000. JAMA 291:1238–1245, 2004. involving claims of damage from general environmental 5. Flegal KM, Graubard BI, Williamson DF, et al: Excess deaths exposures (e.g., possible association of magnetic fields or associated with underweight, overweight, and obesity. JAMA cellular phone use and brain cancer), occupational illness 293:1861–1867, 2005. claims (e.g., occupational lung damage from workplace 6. Kimm SY, Glynn NW, Kriska AM, et al: Decline in physical asbestos), medical liability (e.g., adverse effects of vaccines activity in black girls and white girls during adolescence. N Engl or medications), and product liability (e.g., association of J Med 347:709–715, 2002. lung cancer with tobacco use, of toxic shock syndrome with 7. Swinburn BA, Sacks G, Hall KD, et al: The global obesity pan- tampon use, and of cyclooxygenase-1 inhibitor medications demic: shaped by global drivers and local environments. Lancet with cardiovascular disease). Frequently, the answers to these 378(9793):804–814, 2011. PubMed PMID: 21872749. questions are unknown or can only be estimated by epide- 8. Lakdawalla D, Philipson T: The growth of obesity and techno- logical change. Econ Hum Biol 7:283–293, 2009. PubMed miologic methods. Therefore, expert medical testimony PMID: 19748839; PubMed Central PMCID: PMC2767437. often requires a high level of epidemiologic expertise.46 9. Kumanyika SK: Global calorie counting: a fitting exercise for obese societies (review). Annu Rev Public Health 29:297–302, 2008. PubMed PMID: 18173383. V.â ‡ SUMMARY 10. Popkin BM: Global nutrition dynamics: the world is shifting rapidly toward a diet linked with noncommunicable diseases. Epidemiology is the study of the occurrence, distribution, Am J Clin Nutr 84:289–298, 2006. PubMed PMID: 16895874. and determinants of diseases, injuries, and other health- 11. Anderson PM, Butcher KE: Childhood obesity: trends and related issues in specific populations. As such, it is concerned potential causes (review). Future Child 16:19–45, 2006. PubMed with all the biologic, social, behavioral, spiritual, economic, PMID: 16532657. 12. Berenson GS: Health consequences of obesity. Bogalusa Heart and psychological factors that may increase the frequency of Study group. Pediatr Blood Cancer 58:117–121, 2012. doi: disease or offer opportunities for prevention. Epidemiologic 10.1002/pbc.23373. PubMed PMID: 22076834. methods are often the first scientific methods applied to a 13. Mehta NK, Chang VW: Mortality attributable to obesity among new health problem to define its pattern in the population middle-aged adults in the United States. Demography 46:851– and to develop hypotheses about its causes, methods of 872, 2009. PubMed PMID: 20084832; PubMed Central PMCID: transmission, and prevention. PMC2831354.