PDQ Epidemiology

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Introduction to Epidemiology

WHAT IT IS

Contrary to popular belief, epidemiology is not the study of skin diseases— the root word is epidemic, not epidermis. And if you really want to impress your friends, tell them that the word epidemic itself comes from the Greek epi, meaning among, and demos, meaning the people. One scholar defined epidemiology as the study of the distribution and determinants of health-related states and events in populations and the application of this study to the control of health problems, which no doubt is about as clear and self-evident as a mortgage contract.

For many years, if epidemiology was taught at all in medical schools (oops, that should be health sciences centers or some such euphemism), it was put in the same category as gross anatomy or biochemistry—one of those subjects you had to study so the old crock teaching it could keep a job but probably of no use in the real world. Fortunately, recent history is on our side. Before Legionnaires’ disease came along in 1976, the only people who had ever heard of epidemiology were other epidemiologists. Now that we have toxic shock syndrome (TSS), acquired immunodeficiency syndrome (AIDS), Agent Orange, repetitive strain injuries, the Gulf War syndrome, reactions to silicone breast implants, sick building syndrome, and leukemias purportedly caused by high-tension wires, epidemiology is second on the list of careers advocated by every high school guidance counselor (coming after high school guidance counselor).

We still haven’t told you what epidemiology really is, so we should get down to it. Alderson states that epidemiology includes four different types of studies: descriptive, hypothesis testing, interventional, and methodologic. Descriptive studies address questions like, Who is most likely to develop AIDS? or What do the outbreaks of Legionnaires’ disease have in common? or Is there any association between kids who live near high-tension wires and the development of anemia? This type of research (1) looks at the world as it is without trying to change it, (2) relies on existing data, such as the census, or (3) uses surveys of large groups of people to collect the information.

Once we have (or at least think we have) a good description of what’s related to what, we can ask more specific questions and move into the hypothesis testing phase. For example, if we suspect that the chances of developing breast cancer may be related to the intake of fatty foods, we can see whether countries that have low-fat diets also have a low prevalence of cancer and whether this prevalence is related to fat intake. Similarly, if we think that Legionnaires’ disease is caused by stagnant water in cooling systems, we can immediately test for water purity as soon as we hear about an outbreak. Again, we are pretty much leaving the world alone and simply gathering more focused information—information that can support or refute a specific hypothesis.

If after this stage our hypotheses are still viable (it’s amazing how few can survive the bright light of data), we may want to move on to the third stage, which is intervention studies. Now finally we’re getting a chance to change things. Rather than simply observing the relationship between low-density lipoprotein (LDL) cholesterol and coronary heart disease, we can do a study to see whether lowering cholesterol in one group of people leads to a lower death rate than in people belonging to the group we leave alone. Notice that we’re still using hypothesis testing as with the second stage but with an added wrinkle—we now have more control over some of the variables.

Each of these types of epidemiologic research may require us to develop methods to gather the necessary data or carry out the intervention. For example, we were once interested in seeing whether social support could ameliorate the adverse effects of stress on physical illness. To do so, though, we first had to develop an appropriate measure of social support because none of the existing ones met our needs. We also had to do a pilot study to determine the best way of ensuring compliance among the subjects completing health diaries (and returning them to us) during a 2-year span. These methods studies not only helped us carry out the major study but they also led to a number of publications, which didn’t do our careers any harm (we think).

Thus epidemiology covers a broad spectrum, overlapping with demography at one end, encompassing survey research in the middle, and looking much like experimental medicine at the other end. The common thread uniting all of these activities is a focus on groups of people rather than on individuals, molecules, cells, or mice.

Until relatively recently the field of epidemiology was more limited, covering only the first two aspects, descriptive studies and hypothesis testing. For this reason, studies of these types are sometimes called classical epidemiology or big-E epidemiology. Now the field includes clinical epidemiology, which got its start with the first modern clinical trial in the 1950s, although as we’ll see, the ancestry of studies of health effects of different regimens on humans can actually date back 3500 years or so. Modern epidemiology incorporates both classical and clinical epidemiology. As Cassel noted, epidemiology is an example of a discipline that has expanded beyond its initial boundaries (sort of like the Sahara Desert and our waistlines).

TRENDS IN EPIDEMIOLOGY

We like to think of the development of science as following a straight path. First, some of our primitive ancestors made an astute observation, such as how summer rain storms are often accompanied by thunder and lightning. This led to the hypothesis that a god on Mount Olympus was throwing things at us, which was later replaced by a correct theory (correct because it’s what we believe today). Based on our improved knowledge, we are now able to intervene, such as by seeding clouds to produce rain when we want it or to prevent tornadoes when we don’t want them. Thus we move from observing and hypothesizing (classical epidemiology) to intervening and improving (clinical epidemiology).

Comforting as this picture is, it doesn’t correspond too closely with reality. As we’ll see in the next chapter, epidemiology did in fact start with observation and hypothesis generation. This occurred during what has been called the Age of Pestilence and Famine, when the major health threats were infectious diseases, such as tuberculosis (TB), cholera, influenza, the plague, and so forth. This time was characterized by high and variable mortality rates, very low life expectancy, and a slow growth (if any) in the population. Starting in the 18th century, at least in developed countries, we entered into the first epidemiologic transition, usually called the Age of Receding Pandemics (a term we’ll define in the next chapter). During this stage, many infectious diseases were either completely wiped out (e.g., smallpox) or contained (e.g., polio, TB). Epidemics became less frequent, resulting in greater life expectancy, increased population growth, and less variation in the mortality rate. In a very influential book, McKeown said that at least initially, this was due primarily to an improvement in living standards, which accompanied an increase in income, and had little to do with medicine. For example, deaths in England and Wales from respiratory diseases started declining many years before we had an effective treatment for TB; indeed, before we even knew what caused it. This transition occurred later in developing countries, such as China and Mexico, and was due primarily to effective disease control, rather than individual income. But, no good deed ever goes unpunished. As life expectancy increased, we entered into the next epidemiologic transition, the Age of Degenerative and Man-Made Diseases (although in this era of political correctitude, it should probably be renamed as Degenerative and Person-Made Diseases). We are now dealing with problems that were rarely seen previously, because people didn’t live long enough to develop them (e.g., dementia and glaucoma) or are caused by lifestyle behaviors, such as smoking cigarettes and munching on potato chips while watching the 958th football game of the season. We could also call this the Age of Useful Interventions, because we can now evaluate which medicines, surgical treatments, and behavioral interventions actually produce more success stories than failures.

So far, so good; epidemiology is following the pattern that we would like to see. But at the same time that we’re moving into this latest age, we are suddenly rediscovering outbreaks of infectious diseases in the developed world. Within the past few years, a new Hantavirus outbreak occurred in the mid-western United States, and it took all the tools of the classical epidemiologists to trace it to the droppings of cute-looking mice. Similarly, TB, which we thought was almost completely wiped out through a combination of better drugs and improved housing, has come back in a more treatment-resistant form to attack people living in the city cores and especially people with compromised immunologic systems as a result of human immunodeficiency virus (HIV) infection. Even more recently, we’ve seen outbreaks of new infectious diseases, such as Severe Acute Respiratory Syndrome (SARS) and the avian flu; and in Walkerton, Ontario, in May 2000, seven people died and about 2,500 people came down with severe diarrhea and gastrointestinal symptoms from a well contaminated with a dangerous strain of E. coli bacteria. So it’s back to making observations about acute infections and testing hypotheses.

In many ways, this is similar to the prediction made in about 1900 by an eminent professor who decreed that, given the natural history of physics, approximately 3 more years of research would suffice to solve all the remaining problems. His major mistake was underestimating the survival instinct of researchers. Epidemiologists have been equally adaptive, moving from infections to chronic diseases to drug trials (where the real money is). They have been just as adaptable by moving back to studying infectious and chronic diseases as these have reemerged as major problems (thus guaranteeing many more years of employment).

CURRENT APPLICATIONS OF EPIDEMIOLOGY

In case you’re still confused about what this marvelous new (old) science is all about, this section provides some topical examples of epidemiologic studies and a hint of some of the techniques that were used.

Identifying the Cause of a New Syndrome

The late 1970s saw a number of cases of menstruating women who experienced a cluster of symptoms including fever, hypotension, and a rash, followed by desquamation (a fancy term that simply means peeling) on the hands, soles, fingers, or toes. Within a short time, 50 cases had been r eported to the Centers for Disease Control and Prevention (CDC) in Atlanta, and three women had died. Two questions required an urgent response: (1) Is this a new syndrome? and (2) What is causing it?

Through an examination of the records, it was determined that these 50 cases were presenting a new clinical entity, described by Langmuir as a distinct clinical syndrome of marked severity and considerable clinical specificity. This was labeled TSS. Let’s take a closer look at the history of this disorder because it nicely highlights many of the steps used to discover the cause of a problem and, in this case at least, the interventions needed to alleviate it.

The first step was passive surveillance. Neither the CDC nor the local public health agencies initially went out looking for cases of this new disorder. Rather, they relied on reports submitted voluntarily by local physicians and other agencies. The major advantage of passive surveillance is that no single agency is always on the lookout for an outbreak of something, especially if they don’t know what that something is or if indeed anything is breaking out at all. There is the hope that any new and especially any potentially dangerous syndrome will be noticed by the front-line people (e.g., family physicians, laboratory workers, community health nurses) and reported to the health office. The downside of remaining passive is that reporting is extremely sporadic; a person first has to notice that something is amiss and then take the time and effort to report this to some agency. So passive surveillance can alert people that something is happening, but it can’t really say how big the problem is or where the hot-spots are. This is exactly what happened with TSS; the CDC learned that there was an outbreak of a possibly new disorder, but it was still in the dark regarding the outbreak’s magnitude or what may be causing it.

Perhaps the most widely used versions of passive surveillance are published case reports and case series. Grimes and Schulz describe the case report as the least publishable unit in the medical literature; a report of a single patient with what—at least to the author—appears to be a new syndrome. Although frequently derided as non-scientific and something published simply to enliven the generally drab medical literature, there have been a number of disorders that were first described in case reports— the elephant man written up by Frederick Treves; Paul Broca’s description of aphasia due to lesions in the ventroposterior region of the frontal lobes; and William MacIntyre’s discovery of multiple myeloma. When a number of individual cases have been aggregated into a single article, it’s called a case series. This can be the first signs of an adverse drug reaction or even an epidemic, as happened with asthma patients being killed by their nebulizers containing isoproterenol in the 1960s; AIDS in Los Angeles in 1981; and eosinophilia myalgia due to contaminated L-tryptophan (bought at natural food stores) in 1989. On the other hand, they can simply reflect the co-occurrences of relatively rare events which happened by chance, but are then attributed to some underlying cause. This happened with autism and childhood vaccinations, and with silicone breast implants and systemic lupus. Given the large number of people who have been vaccinated or have had their breasts enhanced (not usually at the same time, though), it’s inevitable that some will develop a given disorder. Putting them all in one case series makes it look like cause-effect relationship. But, without a comparison group, it’s impossible to determine whether the prevalence of the disorder is the same in the group that didn’t have the intervention (it is, in both cases). In the meantime, a lot of mischief can be done—kids not receiving their inoculation because of the parents’ fears of autism in the one case, and the bankruptcy of a company in the other.

Once an agency suspects that a problem may exist, it usually then relies on active surveillance. The agency becomes more active and tries to solicit complete reporting of the new syndrome by contacting family physicians, medical officers of health, or laboratories. Depending on the degree of cooperation received, it’s now possible to get a better handle on the magnitude of the problem and perhaps to develop some hypotheses about what may be causing the outbreak. The CDC and state agencies begin to look for cases, such as TSS, using active surveillance by both getting front-line workers to report to them and examining the charts and discharge codes in selected hospitals.

To sharpen their hypotheses, the agencies began a series of studies in which people who had TSS were compared with those who didn’t (these are called case control studies, and we’ll discuss them in more depth in Chapter 3). They were particularly interested in tampon use because the previous observations led them to believe that TSS may be associated with menses. These case control studies, especially those conducted by the CDC, finally nailed down the cause. In their first study, all 52 cases used tampons, but only 85% of the control women did. In the second study, women who used the Rely brand of tampons were almost eight times more likely to develop TSS than women who used other brands. Finally, it was found that other brands were involved and that the culprit was the increased absorbency of the new and improved versions (so much for the advantages of new and improved anything).

Now to the intervention. In Figure 1-1, we see a sharp increase in TSS cases until 1980. At that point, Rely was voluntarily withdrawn from the marketplace, resulting in a dramatic decrease in reported cases. For the next 4 years, the proportion of women using very high-absorbency products dropped from 42% to 18% and down to 1% by 1986, and the most absorbent tampons, those made with polyacrylate, were taken off the market in 1985. The effect of these changes on the number of reported cases is striking.

Year

Figure 1-1. Incidence of toxic shock syndrome cases per year. (Data from The Centers for Disease Control and Prevention.)

TSS hasn’t completely disappeared, because it is caused by the staphylococcus organism, not by tampons. There are still a few cases every year, usually as a result of surgery, so it occurs in men as well as in non-menstruating women. On the whole, though, this example demonstrates the strength of epidemiologic methods. Even given a relatively rare condition, such as TSS, associated with a common practice, such as tampon use, it could nonetheless be established that high-absorbency tampons were the culprit and that removing them from store shelves could stop the outbreak.

Assessing the Risks Associated with a Harmful Exposure

Epidemiologic methods can be used to assess the risks to health that result from exposure to noxious agents. For example, with the worldwide use of nuclear reactors to generate power, the public, the nuclear power industry, and nuclear regulatory bodies are all interested (obviously for different reasons) in determining the risks associated with exposure to the radioactive emissions resulting from a nuclear accident (a benign term for a malignant condition). These interests are not merely hypothetical or academic. In 1957 the first documented nuclear accident, or substantial release of radioactivity from a nuclear power plant, occurred when a reactor caught fire at Sellafield on the Irish coast of Great Britain; in 1979 a nuclear accident occurred when a reactor was damaged at Three Mile Island; and in 1986 the most severe nuclear accident to date occurred at Chernobyl, in the former Union of Soviet Socialist Republics (USSR), when the graphite core of a reactor caught fire and caused the rupture or meltdown of fuel rods and the release of radioactive fission products into the atmosphere. Winds distributed the radioactive particles over large areas of Europe and the Northern Hemisphere.

It is of obvious importance to determine the immediate and longterm risks to the populations in the immediate vicinity of the nuclear accident and to those farther from the reactor (in other regions or countries). Fortunately, there is already a great deal of evidence available about the risks of cancer, childhood leukemia, birth defects, and so forth that result from exposure to high-level and low-level radiation. By far the most extensive source of human evidence resulted from careful follow-up during the past 5 decades of the survivors of the Hiroshima and Nagasaki bombings. The basic strategy is to document, as carefully as possible, the radiation exposure of each individual and then to compare the rate of onset of various diseases at different levels, from no exposure to a high level. Other sources of evidence derive from the documented exposure of soldiers in the atom bomb tests of the 1950s, workers at the shipyards where nuclear submarines were serviced, populations exposed to the fallout clouds in Utah and Nevada, atomic workers, and even kids (now in their ’60s) who put their feet in fluoroscopy machines at the local shoe store.

Based on this evidence the scientists have predicted that there might be as many as 39,000 additional cancer deaths worldwide during the next 50 years. Because there are expected to be approximately 630 million deaths from cancer during the same period, the increase will not be detectable. Within the former USSR, estimates range from 5,000 to 50,000 excess deaths against a background of 9.5 million cancer deaths; again, the difference will not be statistically significant. However, among the 24,000 people who lived within 15 km of the reactor site, the estimated excess number of cancers is 13, which raises the total to 624; this will be statistically detectable. Interestingly, actual data collected since that time tell a different story. One huge study of childhood leukemia involved national registries of all the European countries. There were 3,679 observed cases versus 3,533 expected cases—a relative risk of 1.04. There was no association between risk and exposure, leading the authors to discount any causal connection between the observed increase in leukemia and Chernobyl radiation. Another study looked at thyroid nodules (an early indicator of cancer from radiation exposure), comparing people in highly exposed