LESSON 2.3 WORKBOOK. How do infectious diseases spread?

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1 DEFINITIONS OF TERMS Thucydides was a philosopher in ancient Greece, who was also named the father of "scientific history" due to the meticulous recordings of his observations. For a complete list of defined terms, see the Glossary. LESSON 2.3 WORKBOOK How do infectious diseases spread? In the last lesson we learned about the invention of microscopes, and how they allowed people to see bacteria for the first time, paving the way for the discovery of diseases transmitted by microscopic 'creatures'. We also learned about methods of culturing bacteria and the identification of the first virus using superfine filters. But how do we actually prove that a particular microbe causes specific disease? Here, we will draw on what we have learned in previous lessons to establish a set of principles to test whether a microbe causes a particular disease. If a disease is infectious what will you see? As we have discussed before, people have known for a long time that some diseases can be transmitted from one person to another, they just didn t know how. Here is the ancient Greek historian Thucydides, describing the infectiousness of the plague of Athens in the 5th Century BC: People in good health were all of a sudden attacked by violent heats in the head, and redness and inflammation in the eyes, the inward parts, such as the throat or tongue, becoming bloody and emitting an unnatural and fetid breath. These symptoms were followed by sneezing and hoarseness, after which the pain soon reached the chest, and produced a hard cough. When it fixed in the stomach, it upset it; and discharges of bile of every kind named by physicians ensued, accompanied by very great distress. In most cases also an ineffectual retching followed, producing violent spasms, which in some cases ceased soon after, in others much later. 75

2 Externally the body was not very hot to the touch, nor pale in its appearance, but reddish, livid, and breaking out into small pustules and ulcers. But internally it burned so that the patient could not bear to have on him clothing or linen even of the very lightest description; or indeed to be otherwise than stark nake What they would have liked best would have been to throw themselves into cold water; as indeed was done by some of the neglected sick, who plunged into the rain-tanks in their agonies of unquenchable thirst; though it made no difference whether they drank little or much. Besides this, the miserable feeling of not being able to rest or sleep never ceased to torment them. The body meanwhile did not waste away so long as the distemper was at its height, but held out to a marvel against its ravages; so that when they succumbed, as in most cases, on the seventh or eighth day to the internal inflammation, they had still some strength in them. But if they passed this stage, and the disease descended further into the bowels, inducing a violent ulceration there accompanied by severe diarrhea, this brought on a weakness which was generally fatal. For the disorder first settled in the head, ran its course from thence through the whole of the body, and, even where it did not prove mortal, it still left its mark on the extremities; for it settled in the privy parts, the fingers and the toes, and many escaped with the loss of these, some too with that of their eyes. Others again were seized with an entire loss of memory on their first recovery, and did not know either themselves or their friends. Figure 1: Thucydides. By far the most terrible feature in the malady was the dejection which ensued when any one felt himself sickening, for the despair into which they instantly fell took away their power of resistance, and left them a much easier prey to the disorder; besides which, there was the awful spectacle of men dying like sheep, through having caught the infection in nursing each other. This caused the greatest mortality. On the one hand, if they were afraid to visit each other, they perished from neglect; indeed many houses were emptied of their inmates for want of a nurse: on the other, if they ventured to do so, death was the consequence. ( In this case, Thucydides described the disease as being infectious because those who visited and cared for the sick fell ill themselves. As we saw in the Ghost Map activity in the last lesson, the link between exposure and sickness is not always so clear. In part because so many communicable diseases have circuitous modes of transmission. 1. The following provides clues about the possible routes of transmission according to Thucydides account EXCEPT: a. infection in nursing each other b. on the other, if they ventured to do so, death was the consequence c. externally the body was not hot to the touch none of the above 76

3 What do infectious diseases have in common? How would you know that a given disease is infectious? Figure 2: Athlete's foot is caused by a parasitic fungus that can be picked up when walking barefoot on contaminated surfaces, like gym floors. We need to prove that the disease can spread The reason that athlete s foot is an infectious disease whereas poison ivy rash is not is that the rash is caused by an oil from a plant, rather than a replicating microbe. More importantly, poison ivy rash is not contagious; you cannot give it to another animal, you must directly contact the oil from the plant. Conversely, athlete s foot can spread from person to person quite easily. Just think, if one person on a basketball team gets athlete s foot, the others may soon follow! We need to be able to associate the disease with a source of infection Let's first consider athlete s foot. Athlete s foot is a transmissible infection caused by a parasitic fungus that lives in the skin. It is transmitted when an infected person contaminates surfaces that others touch with their bare skin, like the floor in a public shower. Would you say that it is an infectious disease because it can spread? For example, how does it differ from poison ivy rash? The poison ivy rash is caused by exposure to toxic oil produced by the plant Toxicodendron radicans. So, both athlete's foot and poison ivy rash are caused by skin coming into contact with something. What makes one an infectious disease but not the other, and how can you tell the difference? Figure 3: The plant Toxicodendron radicans (poison ivy), secretes an oil that causes red, itchy rash when in contact with human skin. This requirement is relatively straightforward; all people with the disease need to be exposed to and contract the infection. If you theorize that a contaminated water source is causing an illness, then those with the illness must have been exposed to the contaminated water (remember the Ghost Map from lesson 2.2). However, just correlating the symptoms with a potential source of disease does not prove that the disease is caused by the exposure. For example, people who use common water may have other things in common such as the food they eat. 2. Which of the following is proof that a disease can spread? a. it is contagious b. it is caused by a toxin c. it cannot be transferred from one organism to another all of the above 77

4 DEFINITIONS OF TERMS Lyme disease an infectious disease caused by a bacteria called Borrelia that is transmitted by ticks. Leprosy chronic infectious disease caused by Mycobacterium sp. It affects the skin, eyes, respiratory tract, and nerves. For a complete list of defined terms, see the Glossary. We need to isolate an infectious agent from all infected individuals Figure 4: To prove that a microbe is causing a disease you need to be able to identify it, and grow it in the lab. If some people with a disease are not infected with the expected microbe, can the disease be caused by that microbe? Say you are trying to prove that Lyme disease is caused by a bacterium passed to humans through ticks. You must prove that the bacterium is present both in the tick and in the infected human. That often times requires you to be able to grow the bacteria from both hosts in the lab. But some bacteria are hard to grow in the lab they might be present both in the tick and the human but you may not be able to show that, if you can't grow them in the lab. We need to show that the infectious agent we isolated can cause the disease How do you know if the microbe that you isolated is causing the disease? Remember, one in ten cells in our bodies is ours, the rest are bacteria comprising our microbiota. So, isolating a microbe does not mean that it is casing a disease. To prove that the microbe is causing the disease, you will need to isolate it and infect a person, animal or another host to show that the infection produces the symptoms of the disease. This requirement is often the most difficult to fulfill it is obviously unethical to deliberately infect someone. Figure 5: Armadillos are used to study leprosy in the lab. Their body temperature is similar to human skin temperature making it an ideal host for the leprosy bacteria. To get around this, scientists often use animals as models of disease. But sometimes an animal model is hard to find for example, armadillos are not the typical model animal for studying infectious diseases but are used as the primary one for studying leprosy. 3. If Lyme disease is caused by a bacterium passed to humans from ticks, you must be able to find a. the bacterium in the tick. b. the bacterium in the infected human. c. the bacterium both in the tick and in the infected human. the bacterium in the environment surrounding the tick and the human. 78

5 DEFINITIONS OF TERMS Autism a neurological disorder presenting as challenges in communication, social interactions, and behavior. Measles highly infectious (easily spread) disease caused by the measles virus. Mumps an infection caused by the mumps virus, characterized by painful swelling of the salivary glands on both sides of the face. Rubella an infection caused by the rubella virus, highly dangerous for a fetus if contracted by the mother in the first 20 weeks of a pregnancy. For a complete list of defined terms, see the Glossary. Correlation versus Causation Perhaps the most common mistake when interpreting data is to assume that correlation means causation. Although there will always be a correlation between a causative agent and its outcome, most correlations are not causative. For example, say there is an epidemic in a neighborhood that shares a common water supply, but the neighbors also all drink milk supplied by the same company. Both the water supply and the milk supply are correlated with the disease, so how do we decide which one is causing the illness? Isolating the same microbe from the sick people and the milk or the water is a start, but still not proof people, milk, and water may share millions of microbes. In fact, we can only prove causation by using a pure culture of a single microbe to cause disease in healthy hosts. The tragedy of mistaking correlation for causation Figure 6: It took decades to link smoking to lung cancer. You can see how tough it is to prove that a particular exposure causes disease! This has resulted in grave errors in both directions. For example, it is now widely accepted that tobacco can cause lung cancer, but for a long time the tobacco industry used scientific studies as proof that it didn t. They were able to do this legitimately because we can only make definite statements about how much tobacco alters the probability of getting cancer. For the latter half of the twentieth century, tobacco companies capitalized on this technicality and claimed that the inability to absolutely prove a causal link means that tobacco is harmless. As evidence they would say that non-smokers get lung cancer too, and many smokers never get lung cancer, therefore... More recently another mistake of correlation for causation has had horrible consequences. The diagnosis of autism have increased dramatically since the 1990s. In the early 2000s, poorly executed but highly publicized research report claimed correlation between the MMR vaccine and autism. The study was later retracte But its initial popularity, led to some parents refusing to provide their children with the MMR vaccine (Measles, Mumps, and Rubella), which prevents serious and highly infectious diseases which can result in death or permanent injury. Vaccination protects more than just individuals; vaccination plays an important role in community health by acting as a shield that stops the spread if an infectious diseases. Furthermore, there are people that can't get vaccinated or become unable to fight infections Figure 7: Most research shows no correlation between vaccination and autism, but many people think they are linke 4. Which statement is true? a. all causal relationships have correlations b. all correlations have causations c. correlation is causation none of the above 79

6 DEFINITIONS OF TERMS Pure culture bacterial culture composed of only one type, species, of bacteria that usually originates from a single cell. For a complete list of defined terms, see the Glossary. because of health conditions such as AIDS, cancer, organ transplantation or pregnancy. And these people rely on the shielding effects of the vaccinated people around them to prevent diseases such as measles. As we will see in more details later in the course, balancing the risks and benefits of any treatment that impacts individuals and community health is quite complex. The first person to formalize a process to demonstrate that a disease is caused by an infectious agent was Robert Koch. Robert Koch was a German physician at the turn of the 20th century whose research won him the Nobel Prize in He successfully isolated the anthrax, tuberculosis, and cholera bacteria and proved that anthrax spores in the soil are the source of a severe wasting disease in cows. His other major contribution to microbiology was developing a set of four criteria he called postulates that have to be satisfied in order to definitively prove a causative relationship between a microbe and a disease. Koch s postulates are summarized below, and will be the focus of our next lesson: 1. Association: The microbe must always be present in every sick person or animal, but not in healthy individuals. 2. Isolation: It must be isolated from the sick animal into pure culture. 3. Causation: The pure microbe must cause the disease in a healthy animal. Figure 8: Robert Koch. 4. Re-isolation: When the microbe is re-isolated from the sick animal it must be the same as the original. 5. Which is NOT a part of Koch s postulates? a. association it must always be present in every case but not in healthy animals b. isolation it must be isolated from the sick animal into pure culture c. causation the pure microbe must cause the disease in a healthy animal re-isolation when the microbe is re-isolated from the sick animal, it must be the same as the original e. none of the above 80

7 STUDENT RESPONSES What is an example of a disease we have seen earlier that does not fit Koch s postulates? Why? What are two types of information that can be learned from tracking patterns of disease? Use a graph or a mathematical explanation to explain why group vaccination can have such a dramatic effect on limiting spread of an infectious disease. (HINT: Think about how many people might be infected in an outbreak after a week if no one is immune or vaccinated vs. if 50% of people are vaccinated, assuming a vaccine is 100% effective how might the vaccination rate change the number of people newly infected each day?) 81

8 TERMS TERM DEFINITION Athlete's foot Autism Leprosy Lyme disease Measles Mumps Pure culture Fungal infection of the skin that affects mostly the webs of the toes and the soles of the feet. A neurological disorder; people who have it experience challenges in communication, social interactions, and behavior. Chronic infectious disease caused by Mycobacterium sp. It affects the skin, eyes, respiratory tract, and nerves. An infectious disease caused by Borrelia species and transmitted by ticks. A highly infectious (easily spread) disease caused by the measles virus. An infection caused by the mumps virus, characterized by painful swelling of the salivary glands on both sides of the face. Bacterial culture composed of only one type, species, of bacteria that usually originates from a single cell. Rubella An infection caused by the rubella virus, highly dangerous for a fetus if contracted by the mother in the first 20 weeks of a pregnancy. 82