BIOL 011, Week 1 Notes
BIOL 011, Week 1 Notes BIOL 013
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This 14 page Class Notes was uploaded by Whit e on Wednesday August 3, 2016. The Class Notes belongs to BIOL 013 at 1 MDSS-SGSLM-Langley AFB Advanced Education in General Dentistry 12 Months taught by Thomas Jack in Summer 2016. Since its upload, it has received 7 views. For similar materials see Gene Expression & Inheritance in Biology at 1 MDSS-SGSLM-Langley AFB Advanced Education in General Dentistry 12 Months.
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Jan. 4th What is an infectious disease? Mary Lou Guerinot Research: Malnutrition Her lab studies malnutrition, which is a massive problem worldwide. They have focused in on iron deficiency, which is the leading nutritional disorder in the world today, affecting approximately 3 billion people. Most people receive iron through plants, which are poor sources of iron. Her lab is trying to determine how plants take up iron, and how does the iron get absorbed by the parts of the plant people consume? Zinc deficiency affects over 2 billion people and has negative effects on childhood development and immune function. Many of the children who suffer from iron and zinc deficiency live in parts of the world where infectious disease runs rampant. They are more susceptible to infectious diseases because of their immunocompromised state. Vitamin A deficiency causes blindness. Iodine deficiency affects approximately 1.5 billion in China leading to goiter problems (enlargement of thyroid gland). The developed world has prevented this by adding iodine to salt. 10 Leading Causes of Death In the 1900, the top three killers were infectious diseasesinfluenza and pneumonia, Tuberculosis, and various forms of Gastroenteritis. Today, the leading causes are non microbial diseases, such as heart disease, cancer, and stroke. From the point of view epidemiology, it might seem that this switch from 1900 to 2015 means that people are dying from cancer, heart disease, and stroke in much higher numbers than they are infectious diseases. However, this data is only snapshot of the United States or a developed country. We need to ask what populations are being represented. These sources of disease may only represent a specific gender or age group. Causes of death in Africa and the Americas, 2008 Almost half of deaths in Africa are due to some type of infectious agent, whereas if we look in the Americas, it’s only 12%. Injuries as the cause of death are about the same in either sector (Am 14%, Afr 6%). Factors responsible for emergence Human demographics and behavior, Technology and industry, Economic development and land use, International travel and commerce, Microbial adaptation and change Breakdown of public health measures can be due to natural occurrences such as earthquakes. There had not been a large outbreak of cholera in Haiti in over 200 years until after the earthquake several years ago. Breakdown of public health measure can also pose a big problem during war, especially because it may disrupt the delivery of services, such as clean water, sanitation, or vaccination. Jan. 4th What is an infectious disease? Brief History of Infectious Disease Contagious Diseases have been around for a long time. We clued into them when mankind found out that diseases were transmissible. Black Death, also known as the Plague, was prevalent during the middle ages. Doctors at the time were ignorant of the etiological agent of Medieval Black Death, which we now know to be gramnegative bacteria Yersinia pestis. It killed roughly ⅓ of the world’s population (25 million people). The first outbreak of the Plague occurred at the end of the classical era around 600 A.D. The plague was one of the factors that contributed to the end of the Roman and Greek empires. The frequent deaths as a result of the plague pushes people into the Dark Age, where people become highly suspicious of travelers, and trade stops, and infected towns. Much to our confusion, the plague disappears from the human population, but remains endemic in the animal population until it reappears in the Middle Ages. The plague came out of Asia and started to travel West. In 1346, the plague is present in Caffa, and in the following spring of 1347, it is present in Constantinople. This is very significant because Constantinople was a major port for the Mediterranean. It took three years for the bacteria to reach Northern Europe, and once it infected all ports along the Mediterranean, people became aware that sailors were bringing in the plague. The first method of control was to employ quarantines (from the Italian q uarentina, meaning forty days for the time of isolation of ships entering the harbor which were suspected of carrying some form of contagion). Although the sailors couldn’t leave the ships, the rats could go as they please. Even rats aboard docked quarantined ships had easy egress, because they could climb down the mooring ropes and onto the docks. Fleas carrying Y ersinia pestis prefer to remain on the rat, but if the rat dies of bubonic plague, the flea will latch onto another warm mammal, which may unfortunately be a human. The flea, however, is does not die from plague; it only carries the bacteria. When it’s infected with Y ersinia pestis, the bacteria prevents the flea from being able to digest its blood meals well. The pathogen modifies the behavior of its host to its own benefit. The flea will continue to bite humans to survive, much to the detriment of mankind. Discovery of Microbes Microbes are too small to see with the naked eye. How small is that? Less than a tenth of millimeter (0.1 mm) encompasses many different kinds of organisms (bacteria, archaea, virus, algae, small animal (protus)) Cause and Effect: The Germ Theory of Disease Antoni van Leeuwenhoek (16721723) contributed to the science of microbiology by making the first microscope to view microbes. He began making more and more powerful lenses, and was able to receive up to 300x magnification. He writes a paper to the Royal Society of London in 1684 about his microscopic observations about animals in the scurf of the teeth. Jan. 4th What is an infectious disease? “…Tho my teeth are kept usually very clean, nevertheless when I view them in a magnifying glass, I find growing between them a little white matter as thick as wetted flower (observation): in this substance tho I do not perceive any motion, I judged (hypothesized) there might probably be living creatures. I therefore took some of this flower and mixt it either with pure rainwater wherein were no animals (methods) or else with some of my spittle (having no air bubbles to cause motion in it) and then to my great surprise perceived the aforesaid matter contained very many small living animals which moved themselves very extravagantly.” Spontaneous Generation Greek Aristotle first put forward the Theory of Spontaneous Generation which held sway for almost 1900s years. Now discredited, it once stated that “living organisms could arise spontaneously from nonliving material.” For example, mice could arise from grain left to sit in a dark place. Redi’s Experiment Franceso Redi (16261678) was a contemporary of van Leeuwenhoek and student of Galileo. He was interested in disproving the theory spontaneous generation. He conducted an experiment to show that if flies were denied access to meat, maggots would not form from fly eggs, causing people to begin to believe that animals could only come from other animals. He also stoppers a flask, preventing flies from depositing eggs onto the meat. This variation of his first experiment seemed like maggots develop on meat when left exposed to air. People thought that because the vital force, oxygen, has been stoppered, spontaneous generation of life is prevented. Louis Pasteur (18221895) He was interested in what he perceived to be organisms that caused milk and wine spoilage, especially wine, which was very important to the French economy. Pasteur poured nonsterile liquid into a flask, used heat to draw out the neck of the flask, and sterilized the contents of the flask using heat. If the flask remained upright, no microbial growth occurred. If microorganisms trapped in the neck of the flask reached the sterile liquid, microbial growth ensued. Jan. 4th What is an infectious disease? Robert Koch (18431910) Robert Koch was a German country doctor very interested in TB (1 in 7 people died from TB) . He is credited with demonstrating the first direct link between a single microbe and a single diseaseBovine Tuberculosis in cows. Koch Postulates . hypothesized a way to determine the source of an infectious disease. Exceptions/Challenges of Applying Koch’s postulates in all Cases Lina Hesse Dr. Hesse came to Germany from the US to work with Robert Koch in determining causative agents for disease. He complained to Lina that his experiments were being ruined by his gelatin melting in the hot summer sun. Lina grew up on the NJ shore, where she extracted agar from seaweed to solidify jams and jellies. Having received the suggestion to use agar to solidify his plates, Dr. Walther Hesse introduced the use of agar to the field. The Petri dish is named after its investor, J. Richard Petri. The closedlid plastic dish is still used by biologists to culture cells because it lessens the risk of contamination from airborne particles. Jan. 4th What is an infectious disease? Golden Age of Microbiology (18541920) Applying principles and methods elucidated by Koch and Pasteur, the causative agents of many important diseases including TB, plague, cholera, tetanus, and influenza were identified. Both guys sent spies to China to retrieve a sample contaminated with the plague bacteria. The bacteria was isolated and using an animal model, showed what the causative agent was. Ignaz Semmelweis (18181865) He is an Austrian doctor, working in Vienna Maternity Ward where women were dying of childbirth fever (puerperal sepsis). He was very concerned and he knew that 50% women would come down with childbirth fever in the hospital. He believed doctors were transmitting the causative agent of childbirth fever by not washing their hands after completing an autopsy then delivering babies. He was committed to an asylum, and later dies of an infected finger caused by the same bacteria that causes childbirth fever. He suggested that doctors wash their hands before seeing a patient. This was effective because the doctors were transmitting the bacteria from cadavers (i.e. patients who had died of childbirth fever) to patients who were about to give birth. Methods of transmission: primary pathogen/inoculation contact exposure (cohousing bats) airborne exposure Jan. 6th Principles of Epidemiology Infectious Diseases are “diseases of infectious origin whose incidence has increased in the past two decades or threatens to increase in the near future.” Drivers of pathogen emergence and reemergence: those related to humans those related to pathogens those related to the environment Since 1980, the number of emerging infectious diseases lies between 2550. Experimental infection of bats with G eomyces destructans (new name is Pseudogymnoascus de structans) causes whitenose syndrome What is Whitenose syndrome (WNS)? WNS is named for the white fungal growth that invades the skin tissue (including the muzzle) of hibernating bats. White nose syndrome has killed over 6 million bats in North America. The fungus is a psychrophile (cold fungus) that cannot grow beyond 20 C, but it can grow between 4 C and 20 C, which happens to be the temperature in the North American caves where the bats are hibernating. Did they fulfill Koch’s postulates? Yes. (by inoculation, contact exposure, air transmission) What criteria did they use to definitely prove this fungus causes whitenose syndrome? Histological examination, or the study of skin tissue under a microscopic lens, showed that treated bats that died during the course of the experiment showed that lesions diagnostic for WNS were apparent by 83 days after treatment. This confirmed that G. destructans is the causative agent of whitenose syndrome. They use histological examination of wing membranes to determine whether or not lesions diagnostic of WNS appear after bats are inoculated with fungal spores. Fungal cell walls are rich in carbohydrates. AcidSchiff stain stains carbohydrates, allowing them to see if there are any fungal structures within the wing of the bats. By this criteria, they have induced whitenose syndrome disease. Negative control: healthy bat Positive Control: Bats naturally infected in the wild are brought into the lab for study Positive Control: Bats treated with G . destructans Jan. 6th Principles of Epidemiology In what ways was the study incomplete? They chose 102 days as the cutoff date for the experiment because that is about the length of time North American bats remain in hibernation. How do they explain the fact that this fungus does not cause huge dieoffs of bats in Europe? Lorch et al explained that P seudogymnoascus destructans is a novice pathogen to North American bats, so it is much more dangerous to the population. European bats, on the other hand, have been coevolving with these fungal spores. What kind of experiment can be done to induce dieoffs in European bats? Expose European and North American bats to the same treatment of fungal spores, and document the results. Likewise, one can isolate spores from the caves of European and North American bats and find comparisons. Robert Koch Robert Koch was a German country doctor very interested in TB (1 in 7 people died from TB) . He is credited with demonstrating the first direct link between a single microbe and a single diseaseTuberculosis. Koch Postulates . hypothesized a way to determine the source of an infectious disease. 1) The bacteria must be present in every case of the disease and absent from healthy animals. T ools: microscopy staining 2) The bacteria must be isolated from the host with the disease and grown in pure culture. Tools: Laboratory culture 3) The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host. Tools: Experimental animals 4) The suspected pathogen must be reisolated and shown to be the same as the original. Tools: Laboratory reisolation and culture Exceptions/Challenges of Applying Koch’s postulates in all Cases 1) S. aureus lives comfortably within the noses of about 40% of humans without showing any symptoms of infection (asymptomatic carriers). Yet, S . aureus can be a deadly pathogen in immunocompromised pathogens. 2) Without the optimal temperature, nutrients, and environmental conditions, we cannot always grow suspected pathogens. In the case of viruses, scientists have to grow them inside a host cell (modified). 3) It is hard to always have a perfect animal model. There are some diseases for which we are the only hosts. It is unethical to challenge the pathogen against healthy humans. For HIV we can use monkeys, but monkeys don’t show the same symptoms as humans with full blown AIDS. Jan. 6th Principles of Epidemiology Epidemiology is the study of the occurrence, distribution, and control of infectious disease in populations (humans, animals, plants, etc.) Pathogenesis o rigin/cause of a disease Mortality incidence of death in a population Morbidity incidence of disease in a population (common cold has high morbidity, but very low mortality) (Ebola has high mortality, but very low morbidity) Reservoir sites in which viable infectious agents may remain alive and from which infections can occur (living, human reservoir where we’re the only host; domesticated animal population is the reservoir for Rabies) (Cholera has an inanimate reservoir, water) Carriers infected individuals not showing any signs of disease (workers in the food service industry S . aureus) Zoonoses diseases which occur primarily in animals but can be passed to humans; A Zoonotic agent is rabies. Endemic disease Epidemic disease constantly present, usually occurs in high number of individuals distributed at low incidence in a population in a community at the same time (plague is endemic to Rocky Mountains) Epidemiologists investigate 5 links in the infectious disease cycle: 1. Characteristics of the infectious organism (what causes WNS) 2. Source and/or reservoir of the infectious organism (sometimes the same, sometimes not) 3. Mode of transmission (airborne disease, waterborne, sexual transmission, animal/insect transmission) 4. Susceptibility of the host (which populations do we have to worry about and protect if there are any protective measures that can be taken. Young children & the elderly are often at high risk Jan. 6th Principles of Epidemiology for different infectious diseases because of immune deficiency. In young children, the immune system has not been built to withstand most infections, and the elderly are experiencing a decline in immune function. HIV patients are also at risk because they, too, are immunocompromised. 5. Exit mechanisms (how the organism is being shed back out into the environment or passed from person to person; TB enters and exits the body via the respiratory route. Protective measures against the spread of cholera typically involve proper treatment of sewage systems. John Snow father of epidemiology (1850s) By being the first to apply geographic principles to the spread of disease, he was able to stop a cholera outbreak in London. Using a map, he marked where new outbreaks of cholera occurred within a neighborhood. He finds a direct correlation between drinking water from the Broad Street pump and cholera outbreaks. Having formed his hypothesis that the cholera outbreak was related to the drinking water supply, he removed the handle off the Broad Street pump, stopping the cholera outbreak. His observations went further to ask what water company was supplying the Broad Street pump. He found that the company supplying water for the Broad Street pump was taking its water downstream of the sewage outfall in London. Another water supply company retrieved its water upstream of the sewage outfall, and the recipients in that neighborhood were not infected by cholera. Typhoid Mary They proved her gallbladder was chronically infected with Salmonella typhi (gramnegative bacteria), the causative agent of typhoid fever. Mary Mallon would work in private homes, and cook for family members, and once the fever became fatal, she would go to work in another house. She was cooking for one family in Long Island and once the entire family fell ill with typhoid fever, George Soper, a health inspector, was sent in to determine the source. When she was accused of being the source of infection, she was outraged and vehemently opposed to removing her gallbladder. She was imprisoned, and after she was released early under the condition that she no longer cook, she changed her name and disobeyed court order. Mary Mallon was a threat to public safety and was shedding Salmonella typhi from her GI tract to food. Because she did not wash her hands, households fell ill. Public health measures for the control of epidemics 1. Controls directed against the reservoir (hard for Rabies; easy when there is a good public health measures to keep drinking water separate from sewage stream) 2. Controls directed against transmission (depends on how it’s transmitteddiseases transmitted via respiratory route can be very hard to tackle) 3. Vaccinations (if we can vaccinate someone against a disease, we are taking a preventative measure against future epidemics) 4. Quarantine (Typhoid Mary) Jan. 6th Principles of Epidemiology 5. Surveillance Herd Immunity and Transmission of Infection Herd immunity is defined as general immunity to a pathogen in a population based on the acquired immunity to it by a high proportion of members over time. We are concerned about how many people have to be vaccinated to prevent the spread of a disease. How infectious is the agent? This clues us into how many people need to be vaccinated to confer immunity. R 0 the number of infectious cases that develop from one infected person. The US government does have the authority to quarantine people but we almost never quarantine alone. Main Factors responsible for Emerging Infectious Diseases 1. Human population growth exacerbates transmission and exposure to infectious disease 2. Increased Urbanization 3. Human Behaviors and attitudes 4. Technological advances 5. Ecological disturbances (particularly in context of Lyme Disease) 6. Rapid development of resistance by diseases and their vectors (e.g. insects) How many cells are in the human body? roughly 10^13 cells How many microbial cells in and on a human body? 10^14 10x as many microbial cells on or in you than the cells in the human body 500 1000 in the gut most are anaerobic (requiring an absence of free oxygen) 500 1000 on the skin “microbiome” we are functioning as a community of several thousand species Definition of Emerging Infectious Diseases (CDC) “Diseases of infectious origin whose incidence has increased in the past two decades or threatens to increase in the near future.” Drivers of pathogen emergence and reemergence: those related to humans (population growth is at the center, urbanization, population health, and hospitalization, travel, and migration patterns) those related to pathogens (capacities to adapt to humans and to acquire virulence factors and antibiotic resistance; failures of disease control programs) those related to the environment (land use, agricultural practices, production and supply of food and water, trade in animals or animal products, and climate change) Overpopulation facilitates all modes of infectious disease transmission All of these modes of transmission will increase as human population increases. Persontoperson (direct) If the density of people and the encounters they have are increased, transmission will be increased. Biotic/abiotic vector to human (e.g., mosquito, tick, waterborne disease, etc.) It is easier for a mosquito to bite an infected person, become infected itself, and bite a second person if a place is densely populated. If there are more people drinking contaminated water, the likelihood of disease increases. For example, the water in New York City must be cleaner than the water in Hanover, NH because NYC is more densely populated. We’re not so concerned about what’s in the water more than we are about it’s potential to cause disease. They have to chlorinate more intensively to lower the number of pathogens. Zoonosis (animal to human) If there are more humans, there are more interactions with animals, and a greater risk of infection in humans. Which components of population demography facilitate EID? population growth. Not necessarily the size of the population, but its density. Population age structure is very important. As we know, Why are tropics important for EID? The temperatures do not remain cold long enough to kill most infectious agents. Tropical climates provide for a diversity of species. Urbanization (world’s population is becoming concentrated in cities) of the human population exacerbates (makes worse) some aspects of infectious disease transmission but in other ways makes it easier to combat infectious disease. Give two examples of each. Makes worse: crowding will enhance person to person contact crowding coupled with poverty will stress health infrastructuresewage disposal, drinking water supply, health care services potential rodent increases (unless waste and garbage is disposed of) Makes Easier: easier to immunize as population is more concentrated easier to provide access to health care services as population is more concentrated easier to provide drinking water and sewage treatment as population is more concentrated. Human Behaviors and Attitudes Societal Factors Increased use of daycare and preschools increases childhood illness. Aging population and increased use of nursing homes. Elderly have compromised immune systems, and with such close proximity to other elderly people, infectious pathogens are constantly being transmitted. Increase in tattooing and body piercing, which can lead to infection. Globalization and central processing of the food supply lead to widespread outbreaks of foodborne illnesses. Intensive Agriculture Increases risk of zoonotic diseases (SARS, MERS, influenza, Nipah virus, Hendra virus) As we farm more intensively, we’re cutting down forests and turning them into farms. The animals that once lived in the forests move closer to where humans reside. We interact with them and become exposed to their viruses. Some of their viruses can cross the species barrier into humans. Nipah virus fruit bats and pigs Hendra virus horses Exchange of viral bits and pieces (swine flu). Human migration (wars, humaninduced disasters, e.g. large hydro dam projects, earthquakes, tsunamis) Internally displaced persons (IDPs) & refugees (transmission/movement of diseases from native lands, overcrowded conditions, breakdown in hygiene) Culture / complacency Funeral practices handling infected bodies Ebola in West Africa; The funeral practices require one to touch the body of a person. While the cultural practice may be good, from the point of view of an epidemiologist, this is a highly dangerous practice because the fluids on that body are the means of transmission. Sex & Drugs p ossible resurgence of AIDS Technology as a Habitat for Diseases Do automated faucets increase hygiene? About 50% water samples from automated handsfree faucets grew Legionella bacteria compared with ~15% from manual faucets. Legionella causes two syndromes: Legionnaires’ disease (pneumonia symptoms) or Pontiac fever (flulike symptoms with pneumonia) Why has nothing become resistant to soap? Soap dissolves the membrane. Before air travel, the probability of a person traveling long distances was low. Now that air travel is in place, global transmission has increased. There are some examples where technology doesn’t work in our favor. Climate change causes ecological and societal disturbances that can increase the incidence and distribution of infectious diseases. As the climate warms, these animals species will be able to expand their range. Technological Advances medical procedures Nosocomial infection (hospital acquired infection): Blood products can be a source of infection: Examples: HIV, hepatitis, syphilis, malaria, Chagas disease Organ transplants or invasive medical procedures, e.g., biopsies, can transmit infectious agents: Examples: HIV & Chagas disease Generally patients with compromised immune systems are most at risk ()e.g., AIDS, TB, etc) Evolution & Adaptation by Disease Organism Antibiotic misuse leads to increase in drugresistant bacteria due to rapid adaptation and intense selection (i.e. Darwinian evolution) that favors resistant types