Bio Final

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Does evolution have an outcome? What do we call the changes that evolution generates in organisms? Are all genetic changes beneficial? Are some neutral or harmful?

A beneficial change in the phenotype due to genetic change is called an adaptation. If a virus changes its surface antigens, and the virus is no longer detected by your immune system, then the virus has adapted to evade your defenses. The virus then persists and induces your cells to make more viruses with the same adaptation. Some mutations are neutral. That is, they confer no benefit and no harm. For example, a gene can change but still make the same protein product. Some mutations are harmful. For example, mutation in a skin cell can cause cancer and in gamete can cause a genetic disorder in offspring.

Evolution can occur in the absence of a force to push genetic change, but most evolution is the outcome of a process. What is that process and how does it work?

A mutation in the genome of an individual will only increase in a population if it confers some advantage to the individual who has it. Thus, if it promotes the survival of an individual, then it will be passed on to succeeding generations if reproduction is also 2 successful. Those who do not have the mutation may be less likely to survive and reproduce. This "selective" process is called natural selection. Some survive and reproduce, others do not survive or, at the very least, do not reproduce and fail to pass their genes on to the next generation.

syndemic

A syndemic or synergistic epidemic is the aggregation of two or more concurrent or sequential epidemics or disease clusters in a population with biological interactions, that exacerbate the prognosis and burden of disease. The term was developed by Merrill Singer, a medical anthropologist, in the mid-1990's. An example is the frequent cooccurrence of Pneumococcus bacterial infection (a form of pneumonia) during an influenza epidemic. A particularly relevant example is the co-occurrence of seasonal influenza and COVID-19. Syndemic interactions can worsen the outcome for a subject or improve the condition. As an example of the latter, an HIV infection is suppressed by an acute measles infection. While the exact mechanism is not known, the number of helper T-cells is reduced during a measles infection, thus reducing the number of cells potentially infected by HIV, or the measles virus may promote chemical secretion by cells that inhibits HIV activity, as two possible mechanisms of HIV suppression.

With respect to infectious disease, define "endemic". Provide several examples of endemic diseases. Is it possible that SARS-COV-2 can become endemic in the U.S. despite the expectations of herd immunity? If so, how might that occur?

An endemic disease is one that repeatedly re-emerges in a population. Examples include: If COVID-19 antibodies do not provide long-lasting protection against the coronavirus, then the disease will re-emerge where vaccination rates are too low to confer herd immunity. Only about 45% of adults in the U.S. get the seasonal influenza vaccine and yet there were 34,000 influenza deaths in 2018-2019.

What is an epidemiological triangle or triad?

An epidemiologic triangle or triad is a tool that scientists use for addressing the three components that contribute to the spread of disease: an external agent (pathogen), a susceptible host and an environment that brings the agent and host together. Where a vector is present it is included at the center of the triangle.

how can analytical studies test the relationship between cause and effect

Analytical studies measure the association between exposure and outcome and include a comparison group. Two commonly used analytical study types are cohort and case control. A cohort study examines a group of similar age or that have another characteristic in common, such as occupation. Members of a cohort exposed to a disease are compared to members of another cohort not exposed to the disease, and the outcomes of exposure are compared. The comparison allows for an assessment of risk to unexposed cohorts in other populations, and the likely outcome for infections. A case-control study compares those who already have a rare disease or a disease with a long period of latency (case) to those who do not have the disease (control). For example, during an outbreak of Hepatitis A in Pennsylvania in 2003, those who contracted Hepatitis A (case) were asked where and what they had eaten. Another group of people who ate the same food at the same restaurant were compared (control). It was determined that green onions in salsa were the source of the virus.

How is epidemiology and the information obtained through epidemiological methods used?

Assessing the community's health, making decisions about individual behavior, Documenting the clinical picture of the illness. searching for causes to avoid future outbreaks,

In what ways can bacteria undergo genetic change? What are some of their adaptations for survival?

Bacteria experience spontaneous mutations in the bacterial chromosome and in plasmids. These mutations can be beneficial, neutral, or harmful. If beneficial, they can increase in frequency in the population due to natural selection. Bacteria also exchange plasmids via conjugation and can acquire plasmids from the environment. If there is a beneficial gene that they do not already have, then natural selection can increase the frequency of a beneficial gene in the population due to natural selection. Bacteria also acquire genes from viruses called bacteriophages. These new genes are generally harmful and are used to create new viruses that eventually destroy the bacterial cell. Genetic engineering frequently uses bacteriophages to insert genes into bacteria that will produce products useful to humans, such as the gene for insulin. As the bacteria grow and divide, they produce large amounts of the hormone insulin. Bacteria have also evolved endospores that are resistant to stressful external and internal environmental conditions. These spores facilitate transmission and infection. Bacteria also form and colonized biofilms where they hide from immune responses and antibiotics. Bacteria have evolved resistance to commonly administered antibiotics.

How did China respond to the outbreak and where is China now with COVID-19?

China took aggressive action at the start of the outbreak, shutting down transportation in some cities and suspending public gatherings. Officials isolated sick people and aggressively tracked their contacts and had a dedicated network of hospitals to test for the virus

What are two most common types of epidemiological studies?

Descriptive and analytical. Descriptive studies attempt to answer the question of "what happened?" and are useful if there is no prior knowledge of a new disease. Typically, descriptive studies attempt to determine three things with regard to a disease outbreak: who (person), where (place) and when (time). The end goal is to formulate a hypothesis that explains the outbreak. Analytical studies test the relationship between cause and effect. The end goal is to test the hypothesis formulated from descriptive studies.

Explain how descriptive studies answer the question of "what happened?"

Descriptive studies begin when there is a disease outbreak. Disease outbreaks may be first identified when similar cases occur close together in time or location. For example, three science faculty (person) at Lock Haven University (place) were diagnosed with Hepatitis A (a foodborne illness) after dining together during Thanksgiving week (time). Disease outbreaks are also identified when public health surveillance systems contain multiple incidents of reportable diseases. A reportable disease is a disease that must be reported to federal, state, or local health officials when diagnosed. For example, diseases that must be reported to the Centers for Disease Control (CDC) include tuberculosis, poliomyelitis, botulism, cholera, smallpox, giardiasis, hepatitis A, B, & C, HIV, Lyme Disease, measles, mumps, rabies, and others. Person. Information about an infected person is useful and includes age, sex, location of residence and work, occupation, travel history, visitations to restaurants and stores, medications, drug and tobacco use, and sexual activity. For Hepatitis A (a foodborne illness), one would want to know which foods were eaten and where you dined, at home or in restaurants? The information for each person is referred to as a case report. Place and time are used to determine incidence and prevalence of a disease outbreak. Place. The distribution of infected persons can help isolate the source of an outbreak and a point map helps identify where a disease is clustered. The place could be inside a building such as a hospital or an office building, or a specific community, or a geographic area. For example, a point map of Ebola outbreaks in equatorial Africa since 1976 (see map in presentation) helps identify where the disease is clustered. Time. When a disease outbreak occurs, epidemiologists plot the number of new cases over time. Such a timeline is called an epidemic curve. The epidemic curve for an outbreak of hepatitis A is shown in the illustration on the presentation. Beginning in late April 2004, the number of new cholera cases rises to a peak of twelve new cases reported on May 12, and then the number of new cases gradually drops back to zero by May 21. Knowing that the incubation period (review the definition of this term in Worksheet #1) for hepatitis A averages about 28-30 days, the investigators concluded that this was a point source epidemic because the cluster of new cases all occurred within the time span of a single incubation period. Epidemic curves that have a series of successively larger peaks, with the successive waves tending to involve more and more people, are known as propagated epidemics. For example, the SARS-CoV-2 pandemic in the U.S. (see propagated epidemic curve in the presentation). COVID-19 has an incubation period of 2-14 days, averaging 6 days. An epidemic curve that shows a continuous infection rate that is longer than the incubation period indicates a common source epidemic. For example, the cholera outbreak in London was from a contaminated well and stopped when the well was disinfected with chlorine and the pump handle removed. Cholera has an incubation period of 1-3 days, much shorter than the length of the outbreak

Can pathogens afford to eliminate their host? When would host destruction result in the demise of the pathogen? In what circumstance would it pay to completely eliminate the host?

Diseases that have an obligate relationship with the host would also be eliminated if the host were to be killed off entirely. This would be an evolutionary dead-end for the pathogen. Diseases that are extremely virulent are most susceptible to this scenario, but pathogens rarely kill off all of the host individuals. As such, pathogens generally evolve to obtain benefit from host without killing it. Many helminth worms complete their life cycle within humans and may make us miserable, but rarely kill us. Diseases that have a facultative relationship with a host and would not be eliminated because they have other compatible hosts or can be free-living in the environment. Many fungal diseases fall into this category because they have alternate hosts and/or can live freely in the natural environment. They generally do not evolve adaptations that prevent killing of the host. Amphibian chytrid fungus is an example of a fungal pathogen that kills off amphibian species but has many alternate hosts. The alternate hosts serve as "reservoirs" should one of the hosts be eliminated by the fungus.

What happened on cruise ships during the outbreak in New York?

During February 3-March 13, 2020, in the United States, approximately 200 cases of COVID-19 were confirmed among returning cruise travelers from multiple ship voyages, including the Diamond Princess and Grand Princess, accounting for approximately 17% of total reported U.S. cases at the time. The Diamond Princess and Grand Princess had more than 800 total COVID-19 cases, including 10 deaths. As of September 2020, the cruise industry had returned more than 250,000 seafarers to their homes from ships around the world. However, an estimated 300,000 crew members remained trapped onboard ships worldwide. CDC had a "No Sail Order" in-place from March 14 to October 29, 2020 that suspended cruise ship passenger operations in the United States from July 20 through September 21, 2020. As of October 30, 2020, CDC is enacting a phased approach to resuming passenger operations. The initial phases will consist of testing and additional safeguards for crew members. CDC will ensure cruise ship operators have adequate health and safety protections for crew members while they build the onboard laboratory capacity needed to test crew and future passengers. Cruise ship operation is currently suspended around the world until at least the start of 2021

Why do epidemics and pandemics occur? What change or event might trigger an epidemic?

Epidemics occur when pathogen and susceptible hosts are present in adequate numbers, and the pathogen can be effectively conveyed from a source to susceptible hosts. More specifically, an epidemic may result from: • A recent increase in amount or virulence of a pathogen. Environmental conditions can increase the abundance of a pathogen. Global warming seems to be associated with an increase in the frequency of a plant and animal pathogens, especially fungal diseases. An increase in virulence can be associated with the pathogen -- evolves means to overcome the host's defenses and/or evolves the ability to cause more than normal damage to the host and/or evolves mechanisms to evade detection by the host's defense systems. This assumes that the host is unable to quickly evolve new defenses against the more virulent form of the pathogen. • The recent introduction of the pathogen into a new setting where it has not been before. European explorers, conquistadors, and colonists brought new diseases, such as smallpox, to the Americas where they wiped out human populations in Central and North America. Fungal diseases from Europe have wiped out amphibian and bat populations in North America. A new fungal disease identified in European newts, called Bsal (Batrachochytrium salamandrivorans), is likely to extirpate many amphibian populations should it be introduced to N.A. 5 An enhanced mode of transmission so that many more susceptible persons are exposed. Entry of pathogens into air conduction systems in buildings has resulted in enhanced transmission. For example, Legionnaire's disease, a pneumonia-like respiratory disease, is caused by the bacteria Legionella pneumophila. Scientists first identified it in 1977, 6 months after a mysterious outbreak sickened 180 people and killed 29 attending an American Legion convention at a Philadelphia hotel. Legionella is an airborne disease carried in tiny water droplets and occurs naturally in the environment. However, the bacteria were discovered in the air ventilation system of the hotel where the outbreak occurred. Since then, the number of cases each year continues to rise (see illustration in the presentation). Is the steady increase related to an increase in the use of air conditioning? • A change in host susceptibility to the pathogen. Host defenses can weaken due to environmental (physical and social) stressors, used of legal and illegal drugs, immunosuppressants, increasing age, and the presence of comorbidities. As with COVID-19, those with reduced defenses are more likely to be placed on life support and die from the disease. • Factors that increase host exposure or involve introduction through new portals of entry. COVID-19 was introduced to N.A. via air travel. Chaga's disease persists and spreads via blood transfusions in N.A. and Europe. In the past, disease transmission increased when maritime transport of goods increased, and even earlier through overland transport of food (grains) and other goods that carried disease vectors such as rats (carried the bubonic plague).

Are epidemiologists' medical doctors? What education do they require?

Epidemiologists are rarely licensed, practicing physicians. They are public health professionals who investigate patterns and causes of disease in humans and seek to reduce the risk and occurrence of negative health outcomes through scientific research community education, and health policy. Epidemiologists require a master's degree known as a Master of Public Health (MPH), to work in their chosen career field; some epidemiologists have doctorates (Ph.D.'s). Their education generally includes biostatistics, behavioral studies, immunology, health services and administration and epidemiological methods. Licensure of epidemiologists is voluntary and is offered by the Certification Board of Infection Control and Epidemiology.

Epidemiology

Epidemiology comes from the Greek epi meaning "upon or among", demos meaning "people or district", and logos meaning "study of". Epidemiology is the branch of medical science that deals with the incidence, distribution, causes, and control of infectious disease and other health factors (such as cancer, heart disease, and obesity) in a population. Epidemiologists study the population, not the individual. The term was first used to describe the study of epidemics in 1802 by the Spanish physician Joaquin de Villalba in Epidemiología Española.

Identify the two infectious diseases for which herd immunity has achieved total global eradication of a specific disease. Name the third disease for which we are on the brink of attaining total global eradication?

Eradication means that the disease has been eliminated. Smallpox and rinderpest have been eliminated globally. Polio still occurs in two countries, Afghanistan and Pakistan, and is on the brink of eradication. The misconception of people about polio vaccine, insecurity within the country and poor health system are the reasons of failure of polio eradication campaigns in these regions. Rinderpest, a serious disease of cloven-hooved animals and domestic cattle, was declared eradicated by the World Organization for Animal Health (OIE) on 25 May 2011. Development of the Plowright tissue culture rinderpest vaccine (TCRV) in 1960 was an important milestone in rinderpest control that gave impetus to the first coordinated effort to eradicate rinderpest from all of Africa. However, potentially infectious rinderpest virus material remains widely disseminated among research and diagnostic facilities across the world and poses a risk for disease recurrence should it be released. Smallpox has existed for at least 3000 years and was one of the world's most feared diseases until it was eradicated by a collaborative global vaccination program led by the World Health Organization (WHO). The last known natural case was in Somalia in 1977. In 1980, the WHO declared that smallpox had been eradicated. Small quantities of smallpox virus officially still exist in two research laboratories in Atlanta, Georgia, and in Russia.

What does the word "evolution" mean in a biological context?

Evolution means change, specifically genetic change. It does not apply just to physical change. Changes can be anatomical, physiological, behavioral, or external appearance. All of these are referred to collectively as "phenotype". The genetic basis for the phenotype is the "genotype".

How can "free-riders" thwart the promised benefit of herd immunity?

Free-riders are those who are unvaccinated or have not been exposed to a particular disease and who at low risk of infection due to herd-immunity. Many free-riders are groups who oppose vaccination and who are high risk for a disease outbreak in their respective communities. Reasons for free-riding are many including a) vaccine safety, b) religious beliefs, c) peer-pressure, and d) the belief that if vaccination rates are high enough then herd immunity will protect you and there is no need to be vaccinated.

Fungal evolution. In what ways can fungal pathogens undergo genetic change? What are some of their adaptations for survival?

Fungi sometimes invade tissues where no immune response is possible. For example, Batrachochytrium dendrobatidis, an amphibian fungal disease also known as chytrid or chytridiomycosis, infects keratinized cells in the epidermis where is there no blood supply to convey antibodies and macrophages. Another adaptation that some fungi have is to grow to a large cell size. Cryptococcus, which causes pneumonia and meningitis in humans, develops titanic, multi-nucleated cells that prevent phagocytosis by the smaller macrophages. Fungal diseases also form and colonize biofilms to hide from immune responses and antifungal drugs. Fungi have evolved resistance to commonly administered antifungals.

Protozoan evolution. In what ways can protozoans undergo genetic change? What are some of their adaptations for survival?

Gene mutations and natural selection also play an important role in the evolution of infectious protozoans. Trypanosoma cruzi and T. brucei have evolved different adaptations to survive inside human hosts. T. cruzi has evolved to exist as an intracellular parasite. As such, it is shielded from our defense systems that cannot antigens that are inside of our own body cells. T. brucei has evolved a very different means for survival in the host. T. brucei is an extracellular parasite that lives outside your cells but within your body fluids. As such, it is subjected to an immune response. 4 T. brucei changes its body form and antigen (protein) coat over time, in a fixed sequence of change. By the time the immune system has geared up to attack the first antigen phenotype, the parasite has changed its protein coat to the second antigen phenotype. The parasite goes through four different protein antigens and is able to produce offspring to start the next generation by the time the last protein coat has been identified by the immune system. Protozoans have also evolved resistance to commonly used antiprotozoal drugs. 12) Fungal evolution. In what ways can f

Helminth evolution. In what ways can helminth pathogens undergo genetic change? What are some of their adaptations for survival?

Helminths are unable to alter their body surface antigens. Instead, they have evolved other adaptations. They include non-living external cuticles that are resistant to defense systems and anthelmintic drugs. Some helminths secrete proteins that modulate (suppress) the host's immune response.

When herd immunity has reached threshold for a particular disease, are you directly protected against the disease? If not, then is this a real form of "immunity"?

Herd immunity does not confer immunity to those who are not immune via vaccination or prior exposure. Thus, it lowers the risk of transmission but does not offer active immunity to unprotected individuals

What is herd immunity and what is the science behind it? That is, how does it work?

Herd immunity is the resistance to the spread of infectious disease in a population due to a significant number of individuals having immunity, either through vaccination or having already been infected previously with the same pathogen. It requires that enough individuals are immune in order to hamper the spread of the disease. That number varies with the disease, the density of the population, and the social conditions that may limit or enhance the spread of disease.

What is "fitness" in an evolutionary context? How do we measure fitness? Is it a measure of physical prowess or something else?

If an individual has a high likelihood of survival and conveying its genes to succeeding generations, then we say that the individual has high "genetic fitness". Thus, fitness is a measure of the degree to which your genes are represented in succeeding generations. If you survive, but do not reproduce, then you have zero fitness. It is not a measure of physical prowess. If you are an oak tree, live for hundreds of years, and produce thousands of offspring who in turn survive and reproduce, then you have high genetic fitness.

Where is Wuhan, China? What happened in Wuhan in December 2019? Who named the disease? Who named the virus?

In late December 2019, public health officials notified the World Health Organization (WHO) that a new virus was causing pneumonia-like symptoms in residents of Wuhan, China. WHO quickly identified the virus as a coronavirus, a virus commonly found in animals, but for which only two forms were known to have jumped from animals to humans - SARS-CoV (first identified in 2002) and MERS-CoV (first identified in 2012). WHO named the new disease COVID-19 — "co" and "vi" for coronavirus, "d" for disease, and "19" for the year when the disease first emerged. The International Committee on Taxonomy of Viruses (ICTV) designated the new virus as SARS-CoV-2.

Do species populations evolve or do individual organisms evolve or both?

Individuals are ephemeral and die. Individual bacteria may only live for a few hours or days. If a few bacteria evolve resistance to a specific antibiotic, and the resistance persists in the bacterial population over time, then the population has evolved resistance to the antibiotic.

For how long does herd immunity persist for a specific contagious disease? Forever?

It really depends on how long antibodies persist in the body for each specific vaccine (see "duration" table). Some vaccines, such as influenza, must be administered every year because the antibody titer drops off dramatically after one year.

Crossing the Atlantic. When and how did the SARS-CoV-2 disperse to North America? When was the first case diagnosed in the U.S. and how and when did it get there?

January 15, 2020, A Chinese national flying into Seattle from Wuhan, China, became the first patient in the U.S. shown to be infected with the novel coronavirus and the first to have a SARS-CoV-2 genome sequenced. This patient was designated 'WA1.' It was not until six weeks later that several additional cases were detected in Washington state

Back to New York. What happened when the SARS-CoV-2 emerged and spread in New York City. How many people were infected? How many died?

March 20, 2020, New York City is declared the U.S. outbreak epicenter. New York City state reports that more than 15,000 people have tested positive for COVID-19 and account for roughly half of the infections in the country. The vast majority of New Yorkers with COVID-19 are in the New York City region. Researchers traced the origin of New York City's outbreak and found it was primarily linked to transmission between the U.S. and Europe.

Genetic change can be due to random events or the acquisition of new genes from the environment or from other individuals. What are these random events? Which organisms can "acquire" new genetic information?

Mutation is the source of most "new" genes. Mutation is generally driven by electromagnetic radiation (such as uV light) or chemicals. New genetic information can be "acquired" from viruses that infect our cells. Bacteria can "acquire" new genetic information when they obtain plasmids from the environment or from other bacteria. Only mutations in the cells used in reproduction (called gametes) can be passed on to offspring in sexual species. Mutations in a bacterial genome can be passed on when the bacteria grow and divide.

Identify at least three things that could have been done to reduce COVID-19 infection rates, hospitalizations, and mortality rates in the U.S.

National plan • Leadership from the top down Federal à State à Local à Everyone • Follow the science Promote public confidence in safety measures Isolation of nursing home residents • Prepare for future waves Step up PPE production Prepare for patient overload ü Hospitals ü Emergency services

What patterns emerged in the number of cases, hospitalizations, and deaths? Where is the U.S. today (December 3, 2020) with COVID-19?

Number of cases in U.S. Total = 13,925,990 Today = 195,695 • Number of hospitalizations in U.S. Today in hospital = 100,226 Today in ICU = 19,396 • Today on ventilator = 2,855 Number of deaths in U.S. Total = 273,847 Yesterday = 3,034

On to Europe. When did the SARS-CoV-2 disperse to in Europe from China and how and when did it get there?

On January 20, 2020, an employee of an automotive supply company in Bavaria, Germany, flew in for a business meeting from Shanghai, China, unknowingly carrying the virus, ultimately leading to infection of 16 co-workers.

Who evolves: the pathogen or the host? Is evolution a race for survival for both the pathogen and the host, or just the pathogen?

Pathogens evolve to be successful within the host, while the host evolves to resist infection, disease progression, and any harmful effects of the pathogen. Our defenses are complex and are the product of evolutionary change in order to be able to survive and pass our genes to the next generation. Could we survive and be healthy without a defense system? Pathogens must evolve mechanisms to counter the onslaught of our defenses and the drugs we concoct to deny success to the pathogens. Thus, natural selection works on both the pathogen and the host, each evolving new adaptations to overcome the adaptations of the other and could be perceived as a race for survival. When species evolve adaptations to each other, the process is termed coevolution.

What drugs are available now to treat those experiencing disease symptoms? What do these drugs do and are they effective? Are there any drugs that prevent COVID-19?

Remdesivir. In October 2020, the FDA approved the use of remdesivir, an antiviral medication originally developed for Ebola, to treat COVID-19 patients requiring hospitalization — even though clinical trials have found that it only has a limited benefit. The drug interferes with replication of the virus. It seems to be most effective in reducing the likelihood of being placed on a ventilator and reduces the mortality rate for those on ventilators. • Hydroxychloroquine. The anti-malarial drug chloroquine (Ques. 9, WS #12) was promoted early on, but clinical trials show that it does not help COVID-19 patients. • Dexamethasone. Dexamethasone, a steroid, has proved useful for patients experiencing the most severe symptoms. It decreases your immune system response to infections, thus reducing the severity of symptoms, many of which arise from the inflammatory response (Question 9, Worksheet #8). • Convalescent Serum or Plasma. "Antibody cocktails" containing a high concentration of SARS-CoV-2 antibodies derived from infected individuals and lab molecular techniques can be used if administered early, before severe symptoms appear. The antibodies can suppress the infection before it spreads throughout the body.

If herd immunity only protects against contagious diseases, does it protect against tetanus? Which members of a population does herd immunity best protect?

Since tetanus is not a contagious disease, and is contracted directly from the environment, it is not possible to have herd immunity against tetanus. If you are unvaccinated and in contact with tetanus, you could contract the disease. 2/10 die. Herd immunity protects those at greatest risk from developing severe symptoms from a particular contagious disease. This group varies with the disease.

Has herd immunity been attempted in any human population for COVID-19? If so, what was the outcome?

Sweden made an attempt at herd immunity. Rather than imposing a hard lockdown in March as most European and Scandinavian countries did, Sweden's strategy in dealing with the pandemic was to rely on people's individual responsibility to curtail the spread of the disease. The health authorities predicted that 40% of the Stockholm population would have had the disease and acquire antibodies by May 2020. However, the actual prevalence figure was around 15%. It is clear that not only are the rates of viral infection, hospitalization and mortality (per million population) much higher than those seen in neighboring Scandinavian countries, but also that the time-course of the epidemic in Sweden is different, with continued persistence of higher infection and mortality well beyond the few critical weeks period seen in Denmark, Finland and Norway.

Where did the SARS-CoV-2 virus originate?

That is, the source, not the location. Initial reports suggested that the virus was acquired at a fish market in Wuhan, but the first patient was never at the market. The animal source of the virus is still not known, but the other two coronaviruses originated in bats and the SARS-CoV-2 virus has a 96% genetic similarity to coronaviruses in bats.

What is status of vaccines under development? Who will likely get the vaccines first? Are there any groups of people excluded from vaccination? Are there any limitations to the distribution of these vaccines? How do these new vaccines work?

Vaccine Successes Moderna - 95% effective Pfizer and BioNTech - 90% effective Astra Zenaca - 90% effective (certain doses) • Vaccine Initial Allocation Health care workers Emergency services personnel Nursing home staff and patients • Vaccine Limitations Cold storage Two doses 3-4 weeks apart Limited number of doses available No children until spring 2021 • Vaccine Distribution Time-Line Vaccine approval expected by mid-December 2020 Mid-to-late-December 2020 - Initial Allocation Mid-to-late March 2021 - General population • How the New Vaccines Work mRNA injected, used by cells to make coronavirus spikes (antigens) Antigens "presented" by T-cells à activate helper T-cells (Q14, Worksheet #8) Activated T-cells à Cytotoxic T-cells and B-cells (antibodies) (Ques. 13, WS #8) See illustration on presentation for the vaccine pathway

What is the Great Barrington Declaration? What are some of the arguments against the premise of this document? Which arguments support the declaration?

The GBD was collectively written by three professors at three different universities. It basically states that we should allow children and youth back in school and permit COVID-19 to spread since lockdowns have adverse effects on physical and mental health. As an example, people postpone preventive healthcare during lockdowns. They propose reducing these harms by ending mandatory restrictions on most activities for most people and, instead, recommend that "life resume as normal" and that individuals choose the risks, activities and restrictions that they prefer. The document leaves out practical details of how we would reduce risk for the 40% of Americans who have an elevated risk of dying from COVID-19. The main argument against the GBD is that this effort at herd immunity will not stop the pandemic and will result in a large number of unnecessary deaths, with the potential for recurrent COVID-19 epidemics, since we do not know if COVID antibodies are longlasting. How can children and youth return to school and not risk the lives of their teachers? How can we have family gatherings and not expect older family members to contract the disease? None of the usual measures, such as contact tracing or wearing masks, are mentioned in the GBD. A group of 80 researchers published a counter memorandum in The Lancet called the John Snow Memorandum denouncing the GBD herd immunity declaration.

What is the herd immunity threshold (HIT) and how is it determined? What factors influence HIT? What is the estimated herd immunity threshold for SARS-COV-2? How does this compare to HIT for other infectious diseases?

The herd immunity threshold is the proportion of a population that is immune to a specific contagious disease such that the risk of further transmission is minimal. This threshold is based on Ro which is the number of individuals likely to be infected by someone who is contagious. HIT can be estimated using a simple formula: HIT = 1- (1/ Ro) For polio, where 6 individuals are co-infected: HIT = 1 - (1/6) or 0.833 or 83.3%. This means that 83.3 % of a population must be immune to thwart the spread of polio. For SARS-COV-2, the HIT estimate is that 60-75% of the population must be immune. HIT estimates are estimates based on the likelihood that everyone in a population is equally likely to be exposed to infection or that the population is well-mixed. However, this is rarely the case. Interaction within groups is more likely than between groups. Measles is a highly contagious disease with an Ro = 12-18 cross-infections per infected individual. This disease resulted in more than 600,000 infections each year prior to 1963 when the first measles vaccine was approved. The HIT is estimated to 90-95% which is the level that was reached in the 1990s and 2000s due to high rates of MMR vaccination in children. Current total measles cases is roughly 1,000 per year

What must occur for adaptations to be successful? What must occur to ensure that new adaptations are maintained within in a species population?

The organisms in a population must 1) survive and 2) produce viable offspring. If you survive and do not have offspring, then your genes die with you. If your offspring are not able to survive and reproduce, then your genes die when your offspring die.

Can herd immunity in one age group also benefit another age group? Can herd immunity for one sex (e.g., females) also benefit the other sex?

Vaccinating adults against pertussis reduces its incidence in infants who are too young to be vaccinated. Youths vaccinated against pneumococcal disease (bacterial pneumonia) reduces its incidence in younger unvaccinated siblings. Vaccinating children against the seasonal flu reduces its incidence in older members of the same household. Vaccines that protect against STDs in one sex will reduce its prevalence in both sexes if the rate of immunization is high.

What is the history behind herd immunity? Was it first applied to humans or animals? Exactly when did the concept first arise and how has its use evolved?

Veterinarian George Potter and Adolph Eichhorn, in 1916 in the Journal of the American Veterinary Medical Association, envisioned "herd immunity". As Potter wrote in 1918, "Abortion disease may be likened to a fire, which, if new fuel is not constantly added, soon dies down. Herd immunity is developed, therefore, by retaining the immune cows, raising the calves, and avoiding the introduction of foreign cattle." In 1923 Sheldon Dudley, professor of pathology at the Royal Naval Medical School, became aware of epidemics of diphtheria at the Royal Hospital School in Greenwich. The school provided laboratory-like conditions, with a homogeneous group of male students, in good physical shape, who entered in batches several times a year, where they slept in dormitories of 70 to 126 beds. In a 1924 article in The Lancet, Dudley applied "herd immunity" to humans. In a 1929 article, "Human Adaptation to the Parasitic Environment", he wrote, "I will now consider the community, or the herd...Nations may be divided into urban or rural herds. Or we can contrast the shore - going herd with the sailor herd, or herds dwelling in hospitals can be compared with those who live in mental hospitals."

Viral evolution. In what ways can viruses undergo genetic change? What are some of their adaptations for survival? How do viruses "jump" between species?

Viruses are recognized by their antigen coat. Mutations can change the antigen so that it is no longer recognized by the host's defense systems. Mutations can also render a virus resistant to anti-viral drugs. If we recognize that many animal viruses are unable infect humans successfully, then a mutation can allow an animal virus to "jump" to humans and become infective, or vice versa. For example, the swine flu virus, H1N1, jumped from pigs to humans in 2009. it is thought that the first SARS-COV virus jumped from wild animals to humans, and although it Is not known from which species, a similar COV virus occurs in bats. In the reverse scenario, the COVID-19 virus, known as SARS-COV-2, has evolved a new strain that has "jumped" to captive-reared mink. Viruses can also acquire DNA from their hosts to expand their genome.

Can herd immunity be a driving force in the evolution of disease organisms?

Yes. Vaccination seems to promote the success of emerging diseases, especially new influenza viruses.

John Snow

famous for his investigations into the causes of the 19th-century cholera epidemics and has become known as the father of epidemiology. In 1854, he began noticing the significantly higher death rates from cholera infections in the Soho district of London supplied with water by the Southwark Company. His identification of the Broad Street water pump ("X" on the presentation map) as the cause of the cholera epidemic is considered the classic example of epidemiological investigation. Snow used chlorine in an attempt to clean the water and also removed the pump handle, and this ended the outbreak. His work in Soho has been perceived as a major event in the history of public health and is regarded as the founding event of the science of epidemiology, having helped shape public health policies around the world. However, Snow's research and preventive measures to avoid further outbreaks were not fully accepted or put into practice until after his death due to the prevailing Miasma Theory at the time -- a model of disease in which poor air quality was blamed for illness. This was used to rationalize high rates of infection in impoverished areas instead of addressing the underlying issues of poor nutrition and sanitation and was proven false by Snow's work.


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