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BIOL 449 (8)
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Biol 449 Exam Review.docx

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Department
Biology
Course
BIOL 449
Professor
Barbara Butler
Semester
Winter

Description
Lecture 8 – Emerging Diseases Emerging and Re-emerging Diseases: ­ CDC defines emerging and re-emerging infections as those whose incidence in humans has increased within the past 3 decades or whose incidence threatens to increase in the near future. ­ Emerging – Ebola. Nothing new ­ Re-Emerging – TB; has been in human history before and threatens to come back again. ­ There has been a rise since the 40s. ­ Wit the availability of antibiotics, immunization etc people thought infectious diseases could disappear. Microbial Evolution: ­ Emergence of antibiotic-resistant strains of pathogens – picking up resistance genes undergone mutations. ­ Serotype O139 – new strain; can cause epidemic cholera. ­ Evolved from O1 – source of pandemics but recently it evolved to O139. ­ Closely related, but capsule & altered O antigen. ­ Apparent evolution: o Lives in marine environments. o Started with EI Tor O1  at one side it picked up the non O1 strain and on the other side a DNAsegment was deleted  O139. o These also include different O antigen capsule  changes antigenic surface, which makes it hard for the immune system to not find it. Complacency – Breakdown of Public Health Infrastructure: ­ Re-emerging of TB in the USA. They tried to terminate it, developed antibiotics but that stopped working in the 70s. ­ AIDS + TB are synergistic. AIDS destroys immune system, TB can thrive (immune system is destroyed) ­ In 1989 – CDC started strategic plan for the elimination of TB in the US. More aggressive treatment – TB rates started declining again. But that doesn’t mean it was eradicated. ­ The plan: aggressively identify, treat people with high-risk groups. Poor people,AIDS patients, prisoners, immigrants etc. ­ DOT – Direct Observation of Treatment, for noncompliant individuals. ­ Potential Problem – antibiotic resistant strains in developed countries or exported form developed countries to developing regions. Changes in Human Behavior: ­ Day care centers allow children who are still developing their levels of immunity to mingle. The lack of sanitation and hygiene poses a risk ­ Easy transmission of colds and diarrhea – low infectious dose. Doesn’t take many live cells to infect. ­ Sexual Revolution – sexually transmitted infections in young people. ­ Birth control; STIs and HIV. Sometimes people don’t take proper precautions – can lead to these diseases. For example – Oral sex, you won’t get pregnant but can get STIs. ­ 2002 showed the highest level in Canada of Chlamydia. People are at more risk especially males and females between 20-29. Advances in Technology: ­ Air travel allows emergent pathogens and potential vectors to more rapidly around the globe. ­ The confined space and air system of an airplane is a perfect place for rapid spread of disease. People carrying the disease can’t really go anywhere else. Even if there are protocols, the reaction time might not be as fast. ­ Contact Lenses and Solutions – new potential habitat for microorganisms – eye infections. You are giving them a new exploitable environment. ­ CentralAir Conditioning – another exploitable habitat especially for legionellosis. ­ Modern Medicine –chemotherapy, transplant technology saves lives but it also increases the proportion of immune-compromised individuals. ­ People are getting older as well this creates a subpopulation that is have a weaker immune system. Human Population Expansion: ­ We have moved into new areas; run into new pathogens that have never been exposed to humans before. ­ Ebola Virus – reservoir is unknown. It is capable of human infection and will kill you. But it isn’t capable of human-human transmission. Not Subtle, lack of adaption so you get a lot of symptoms. ­ HIV – resembles feline (FIV) and monkey (simian, SV) retroviruses. Mutated from SV, crossed over to humans from contact with infected monkey. SIV infected humans mutated  natural selection of mutants better-adapted to human host than SIV. ­ Lyme Disease – zoonosis – disease of rodents (white-footed mouse). Transmitted in rodents by deer ticks (vector). Ticks use deer as a blood meal source. Deer don’t show symptoms, but are involved in transmission. Tick then bites mouse. ­ Blood is blood and unlike deer, humans show symptoms when infected with Borrelia. Development: ­ Changing habitats for vectors. Urbanization. ­ Aswan Dam (Egypt) – built to provide source of power. Increased range of habitat of snail that is the host for parasitic flatworm. (schistosoma) ­ Parasite is acquired by wading or swimming in contaminated water with the snails. ­ It can burrow through the skin; larva can mate or live in the human circulatory system for up to 25 years. This is a highly evolved parasitic interaction. ­ Ova can be laid in veins of intestine, bladder. Some of them can be expelled in feces but gets back into the water. Others enter the liver and cause serious damage. ­ Rift Valley Fever – arthropod borne virus – increased breeding grounds for mosquito vector (human to human). Mass Distribution and Importation of Food: ­ E. coli O157:H7 – undercooked meat – huge outbreak in NA– many were hospitalized, few developed hemolytic uremic syndrome (complications that can cause kidney damage can be lethal). ­ There was lack of lab testing and surveillance for this strain with respect to earlier cases – this resulted in no recognition of the outbreak. ­ 90% of the cases were associated with eating at a single fast-food restaurant chain. Contaminated group beef patties centrally produced and supplied to chain restaurants and insufficient cooking by the chef can lead to the outbreak. ­ The restaurant chain standard wasn’t high enough – not high enough temperature. War and Civil Unrest: ­ Cholera, Dysentery and other diarrheal diseases occur in refugee camps due to inadequate sanitation, toilet facilities, poor drinking quality ­ Temporary truces have been called in someAfrican to allow polio vaccination days. ­ Natural Disasters – tsunamis, hurricanes, earthquakes – potential for similar disease outbreaks. ­ Out normal infrastructure is severely degraded. It is important to get proper water treatment. Haiti – combo of poor infrastructure, source of cholera led to epidemic. Climate Changes: ­ Changes in temp. Rainfall level can affect incidences of certain diseases. Often animal or insect host, vector involvement. Vector usually shifts and expand their ranges. ­ Warm water and temps may favor reproduction and survival of insect vectors. ­ Hantavirus outbreak – not a human virus but if exposed to rodent droppings – can inhale dust (if dry) and inhale the virus ­ Non-transmissible from human to human. Lecture 9 – Immunization and Immunization Strategies Immunity: ­ Active Immunity – direct stimulation of the immune system by antigen. ­ Passive Immunity – indirectly by donation of pre-formed immune substances (antibodies) produced in the body of another individual. Immune cells, no memory association. ­ Natural Immunity – any immunity acquired through normal biological experiences of an individual. Get the infection – natural active immunity; maternal antibodies (natural passive immunity) – pre-natal IgGs; post-natal IgAs – born being immune to whatever mom was immune to – protects new born through the internal of when it’s born and able to take care of itself. ­ Artificial Immunity – protection from infection obtained through medical procedures. Instill immunity on purpose. Immunization with vaccines (artificial active immunity; vaccination) or with immune serum (artificial passive immunity; immunotherapy) ­ Immuno-competent = functional immune system; acquires experience as you go through life. ­ Direct stimulation of the system by pathogen. ­ Acquired immunity is important for MEMORY. Active Immunization: ­ Preference because it is vaccination. ­ Example: Smallpox. ­ Started in China in 6 C. In 10 C there was a deliberate inoculation of dried pus from smallpox pustule into the arm of a healthy person. This was virolation – hopes for a small case, 10% got severely infected. ­ 1796 – Jenner – material from human cowpox lessions (vaccinia virus; smallpox vaccine) used to confer protection against subsequent smallpox. ­ People, who survived the first time, seemed to be immune during the second wave. ­ 1880s – Pasteur – concept of attenuated strains; terms vaccine, vaccination. ­ Measles, Mumps and rubella – once an effective vaccine has been introduced, it takes effect immediately. Requirements for an Effective Vaccine: ­ Vaccination – proven public health measure that does work. ­ Levels of side effects or toxicity should not cause serious harm ­ Should protect against exposure to natural, wild natural forms of pathogen –influenza vaccine not 100% perfect.Aim is to protect against wild type. ­ Should stimulate both B-cell and T-cell response.Adaptive response. ­ Should have a long-term, lasting effects (produce memory). ­ Should not require numerous doses ­ Should be inexpensive; have a relatively long shelf life, be easy to administer. ­ Successes – against pathogens that cause acute infections  vaccines mimics the pathogen. Infected person gets better or dies. ­ Not so successful – against pathogens that cause chronic infections – pathogens MO is to hide from immune system (inside cells) or subverting system + shut it own (Ex.AIDS wipes out immune system). Types of Vaccines: ­ Trojan – engineer vaccine; genes that produce antigens of a virulent virus (ex. vaccinia). Vaccinia virus carrying genes belonging to another virus, but will produce proteins of real pathogen. ­ Tocids – purified macromolecules ­ Capsular polysac – purified macromolecules. Problems – repeating polymers (not highly immunogenic) can tack onto a more virulent protein ­ Goal is that whole organism – killed, attenuated. ­ Examples on slide. Need to go over them. Recommendations for Travelers (USCDC): ­ Age 2 or older – following immunizations should be up to date: o Measles, mumps, & rubella (MMR) vaccine; DTaP (DT) Vaccine. o Polio Vaccine – 3 doses – still needed o Hib Vaccine – not recommended after 5 years o Hep B – 3 doses o Varicella – people who have never had chicken pox – shingles? ­ Country of travel: o Flu vaccine; pneumococcal vaccine for people > 65 years old. o If infrastructure + medical case in places of travel aren’t that great, and you want to stay out of that medical system ­ Booster or additional doses: o DT booster recommended every 10 years o Measles if born after 1957 o 1 dose of inactivated polio for people > 18 years with complete polio series travelling to Africa, Asia, Middle East, India, former USSR ­ Immunizations recommended based on destination: o Yellow fever –Africa, SouthAmerica o Hep A– everywhere except Japan,Australia, New Zealand, N&W Europe, NA (not mexico) o Hep B – if staying > 6 months – SEAsia, Middle East, S&W pacific islands, Amazon o Typhoid – developing countries. o Meningococcus – sub SaharanAfrica o Japanese encephalitis or tick-borne encephalitis – areas of risk o Cholera – vaccine sucks Routes of Administration, Side Effects of Vaccines: ­ Most vaccines are injected, some are given orally. ­ Adjuvant – compound that enhances immunogenicity; prolongs antigen retention at injection site. Mostly alum (Al hydroxide salts). ­ Side effects – local reactions at injection site, fever, allergies, other adverse reactions. Not necessarily to antigens but sometimes how the vaccine is prepared. Much less problematic. Development of vaccines takes a long time! ­ Rare occurrences: o Panencephalitis – from measles vaccine. o Back-mutation to virulent strain – polio o Neurological effects to unknown cause – swine flu ­ Altered vaccines: o Whole cell pertussis – acellular pertussis – take parts of cell, use a bunch of surface proteins, DTaP – acellular – cut down the amount of side effects – but might not be as effective. o Live oral rotavirus vaccine – recalled when kids suffered intestinal blockage  Affects kids – causes diarrhea – blockage; but now sure how its connected “Vaccine-Related Microbial Ecology” ­ Childhood vaccines aren’t always enough. ­ Adults can require some too to boost older immunization; to protect against adult infections; to protect very young – can protect children. ­ Vaccination for one purpose can have other side effects. ­ Hib vaccine – reduced the incidence of epiglottitis in young children – rare but also caused by hemophelus influenza; blocks the airway, child suffocates. ­ Vaccination of young against earache – seems to be influencing incidence of “classical” bacterial pneumonia in the elderly. Probably because in family units don’t have the same degree of bacterial strain transmission. Many of us carry this bacteria, lessen the degree of transmission can be a positive thing. Lecture 10 – Smallpox Smallpox: ­ Variola Virus – cowpox – large genome – codes for ~200 genes. o Large dsDNA o Relatively stable in the environment – person-to-person – viable if aerosolized and potentially become infected – eradicated. o Only exists in 2 WHO centers (USA and Russia) ­ 1 appeared in 10,000 BC:Asia/Africa  Europe  Middle East  Mexico  CentralAfrica  India  SouthAmerica Australia ­ Humans are the sole host and reservoir for this ­ Variola Major – more severe – fatality rate ~30% (unlikely to transmit); Variola Minor – less severe – fatality rate less than 1% (spreads faster) ­ Vaccine existed since 1796 (since Jenner invented it) HOW IT WORKS: Disease Pathogenesis & Symptoms: ­ Has a long incubation period, which lasts approximately 12-14 days. In that time it is not infectious. ­ Virus starts at the throat ▯ respiratory tract (moves up lymph nodes) ▯ infect phagocytes (multiplies and onsets flu like symptoms – hidden process) ▯ blood cells o Flu like symptoms – fever, backache, headache, vomit (stressful); goes away after 2-3 days  onset of lesions (in throat, virus released in mouth), rash after (extremities). ­ Centrifugal distributions of the lesions are mostly on the face and extremities. ­ They progress from macules  papules  vesicles  pustules. Lesions in a given evolve together. ­ Pustules eventually turn into scabs and scars. Scarring can also sometimes lead to blindness. ­ Transmission – face-to-face contact with infected person. ­ Considered contagious until last scab is gone. Lesions look like chicken pox. ­ There is no treatment for this. The disease develops slowly. 2-3 weeks interval between each generation of cases. Erythrotherapy: ­ Put them in red room ­ Though red was therapeutic it can be associated with bleeding walls. ­ WHO started to eradicate work world wide not just in theAmericas. Eradication of Smallpox: ­ It is a human reservoir. Acute infection with obvious clinical features – don’t need medical training to ID it! ­ No transmission during asymptomatic phases – incubation period ­ Person-to-person transmission. Short period of infectivity (recover or dead) ­ Effective immunization procedure developed during 1796 ­ PASO – Pan American Sanitary Organization – wanted to eradicate in the western hemisphere. ­ Smallpox Eradication Programme (SEP) 1959-1966 ­ WHO’s intensified SEP – D.A. Henderson of US Public Health Service ­ Strategy – massive vaccinations, followed by intensive surveillance Immunization Procedure: ­ Subcutaneous injection – really difficult to do, sometimes didn’t work. Failed ­ Jet injectors improved on “traditional” methods. ­ 1967 – WHO vaccinated 25 million people but still missed a large population. Problem was this epidemic was going on in a lot of places. ­ They initiated obligatory compulsive vaccine. ­ Vaccination didn’t work – shifted to surveillance/containment. ­ Used aggressive surveillance to locate an outbreak. Built a firewall of immunity around it (containment) by vaccinating everyone in the area. Ex. picks a village, vaccinate everyone and move on to the next. ­ Smallpox eventually wasn’t as infectious as originally considered. ­ WestAfrica: Eradication Escalation (E2) – spread information, newspapers, radio announcements, etc. ­ Ongoing research and Innovation: o Freeze-dried vaccine stored in heat-sealed ampoules (will be fine for months). Was easy to transport. Can be used multiple times. Gives subcutaneous injection of the perfect dose (almost never fails) o Bifurcated needle – rapid, effective vaccination possible in remote areas, under most primitive conditions. o Smallpox recognition cards – case recognition by workers with minimal training. o Rumour registers – locate outbreaks o Field trained – epidemiologists; evaluated performances & suggested improvements ­ Ethiopia – SEP came closest to failure. Populations were scattered. Not much infrastructure. There were more problems that got priority over smallpox. Variola minor. ­ 1975 – India, Bangladesh stopped transmission, recorded world’s largest last cases or variola major. ­ 1976 – last case of endemic smallpox in Ethiopia. ­ 1986 – routine vaccination for smallpox has ceased in all countries. ­ Direct legacy of SEP – Expanded programme for immunization (EPI) – aimed to deliver vaccines to at least 6 diseases to children – measles, polio, diphtheria, pertussis, tetanus, TB. Still going on today. Benefits of Eradication Programme: ­ 240 million people have been spared smallpox for over 20+ years now. ­ Global savings of about $US 1 billion per year ­ Contribution towards building public health infrastructure – more long lasting. Took advantage of underutilized heath personnel in most countries. ­ Showed importance of research initiatives. New vaccine devices were developed; revealed true epidemiology differed from the textbooks. Raise efficiency and effectiveness. ­ Showed surveillance was ultimate quality control measure in SEP – if you didn’t know how well your program is doing it is useless. ­ Read over program innovations. Lecture 11 – Randomization Assessing the Efficacy of Preventative and Therapeutic Measures: ­ Randomized Trial – ideal design for evaluating the effectiveness and side effects associated with a new for of intervention ­ Eliminate as much bias as you can – gold standard. ­ Done through clinical trials, community-based trials, treatments, and strategies. ­ Choose a defined population; divide them in a randomized order into pop.A(receives new treatment) and pop. B (receives current treatment). Monitor whether the infected individuals improved or not. Selecting Subjects: ­ A selection criterion needs to be well defined before the selection begins. CANNOT BE BIASED. Therefore there should be no element of subjectivity. ­ The study should be made in the sense that it can be replicable and same results can be obtained. Allocation of Subjects to Treatment Groups: ­ Studies without comparison: o Case study – no comparison is made with untreated groups or groups receiving the same treatment. It is a series of one-offs. o This person could have gotten better for other reasons. ­ Studies with comparison: o Historical Controls – use a comparison group from the past.  Obtain the records of patients from before who have been treated for this disease.  Issue is that the results might not be available (clinical use only).  Any difference could be due to something other than therapy. Can’t fully account for all changes. o Simultaneous by not randomized controls:  How to avoid bias?  Ex 1 – anti-nausea pills. Control subject were passengers and study group was sailors – but sailors are in sea all day long… They didn’t even know what the pill really did.  Ex 2 – kids with TB, doctors only gave vaccination to kids whose parents were cooperative. Biased opinion. This was fixed by giving children vaccination by giving it to the first one and not the second. Tested out the effectiveness of the medicine. Randomization: ­ Assignment of a patient is essentially a coin toss. ­ Use random number table, or number generator. Randomization is done before hand. ­ Aim is non-predictability in the assignment of the next patient. Eliminate subjective biases of investigators (overt or covert). Increase likelihood the groups will be comparable in regard to characteristics. ­ Inherent conflict is experienced often. Doctors are obligated to do the best for the patient. They are obligate to step aside from any decision-making procedure. They are assigned patients through a central coordinating centre. ­ Go over example in slide 8 ­ We can only match and measure variables we know about. ­ Randomization DOES NOT guarantee comparability with respect to variables of interest; it DOES increase the likelihood of comparability of groups in the study. Startified Randomization: ­ Age and sex are important determinants of prognosis. ­ Groups can be stratified then randomized. Example on slide 10. ­ Stratified by sex, age and then randomized. Data Collection: ­ Patients are usually assigned to a treatment group. Sometimes however patients might not want to be in that group and they drop out or they get their own treatment. Must check up on them. Get the data that they cannot influence. Make sure that the data collected from the control is as robust as the treatment group.All data needs to have the same quality ­ Outcome – improvement (desired effect), any side effects. Need to explicitly stated criteria for all outcomes and must be measured comparably in all study groups. ­ Prognosis profile entry. ­ Masking (blinding) – don’t want subjects to know group to which they are assigned. ­ Use a placebo but that doesn’t guarantee subjects are blinded though. ­ Can also blind data collectors or data analysts – double blinding. Physician’s Health Study: ­ 2 tested hypothesis – whether Aspirin reduced mortality from heart disease whether beta- carotene decreased incidence of cancer. ­ People divided into 4 groups: Both compounds, 1 or other compound, compound + placebo, placebo only ­ Aspirin – physicians taking aspirin only 56% as likely to have heart attack as group taking placebo. ­ Beta-carotene – no significant difference in incidence of cancer between “beta carotene” group & “placebo” group. Crossover: ­ Planned crossover – in effect each subject can serve as his/her own control. ­ There cannot be a carryover when switching therapy. ­ Unplanned crossover – patients can drop out. In certain studies it may become necessary to conduct a surgery ­ No real way to solve if it becomes significant within a study. Can compromise study. Adequately educate the population – make sure they understand what they are getting into. Go back after (if there was a crossover) and see how much it influences the study. Factorial Design: ­ Can be incorporated in randomized trials. Two things are completely independent of each other. Anticipated outcomes are different. Noncompliance: ­ Patients change their minds! ­ Overt – articulate result to comply – drop outs ­ Covert – stop taking the agent and don’t report it. ­ Build in checks whenever possible to keep track ­ Drop-ins – patients in one group may accidently take the agent assigned to the other group and not realize they did that. Control their in-take of such “banned substances” and conduct routine checks. ­ Always include both populations in your study; those who comply and those who don’t to get a more accurate assessment. Possible Study Outcomes: ­ Sample population is supposed to be representative of the larger population. There is a probability that the results, decision is incorrect. We want to be aware of that. ­ If the treatments are not different and we conclude that they are indeed not different, we have the correct decision. ­ If the treatments are not different and we conclude that they are different, we have the type 1 error – probability = alpha; probability that we made an error can be assessed. ­ If the treatments are different and we conclude that they are not different, we have the made a type 2 error – probability = beta. ­ If the treatments are different and we conclude that they are different, we have the correct decision – probability = 1-beta (power). ­ P-value – alpha; probability that the difference between the groups does not reflect any true difference between therapiesAand B. If this value is less, we are fine. ­ Power – probability of correctly concluding that the treatments differ. Sample Size: ­ To estimat
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