MICRO 4000: Exam 3 Study Guide
What are the troubling trends that were found in the 2018 CDC report regarding Chlamydia?
1.8 million cases 19% increase since 2014 Increasing in women and men overall 15-24 age group is highest
why did HIV in 1981 cause alarm
1981: Opportunistic infections in homosexual males in U.S. (in cali and NY) Individuals who should have been healthy but were found to be immunocompromised Low levels of T cells → destruction of immune system → leading to opportunistic infections only found in immunocompromised people Kaposi's sarcoma: easy to treat in healthy, in these men it was invasive and deadly Pneumocystis jiroveci pneumonia
Is VRSA something we should be concerned about? Why or why not?
1997 - reduced susceptibility reported As of 2015 - 14 cases in the U.S. total (not common) At least 7 from Michigan 2002 Detroit! → horizontal gene transfer Diabetic foot ulcer treated for MRSA didn't get better, vancomycin resistant→ MRSA + VRE led to = VRSA Mostly minor skin infections → All had been treatable No person to person spread, All of VRSA strains have arisen from separate Horizontal Gene transfer events VRSA is thought to be less fit so it will not be persistent and Classified as medium and All have been treatable but keep eye on it BUT If we get a fit VRSA it will be very bad
How was Timothy Brown and "the London patient" "cured" of HIV?
2007 Timothy Brown 'berlin patient': HIV positive but developed leukemia as well→ to treat leukemia did bone marrow transplant from donor who had a genetic mutation CCR5 delta 32 genetic mutation in the transplant → This meant the HIV couldn't use CCR5 as coreceptor which shut down viruses ability to invade host cells Cured from treatment to until death (Died from leukemia ) Problem: bone marrow transplants are highly risky 2019 london patient cured: Same type of approach as timmy and appeared to have cure
Explain the differences between HIV and AIDS
3 stages of HIV 1. HIV positive don't have aids 2. HIV positive don't have aids 3. HIV positive you do have aids Stage 1: HIV Infection → lasts a few weeks or a month following infection, High levels of virus in bloodstream , Very contagious period, Asymptomatic or ARS (flu) Stage 2: HIV Infection (clinical latency) → Most people asymptomatic, HIV set point where viral load stays, Low HIV levels and high T cells with effectiveness Can last years → untreated lasts up to 10 years Treatment → lasts decades (Effective antiretroviral therapy) Stage 3 HIV Infection (AIDS): Immunocompromised (low CD4+ T helper cells), High viral loads, Opportunistic infections: When you enter AIDs stage where immune system crashed you enter 3 years until death
Explain the basic disease progression in a Syphilis infection.
3 stages with one latent (intermediate) Primary stage→ most treatable, heal on own so many don't seek treatment Single sore Secondary stage (if not treated in primary) Rash on hands or feet Fever, headache, fatigue, flu like (resolve without treatment) Latent stage→ lasts decades Late stage → 15% of people progress here if not treated in other stages Severe - organ and neurological damage, Damage to brain heart, Blindness, dimentia
What are leprosy reactions? When can they occur? What are the risk factors for each type?
30-50% of people with leprosy have leprosy reactions which Start after we begin treatment Inflammatory response to dead bacteria Type 1: Patients with borderline types of disease, Inflammation/pain in pre-existing lesions Risk factors - starting treatment which Flares lesions Type 2: Patients with disease, Inflammation, new nodules under skin, fever, malaise, cause expansion of disease (more lesions ) Risk factors - starting treatment, lepromatous leprosy, stress, hormonal changes
hat are the troubling trends that were found in the 2018 CDC report regarding Gonorrhea?
583,405 cases 63% increase since 2014 179.1 cases/100,000 people 2009: historic low of 98.1 cases/100,000 people (steady increases since) Resistance is still a major concern (multidrug resistant) Men and women increasing and the 15-24 age group is increasing too Some increase in older people
How must Naegleria fowleri enter the body in order to cause illness?
A problem in warm freshwater and improperly maintained swimming pools Organism enters through nose and in nose attaches to nasal mucosa and goes up through olfactory bulb to brain and spinal cord
What is ART/HAART regarding treatment of HIV?
ART is the historical version we use HAART now (highly active antiretroviral therapy) Multiple drugs from different classes above Argument is because of genetic diversity and mutations, by targeting three areas of replication, can keep virus suppressed
What are the symptoms associated with infection with the polio virus?
About 95% have no symptoms: Active disease but asymptomatic, Not usually long term About 4% have mild symptoms → Upper respiratory tract (Fever, headache), flu like, GI tract Less than 1 % have paralysis: Mortality rate of 5 to 10%
Is aerosol transmission of smallpox a viable bioterrorism threat? Why or why not?
Aerosol possibility → bioterrorism Pros: No immunity (big susceptibility) , huge fear Cons: prolonged face to face and most people are very sick so won't spread, not effective
What are the current treatments for MRSA infections?
Antibiotics for skin infections, sometimes drainage For severe infections, possible antibiotics or surgery, typically IV or surgery
How is HIV infection diagnosed?
Antibodies: historically used Problems: it takes time for people to develop detectable antibodies Viral proteins (viral RNA): accurate test in 9 days, Viral genes Home access HIV 1 Test and OraQuick in home test: Antibody detection
Why is there particular interest in developing a vaccine for Chlamydia?
Arguments on fact that we can eradicate with effective vaccine Phase 1 clinical trial → vaccine tested on people and found to be safe
MRSA is resistant to
At least resistant to all beta-lactams (Methicillin, Oxacillin, Penicillin, Amoxicillin) due to altered penicillin binding protein
What mechanisms of prevention of HIV are in place?
Avoid body fluids (low saliva levels) Safe sexual practices Avoid illegal drug use Medications during pregnancy Blood donation ban/deferment Antiretrovirals Vaccine
BCG
BCG is a vaccine (Previously thought to be very ineffective against pulmonary TB) In UK 80% effective in south india 0 efficacy which Has to do with rate of childhood TB Vaccine is only effective if given early enough → by the time vaccine released, many kids already had it in places like south india Recent research on efficacy : decently effective vaccine
is there a vaccine for leprosy prevention currently in use? What is it?
BCG vaccine : Gives some level of tuberculosis due to the mycobacterium protection, Also used to tuberculosis In india, new vaccine in development specifically for leprosy Multidrug therapy (rifampin, clofazimine and dapsone) → multidrug is much more effective, Combination of 2-3 drugs in attempt to be more effective and decrease antibiotic resistance
HIV lifecycle
Bind and fuse to target cell → Coreceptor binding: binds to CD4 and coreceptor (target) Viral fusion: Viral and host envelopes fuse (target) Replication and integration of virus into host chromosome Reverse transcription: ssRNA to ssDNA to dsDNA (target) Integrase enzyme: Integrates as dsDNA into host genome, Sits as a provirus (incorporated self into host cells) (Target) Provirus activation, assembly, and release (targets protease) expression from viral genome begins → Viral proteins and rna being made Proteins made in one long strand and protease cleaves them into active proteins
What is similar between the causative agents of TB and leprosy?
Both are acid fast making them have slow doubling times → hard to culture (slow growing)
What is the significant of the CCR5delta32 mutation for the "cure" of HIV?
CCR5 delta 32 genetic mutation in the transplant → This meant the HIV couldn't use CCR5 as coreceptor which shut down viruses ability to invade host cells
How does the initial presentation of HSV differ from subsequent outbreaks?
Can be asymptomatic or very mild (unnoticeable) Small blisters (mouth, genitals, or rectum) - can rupture and take several days to weeks to heal First outbreak is usually the longest and most severe (also evidence of higher shedding)
What is the possible explanation for the way that Treponema Pallidum evades the immune system to cause latent infection?
Can escape immune system with... Antigenic variation (which surface proteins expressed) Flagella and proteins covered
2013 Toddler "cured" of HIV infection
Child born to HIV+ woman, To prevent transmission they pumped baby full of antiretroviral drugs Supposed to be on for rest of life → stop virus from getting foothold, but mom stopped giving No sign of infection at age 2 (Lasted for several years) Considered 'functional cure' because didn't have continued use BUT....when she was 4 HIV gained foothold
What is monkeypox? Why is it a concern?
Concern of susceptibility Cross protection between orthopoxviruses, when people stopped getting smallpox vaccine, increase in animal to human spillover Monkeypox: carried by rodents, increasing since eradication of smallpox and is continually spilling over because we lack immunity to any orthopox (85% similarity in the DNA sequences of the two viruses) spillover events from rodents then there is human to human transmission Central africa monkeypox: 10-16% mortality rate (similar to smallpox), 200 lesions → severe, 7 rounds of person to person spillover after transmission from rodent to person Western africa monkeypox (Also came to US): Low mortality rate , Fewer lesson (1-50 ), Spreads less effectively
Explain the diagnosis process for MRSA. Make sure to include any potential problems with accurate diagnosis.
Consider any skin infections, investigate all "spider bites" as this Obtain cultures (Because of drug resistance) Determine antibiotic susceptibility in order to prescribe correct antibiotic Complications: heteroresistance (organism / group has the genes for resistance but for whatever reason they don't express those genes under the conditions your growing them at) Disk diffusion testing of MRSA will make them appear to be sensitive to methicilin but in the body it won't respond to body → hides resistance genes Determining antibiotic susceptibility Test against oxacillin and cefoxitin → Beta lactams that store better and can keep around longer and force exposure of resistance genes Do NOT test against methicillin → This is because methicillin is no longer available
How is naegleria fowleri diagnosed?
Diagnosis is key to survival: Detect the organism or the product of organism and start treatment early In US less than ⅓ of cases are accurately diagnosed before the patient dies Organisms: Visualization (see moving) in cerebrospinal fluid DNA from biopsy or tissue sample Variety of subtypes/strains of DNA but don't know the impact but we have sequenced it Antigens (serological) Culture can be used Fresh sample and heat to 108 degree F and wipeout other bacteria and then spread lawn of e coli and then put sample on plate and then can see if its naegleria if it consumes the plated bacteria
Describe multidrug treatment for leprosy. Why is this better than monotherapy? (there are a few reasons).
Drug resistance originated when it was a single drug meaning most strains have single drug resistance → by using multiple drugs it counteracts the single drug resistance meaning that there is the first line drug plus any fluoroquinolone and at least one of the second line drugs Multidrug therapy (rifampin, clofazimine and dapsone) → multidrug is much more effective, Combination of 2-3 drugs in attempt to be more effective and decrease antibiotic resistance 6 months to 2 years Side effects: some of the drugs (clofazimine) causes skin side effects (scaliness, dry skin, patches) → leads to stigma against people even when being treated
CA-MRSA drug-resistance, virulence, types of infections, symptoms, and risk factors?
Drug resistance: only resistant to beta lactase Virulence: said to be more virulent and easier to transmit Type of infection: tuberculosis, hepatitis, HIV/AIDS, STDs, influenza Symptoms: pustules/boils, "spider bites", wounds that are red and swollen and painful with drainage Risk factors : skin to skin contact, skin openings, contaminated surfaces, poor hygiene, crowded facilities (military, jails, daycares, athletes, dorms)
HA-MRSA drug-resistance, virulence, types of infections, symptoms, and risk factors?
Drug resistance: resistance to more/additional antibiotics (erythromycin, clindamycin and tetracycline) Virulence: said to be less virulent Type of infection: severe infections, Clostridium difficile, MRSA/VRSA/VRE, Klebsiella sp., acinetobacter sp (central IV and blood stream issues, ventilation and pneumonia, catheter and UTI) Symptoms: severe infections and symptoms Risk factors/transmission: patients in hospitals are susceptible because weak immunity already and visitors are at risk
What is dual-purpose research? How does this apply to smallpox?
Dual research purpose: research done in name of good but could be used for bad purposes 2002 reconstructed a polio virus and since then now we wonder what other viruses can be reconstructed in a lab Laws that no one is allowed to remake more than 20% of variola genome (Companies that you can order sequences from regulate it ) Recently lab guy in canada ordered dna fragments from multiple different companies in the mail and stitched them together and made an active horsepox virus and said he did it so he could make a vaccine but... → means he could probably recreate smallpox
How is the HIV virus able to mutate rapidly? (thus causing problems with treatment and vaccine development)
Due to the fact that it is a retrovirus and therefore uses reverse transcriptase Reverse transcription, comes in with rna genome which will be reverse transibes with reverse transcriptase enzyme from RNA to DNA Will take viral genome from ssRNA to ssDNA and then dsDNA (All done by one enzyme) Highly error prone → no proofreading mechanism which causes mutations that occur have no chance of being corrected and stay around Overall high mutation rate and mutations accumulate very fast → problem for treatment and vaccine development This high mutation rate means high genetic diversity of HIV virus in a human which makes it hard for immune system to fight Resistance to treatment is easily developed Vaccine development is hard
How did awareness of HIV infection first emerge?
Earliest news report on AIDS: first national report of HIV epidemic (1980s) Awareness first began in 1981: Unsure when spillover occurred but was NOT in 1981, was circulating in human population for decades before 1981: Opportunistic infections in homosexual males in U.S. (in cali and NY) 1982: hemophilic individuals, africa people seeing since 70s 1983: virus was isolated→ Pandemic declared soon after 1985: first antibody test for HIV 1986: first antiretroviral drug Since start of pandemic (81) over 70 million people globally are infected with HIV → 35 million died 2017: 36.9 million HIV-positive individuals, Majority in southern African nations (4% of population in Africa)
During which stages of smallpox are individuals contagious? Approximately how long does a person remain contagious during a smallpox infection?
Early rash to after the last scab falls off is contagious (4th-18th days) 4th-8th day most contagious (early rash period)
effectiveness and safety of HPV vaccine
Effectiveness: suggested around age of 11 In both males and females, 99% seroconverted (protection) against all 9 serotypes Immunity for 10-15 years Very effective Safety No significant issues Normal things: pain, swelling at injection site, painful vaccine
Mechanism of N. Fowleri
Exact mechanism of action isn't know but is combinations of microbe itself and immune response and work together and cause death Microbe mechanisms Consumes tissue, release cytolytic compounds to case cell lysis, have proteas that degrad ce;; proteins, phagocytosis of host cells, avoid host immune system Immune mechanism Inflammation causes damage → swelling of the brain leading to death
What is EPT?
Expedited partner therapy (EPT): used with chlamydia and gonorrhea Stigma with STI and testing is shamed and large number of people asymptomatic If indivudual comes to doctor and is diagnosed, the doctor can give prescriptions to treat partner Legality is questionable with drug interaction and pharmacy/prescriptions Permissible in 45 states, potentially allowable in 4 states prohibited in .....SOUTH CAROLINA→ highest state with gonorrhea and chlamydia
What is CRE? Why is it a problem?
Found in all 50 states across many countries and is resistant to all antibiotics and it is the last resort so if something develops resistance to it that would be horrific (if CRE enters blood then there is 50% mortality rate)
What are some of the differences between CA-MRSA and HA-MRSA, including drug-resistance, virulence, types of infections, symptoms, and risk factors?
HA is resistant to more antibiotics risk factors are patients in hospital and visitors of hospital CA is more virulent and easy to transmit risk factors are more general places
General information about causative agent of AIDS
HIV is the causative agent → human immunodeficiency virus Retrovirus : ssRNA genome Can be HIV+ but may or may not have aids Slow virus in terms of amount of times to infect and amount of time to show infection
Why are HIV and TB co-infections so problematic?
HIV targets T cells → substantially harder to maintain granuloma and contain TB
How are HSV-1 and HSV-2 transmitted?
HSV-1: orla (saliva), in childhood, gives protection to HSV2 Can be HSV1 genital through oral genital (increasing) HSV-2: genital
Benefits Phage therapy and antibiotics
Had bacterium (man got multidrug resistance from heart) P aerogenios : resistant because had multidrug reflex pump→ This means any drug that gets pumped in will immediately get pumped out (effective) Found exact bacteriophage that attacks the strain and attacked it by entering through drug efflux pump Co delivered antibiotics and page at same time → cells that maintained the efflux pump were susceptible to phage and cells that lost efflux pump were susceptible to antibiotic
How was Timothy Brown (the "Berlin patient") cured from HIV?
He was given a stem cell transplant from a donor with a CCR5 mutation.
How prevalent are HAIs? What types of infections are common? What types of causative agents?
Healthcare-associated infections (Noncomosial) infection acquired in any medical setting , 1/20 patients are hospital Types of infections: UTIs, pneumonia , MRSA/VRSA. Clostridium difficile
describe the causative agent of herpes and the presentations of herpes
Herpes Simplex Viruses (HSV-1 and HSV-2) Herpesviridae family Also known for epstein barr and chickenpox HSV1 is oral herpes (cold sores and blisters), HSV2 is genetal herpes Rates of herpes dropping but the proportions are changing HSV2 rates dropping but HSV1 rising
How is TB diagnosed?
Historically TB skin test: Inject tuberculin (extract from TB) under the skin, Look for swelling → looking for immune response TB blood test: (more accurate in differentiating vaccine and infection) Measure immune response
How is TB spread?
Historically, spitting used to be fashionable but when TB came out we stopped spitting Airborne droplets: breath it in, goes into lungs into alveolar sacs
What strategies were used to eradicate smallpox?
Huge help was vaccine and vaccine strategy used Mass vaccination: vaccinate everybody Ring vaccination: identify someone whos sick and vaccinate everyone's contacts (Huge credit to eradication)
Blood donation ban in HIV
In 80s bans on blood donation from homosecxual men → changed as screening developed and understanding, instead of lifelong ban on homo men, wait 3 months (now) Not right because we can detect in 9 days so doesn't make sense because we are very good at screening In other countries, there is waiting period on risky behavior (ie drugs or prostiution)
What are some of the problems facing HIV vaccine development? What progress has been made?
In the works but all clinical trials failed so far because... high mutation rates and not getting broad recognition by immune and lack of understanding regarding proper immune response High mutation rates are problematic Resistance is common due to mutation (from lack of proofreading), the number of replication cycles, recombination and viral hideout (Areas low of drugs and virus hides) Promising vaccine attempts : RV144, HVTN702, Imbokodo (HVTN705/HPX2008)
Compare the two general types of polio vaccines. What problems exist with each type? What are the benefits to each type?
Inactivated polio vaccine (Salk) → vaccine US uses, injected Grow in monkey kidney cells and inactive with formaldehyde Immunity: 2 doses give 90% immunity, 3 doses 99% immunity Duration: unsure Really good at preventing paralytic Problems with inactivated Not good at protection for wild type polio viruses Not good immunity in GI tract Oral polio vaccine (sabin) → live attenuated, oral Immunity: 3 doses gives over 95% effective Duration: lifelong Excellent GI protection Problems with oral: Vaccine associated paralytic polio (very rare) → 1/ 2.7 million doses In injected individual, it reverts to virulent → In areas like US where its not circulating, out of 152 total cases of paralytic polio in US, 144 were vaccine associated paralytic polio Because it is live virus, people shed attenuated form → In undervaccinated area, this form sheds and gets into water and goes from water to people so many times that this vaccine derived virus circulates in population (After 12 months risk going back to paralytic form )
What is the basic disease progression for smallpox?
Incubation: 7-17 days Initial symptoms (2-4 days): High fever of 101 to 104, fatigue, achy, Most not contagious Early rash (4 days): Highly contagious, Blisters in mouth and blisters pop in mouth and then spreads from Tongue and mouth to arms/legs to hands/feet Pustular rash (5 days): Blisters get hard Scabs (5 days): Pustular rashes fall off Scabs resolve: 6 days 20 days total, really long term care
What are some resistance mechanisms that microbes can use to evade antibiotic action?
Inhibit cell wall synthesis, inhibit protein synthesis, metabolic antagonist, inhibit nucleic acid synthesis Resistant mechanism : target of mechanism gets changed, drug is modified or broken down, prevention of entry of drugs, drug that did get in got pumped out
The idea behind anti-virulence drugs and the potential benefits and concerns associated with using these drugs
Instead of killing bacterium, since in so many cases the illness is caused by virulence factors (IE all of c diff are from toxin production, if you don't have toxin production you don't get sick ), Target virulence factors so immune system can get into it Pros: less evolutionary pressure for resistance, Target is rapidly inactivated, Used in addition to antibiotics to alleviate infections, Used in people who can't get antibiotics Cons: develop resistance to these relatively fast, Specificity, Not as effective (If bacteria can hangout without causing disease will they just reactivate when done taking anti virulence )
TB skin test problems
Issue is that if you had an affection that you cleared on own, you'll test positive from antibodies or if you had vaccine you'll test positive → doesn't differentiate
Explain the differences between latent TB infection and active TB disease.
Latent TB: 25% of population, bacteria are not growing, not contagious or symptomatic, Fight between immune system and TB and immune system is maintaining control TB disease (active TB): becteria are growing, contagious, symtomatic,
What problem may be associated with the smallpox vaccine?
Made from the vaccinia virus (lab derived virus) → in healthy people causes localized effect but do get long term immunity (3-5 years immunity not lifelong) Inadvertent inoculation → dangerous in immunocompromised people One blister forms, is contagious so people may inadvertently spread vaccina virus to other parts of the body Post-exposure vaccine protection: lowers chance of active virus (within 3 days of exposure either get mild disease or no disease), Unsure of mechanism, 2-3 weeks to develop immunity Given differently from other vaccines → Bifurcated needle
What complications can arise from Gonorrhea infections?
Men → epididymitis (inflammation of ducts which can lead to infertility) Women - PID Both → higher risk of HIV (could get into joints or blood stream and you can die)
causative agent of Tuberculosis and its characteristics
Mycobacterium tuberculosis mycobacterium are acid fast, slow growers, non spore forming→ the slow growing makes it hard to culture
What is meant by the fact that infection with HPV is necessary, but not sufficient to cause cervical cancer?
Necessary, but not sufficient: HPV infections is necessary for cervical cancer development but this by itself is not enough Need cofactor like smoking, birth control pills, many children, HIV Suspected cofactors: immunocompromised or chlamydia
What is neonatal herpes?
Neonatal herpes→ can be transmitted to baby and lead to prematurity and repent skin lesions, brain development problems (microcephaly), rarely babies die
Do all HPVs cause genital warts? Explain.
No , some cause cancer, some are asymptomatic, some warts
What type of vaccine is available for HPV? Is this form infectious or noninfectious? Why?
Noninfectious form because just proteins Made using Non-infectious virus- like particle vaccines Express capsid protein in yeast cells and take each of 9 serotypes and purify it L1 self assemble in spears and are now empty protein capsids → antigens are there for immunity but virus particles can't cause infection! Effectiveness: suggested around age of 11 In both males and females, 99% seroconverted (protection) against all 9 serotypes Immunity for 10-15 years
Why is BCG not available in the U.S.?
Not widely used in the U.S. → Overall low risk of TB, questions about efficacy, skin test for screening is huge in US and the vaccine would invalidate/nullify the skin test
What characteristics of smallpox made eradication possible?
Only carried in humans, identify contagious people, isolation is effective, not big numbers of asymptomatic, cheap and effective vaccine, immunity from infection (only get once)
general information about smallpox
Only human disease eradicated (No one has had since 1970s), Variola virus= an orthopoxvirus, Probably an animal disease that spilled over, Significant threat in bioterrorism
What are some of the difficulties to achieving eradication?
Pandemic pushed us way back → Failure to vaccinate kids Still present because of Areas of conflict and failure to vaccinate, circulating environmentally, mutations in disease Type 2 eradicated in 2015, type 3 eradicated in 2019
How is leprosy transmitted?
Person to person: Droplets with sustained contact → not very contagious Armadillos to people → zoonotic transmission, most cases in US are in texas and florida but not sure if its touching or eating Transmission of leprosy to armadillos is relatively new (Early explorers on US )
describe the causative agent of polio
Piconavirdiae family, Enterovirus genus single stranded RNA genome, Replicates in GI tract and is shed in fecal material Transmission: only carried in humans but highly contagious within family members due to respiratory and fecal spread Fecal oral most common with oral to oral possible Shed for a few weeks following infection, Shedding starts before symptoms begin
What is known about "dry infection" of naegleria fowleri?
Possibility of dry infections in india and africa have evidence of dry infection (proof is not definitive) When someone inhaled cysts → nigeria in dry season, cysts in air don't last long but can get inhaled All cases in US are known to be wet (water in nose)
Why has antibiotic resistance spread so quickly?
Prevalent and emerging antibiotic resistance is worsening When we first started using antibiotics we haven't done much with new antibiotics just modified old ones
Why is Candida auris a concern?
Prevalent and found in various countries in the world, multidrug resistant with some untreatable strains, causes outbreaks in healthcare facilities, mortality rate of up to 50%, huge increase in 2020-2021
What are some possible solutions to the worsening problem of antibiotic resistance?
Preventing emergence or spread of resistance by giving appropriate doses, stricter control of OTC drugs, patient compliance by direct observed therapy (watching them take drugs for whole time) Development of new treatments by identifying new natural comounds, genomic approach, drugs that act as synergist and resensitize microbes, antivirulence, bacteriopahges New natural compounds: We can't culture 90 to 99% of microbes that exist → microbial dark matter, If most of the antibiotics are natural compounds and we can only culture one to ten % there should be a lot more new natural compounds
What are the troubling trends that were found in the 2018 CDC report regarding Syphilis?
Primary and secondary 35,,063 cases 71% increase since 2014 2000 and 2001 - 2.1 cases/100,000 (lowest since reporting began in 1941) Increasing overall and in males and females Increasing in age group 20-34 Congenital syphilis (in babies) 1306 cases 185% increase since 2014
How is smallpox spread?
Prolonged person to person with bodily fluids: Droplets, coughing and talking (long time) Air (Aerosol possibility) → bioterrorism , possible but not big , Happened in last death, not effective Rash: contagious in most cases, Blister or scab
What are some pros and cons to in-home HIV testing?
Pros: more comfortable testing in home, better to know than not know Cons: tests are not accurate (false negatives and false positives), worry of lack of support when positive HIV has stigma so people wouldn't seek out testing
What portions of HIV (or the life cycle) do antiviral drugs target?
Reverse transcriptase inhibitors Protease inhibitors Viral integrase inhibitors Coreceptor binding inhibitors Viral fusion inhibitors
The discovery of Teixobactin through the use of the iChip
Small chips with a bunch of wells and diluted soil sample to have one cell per well and put film over top and put back in soil Something in the soil might promote the growth of the organisms and the film will let things diffuse 40% of isolates did grow and transferred them to plates and one produced compound teixobactin
Problems with phage therapy
Specificity can go all the way down to strain for bacterial target so have to find a new phage for each infection (Time it takes to do that in some cases leads to death), Lysis of gram negative (Releases massive amounts of LPS into bloodstream/Release of toxin), Resistance to phages is possible, Some phages trigger immune response
What type of illness does naegleria fowleri cause?
Symptoms (1 to 7 days after infection) → meningitis symptoms Fever, nauseous, vomiting, headache Then goes to confusion, hallucinations Destroys brain tissue Primary Amebic Meningoencephalitis (PAM)
How is leprosy diagnosed?
Symptoms plus skin biopsy/slit skin smear : Most common (do this by testing or looking at lesions PCR occasionally: Are the right tools available Serological tests: Not used, not very sensitive and not specific enough
What are the symptoms associated with leprosy?
Symptoms: extremely variable due to long incubation period of 5-20 years (slow replication) Skin and nerve symptoms: lesions, growth, numbness in extremities, weakness Sometimes severe effects like amputation or blindness
Why does tuberculosis go from latent to active
TB disease (active TB): becteria are growing, contagious, symtomatic, Active in replication bevause either something happened to immune system or immune system never had control in the first place Risk originally when first get it if immune system can't handle it Risk over time because other disease or getting older Go from latent to active by: Recent infection, Health issues (HIV, Diabetes), Alcohol or drug abuse, Incorrect treatment
antiretrovirals and HIV
TasP (treatment as prevention): used in HIV positive person so they don't spread to someone who is negative → Keep low viral set point (lowers risk of transmission) PrEP (pre-exposure prophylaxis): HIV negative people on antiretrovirals daily in lower dose → Used in individuals who engage in risky behavior (positive partner, illegal drug use) PEP (post-exposure prophylaxis): Emergency use → When someone has known potential exposure (suspect exposure, start in 72 hours)
How is antibiotic resistance thought to develop and spread in microbes?
They have always had antibiotics resistant genes sometimes they get resistance from spontaneous mutations but it is rare (passed vertically) Horizontal: horizontal gene transfer, One antibiotic resistant will end up passing the gene to a new organism ( Conformation, transformation )
List several reasons MDR and XDR-TB are problematic.
This is about drug resistance which causes treatment and clearing issues Multidrug resistant (MDR) TB: Resistant to at least the first line drugs (isoniazid and rifampin), Prevalent and spread out Extensively drug resistant (XDR): Resistant to two first line drugs plus any fluoroquinolone and at least one of the second line drugs
What are some of the misconceptions about leprosy that have persisted?
Thought to be not around anymore and one of the most contagious diseases → both of these are misconceptions, Lots of stigma However, it is almost eliminated, some of this due to 95% of the world being naturally immune due to either Innate and adaptive immunity or genetics
How many poliovirus serotypes commonly cause human disease?
Three serotypes (P1, P2, P3) with no cross protection to provide immunity so... Vaccines have to contain all 3 strains to protect against polio
What are the three stages in the life cycle of Naegleria fowleri? Which one is infectious? Which one is the most stress resistant?
Trophozoite: infectious form, active and reproducing, Most likely form to find in humans, Can switch to either of the other two forms Flagellate: typically found in low low nutrient water, Long distance movement (for protist), Occasionally found in CSF, Intermediate form, just moves , Can convert back to trophozoite Cyst: dormant form, Stress resistant, Doesn't feed or reproduce , Can convert back to trophozoite
classifications of leprosy
Tuberculoid (paucibacillary): less severe form Localized and raised lesions, not many bacteria, TH1 immune respponse (innate immunity), Lepromatous (multibacillary): more severe TH2 immunity, lots of bacteria, not localized , thickening of skin Borderline: most common form In Between the two above Doesn't usually kill people
Explain what occurred during the 40 year Tuskegee Syphilis study
Tuskegee study 1932-1972: example of how distrust in medical community in black people specifically In alabama on campus of tuskegee In 1932 no known treatments In 1947 found penicillin Study was only going to be a few months to see natural progression 600 participants illiterate black individuals, Men were never told they had syphilis, No attempts at treatment even after 1947!! Prevented men from getting treated or leaving study Never informed about what would happen Men were told they had bad blood Promised they would get medical care, rides to and from clinics and burial ground after death Many wives and kids also got it from them Many of them died Therapeutic study 399 with syphilis 201 controls Biomedical ethics No withdrawl, no treatment, no informed consent, not treated like people
forms of smallpox
Two major forms of disease: variola major and variola minor (less severe) Variola major Ordinary: very common when circulating (90%) Modified: mild form in people who were vaccinated Flat: rare and very deadly (90% mortality) Hemorrhagic: rare and very deadly (90% mortality)
Describe the emergence (history) of community-acquired MRSA.
Used to just be HAI (hospital type) but in 1982 in detroit, there were the first vague reports of community acquired MRSA but the patients had risk factors associated with HA-MRSA 1990s (Western Australia) first "genuine" cases: All in people who lived in remote low populated areas and none of them had been in hospital and all had MRSA Late 1990s (Midwestern United States) : 4 healthy children died from MRSA and had not been in hospital or around people who were in hospital
What problems are associated with S. aureus carriers?
Usually carry in nose, sometimes skin, 25 to 35% of individuals carry, Increase in carriers of MRSA Problems for carries : if hospitalized or have surgery more likely to get MRSA themselves Problems for others: shedding→ touches skin or nose and then doesn't wash hands and infect others this way
What are some of the barriers to achieving high levels of HPV vaccination?
Vaccine hesitancy across board (unsubstantiated side effects) 60% of people who can get it, do get it Lack of knowledge in parents, kids aren't sexually activated, seems not necessary Doctors need to include this as childhood vaccination (not make it sound like a separate thing) Don't want to think kids are sexually active at 11 → have to protect at this age to protect at assumed age of sexual activity
Naegleria fowleri is a waterborne parasite, yet we don't commonly screen for the pathogen as part of water treatment. Why?
We don't test for it in treated water because hard and expensive and its not a threat with the way we should be using water Two cases of N. fowleri in Louisiana in 2011 (Both died ) from using tap water in neti pots
What are the changing developments related to global eradication of polio? What are some of the difficulties to achieving eradication?
Why polio can be eradicated: Only circulates in humans (no animal reserve) Effective and cheap vaccine (Even though neither is perfect ) When you get immunity from either infection or vaccine, immunity is life long Virus needs human host (won't persist without human host) In 2015 polio transmission stopped (except in pakistan and afghanistan where endemic )
Should the remaining smallpox stocks be destroyed?
Yes because... The thought of accidental release from a lab or Risk of intentional release from bioterrorism , Genetic tools advanced enough so we could make one If released don't know adequate treatments, how to make vaccines, don't have good animal model, do we have immunity? No because... Smallpox research is incredible controlled
HA-MRSA infects people who...
are already sick
What are STDs? What are STIs?
differs because infectious agents are generally more asymptomatic (STIs), Diseases have different symptoms ,
What treatments are available for naegleria fowleri?
don't have a definitive treatment or a treatment that we know will work/use every time Drugs shown to be effective in laboratory settings but most patients die regardless of treatment argument that they should have been given earlier and would be effective if given earlier Issue is that drugs have trouble crossing blood brain barrier so there is a push for using drugs that we know can pass through the blood brain barrier amd see if they are effective Amphotericin B: anti fungal treatment Mitelfosine: approved as breast cancer drug → was used as a treatment in one of the 4 survivors
What are some common STDS?
gonorrhea, chlamydia, HIV Chlamydia (nationally notifiable): bacterial , Gonorrhea (nationally notifiable): bacterial, Bacterial vaginosis (microbiome), Viral hepatitis (viral STD/STIl), Genital herpes, HIV/AIDs, Human papillomavirus (HPV), Pelvic inflammatory disease, Syphilis (nationally notifiable): bacterial, Trichomoniasis (lab)
mechanism of active TB
immune system can form granuloma and the bacterium infects the alveolar macrophages Body contains in granuloma which are surrounded by T and B cells Appears bacterium are dormant (possibly even metabolically inactive ) when in granuloma immune system to weakens, Something then happens that causes granuloma to break down and the bacteria begin to replicate in immune cells and produce large numbers and go to blood
The __________ polio vaccine can prevent paralysis, but cannot prevent gastrointestinal infection.
inactivated
Paralysis occurs in approximately ______% of polio infections.
less than 1 %
Explain the mechanism of methicillin resistance for MRSA.
mecA is the resistance gene and is the main mechanism of methicillin resistance in MRSA Gets a 5th penicillin binding protein (PBP2a) Penicillin comes in and binds to the initial 4 PBP but because of the 5th PBPa can complete the transpeptidase reactions
symptoms of TB
respiratory infection (can be in kidneys or brain or bone), cough, chest pain, fatigue, weight loss, fever, night sweats
A rash, often found on the palms of hands or the soles of feet, is associated with the ________ stage of Syphilis.
secondary
Not all people with HIV have AIDS. True or false
true
how do we differentiate between CA and HA MRSA
used to be distinct but now interchanging so we base off on: Time of when you presented with the staff → Have you been hospitalized recently ? Medical history Risk factors: are you an athlete do you attend day care
What are the problems with second-line drugs that are often used to treat resistant infections?
when 1st line drugs are not effective / pathogens are resistant we turn to 2nd line drugs which are more expensive and less effective and longer hospital stays
