BIO EXAM #2

antiseptics

can be used on living body tissues e.g. a wound

sterilization

destroying all live microbes, spores (bacterial and fungal) and viruses

pasteurization

reduction of the number of microbes, especially liquids

What are the three most important factors that led to a sharp decline in deaths due to infectious diseases in the 20th century

(1) sanitation (2) vaccination (3) antibiotics

The Black Death, aka Bubonic Plague

- "plague" is from the Latin meaning "to strike" or "wound - zoonotic disease: transmitted from animal reservoirs (especially rats) by the bite of a flea with an incubation period of 4-6 days - bubonic plague is fatal in about 30-60% of untreated cases - causes systemic disease (spreads through the body) - when its infects the airways it is known as pneumonic plague and can spread person-to-person - pneumonic plague is always fatal if untreated - early signs of the disease: fever, headache, chills, and buboes: enlarged, painful, swollen lymph nodes in the groin, armpits, neck

Why/How are chemical antimicrobial agents different than antibiotics? Why can resistance develop to antibiotics but not to CAA?

- Chemical (and Physical) antimicrobial agents target the basic biochemistry of microorganisms: disrupting lipids, denaturing proteins, etc. which aren't very specific. Act generically and equally well on all microorganisms of a particular type (G+ bacteria, non-enveloped viruses, etc.) - Antibiotics work by targeting specific enzymes used by bacteria. Because of minor genetic differences, not all bacteria within a type will be equally susceptible -mutations in DNA can lead to slightly different enzyme which results in an enzyme resistant to antibiotic

Attachment and entry of SARSCOV2

- SARCOV2 attaches to the Angiotensin-Converting Enzyme 2 (ACE2) receptor found on (virus must attach to ACE2 in order to infect cells)(inhibit that attachment step to stop the infection) - chloroquine interferes with glycosylation of ACE2, (possibly inhibit the binding of coronaviruses to ACE2 receptor) and may inhibit the binding of the virus to host cells (cannot infect our cells and we remain healthy)

What is the bacterium and vector of the plague

- Yersinia pestis - small, gram-, bacillus-shaped bacterium - a SINGLE BACTERIUM is infectious and can be lethal in 50%of cases - infects many types of mammals - usually transmitted by the bite of the Rat Flea, Xenopsylla cheopis, but other fleas can transmit as well

What is necrotizing fasciitis?

- aka "flesh-eating streptococci" - caused by streptococcus pyogenes - invasive infection of connective tissue where bacteria rapidly spread, destroying muscle and fat - begins with a small, often trivial or unapparent wound - flu-like symptoms (diarrhea, fever, nausea, weakness) - skin discolors: dusky blue/ purple in color -tissue is rapidly destroyed (up to 1 inch/hour) by the activity of secreted enzymes: streptolysin, streptokinase, DNase, proteinase, hyaluronidase THESE ARE VIRULENCE FACTORS - treatment requires removal of infected, dead, tissue, in addition to antibiotics to protect the healthy tissue - about 10k cases occur in US each year (10-20% of patients with necrotizing fasciitis will die of the infection) hyaluronic acid capsule as an immunological disguise and to inhibit phagocytosis; M-protein to inhibit phagocytosis (3) invasins such as streptokinase, streptodornase (DNase B), hyaluronidase, and streptolysins;

ebola

- an enveloped filovirus because of its threadlike. filamentous structure - four other related viruses (ebola Reston was found in Reston, Virginia in non-human primates) - causes ebola hemorrhagic fever, which can have an 80% fatality rate ORIGINS AND PRESENT OUTBREAK IN EBOLA - emerged in 1976 in the village of Yambuka, Zaire, where the first cases appeared - named after the ebola river to avoid stigmatizing the village - reservoir is believed to be a fruit bat, though some related viruses may infect pigs - outbreaks have occurred in (Zaire [DRC] 1976, 600 cases/ sudan, 1979, 34 cases/ Zaire and Gabon, 1995-6, 465 cases/ Uganda, 2000-1, 425 cases/ West Africa, 2014-16, 28,610/ DRC 2018-current, 3452 cases, 2264 deaths) TRANSMISSION, SYMPTOMS, TREATMENT - transmitted in bodily fluids (blood, saliva, vomit, feces, sweat) enters via mucus membranes, cuts in the skin in original outbreak, reuse of needles to give anti-malarial drugs may have contributed to spread Ro=2: not very contagious very infectious: only 1-10 virus particles are needed for infection does not spread through casual contact, food, water - incubation period, 2-21 days, but 8 days is average - initial symptoms are fever, severe headache, muscle, pain, fatigue (not unlike flu, malaria) - a person is not contagious until after symptoms begin (unlike flu!) - as disease progresses, diarrhea, vomiting, and bleeding/bruising is common - only treatment is to manage the symptoms

What are some enzymes and how do they contribute to pathogenesis?

- an offensive strategy is that some bacteria produce enzymes that help them survive in a tough environment (i.e. to colonize/grow & avoid elimination/ disrupt normal cell function) UREASE - Helicobacter pylori, the bacterium that causes peptic ulcers, secretes the enzyme urease, which enables it to survive in a highly acidic environment of the stomach (H. pylori lives in the mucus layer lining the stomach, the bacteria manufacture the enzymes urease, which splits urea into ammonia and carbon dioxide. The ammonia neutralizes stomach acid, protecting the bacterial cells. The bacteria secrete toxins that contribute to the formation of stomach ulcers.) - Urease activity is the basis of acid acclimation that enables Helicobacter pylori to colonize the acidic environment of the human stomach. COLLAGENASE - dissolves collagen that constitutes the basement membrane and allows bacteria to penetrate and spread Clostridium species excrete collagenase to eat through tissue and, thus, help the pathogen spread throughout the body. They assist in destroying extracellular structures in the pathogenesis of bacteria such as Clostridium. They are considered a virulence factor, facilitating the spread of gas gangrene. - Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as Clostridium. They are considered a virulence factor, facilitating the spread of gas gangrene. HYALURONIDASE - dissolves hyaluronic acid that holds epithelial cells together (Streptococcus sp.) Epithelial cells are cells that come from surfaces of your body, such as your skin, blood vessels, urinary tract, or organs. They serve as a barrier between the inside and outside of your body and protect it from viruses. - enzymes alter the env't to help bacteria go undetected COAGULASE - causes blood to clot which keeps bacteria from spreading, but also protects against the immune response EX Staphylococcus aureus (but not other species of Staph) can cause boils to form in the outer layers of the skin (1) bacteria produce coagulase (2) clot forms (3) bacteria later produce kinase, dissolving clot and releasing bacteria - a bacterial enzyme which brings about the coagulation of blood or plasma and is produced by disease-causing forms of staphylococcus. - In the human host, the action of coagulase produces clotting of the plasma in the immediate vicinity of the bacterium. The resulting increased effective diameter of the bacterium makes it difficult for the defense reactions of the host to deal with the infecting cell. In particular, the defensive mechanism of phagocytosis , where the bacterium is engulfed by a host cell and then dissolved, is rendered ineffective. This enables the bacterium to persist in the presence of a host immune response, which can lead to the establishment of n infection. Thus, coagulase can be described as a disease-causing (or virulence) factor of Staphylococcus aureus - Coagulase is an enzyme that is produced by some types of bacteria . The enzyme clots the plasma component of the blood. The only significant disease-causing bacteria of humans that produces coagulase is Staphylococcus aureus. - notable for the bacteria's ability to produce coagulase, an enzyme that can clot blood.

selective toxicity

- antibiotics are very toxic for bacteria, but less toxic for mammals (antibiotics harm the bacteria without harming the host) - antibiotics usually affect a specific enzyme (protein that catalyzes a chemical reaction) that is essential for the bacteria, but not for the host - some antibiotics are not safe for internal use because they are too toxic to humans An important quality for an antimicrobial drug is selective toxicity, meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host.

What are some alternatives to "chemical" antibiotics that are not economically viable?

- bacteriophage (viruses) that kill specific bacteria - antimicrobial peptides small proteins, easy to make proteins that disrupt bacterial cell membranes

What are the three forms of Plague?

- bubonic: bacteria grow in lymph nodes of groin, armpits, neck, and cause swelling (buboes that are hard, red, painful) usually nearest the bite of the flea - septicemic: bacteria move from infection site and grow throughout the body - can cause shock, bleeding, and death of tissues resulting in the black color -pneumonic: in septicemic plague, bacteria move to lungs, OR are inhaled when another person with pneumonic plague produces respiratory droplets - causes pneumonia, shortness of breath, cough, blood/ water mucous

Doctors without Borders during Ebola outbreak

- built several large Ebola Treatment Units (ETUs) - well-trained staff, proper PPE to protect workers, prevent spread WORKING IN AN ETU - suspected and confirmed cases are separated - workers wear PPE that must be carefully put on and removed - personnel are present to observe and ensure to proper donning and doffing VOLUNTEERS FACED QUARANTINE UPON RETURNING HOME - although asymptomatic, subjected to restrictions for 21 days following last known contact with an ebola patient - twice daily fever checks via smartphone - no travel, no work, no public places - maintains a 3 ft distance from others QUARANTINE IS INEFFECTIVE BC IT IS NOT VERY CONTAGIOUS Quarantines are probably only useful when a disease is highly contagious person-to-person and the person is contagious before showing symptoms Ex: Measles 4 CASE OF EBOLA IN THE US - Dallas, Sept 2014: man who had traveled from Liberia. Died. All contacts were quarantined for 21 days - Dallas, Oct 2014: healthcare worker who helped care for the Dallas patient. Treated successfully at NIH - Dallas, Oct 2014: healthcare worker who helped care for the Dallas patient, and traveled to Ohio before developing symptoms. Treated successfully at Emory University. - New York, oct 2014: Aid worker who had returned from Guinea. Treated successfully in NYC

Cholera and Haiti

- cholera was carried to Haiti by an asymptomatic UN aid workers from Nepal who did not exercise good sanitation 2010: Cholera comes to Haiti - Cholera appeared in Haiti for the first time in more than 100 years - Haiti is the poorest country in the Western Hemisphere - poor sanitation - poor healthcare system - less than 2/3 have access to clean drinking water - following Jan 2010 earthquake, many aid workers came to Haiti - killed about 316k people; 1.5 million homeless - some from Nepal were asymptomatic carriers; the strain circulating in Haiti is identical to one causing an outbreak in Nepal - has killed an estimated 10k people and sickened 800k people, 5% of the population of the island ( probably more) (compare to 11.3k died of Ebola in West Africa) - clean drinking water and sanitation systems are lacking in Haiti

chemical antimicrobial agents

- commonly used on SURFACES: chlorine bleach, alcohol, dimethyl Benzyl ammonium chloride, formaldehyde SKIN: Benzethonium Chloride, Iodine, Triclosan, Phenol FOOD: salt, sugar, acid, chemical preservatives EMBEDDED IN PLASTICS/CLOTH: microban, triclosan, silver threads - effective against a wide variety of pathogens -works in the presence of organic material - those in consumer products have low toxicity - work by damaging common cellular components, like denaturing proteins (enzymes) dissolving lipids (used to make cell membranes) -resistance rarely if ever develops since generic aspects of biochemical make-up are targeted

Characteristics of the coronavirus

- corona viruses are responsible for up to 1/3 of upper respiratory infections - as a group, coronaviruses are pathogens of animals and humans. They are found in birds, mammal, and especially bats - medium-sized, enveloped, positive sense RNA viruses - has a genome that contains a single strand of RNA -genome of 27-32 kb (largest genome of any RNA virus) that may mutate rapidly - helical capsid - named for the "crown" of spikes when viewed with electron microscope -SARS-CoV-2 is a betacoronavirus (subgroup) - other related viruses (SARS-CoV-1, sudden acute respiratory syndrome in 2002) (MERS-CoV, Middle East Respiratory Syndrome in 2012) - encodes 5 proteins: S, M, N, HE, and E (these five proteins would represent possible targets for antiviral drugs - if a scientist wants to design a drug to stop coronavirus, they would want to inhibit the function of these proteins

West African Ebola Outbreak

- first cases in December 2013 in Guinea; spread to Liberia and Sierra Leone - spread because of burial practice - occurred in densely-populated urban area - poor healthcare, poverty, distrust of government, lack of response amplified outbreak - total cases: 28,652 - total deaths: 11,325 HEALTHCARE - hospitals were overwhelmed and ill-equipped to deal with the outbreak - many hospitals closed due to a shortage of staff, so no healthcare for ANY condition was available - lacked personal protective equipment (PPE), training, preparation to deal with Ebola - Liberia (before outbreak: 200 doctors for 4 million people/ after outbreak: 50 doctors) - healthcare workers accounted for 10% of the deaths - not enough beds

Modern time: Plague in Madagascar

- in 2017: 2348 cases and 202 deaths, mostly pneumonic - rapid response and investigation of cases; treatment and monitoring of contacts of those who had disease - rodent and vector control - the CDC Division of Global Migration and Quarantine (DGMQ) responded to help prevent the spread of Plague to other countries

What is the pathogenesis of Bubonic Plague?

- incubation period is about 2-7 days after flea bite - fever due to immune response - the bacteria spread rapidly through the bloodstream and infect lymph nodes, forming a bubo (painful welling), usually in the groin or armpit - untreated, bacteria multiply in blood and patient dies of Gram-negative septic. endotoxic shock - drop in blood pressure, poor blood circulation - blood clotting, poor oxygen delivery to the tissue

What is the pathogenicity of Coronavirus?

- infection is often mild or asymptomatic in children - can detect coronaviruses along with other viruses in adults with severe symptoms - When infections are mild, people don't seek health care (like SARS-CoV-2)/ compare this to ebola and how/why it didn't spread in US in 2015 EBOLA FATAL SO MORE PEOPLE SOUGHT MEDICAL CARE AS THEY KNEW THEY HAD EBOLA FROM SYMPTOMS, EASY TO CONTROL - spread disease through travel, work, etc. (continue their behavior because of the mild symptoms and can unknowingly spread it - containment is difficult COV2 was only noticed when they saw a number of patients with very serious infections and by that time they probably were at a point where the virus had already spread through the population through mild or asymptomatic infection

How do you prevent antibiotic resistance?

- limit the use of antibiotics and use only when needed Do not take antibiotics for viral infections do not use antibiotics in animal feed (accounts for 70% of antibiotic use in US) - ensure proper use: correct dose (adequately high, patient compliance) - use multiple antibiotics in combination (EX: tuberculosis - stop using certain antibiotics when resistance is emerging to remove the selective pressure for maintaining resistance public health officials monitor the situation in certain locales

What are A-B toxins?

- many exotoxins are A-B toxins - toxins that have specific tissues/cells that they affect - "A" subunit disrupts normal cell functions - "B" subunit binds to a specific receptor on a specific cell type (can stop toxins from affecting cells by blocking the binding of the "B" component to the target cell) They are called AB toxins because they are constructed from two parts (A and B) that play different roles in toxin action. The B component (pink in the picture below) binds to molecules on the surface of target cells (light orange). The toxins are then taken up into the target cells by endocytosis, at which point the A component (dark orange) enters the cytoplasm and (depending on the particular toxin) carries out some toxic enzymatic reaction inside the cell.

How can you stop (reduce) or kill (eliminate) a microbe?

- mechanical removal (scrubbing/filtration) - physical methods (refrigeration/freezing/radiation/Heat: boiling, baking, burning, autoclaving [heat and pressure]) - chemicals (metals: mercury, silver [in some cloth], copper/ alcohol: hand sanitizers/ halogens: chlorine, bromine, iodine/ salt/ "quats": found in mouthwashes, other consumer products EX. Benzalkonium chloride/ hydrogen peroxide - these methods work generically by removing microbes or attacking their basic biochemistry/ resistance does not develop

Contributing factor: population and ubranization

- more people living in more crowded areas create more opportunities for diseases to spread - lack of clean water, sanitation, rodents, insects

How are SARS and MERS different than COVID-19?

- more severe disease, so people sought health care - both SARS and MERS had "super-spreader" events: one person transmitted it to many others in the hospital (i.e nosocomial transmission) SARS: hong kong to Toronto/ 1 infected person to 128 others in hospital (contained in hospital) MERS: Saudi Arabia to South Korea/ 1 infected person to 186 cases nosocomial transmission- nosocomial means that transmission occurred in a healthcare setting - lack of severe disease/symptoms makes contact tracing (identify and isolate infected individuals) difficult, so virus is hard to contain (COVID-19) "In this manner, a virus that poses a low health threat on the individual level can pose a high risk on the population level, with the potential to cause disruptions of global public health systems and economic losses."

What can lead to antibiotic resistance?

- overuse and misuse of antibiotics can lead to the development of antibiotic resistance Antibiotic resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections.

What are some contemporary examples of poor sanitation?

- poorly constructed latrines, crumbling hillsides, crowded conditions

What are some factors contributing to emerging infectious diseases?

- population growth - urbanization - ecological disturbances (deforestation/ climate change) - global travel/ migration - changes in human behavior/ activity - medical interventions - food production and processing (e. coli) - technology (air conditioning systems/ dams/ super absorbent tampons)

Contrast SARS-COV-2 diagnosis to rapid tests for influenza or strep

- rapid, in-office tests are based on reaction of viral or bacterial proteins with monoclonal antibodies - it takes at least 3-4 months to make a monoclonal antibody, and longer to develop/validate the test which means no rapid COVID-19 test yet! - whereas the covid 19 tests is based on genetic material from the virus and uses PCR, tests for influenza and strep throat are rapid tests that are based on detecting viral or bacterial proteins using monoclonal antibodies - ISTT- sample is taken from a patient and then reagents are added involving monoclonal antibodies, then these antibodies can detect the presence of proteins from the influenza virus or streptococcus pyogenes bacteria and you can get the results rapidly - not available for COVID-19 - in order to develop the reagents and these MA that are needed for such tests, it takes at least 3-4 months to make tho antibodies, and additional time develop and validate a test using MA for COVID19 - antibody-based COVID19 test because of cross reactivity and the ability fo those antibodies to recognize much more common, less virulent coronaviruses we have been exposed to

mechanical removal of microorganisms

- scrubbing physically removes the microorganisms, as well as oils and dirt that help germs cling to surfaces - filtration membrane filters are good for liquids (especially if the liquids are heat-sensitive) as well as air traps microorganisms that are larger than the pores of the filter RECALL: cholera can be reduced by filtering water through multiple layers of cloth, because the cholera bacteria are stuck to copepods, which are larger than the "pores" created by cloth

What are the incubation time and characteristics of COVID-19? its severity?

- severity of coronavirus infections can be somewhat linked to the cells they infect based on the receptors to which they attach - common cold viruses: attach to and infect cells of the upper respiratory tract which results in a mild disease - SARS viruses infect cells of the lower respiratory tract (LUNGS not so much our sinuses and throat) which results in a more severe disease - ( after a person contracts CV symptoms will appear anywhere from 1-14 days later with 3-7 days being the typical time frame for them to develop) incubation time: 1-14 days, with 3-7 days typical (individuals are infectious BEFORE symptoms appear - mild flu-like symptoms (fever, cough, fatigue) - some develop sever symptoms: respiratory distress, respiratory failure, organ failure

How is one diagnosed with coronavirus?

- since treatment is non-specific, diagnosis is of little value EXCEPT in epidemic/pandemic situation - diagnosis is important in understanding epidemiology and following transmission (diagnosis is important for contact tracing and isolating those you interacted with) (the value of the diagnosis is more in controlling the spread of cv) - uses the polymerase chain reaction (PCR) to detect SARS-CoV-2 viral RNA (requires special reagents and equipment not available in every medical office/lab (1) samples are collected from the nose or throat of a patient with a swab (2) the sample is sent to a lab where the genetic material in the sample will be seperated out (3) the genetic material is mixed with substances that will cause a reaction (4) if COVID-19 is present the substances will create copies of a unique part of the virus's genetic blueprint (5) all the copies will show up as a spike on a machine that confirms the presence of COVID-19 -tests are limited and take a long time to get results

Zika virus and microcephaly

- some speculated that microcephaly was caused by pesticides used to control mosquitoes - definitively provided a link between Zika virus infection and microcephaly with a case-control study: - compares babies born with microcephaly to normal babies born in the same place during the same time period - found that babies with microcephaly were 55x more likely to be infected with Zika than unaffected babies - examined other factors as well (including Dengue infection, syphilis) and did not see any other correlation

How is the plague transmitted?

- the bacteria can reside in domesticated, urban animals, or wild animals - transmitted by fleas or by direct contact - can sometimes be transmitted directly from one infected individual to another - pneumonic form could be weaponized

Zika in the US

- the peak of Zika was in US was 2016, most associated with travel - 5,168 confirmed cases (421 in CA) - over 35k cases in Puerto Rico - 218 cases in Florida and 6 in Texas were acquired locally - local transmission could elsewhere where Aedes mosquitoes are found - 2019= 20 cases, 2020= 0 cases - in 2016, 28 babies have been born with brith defect in US; may be more in ongoing pregnancies - 5 pregnancy losses associated with Zika infection - 5-10% of pregnant women with zika give birth to a baby with birth defects; risks is much higher earlier in pregnancy

How do antibiotics work?

- to achieve selective (aka Differential) toxicity, antibiotics target enzymes found in bacteria but not eukaryotic cells (1) inhibition of cell wall synthesis - animal cells don't have cell walls and peptidoglycan PENICILLIN (common allergies) AMOXICILLIN (2) inhibition of protein synthesis (by ribosomes) - eukaryotes have 80s ribosomes while bacterial cells have 70s ribosomes CHLORAMPHENIOL (not approved for use in humans in USA bc it can damage bone marrow and cause anemia) DOXYCYCLINE (3) inhibitors of nucleic acid synthesis (DNA or RNA) - replication (synthesis of DNA) or transcription (synthesis of RNA for protein production) FLUOROQUINOLONES LIKE CIPRO (increased risk of tendon rupture) CIPROFLOXACIN (CIPRO) (4) inhibition of metabolic pathways (antimetabolites) - some antibiotics bind to the enzyme that is carrying out the reaction, preventing the reaction from occurring SULFANILAMIDE (sensitive/allergic) SULFAMETHOXAZOL (5) disruption of cell membrane - only rarely, because of similarity in prokaryotic and eukaryotic cell membranes POLYMYXIN IN POLYSPORIN (highly toxic to the kidney)

Zika Virus

- transmitted by Aedes sp. active during the day (also transmitted sexually, via blood transfusions, mother to fetus) - a flavivirus related to West Nile, Yellow Fever, and Dengue viruses - often causes an unapparent infection - symptomatic infections characterized by fever, muscle aches, joint pain, malaise, maculopapular rash - not much known about pathogenesis, but causes birth defects (microcephaly, deafness, club foot, abnormal eye development)

How is coronavirus transmitted?

- transmitted by respiratory droplets, secretions, and aerosols SARS-CoV-2 (COVID-19 transmission - person-to-person spread, including from people who didn't feel sick or have only mild symptoms (which is why isolation and social distancing is so important for all groups, bc one infected person who doesn't feel sick could be a link between an infected case and somebody who is much more susceptible and will experience severe illness) - remains viable in aerosols for up to 3 hours - fomites, including plastic and stainless steel (5-7hr), copper cardboard (after 5-7 hours, half the amount of original virus may still be present on these surfaces) stable SARS-CoV-2 detected on plastic and stainless steel after 72 hours

What is the epidemiology of coronaviruses? Why are there cycles every 2 yrs?

- typically seasonal, with winter peaks and occasional spikes in Fall or Spring, but can occur at any time - follow a seasonal pattern much like the influenza virus (graph with coronavirus and influenza virus following 3 yrs) - dominant strains appear to come EVERY OTHER winter, possibly due to loss of immunity in two year's time ( short immunity or weak immune response) OR due to antigenic variation (mutations and changing of the virus that can cause it to go undetected) - reinfection with the same strain is common

Contributing factor: medical interventions and human behavior

- use of (unclean) needles in the administration of medicines - use of blood products which led to spread of HIV - antibiotic resistant infections

Where is Plague today?

- very sporadic in US - most cases are in small towns/ rural areas rather than in cities - 1 case in 2018; 17 cases and 2 deaths in 2006 - 3248 cases 2010-2015, 584 deaths - most cases are in the DRC, Madagascar, and Peru

Current Ebola Outbreak in Democratic Republic of Congo

- violence against those who are trying ot help control the outbreak - 25% of people don't believe this outbreak is real - mistrust of healthcare workers leads to attacks on workers, death of an MSF epidemiologist leads ot MSF has suspended work NEW THIS TIME: A VACCINE - approved for use in 4 countries - estimated to be 97-100% effective - using ring vaccination strategy cut transmission by 75% - and: two monoclonal antibodies that show promise as treatments BUT VIOLENCE - trying to build community trust by training members of the community to do burials

Why are antibiotics ineffective against viral infections?

- viruses are not bacteria they do not have cell walls, synthesize their own proteins or nucleic acid, and do not carry out their own metabolism - viruses use host cell's machinery in order to replicate (the host cells are YOUR cells) eukaryotic cells! - however, viral infections can make a person more vulnerable to certain bacterial infections, and antibiotics may be prescribed to stop these secondary infections Antibiotics block metabolic pathways in bacteria: i.e. inhibit cell wall formation;protein synthesis.Viruses use host cell metabolic pathways;Viruses do not possess a cell wall and soare not affected by antibiotics.Antibiotics are not used to treat viral diseases because they are ineffective and may harm helpful bacteria.

What are the principles of vector-borne diseases?

-interaction between host, parasite, and vector are all important EX. vector produces compounds that suppress host immune responses (leishmaniasis) EX. Parasite undergoes specific phases of development in the vector EX. parasite causes disease in the host - disease transmitted by a biological vector are limited to areas where the vector exists - sometimes, temperature limits the replication of the pathogen in mosquito populations in certain areas - vector-borne diseases can be controlled by controlling the vector

How do you properly write a scientific name, genus, and species?

Bacteria are named using binomial nomenclature, a two-term naming system. Binomial names are typically composed of two terms, the genus name, and the species name. Both names are italicized but the genus name, which comes first, is capitalized while the species name is not. After the name is first introduced, the genus name can be abbreviated. For example, Escherichia coil becomes E. coli after its first use. Additionally, bacteria names are typically informative. With regard to E. coli, Escherichia takes its name after Theodor Escherich, who had originally discovered the bacterium, and coli refers to its habitat in the large intestine.

How do you describe the shape and arrangements of bacteria: bacillus, coccus, staphylo-, strepto-, diplo-, vibrio, spirillum, spirochete?

Bacteria are typically categorized into three classes based on their shape: bacilli (rod-shaped), cocci (spherical-shaped), and spiral (spiral-shaped). Bacillus, as its name suggests, belongs to the plural bacilli class, and is a single rod. Similarly, coccus is a single round bacterium. Staphylo- is a prefix that is used to signify a cluster. For example, under a microscope, staphylococci resemble a cluster of grapes due to its arrangement (cluster) and shape (spherical). The prefix, strepto-, describes a chain-like arrangement such as that of streptobacillus and streptococci. The prefix, diplo-, indicates a pair of bacteria such as diplobacillus and diplococci. Spiral bacteria tend to come in three forms: vibrio, spirillum, and spirochete. Vibrio is a comma-shaped rod, spirillum is a thick, rigid spiral, and spirochete is a thin, flexible spiral

Name the (1) function, (2) location, and (3) importance to virulence (if applicable) of the following bacterial structures: - cell/plasma membranes - cell walls (Gram-negative, Gram-positive) - flagella - pili/ fimbriae - capsules - spores - endotoxin - exotoxin - proteases - enzymes

CELL/PLASMA MEMBRANE As the cell membrane is selectively permeable, it regulates the entrance and exit of substances to or from the cell. Its location outside of the cell also acts as a boundary, maintaining the integrity of the cell which contains the cytoplasm CELL WALL The cell wall provides additional support and protection to a cell, especially against osmotic rupture, as it is a rigid layer that surrounds a cell. There are two types of bacterial cell walls, (1) gram-negative cell wall and (2) gram-positive cell wall. Gram-negative bacterial cell walls have a thin peptidoglycan layer and an outer membrane while gram-positive bacterial cell walls have a thick peptidoglycan layer and no outer membrane. Both gram-negative and gram-positive bacteria have the ability to cause disease and the structure of their respective cell walls can contribute to its virulence. Gram-negative bacteria contain Lipopolysaccharide (LPS) molecules in their outer membrane. EXOTOXIN/ ENDOTOXIN LPS, an endotoxin, can cause humans to experience septic shock when it enters the bloodstream after cell death. Similarly, gram-positive bacteria can disrupt or damage normal cell functions by secretion of exotoxins into the host's tissues. There are three types of exotoxins: cytotoxins which kill or damage cells, neurotoxins which block nerve impulse transmission, and enterotoxins which affect cells lining the gastrointestinal tract - gram-positive stains purple in the gram stain procedure while gram-negative stains pink because of the thick peptidoglycan layer in GP cell wall and GN cell wall structure does not retain the crystal violet stain - EXOTOXIN: released from the cell during growth an metabolism. ENDOTOXIN: retained (for the most part) within outer membrane and released when cell disintegrates. FLAGELLA A flagellum is a hairlike structure, commonly found at the backside of a cell, that allows bacteria to get to the site of infection PILI/FIMBRIAE Pili or fimbriae are short, protein projections that surround the exterior of the cell. These organelles of adhesion mediate the attachment of the bacteria to the surface, a defensive strategy that allows the bacteria to stay at the site of infection. STAY AT THE SITE OF INFECTION (DS/VF) CAPSULE The capsule is a polysaccharide layer found outside of the cell wall that protects the bacteria from phagocytosis, a process carried out by certain cells of the immune system to defend against infection. AVOID ELIMINATION BY IMMUNE RESPONSE (DS/VF) SPORES Spores are a dormant form of bacteria that is extremely resistant to elimination methods of heat or drying ENZYMES Enzymes are proteins that can increase the pathogenesis of bacteria by disrupting or damaging normal tissue and can help them survive in a tough environment. For instance, the suffix -ase, which is typically found in the names of enzymes, indicates the destruction or breakdown of other molecules. DISRUPT OR DAMAGE NORMAL CELL TISSUE (OS/VF)

Contributing factor: ecological disturbances

DEFORESTATION - people living in closer proximity to wildlife - destruction of habitat driving wildlife into inhabited areas - more contact between humans and animals (or the vectors they harbor) EX. Lyme disease, spread by deer ticks EX. Leishmaniasis, spread by sand flies CLIMATE CHANGE - expanding range of mosquitoes into areas previously too cold for them

Diagnosis, Treatment and Prevention of the Plague

DIAGNOSIS - recent flea bite and/or presence of a bubo in bubonic plague (black color of tissue is due to death of tissue) - plague should be suspected in individuals that have been in an area with cases, including the Western US - can remove fluid from the "bubo" and observe gram-negative bacillus - septicemic and pneumonic plague require blood and sputum cultures which leads to observe the Gram negative bacillus TREATMENT - antibiotics (Fluorquinolones like Ciprofloxacin, Doxycycline, or Trimethoprim) are given intravenously (IV) PREVENTION take precautions against flea bites, control rodents

How are endotoxins different from exotoxins?

Endotoxins are lipopolysaccharides whereas exotoxins are secreted proteins. Bacterial toxins are important virulence factors and they are usually classified as exotoxins (exo = outside) or endotoxins (endo = inside). Exotoxins are actively synthesized and secreted, whereas endotoxins are part of the bacteria and are released upon bacterial death and lysis

What is the difference between gram-negative, gram-positive, and acid-fast cell walls? Which of them contains lipopolysaccharide, mycolic acids, and peptidoglycan?

Gram-negative bacterial cell walls have a thin peptidoglycan layer and an outer membrane that contains lipopolysaccharide (LPS) while gram-positive bacterial cell walls have a thick peptidoglycan layer and no outer membrane. Acid-fast cell walls consist of a thick outer lipid layer, composed primarily of mycolic acid, on top of a thin layer of peptidoglycan.

How can you prevent getting infected with the coronavirus?

HANDWASHING - Ignaz Semmelweis, Hungarian physician working in Vienna in 1847 who mandated handwashing to reduce the transmission of disease by physicians to new mothers in his hospital SURFACE DISINFECTANTS - 70% ethanol kills in seconds - Benzalkonium chloride and chlorhexidine (antimicrobial agents) are NOT effective unless there is also 70% ethanol VACCINES - issue: antigenic variation (become unrecognizable to immune system) - in animal models, vaccine may enhance disease - but... vaccine trial is underway - new technology that is faster to develop: injection of mRNA (new method/ can be injected to illicit an immune response) rather than viral proteins (traditional way was to injecting proteins isolates from the viruses or the bacteria) MUCH FASTER - if all goes well... 12-18 months before vaccine is available

What is are characteristics and examples of bacteria lacking cell walls?

Mycoplasma is a genus of bacteria that lack a cell wall around their cell membranes. This characteristic makes them naturally resistant to antibiotics that target cell wall synthesis. Absence of a cell wall requires a cell membrane that is reinforced with sterols for strength Similarly, obligate intracellular bacteria lack a cell wall and live within a cell. One such example is that of Chlamydia trachomatis and Rickettsia prowazekii

Historically Significant Plague epidemics

PLAGUE OF JUSTINIAN: 541-542 AD - estimated 40 million deaths - outbreaks for about 200 years BLACK DEATH - 1347-1351 in Europe - 1/3 of population of Europe died; half the population of Paris GREAT PLAGUE OF LONDON: 1665-6 - killed 100k people, 25% of the population THIRD PANDEMIC: 1855-1945 - began in China - spread to India, Africa, South America, Australia, Hawaii, and San Francisco by 1900 - spread in rodents from SF to LA, 1923-24 and caused an outbreak of pneumonic plague downtown in 1924 RESPONSES TO THE BLACK DEATH WERE QUARANTINE

physical control

RADIATION - ultraviolet (UV) damages DNA good for surfaces, but it penetrates materials poorly - ionizing damages DNA uses a radioactive source (Cesium, Cobalt-60) penetrates materials well HEAT - works by denaturing enzymes and proteins, degrading nucleic acids, and disrupting cell membranes DRY HEAT: incineration (Bunsen burner) MOIST HEAT is more effective than dry heat because better transfer or heat water is available for hydolysis AUTOCLAVE: moist heat (121 C + 15 pounds pressure) can kill bacterial spores

What are the proteins of coronavirus?

S= SPIKE PROTEINS -homotrimer (3 identical proteins that form the spike on the surface of the virus) - mediates attachment and fusion to the host cell M= MEMBRANE PROTEIN - involved in virus assembly N= NUCLEOCAPSID - associates with the RNA genome; may interact with M and be involved in assembly HE= HEMAGGLUTININ-ESTERASE GLYCOPROTEIN - mediates attachment of virus to neuraminic acid on host cell/ can be found on viral envelop as well smaller than the spike proteins E= SMALL ENVELOPE PROTEIN - function is unknown, but may be involved in Viral Assembly If you can understand their role of these proteins and their importance in the viral life cycle you can design drugs to inhibit the function of these proteins and have an antiviral treatment for diseases caused by these viruses

What is the derivation of the name coronavirus?

SARS-Cov-2 -refers to the virus that is causing the current pandemic - was previously known as 2019-nCoV for novel coronavirus - once it was further characterized it was found to be closely related to another corona virus, the SARS virus, which emerged in 2002 - the disease that SARS-CoV-2 causes is COVID-19

How can you treat coronavirus?

SUPPORTIVE CARE (no approved, specific treatment for CV) - IV fluids, oxygen, ventilator, etc. - need that care to maintain themselves until the virus is essentially taken care of by their immune system and goes away CHLOROQUINE - best known as treatment for malaria -effective against SARSCOV2 in cultures of primate cells (no human studies to establish safety and efficacy of chloroquine for the treatment of SARSCOV2 ) - efficacy in humans has not been established through clinical studies DATA SHOWING THAT PRE-TREATMENT OF VERO E6 (MONKEY KIDNEY) CELLS WITH CHLOROQUINE INHIBITS SARCOV2 INFECTION - higher dose of chloroquine, less SARSCOV2 protein/ greater viral inhibition (Green= SARSCOVE2 PROTEINS) - chloroquine affects ACE2, which may prevent the attachment of the virus to host cells REMDESIVIR - experimental drug developed to treat Ebola infections - has not yet been approved - currently in clinical trials to determine safety and efficacy of this drug in the treatment of COVID-19 - other possible treatment that is being explored

Cholera

SYMPTOMS - sudden onset of acute diarrhea with massive loss of electrolytes and fluids (gallons)/ Loss of potassium causes cardiac problems, acidosis/ dehydration leads to low blood volume which leads to shock - "rice-water stool" because of mucus and epithelial cells that are shed from intestines - can be rapidly fatal: as little as 2-3 hours from onset - death due to collapse of the circulatory system in 50-60% of untreated patients CHOLERA TODAY - WHO estimates that there are about 1.3-4 million cases of cholera yearly worldwide - 21k-143k deaths per year - about 6 cases/yr in the US which are associated with international travel, but more since the outbreak in Hispaniola -recent outbreaks: Haiti (2010-2018: 665k cases, 8.1k deaths), Yemen (2017: 1mil cases and 2k deaths) - areas of concern: Rohingya Refugee camps in Bangladesh CAUSE -vibrio cholerae: the causative agent of Cholera - gram-negative curved rods (aka vibrios) - single polar flagellum - survives in fresh and saltwater - related to organisms that live harmlessly in association with aquatic animals and display bioluminescence (they glow!) - can be carried and spread by asymptomatic individuals - exacerbated by poor sanitation, flooding TRANSMISSION - non-communicable: transmitted in contaminated food and water, especially in places with poor sanitation and unclean drinking water - about 1 million bacteria required to cause an infection because most cholera bacteria don't survive the acidic conditions of the stomach - incubation time: 2 hours to 5 days VIRULENCE FACTORS OF VIBRIO CHOLERA - flagellum: helps v. cholerae to reach intestinal mucosa - pili: mediate attachment to the villi on the brush border of the intestinal cells - enzymes: help it get through the mucus layer in lining of intestines - cholera toxin, a secreted exotoxin HOW THE CHOLERA TOXIN WORKS -toxin binds to intestinal epithelial cells and causes large amounts of chloride ions (CI-) to be pumped into the lumen of the intestine (NOTE: cholera toxin is an A-B toxin where the B subunit directs it to bind to an intestinal epithelial cell and the A subunit affects the working in the cell - due to osmosis, water (H20), sodium (NA+), and other electrolytes follow - results in large amounts of fluid and electrolytes (salts, like NaCI) in the lumen of the intestine leads to diarrhea - fluid leave bloodstream to compensate to try to balance the fluids lost through the gut leads to dehydration TREATMENT - best prevention: CLEAN WATER and sanitation! - oral rehydration therapy (solution containing ions and glucose) reduces mortality to just 1-2.5% - individuals are often immune to re-infection but may become asymptomatic carriers of the bacteria - vaccines offer short term, incomplete protection (less than 1yr)/ Vaxchora was approved for use in the US in 2016, protects for about 3-6 months/ Dukoral and ShanChol are oral vaccines available in other countries - a simple water filter to remove cholera - V. cholerae often found associated with copepods/ copepods are tiny crustaceans 1-2mm in length/ often, V. cholerae clings to copepods - filtering drinking water through multiple layers of cloth removes the copepods and reduces the risk of cholera/ V.cholera on its own would pass through the cloth because of its small size, but is trapped along with the copepods

Symptoms, treatment, and CDC recommendations for Zika

SYMPTOMS AND TREATMENT OF SIKA - many people don't experience any symptoms - when symptoms occur, they are usually mild: fever, rash, joint pain, red eyes; sometimes muscle pain and headache - associated with birth defect: microcephaly, bone deformities, hearing and vision problems - treatment: rest, fluids, pain reliever CDC RECOMMENDATION REGARDING ZIKA AND PREGNANCY - do not travel to areas where Zika infection is occurring if you are pregnant - if you must be in Zika areas, protect yourself from mosquito bites

What is symbiosis and what are some types? What are frank pathogens and opportunistic pathogens?

Symbiosis is a term that describes the living arrangements of two dissimilar organisms in close association. There are three types of symbiosis: (1) mutualism: where both organisms benefits (2) commensalism: where one organism benefits and the other neither benefits or is harmed by the interaction (3) parasitism: one organism benefits and the other is harmed. *microbes that always have this relationship with their host are known as frank pathogens the relationship can change when the host is: - immunosuppressed - has burns - a mutualistic or commensal organism gains entry to a site where it isn't normally present *microbes that exploit these conditions are known as opportunistic pathogens which can cause disease under these certain conditions (1 and 2) - Opportunistic pathogens- microbes that normally do not cause disease, but may under certain circumstances. - Frank pathogens- microbes that always cause disease.

What is the importance of cell walls?

The cell wall provides additional support and protection to a cell, especially against osmotic rupture, as it is a rigid layer that surrounds a cell.

What is the "disease triangle"?

The disease triangle model: a change in the host, environment, or pathogen can result in a disease that strikes the population How can a host change? How can a pathogen change? How can the environment change?

What is the microbiome? Why is it important?

The microbiome is the aggregate of all microbiota or microflora (microorganisms) that live on and inside the human body. It is important because it defends against "bad" bacteria by crowding them out and 99% of the genetic information in our bodies is bacterial. It might also affect or behavior and moods, nutritional benefits, the efficacy of drugs, etc. - Normal flora are the microorganisms that live on another living organism (human or animal) or inanimate object without causing disease. - helps to defend against bad bacteria EX. taking a lot of bacteria kills both good and bad bacteria when these good bacteria are eliminated, it allows for clostridium difficile to grow in the gut which results in diarrhea (Inflammation of the colon caused by the bacteria Clostridium difficile. Clostridium difficile colitis results from the disruption of normal healthy bacteria in the colon, often from antibiotics. C. difficile can also be transmitted from person to person by spores. It can cause severe damage to the colon and even be fatal.) antibiotics do not kill spores and spores can grow when they realize it is not crowded, a fecal transplant is necessary to restore good bacteria A fecal transplant, also known as fecal bacteriotherapy or fecal microbiata transplant (FMT), is the process of restoring the bacteria commonly found in the digestive tract with an infusion of feces (stool) from a donor. When the bacteria in the digestive tract is destroyed as the result of an illness, it can be very difficult to get back. A fecal transplant can help with this. Feces are most commonly transplanted as a treatment for severe Clostridium difficile colitis, commonly known as C. diff. A C. difficile infection can occur when the bacterial flora in the large intestine is altered, allowing the C. difficile to proliferate and produce toxins, which can cause severe and even life-threatening colitis and diarrhea. This typically results from a course of therapy with antibiotics that kill good bacteria in the process of killing bad bacteria. 1 gram of human feces contains about 1 trillion bacteria

What are the virulence factors of Yersinia pestis?

VIRULENCE FACTORS IN THE FLEA - flea-specific virulence factors like YMT allows bacteria to replicate in the flea, and causes ingested blood to clot in the gut of fleas, so fleas feel a need to feed more and regurgitate bacteria bacteria into their next host - remember: in vector-borne diseases there is a specific interaction between the pathogen and the vector VIRULENCE FACTORS IN THE MAMMALIAN HOST - when bacteria enter their host, an increase in temperature (to 37 C) causes bacteria to turn on virulence factors that help it survive in this new environment - F1 protein capsules that prevent phagocytosis by immune cells, allowing bacteria to multiply - Pla helps bacteria to spread in tissue - Yops have enzymes that disrupt and kill host's cells, including phagocytic cells of the immune system

disinfectant

a chemical that can be used on inanimate objects and surfaces but is too toxic to the body

disinfection

reduction of pathogenic microbes on an inanimate object

What is an emerging disease?

the appearance of an entirely new disease never before recognized (SARS-CoV-2) known diseases that are increasing in incidence, expanding in geographic range, or were once under control, but then make a resurgence (TB) a disease that was only recently recognized to be caused by an infectious agent (Helicobacter pylori as cause of stomach ulcers)

What is a vector? Mechanical? Biological?

vector- insect that transmits an infectious agent (virus, bacteria, parasite) mechanical vector- no specific interaction between insect and pathogen - passively transfer pathogens on their feet biological vedctor - has a specific, complex relationship with the pathogen - pathogen lives, grows, and carries out key parts of its life cycle in its insect host

What is a virulence factor and how does it help a bacterium become pathogenic? What are the five things a microorganism must be able to do to cause disease? How do virulence factors help them do such things?

virulence factor- any structural or soluble factor that increases a microbe's pathogenesis, i.e. the ability to cause disease to be a pathogen, a microorganism that causes a disease, a bacterium usually must: - get to the site of infection - stay at the site of infection (DS) - colonize (grow at) the site of infection - avoid elimination by the immune response (DS) - disrupt or damage normal tissue (OS) PATHOGENIC BACTERIA HAVE VIRULENCE FACTORS WHICH HELP THEM DO THESE FIVE THINGS !!