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153 Cards in this Set

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What are the viral Acute Respiratory Diseases
Rhinitis, Pharyngitis, Tonsillitis, Stomatitis

What are the causative agents?
Rhinovirus
Coronavirus (including SARS)
Adenovirus
Describe basic characteristics of viruses and diagram the structure of a representative virion.
Characteristics
i.Obligate Intracellular Parasites - Can produce in living cells only and has No independent metabolism
ii.Small size – between 15-300 nm
iii.Replicate in a pattern that is fundamentally different (assembly line replication and one-step growth curve)
iv.Specialized techniques and equipment are required to directly observe and quantify viruses - EM microscope

Representative structure
i.Protein (capsomeres) form structure (Capsid) around nucleic acids (RNA or DNA)
ii.Makes a 20-sided die. 5,3,2 symmetry refers to sides of die (5pt, 3,pt, 2pt)
iii.Usually has an outer envelope with pepsomere attachments (spikes)
Outline the fundamental process of viral replication and explain how the one-step growth curve revealed the unique nature of virus replication.
1.Attachment – receptors determine tropism
2.Latent Period
i.Penetration – several methods (host eclipse, membrane fusion, endocytosis)
ii.Uncoating – removal of capsid. host directed (except for Pox)
iii.Synthesis – built inside-out- genome then capsid
3.Maturation/Release
i.Burst (lysis) – cause of one-step growth curve. First they’re not there. Then there’s a whole bunch of them.
ii.Budding (chronic production)
Describe the effects of viral replication on the host cell.
All viral replication is at expense of host cell. Burst maturation destroys cell quickly. Budding my keep host cell alive indefinitely to chronically pump out virus.
Where does DNA virus replication occur?
In the host nucleus
Where does RNA virus replication occur?
In the host cytoplasm
Where do the enzymes for viral RNA synthesis come from?
The host has no enzymes capable of performing the needed RNA copying tasks for the RNA virus and these molecules are either transported into the host in the virion itself or synthesized from the virus genome
What is destructive replication?
Retrovirus replication strategy. DNA Reverse Transcription.
One double stranded DNA is substituted for the two molecules of single stranded RNA genome that originally entered the cell.
The DNA copy of the RNA genome must then be integrated into the host cell genome (becoming a provirus) for expression.
RNA -> DNA -> RNA
List known viral transmission mechanisms
Aerosols
Direct contact
Fomites
Ingestion
Injection
Vector
Transplacental
How are certain viruses able to produce malignant transformation of the host
• Inactivating cell cycle control mechanisms (antagonism of host tumor suppressor proteins)
• Providing genes (oncogenes) that activate the host cell
• Enhancing transcription of key host genes (transactivators)
• Preventing the host from inducing apoptosis
Which specific virus infections are strong risk factors for cancer development in humans
Human papilloma virus types 16 and 18 (cervical/oral cancer)
Hepatitis B and C viruses (liver cancer)
Epstein-Barr virus (Burkitt’s lymphoma, nasopharyngeal cancer and others)
Human herpes virus type 8 (Kaposi’s sarcoma with HIV)
Human T cell lymphotropic virus type 1
Which “Tumor” viruses are mostly linked to non-neoplastic conditions?
BK and JC (human)
SV40 (primarily simian)
In terms of viruses, what is the zoonotic pool
animal viruses that invade humans
What is meant by an "emerging" viral disease?
- Newly evolved pathogens (new to medicine)
- Previously-recognized pathogens causing disease in new regions (expanding range) or at greater frequency than in the past
- Previously-recognized pathogens that are causing a more severe form of disease
what are the “Slow” Virus Infections
Misnomer. Most slow virus infections are slowly progressive CNS infections, not caused by viruses, but due to a newly recognized agent, the prions.
What is a prion and how does it differ from a virus?
Prions are infectious proteins. They are not organisms unto themselves.
Very long incubation periods, always lethal
The slow virus label was attached because clearly nothing else would work to classify these infections.
• Mad cow disease (Bovine spongiform encephalopathy, BSE) in cattle
• Scrapie in sheep
• Creutzfeldt-Jakob disease (CJD) and new variant form in humans
What are the existing methods to control Viral Infections
Best defense is Avoidance
- Quarantine
- Vaccination
- Passive immunization
- Antiviral agents
What is main concern with antiviral agents?
Many agents that will halt viral replication are often also toxic to host as well.
what is passive immunization?
Immunoprophylaxis by provision of immune serum globulin or humanized monoclonal antibodies
What are the diagnostic features to look for in a virus culture?
1. Cytopathic effects (CPE) in tissue culture
2. Plaque formation (cell killing) to assay virus
3. Pock formation in embryonated eggs
4. Death or pathology (LD50 or ID50 assays) in a whole animal assay
which viruses create giant cells and why do they do it?
Herpesviruses, Respiratory Syncytical Virus, Measles virus all create giant cells

Why?
Enables viruses to evade immune clearance for substantial periods
What are Negri bodies and what infection will you find them in?
Negri bodies are an example of inclusions or a cytopathic effect (CPE) that can be useful in identifying a virus.

Negri bodies are specifically used to identify rabies
what is viremia?
Viral dissemination through the blood. Amplifies infection.
What are three basic types of persistant infections?
1. Latent
2. Chronic Infections
3. Transforming
What are latent (or hidden) viral infections?
intermittent acute episodes of virus production between which there may be an absence of virus particles and very limited viral macromolecular synthesis (Herpes simplex)
what are chronic viral infections?
quasi-nonlytic production of virus, continued presence of virus during periods in which overt clinical disease is absent (Hepatitis B virus)
What are transforming infections?
cells are immortalized and properties altered (transformed) to those of cancer cells (Human Papilloma Virus and cervical cancer).
how are persisting viruses are able to avoid, modify or evade immune functions?
• Avoidance
• Blockade antigen presentation mechanisms by interfering with MHC expression.
• Interrupt cytokine synthesis or interfere with cytokine receptors.
• Inhibit apoptosis induction.
• Evade antibody/complement killing
In regards to persisting viruses, what is meant by avoidance?
infect nonpermissive cells or quiescent cells to store genome without lytic consequences or invade immunologically privileged sites such as neural tissue that lacks MHC markers.
What is a "hit and run" viral infection also known as?
Lytic infection.
successive propagation in a series of hosts, destroy host cells in which they multiply rapidly until immune responses catch up.
What is Lysogenic Conversion?
Occurs when a bacteriophage establishes lysogeny in a host cell and alters the phenotype of the host cell.
The lysogenized cell obtains and expresses genes that are actually a part of the viral genome, such as Toxin genes and New surface structures.
Most commonly, the term lysogenic conversion is used to describe lysogeny establishment-linked changes in the pathogenic capability of the host bacterium.
Highly medically significant, lysogenic conversion may produce a dangerous pathogen from an otherwise completely nonpathogenic organism.
What is Lysogeny Termination and why is it harmful to the host?
Also termed prophage induction. Occurs when lysogenic virus recognizes that the host is damaged and switches to the lytic cycle quickly to escape from a dying host.
My provoke severe intoxication from the rapid release of virions.
What is a virus called when it establishes a non-lytic interaction with a hist cell?
The quiescent virus is referred to as a PROPHAGE (if bacterial) or PROVIRUS in a eukaryotic cell.
Do proviruses use lysogeny to reproduce?
No. Lysogeny is strictly a prophage replication technique. To a first approximation, persistent infections by proviruses resemble bacterial lysogeny (a model system). The biochemical details are not as well understood for any of these systems, however.
What are the ARD Clinical Manifestations?
Nasal discharge/obstruction
Sneezing, cough, malaise, throat discomfort with 2-4 days incubation
No fever.
What is clinically important to remember about viral acute respiratory diseases?
These infections are typically benign, transitory and self-limited
What do ARD viruses like about the upper respiratory tract?
Like temperature.
Mostly like mucosa cells.
These cells support substantial viral replication
Which infections predominate ARD?
Viral 40%
Bacterial 30%
What are main things for a physician to consider when diagnosing viral ARD?
One or two agents account for most cases
Age, season, location (epidemiology)
What are some classification elements to know about Rhinoviruses?
1. Picorna virus family (literally, small RNA viruses)
2. Single stranded RNA genome, + sense
3. Nonenveloped
4. Over 130 antigenic types known. Complete cross neutralization is rare or transient, so patients will get colds repeatedly
5. human forms use ICAM-1 as cell surface receptor (canyon hypothesis)
What is the canyon hypothesis?
Partially explains human inability to stay immune to colds (rhinovirus).
Binding site for ICAM is located in deep clefts (canyons) in the virion capsomeres.
The inaccessibility of binding sites at least partially explains why recovery from one cold virus does not guarantee immunity to the other types that use the same receptor.
What do I need to know about Rhinovirus epidemiology?
1. Season - Infections are hyperendemic in winter months
2. Age - Greatest incidence is in children and young adults.
3. Transmission - These viruses are rather stable and can persist in the environment (fomites)
Hands and direct contact are a major factor in person-to-person transmission
Existence of a human carrier state is considered highly probable. Clinical illness observed in only ~50% of infected individuals although virus production occurs
4. Resistance - An antibody response occurs with infection, but solid immunity is only transient (perhaps 18 months)
Why are rhinoviruses so infectious?
1. Limited resistance due to canyon hypothesis and transient antibody response
2. Induce their own receptors - 90% of rhinoviruses use ICAM-1 cell surface receptor. Expression of ICAM is stimulated by interferon (a host response to viral infection)
How can we control the Rhinovirus?
1. Handwashing and disinfecting exposed objects is most important defense
2. Picovir (Pleconaril) is new possible drug. Prevents receptor binding and proper virion uncoating. Effective in several trials, but not approved for general use as an anti-cold treatment as yet. Even so, it has limited defense because several agents cause the common cold
3. 3C protease inhibitors – prevents maturation of virus by halting intracellular protease activity
4. BIRR4 - Binds viral receptor site, interferes with cell infection. Soluble engineered form of ICAM-1 delivered by nasal spray
5. Heed Zicam warning. While pharmacological treatment for colds would be nice. All drugs have potential side-effects, while ARDs are benign, transitory, and self-limiting. Could be exposing patients to unneccasry risk for something that will go away on its own.
Important viral classification elements of Adenovirus?
1. double stranded DNA
2. nonenveloped,icosahedral capsid.
3. 52 known antigentic types; 4 and 7 most common in US
Why do adenoviruses make great fomites?
complex icosahedral capsid structure are typically quite resistant to physical and chemical agents and survive well outside the body.
What infection strategies does Adenovirus use?
- Lytic, persistent, and latent infections known
- Infection of epithelial cells of respiratory and enteric organs
- Latency observed in lymphoid tissue with reactivation by immunosuppression possible
How does adenosviruses replicate?
- Viral DNA replication and assembly occur in cell nucleus.
- Dense inclusions observed in infected cell nucleus
- Virus protein E1A inactivates cell tumor suppressor protein Rb to promote cell cycle progression and transcription of viral genes
- Virus produces additional proteins, E1B- 55K and E4-ORF3 to antagonize host cell p53 protein, increase its destruction and prevent it from activating other genes
What diseases does adenovirus cause?
1. Adult pharyngitis
2. Pharyngoconjunctival fever (PCF)
3. Pertussis-like syndrome of young adults (types 4 and 7)
Whats the important epidemiology of the adenovirus?
1. Age - children and young adults
2. Season - likes winter months best
3. Transmission - Spread by aerosol, fomites, close contact, or fecal-oral route. Fingers may spread virus to eyes (PCF).
4. Opportunistic - Adenovirus can evade host immune responses and establish permanent latency with reactivation during immunosupression.
What do I need to know about adenovirus detection?
1. Can be close to impossible to culture
2. Antigen detection means rapid tests are available
3. PCR tests to detect virus genome
4. Due to latency, difficult to be sure virus detection is correlated to the patient disease at the time of the test.
Is there a vaccine against adenovirus?
Yes, but you don't want it. Created by military against types 4&7. linked to possible transforming infection.
Risking cancer to prevent something that will go away on its own? Doesn't make sense.
Adenovirus treatment?
There is NO virus-specific therapy and serious infections are managed by treating symptoms and controlling complications.
What are the classification factoids about Coronavirus?
1. Single stranded RNA, + sense strand
2. Enveloped capsid with helical symmetry
3. Pleomorphic virions with unique crown-like surface projections
4. Identified in 1965 by it's unique "corona-like" appearance on EM.
5. 2 major antigenic types are recognized, each with multiple unique subtypes
Is there anything special about coronavirus replication?
Likes colder temp 33-35C
Likes epithelial cells of respiratory tract.
What diseases are caused by coronavirus?
Colds. 2nd behind rhinovirus.
Possible GI infections
SARS is coronavirus variant
Coronavirus Epidemiology?
1. Age - all agges affected. Children and infants most susceptable.
2. Season - Infection sporadic or in winter-spring season outbreaks (one strain typically predominates).
3. Transmission - aerosols and droplets
Any coronavirus controls?
Not really. Cover mouth when you sneeze to limit spreading via droplets.
Most adults have antibodies against. Infections reduced but still possible.
what does SARS stand for?
Severe Acute Respiratory Syndrome
SARS factoids
1. What caused SARS?
2. How deadly was it?
3. What was so significant about it?
1. newly emerged coronavirus (2002 PRC), now thought to be extinct (we hope)
2. >8,450 cases and >800 deaths
3. The fear factor – SARS spread across the world very quickly
What makes SARS different from coronavirus?
The SARS agent is a coronavirus, but sequence analysis has revealed that it is unlike any known human or animal coronavirus.
Where is the resevoir for SARS outbreak?
food animals. In 2002, only about 50% of original cases were traceable to human patients
What did SARS teach us about virus preparedness?
revealed a need for an easy to perform test to detect patients early in disease course.
Still don't have it yet. We have Genome detection by PCR
Patient antibody detection – low sensitivity and specificity
What's a "superspreader?"
Uncommon individuals who are able to spread disease to many contacts. May account for rapid spread of SARS.
Describe influenza virus structure
1. family Orthomyxoviridae
2. Segmented, single-stranded RNA genome
3. capsid with helical symmetry
4. enveloped
5. surface is covered with spikes
6. 3 major serotypes of influenza viruses (designated types A, B, and C). distinguished by nucleocapsid proteins. Each has distinct biologic properties
what differentiates the large number of Influenza A subtypes?
differing envelope spike proteins:
- H (hemagglutinin) - virion attachment and entry
- N (neuraminidase) – progeny virion release and spread from infected cells
Why are the H and N spikes on influenza important?
An individual with specific antibodies to subtype H and N spikes will be immune to infection with that particular virus
Define influenza nomenclature (naming system)
Type/Location of discovery/Isolate number/Year/ Antigenic subtype
Examples:
A/Hong Kong/68/H3N2
A/California/2009/H1N1
A/Asian/57/H2N2

Note: Type B does not have H/N subtype
B/Malaysia/2506/2004
In regards to influenza, what does the "novel" designation mean?
In 2009 a new virus and a new designation -
“Novel” influenza A (H1N1) denotes the newly emerged H1N1 virus which has different pathogenic properties from the ‘seasonal” flu H1N1.
in other words, it's built the same, but it acts differently.
Why do influenza viruses experience so much antigenic drift?
RNA viruses do not replicate with high fidelity – this is actually an evolutionary advantage
It accounts for Point mutations of H or N proteins that result in minor variations.
Enough to allow it to infect human populations at a constant level
But not enough so as to destabilize genome.
What accounts for influenza pandemics?
Mostly Antigenic Shift
although antigenic drift could result in pandemic under proper circumstances.
What is antigenic shift?
genome segment exchanges
Recombination involving complete genome segments encoding H or N genes
Shuffling of genome segments within the virion during a mixed infection
Creates a sudden change in virus antigenic composition to which many are NOT immune and results in epidemics or pandemics
epidemiology of influenza
1. Age - affects everyone but rates of infection are highest in children. Severity of infection, including complications, hospitalizations and deaths are typically more prevalent with infants, elderly and in persons of any age with underlying medical debilitation (immunosuppressed)
2. Season - Winter season primarily. Typical peak in community in approx. 2 weeks after initial outbreak appears
3. Transmission - Virus retains infectivity on hard surfaces for 1-2 days, fomite and/or hand transmission is considered probable.
4. Resistance - transitory w/o vaccine due to constant antigenic drifts
5. Large distribution potential (humans, birds, pigs, horses, etc) give rise to high rate of antigenic shift creating possibility for pandemics.
Clinical course and manifestations of influenza
1. Short incubation (1-2 days) and abrupt onset of symptoms
2. Acute stage lasts about 7 days.
3. Long convalescence - 1-2 weeks.

Typical adult symptoms include Fever, aches, chills, and cough. Children have same suite plus more GI symptoms, otitis media and sometimes croup.
Elderly, infants, and immunocompromised are at highest risk for complications.
What are the typical complications associated with influenza?
1. Severe pulmonary disease
a. Primary influenza viral pneumonia
b. Secondary (bacterial) pneumonia - note: Influenza infection promotes bacterial adhesion
2. Reyes syndrome - acute systemic disorder attacking brain and liver.
3. Guillain-Barre syndrome (GBS) - Peripheral nervous tissue demyelination,
4. Nosocomial Infections – outbreaks in hospitals, nursing homes, and closed communities
What's a bad sign to see with someone in the convalescent stage of influenza?
Return of fever. Indicates secondary infection. Most deaths from influenza are typically due to secondary infections.
How does Influenza infection promotes bacterial adhesion?
by compromising the muco-ciliary escalator system activity and exposing binding sites on the epithelium
What are the most common bacteria causing secondary infection in flu patients?
1. Streptococcus pneumoniae
2. Staphylococcus aureus (MRSA infections are increasing)
3. Haemophilus influenzae type B (Hib)
Who is most at risk for Reyes syndrome?
Primarily observed in children aged 6 months-15 years and correlated with Influenza A/B or chickenpox infections treated with ASPIRIN
Other than a fear of needles, why are people afriad of flu vaccine?
Guillain-Barre syndrome (GBS) - Peripheral nervous tissue demyelination, often within 2 weeks of vaccination
- 1976 swine flu vaccine recipients had a very high rate of this complication (7X over normal)
- Retrospective studies suggest that risk of GBS from vaccine is substantially lower than that posed by a natural infection with the virus
What does "nosocomial infection" mean?
Infections acquired from exposure to hospital environment.
Why are Nursing home residents disproportionately affected by influenza?
1. Nosocomial outbreaks
2. Underlying disease (immune system already compromised)
3. Lack of vaccine response (unable to produce antibodies)

Note: In 2010 – a new high-antigen dose inactivated flu vaccine became available for patients over age 65
Do you need a lab confirmation to diagnose influenza?
Not usually. Clinical findings are considered diagnostic during epidemic situations, a.k.a. "It looks like flu, smells like flu and It's flu season, ergo... you have the flu."
What lab tests are used to confirm influenza diagnosis?
1. Direct viral isolation from throat nasopharyngeal swabs for culture
2. Enzyme Immunoassay
3. HI (hemagglutination inhibition) tests available for some strains (this virus will naturally cause RBC aggulutination)
4. Rapid tests are now available (30 minutes) to detect presence of virus types A/B core antigens.

Note: The sensitivity and specificity of rapid tests are lower than viral culture and vary by the test manufacturer
What's the treatment for influenza?
1. Typically supportive, symptomatic relief
2. Early treatment with antibiotic not recommended. May select and promote drug-resistant Staphylococcus aureus overgrowth.
3. Amantadine and Rimantadine - Effective against type A virus only
4. Neuraminidase inhibitors - Effective against A & B. Must be applied within 48 hrs of symptom onset.
What are Amantadine and Rimantadine and when would you administer these drugs? Who should you not give them to?
Treatment for Type A influenza.
Stops uncoating/penetration by halting hemagglutinin conformational changes.
Given prophylactically along with vaccine to immunocompromised patients (especially nursing homes).
Does not interfer with vaccination process. Can increase resistance.

Not recommended for children because it could lead to selection of resistant strain.
What are Neuraminidase inhibitors? When are they used? What's the brand name? When are they not recommended?
Antiviral agent effective against Influenza A and B.
Analogues of sialic acid, block the active site of neuraminadase and leave uncleaved sialic acid residues on the surface of both the host cell and viral envelopes. Because the viral hemagglutinin binds uncleaved sialic acid residues, these agents lead to viral aggregation at the cell surface and inhibit the cell-to-cell spread of infection.
**Must be applied with 48 hours of symptoms!!
Brand names are:
Zanamivir (inhaler, use with caution with severely asthmatic patients)
Oseltamivir (oral)
What are the common influenza vaccines and who are they made for?
1. Trivalent, inactivated vaccine (TIV) - patients aged 6 months and older
2. Live, attenuated (LAIV) - delivered by nasal spray (Flumist) for non-pregnant patients age 2-49 years
3. Fluzone High Dose - For patients over age 65
4. Intradermal TIV -
Decreased levels of antigen and injected dose volume. Hoping to stretch vaccines farther.
How long does flue vaccine work?
18 months.
recommended you get one every year to protect from new, predicted strains.
Do kids get the same flu vaccine that adults get?
Yes, but more of it. Recommend 2 administrations of vaccine (4 weeks apart) for children 6 months-8 years of age
Who is it most important to vaccinate for flu?
o Persons age 65 or older
o Residents of nursing homes or other chronic care housing facilities
o Adults and children with chronic pulmonary or cardiovascular system disorders
o Adults or children with debilitating chronic diseases such as asthma, diabetes, renal dysfunction or hemoglobinemias or immunosuppression (any cause)
o Pediatric patients on long term aspirin therapy- Reyes syndrome development risk
o Health care workers
Does vaccine target all flu strains?
No. Target two most common Type A and 1 most common Type B. Hence the name "Trivalent"
How do they design flu vaccine?
Formulation is a guess based on the most prevalent viruses in circulation 6-9 months before the projected delivery date of the vaccine.
What time of year is flu vaccine recommended?
October.
well in advance of predicted winter outbreaks.
What viruses account for 10-40,000 excess U.S. deaths annually
Influenza A & B
Why is Influenza B less likely to cause pandemic outbreaks than influenza A?
Does not cross species as readily.
What are the Three great influenza pandemics
1918 Spanish [H1N1]
1957 Asian [H2N2]
1968 Hong Kong [H3N2]
What was exceptional about Spanish Flu?
1. It appeared early (October) and departed quickly
2. It had an exceptional lethality rate
3. It frequently killed patients rapidly and directly
4. The highest death rate was in young adults
How many influenza strains are in wide circulation every year
3-4
Describe the spectrum of diseases associated with the URT.
1. Rhinitis – common cold. Viral
2. Sinusitis: Acute - viral origin. Chronic ‐ typically polymicrobial
Anaerobic bacteria
3. Pharyngitis ‐ an inflammatory condition of pharynx. Both viral and bacterial.
4. Epiglottitis - Acute bacterial infection; potentially lethal in 6-12 hrs from symptom onset,
5. Laryngitis ‐ rhinovirus, parainfluenza viruses
List the potential bacterial pathogens that may be residents of the upper respiratory tract.
1. Staphylococcus aureus (G+)
2. Streptococcus pyogenes (G+)
3. Streptococcus pneumoniae (G+)
4. Moraxella catarrhalis (G –) 5. Neisseria meningitidis (G –)
6. Haemophilus influenzae (G –)
7. Bacteroides fragilis (G –)
What are the general characteristics of the genus Streptococcus?
A. Morphology - Cells arranged as chains or pairs and are gram‐positive,
catalase‐negative and nonmotile
B. Hemolysis – alpha (α); beta (β); nonhemolytic/gamma (γ)
C. Typical Cultivation - Fastidious, Mesophilic Capnophiles
D. Lancefield Scheme of Classification - Typing generally done for Groups A, B, C, D, F and G
What is the source molecule that is the basis for the Lancefield scheme of classification?
cell wall carbohydrate
GAS = NAG + rhamnose
Describe the contributions of 3 components of the cell envelope to the pathogenicity of GAS.
1. M protein ‐ major virulence factor. Protects cell from phagocytosis and inhibits activation of complement
2. Protein F and LTA – tissue tropism; F binds to fibronectin on surface of host cells. LTA ‐ attaches to pharyngeal epithelium
3. Capsule – composed of hyaluronic acid – “stealth” advantage to inhibit phagocytosis
Describe the roles played by extracellular compounds (eg, streptolysins, hemolysins,
streptokinase, pyrogenic exotoxins) of GAS in the disease process.
1. Streptolysins O and S - β‐hemolysis; Lyse leukocytes and erythrocytes
2. Streptodornase - Enhance spread of bacteria; breakdown DNA of host cells
3. C5a peptidase - Inhibits attraction of phagocytes by destroying C5a
4. Streptokinase - Activates plasminogen to plasmin; Dissolves blood clots
5. Streptococcal Pyrogenic Exotoxins (Spe A, B, C) - SpeA responsible for scarlet fever and toxic shock
List the patient groups and other epidemiologic variables that affect the occurrence of GAS pharyngitis
Most common bacterial infection of the throat
1. Humans ‐ only reservoir for Streptococcus pyogenes; colonizse nose and skin (carriers)
2. Age - Acute cases at all ages (peaks at 5‐15 years)
3. Season - More prevalent during the winter and early spring
4. Transmission - Respiratory droplets and person‐to‐person contact in crowded spaces enhance spread. Does not survive well in environment; fomite transmission – low probability
Describe a clinical course with specific signs for scarlet fever. What mechanism is responsible for this genotype of S pyogenes?
1. Child with h/o strep infections. Presents with Subacute nasopharyngitis -c/s extension to middle ear and mastoid; Cervical lymphadenopathy; purelent exudates on tonsils and pharynx; high fever (>101F); Illness recedes then...
2. Relapse - return of acute symptoms plus Punctate erythematous rash spreads from below ears, axilla and chest to trunk and
extremities. Lesions/pimples form and create sandpaper‐like skin. Pastia’s lines – accentuated petechial lesions on flexor skin creases/folds. Mouth ‐ circumoral pallor and “strawberry tongue”
3. Mechanism - Requires infection with a lysogenized strain ‐ releases the pyrogenic exotoxin (SpeA)
Identify the reasons for early diagnosis and prompt treatment of streptococcal pharyngitis.
Early diagnosis and prompt treatment of streptococcal pharyngitis desirable for various reasons:
1. Prevention of overuse of antibiotics
2. Reduction in duration and severity of symptoms
3. **Prevention of suppurative complications and ARF
4. Prevention of disease transmission
Based on the course of infection as well as signs and symptoms of disease, create case studies for acute rheumatic fever (ARF)
ARF - tropical country, 1-4 weeks after untreated GABHS receeds, pt present with 2 major or 1 major + 2 minor of following list:

Major manifestations
1. Myocarditis
2. Joint swelling
3. Chorea
4. Subcutaneous nodules
5. Rash – erythema marginatum

Minor manifestations
1. Arthralgia
2. Elevated ESR or C‐reactive protein
3. Fever
4. Prolonged PR interval (on ECG)
Describe the advantages and disadvantages of the different GAS diagnostic methods.
1. Culture - Gold Standard. Sensitive and Specific. Takes too long.
2. RADT - Fast (30min) and Specific, but not as Sensitive as Culture. 5-10% more FN. Negative test in children should still be confirmed with culture
3. Bacitracin sensitivity. Takes time. Can help ID specific strain, once Strep has been confirmed.
4. PYR - presumptive test. takes time. Useful in establishing correct treatment.
Describe the recommended treatments for Streptococcus pyogenes (GAS/GABHS) pharyngitis.
DOC: Penicillin G 10 days,
Erythromycin if allergic, or 1st generation cephalosporin
Treat before day 8 to stop Rheumatic fever and glomerulonephritis
What GAS vaccines are currently available or in experimental/clinical trials?
No vaccine is currently available.

Experimental:
1. 2006 successful mouse experiment – intranasal vaccination with peptides from both the M
protein and fibronectin binding protein repeats.

2. 2008 Synthesis of a Streptococcus pyogenes vaccine candidate based on the M protein PL1
epitope.

3. 2011 HLA class II transgenic mice develop a safe and long lasting immune response against
StreptInCor, an anti‐group A streptococcus vaccine candidate.
A vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C‐terminal
portion of M protein that encompasses both T and B cell protective epitopes
Based on the course of infection as well as signs and symptoms of disease, create case studies for poststreptococcal acute glomerulonephritis (AGN).
Child recently sen and treated for GABHS 1-3 weeks prior presents with
1. Puffy face – fluid retention/kidney damage
2. Hematuria – dark urine – blood
3. Possible hypervolemia – secondary to fluid retention

Due to Type III hypersensitivity and is likely not preventable with antibiotics
What can happen to pt with previous ARF who contracts GAS again?
Reactivated ARF
Can lead to left‐side heart damage; mitral and aortic valves
Damage apparent – heart murmurs
Damaged valves more susceptible to infection/biofilms of other bacteria
Protect patients with prophylactic penicillin
What are Pathognomonic lesions?
Aschoff bodies – perivascular granulomas in myocardium
Replaced by scar tissue
Describe the spectrum of diseases associated with the URT.
1. Rhinitis – common cold. Viral
2. Sinusitis: Acute - viral origin. Chronic ‐ typically polymicrobial
Anaerobic bacteria
3. Pharyngitis ‐ an inflammatory condition of pharynx. Both viral and bacterial.
4. Epiglottitis - Acute bacterial infection; potentially lethal in 6-12 hrs from symptom onset,
5. Laryngitis ‐ rhinovirus, parainfluenza viruses
List the potential bacterial pathogens that may be residents of the upper respiratory tract.
1. Staphylococcus aureus (G+)
2. Streptococcus pyogenes (G+)
3. Streptococcus pneumoniae (G+)
4. Moraxella catarrhalis (G –) 5. Neisseria meningitidis (G –)
6. Haemophilus influenzae (G –)
7. Bacteroides fragilis (G –)
What are the general characteristics of the genus Streptococcus?
A. Morphology - Cells arranged as chains or pairs and are gram‐positive,
catalase‐negative and nonmotile
B. Hemolysis – alpha (α); beta (β); nonhemolytic/gamma (γ)
C. Typical Cultivation - Fastidious, Mesophilic Capnophiles
D. Lancefield Scheme of Classification - Typing generally done for Groups A, B, C, D, F and G
What is the source molecule that is the basis for the Lancefield scheme of classification?
cell wall carbohydrate
GAS = NAG + rhamnose
Describe the contributions of 3 components of the cell envelope to the pathogenicity of GAS.
1. M protein ‐ major virulence factor. Protects cell from phagocytosis and inhibits activation of complement
2. Protein F and LTA – tissue tropism; F binds to fibronectin on surface of host cells. LTA ‐ attaches to pharyngeal epithelium
3. Capsule – composed of hyaluronic acid – “stealth” advantage to inhibit phagocytosis
Otitis externa
Clinical presentation?
Causative agents?
Diagnosis?
Treatment?
Clinical presentation: inflammation of the external auditory canal. Signs & symptoms: otalgia and otorrhea. Moisture is most common predisposing factor.
Causative agents: Pseudomonas aeruginosa and Staphylococcus aureus. Diagnosis: Physical examl UV light to see pigment; gram stain to identify bacteria
Treatment: topical antibacterial agents if localized, oral antibiotics if fever, analgesics
Otitis media
Clinical presentation?
Causative agents?
Diagnosis?
Treatment?
Clinical Presentation: very common in children. inflammation of middle ear, tympanic membrane, fluid build up
Causative agents: bacterial - streptoccocus pneumoniae, Haemophilus influenzae, Moraxella catarrhailis
Diagnosis: clinical presentation
Treatment: DOC is amoxycillin c/s clavulanic acid. If allergic: cefuroxime or azithromycin. If chronic: tympanic tubes
Sinusitis
Clinical presentation?
Causative agents?
Diagnosis?
Treatment?
Clinical presentation? inflammation within the paranasal sinuses, may or may not be purulent
Causative agents? bacterial - Streptoccocus pneumoniae, Haemophilus influenzae, Moraxella catarrhailis
Diagnosis? Clinical presentation and history is most common; nasal cytology and CT scans can be performed if needed; allergy testing if allergens are suspected as the cause.
Treatment? varies, depending on the stimulus: Nasal irrigation, Analgesics, OTC decongestants, Antibiotics, Nasal steroids, Nasal surgery
Diphtheria
Causative agent?
Virulence factors?
Pathogenesis?
Clinical Symptoms?
Epidemiology?
Diagnosis?
Treatment?
• Causative agent: Corynebacterium diphtheriae: Gram-positive pleomorphic bacillus; “Chinese letters”, metachromatic granules
• Virulence factor: phage-encoded A-B exotoxin
• Pathogenesis: exotoxin results in cell death via inhibition of protein synthesis
• Clinical symptoms: Exudative pharyngitis, pseudomembrane, bull neck
• Epidemiology: person-to-person transmission; uncommon in US due to vaccination
• Diagnosis: clinical presentation, culture on various agars (e.g., black colonies on cysteine-tellurite agar), various tests for toxin gene or toxin production: Elek test, PCR, ELISA, Immunochromatography
• DOC: penicillin or erythromycin; use of antitoxin; vaccinate
Pertussis
Causative agent?
Virulence factors?
Pathogenesis?
Clinical Symptoms?
Epidemiology?
Diagnosis?
Treatment?
• Causative agent: Bordetella pertussis: Gram-negative coccobacillus
• Virulence factors: endotoxin, adhesins (three) and exotoxins (four).
• Pathogenesis: exotoxin-mediated damage to epithelium; increased lymphocytes
• Disease: catarrhal, paroxysmal, and convalescent stages of disease (know differences and clinical symptoms of each stage)
• Epidemiology: Serious disease in children; endemic in US
• Diagnosis: culture on Bordet-Gengou or Regan-Lowe agar, PCR
• DOC: macrolides, vaccinate
Otitis Media/Sinusitis
Causative Agent?
Clinical Symptoms?
Diagnosis?
Treatment?
• Common organisms:
1. Streptococcus pneumoniae: Gram-positive lancet-shaped diplococcus; α-hemolytic; encapsulated strains are virulent
2. Nontypeable Haemophilus influenzae: Gram-negative coccobacillus
3. Moraxella catarrhalis: Gram-negative diplococcus; oxidase positive
• Clinical symptoms: bulging, inflamed eardrum, fluid/pus in middle ear
• Diagnosis: examination, isolation of organism not routine
• DOC: amoxicillin (but not for viral infections); tubes in chronic cases
Otitis Externa
Causative Agent?
Clinical Symptoms?
Diagnosis?
Treatment?
• Common organisms:
1. Pseudomonas aeruginosa: Gram-negative bacillus, pyocyanin and pyoverdin pigments, encapsulated
2. Staphylococcus aureus: Gram-positive staphylococcus, catalase & coagulase positive, β-hemolysis on blood agar
• Clinical symptoms: otalgia, otorrhea
• Diagnosis: examination, Gram stain
• DOC: many agents available; depends on organism
Identify and Distiguish three stages of disease in Pertussis.
1. Catarrhal Stage: inflammation of mucous membrane, non-specific URT infection last 1-2 weeks, not very ill feeling but very contagious,
2. Paroxymal Stage: Paroxymal coughing with vomiting, whoop, epithelial cells are extruded impeding mucus clearance last 2-4 weeks,
3. Convalescent Stage: paroxysms decrease in number/severity, 2-6 weeks, can get secondary complications
What are the four main exotoxins that play (or may play) a role in disease process of Pertussis?.
1. Pertussis toxin = an A-B exotoxin: functions to inactivate Giα, which increases cAMP leading to increased respiratory secretions; it also mediates attachment (ie, functions as an adhesion as well) and promotes lymphocytosis.
2. Adenylate cyclase toxin: also increases cAMP levels and functions to reduce phagocytic activity.
3. Tracheal cytotoxin: causes ciliostasis and stimulates IL-1 secretion.
4. Dermonecrotic toxin: involved in localized tissue destruction and vasoconstriction in animal models. Role in human disease is unclear.
Streptococcus pneumoniae
Identify/Classify
Gram-positive, encapsulated, lancet-shaped diplococcus; exhibits α-hemolysis on blood agar.
often involved in otitis media and sinusitis
Haemophilus influenzae:
Identify/Classify
Gram-negative coccobacillus; the nontypeable strains are often involved in otitis media and sinusitis.
Moraxella catarrhalis:
Identify/Classify
Gram-negative diplococcus; oxidase-positive organism; β-lactamase producer and non-fermenter of carbohydrates (to allow differentiation from Neisseria species). often involved in otitis media and sinusitis
Pseudomonas aeruginosa:
Identify/Classify
Gram-negative encapsulated bacillus; pigment producers – pyocyanin & pyoverdin are the most common.
• Pyocyanin: nonfluorescent bluish pigment (many strains produce this pigment)
• Pyoverdin: fluorescent green pigment (virtually all strains produce this pigment)
Often involved in otitis externa
Staphylococcus aureus:
Identify/Classify
Gram-positive encapsulated coccus, coagulase-positive organism, β-hemolytic on blood agar.
Often involved in otitis externa
Which bacteria are responsible for "typical" community-acquired pneumonia
Strep. pneumoniae
Haemophilus
Staphylococcus
Klebsiella
Which bacteria are responsible for "atypical" community-acquired pneumonia
Legionella
Mycoplasma
Chlamydia
Compare and contrast typical and atypical CAP
Typical pneumonia is inflammation and consolidation of the lung tissue due to an infectious agent. It is very common, affects all ages, although is most frequent in the elderly.
Atypical pneumo has all of the above plus systemic organ invovlement and an unresponsiveness to B-lactam therapy. Atypical is far less common than typical, accounting for 15% of all CAP
Which CAPs are communicable between animals and humans? Are these considered typical or atypical?
Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia) and Coxiella burnetii (Q fever)
All atypical.
What is the most common infectious cause of death?
Pneumonia
S. Pneumo.
Morphology?
Epidemiology?
Virulence factors?
Pathogenesis?
Manifestation?
Diagnosis?
Vaccinations?
Morphology: G+, Lancet shaped diplococci, a-hemolytic, capnophile

Epidemiology: Resevoir=Asymptomatic carriers; Age=everyone, esp elderly; Season=more common in cold, wet months; PredisposingRisk=CVD, DM, pulmonary disease, viral infection of pharynx

Virulence factors: Capsule (inhibits C3a and phagocytosis); Pneumolysins (creates pores and then lysis); Techoic acid (immunomodulator); IgA protease (Degrades IgA); H2O2; Haluronidase and neuraminidase; Pili and choline binding proteins; Autolysin (Release of pneumolysin and neuraminidase)

Pathologenesis: 1) Entry of cocci to alveoli; 2) Survival and multiplication (due to techoic acid and autolysin); 3) Disease results from multiplication (no true toxin, but virulence factors and bacterial build-up); 4) Pneumonia (may spread via blood or lymph)

Clinical Manifestations: 1. Sudden onset; 2. High fever and chills; 3. Blood tinged sputum; 4. 2nd infections (meningitis, otitis media, sinusitis, bacteremia, arthritis, peritonitis)

Diagnostic tests: 1. Swab and growth; 2. Optochin sensitivity confirms visual identification; 3. Lysed by bile salts; 4. Quelling rxn; 5. Polysaccharides detected in CSF via agglutination; 6. 24 hr “AccuProbe” RNA test

Vaccine: 23-valent capsular polysaccharides given to adults >65yo, conjugate vaccine 7 most common serotypes, given to higher risk people, children < 2yo
Haemophilus influenzae
Morphology?
Epidemiology?
Virulence factors?
Pathogenesis?
Manifestation?
Diagnosis?
Vaccine?
Morphology: G-, coccobacillus in pairs or short chains

Epidemiology: Opportunistic, normal flora; Not often the cause of disease; Type B - Found in 2-4% of individuals and is usually the causative agent in infants, young children and debilitated hosts

Virulence factors: 1. Capsule; 2. Neuraminidase; 3. IgA protease; 4. Fimbriae; 5. Lipooligosaccharide (LOS)

Pathogenesis: 1) H. influenzae type b enters via respiratory tract. 2). Infection from non-typeable strains results from an imbalance of colonization. 3) Non-encapsulated strains possess adhesins that bind to mucins on the epithelial cells of the respiratory tract. Following colonization, release of LOS results in loss of cilia, inflammation and sloughing of damaged epithelial cells.

Clinical: Standard typical pneumo

Diagnostic tests: 1. Specimens collected from blood, pus, sputum and spinal fluid; 2) Gram staining for gram negative coccobacilli; 3) Serological testing for capsulization; 4) ue to its grculture on chocolate blood agar (difficult to grow in lab); 5) Rapid test for agglutinization

Vaccine: Hib vac
Klebsiella pneumoniae
Morphology?
Epidemiology?
Virulence factors?
Pathogenesis?
Clinical Manifestation?
Diagnosis?
Vaccine?
Morphology: G- bacillus w/ Thick, slimy capsule

Epidemiology: Resevoir=Normal flora in mouth, skin, intestine; Predisposing Risks: Diabetics, alcoholics, homeless; Causes both CAP and NP; small % of total illnes but 50% mortality

Virulence factors: 1. Capsule; 2. Adhesins and attachment pilli; 3. LPS

Pathogensis: 1. P2P direct contact; 2. Host aspirates oropharyngeal microbes into the LRT; 3) necrotic destruction alveolar spaces; 4) inflammation and hemorrhage in the lungs

Clinical: rapid onset of High fever, Productive cough, Thick bloody sputum (Black currant jelly); often with pleuritic chest pain.

Diagnostic tests: 1) Gram stain; Culture; 2) Black currant jelly sputum is diagnositic; 3) X-ray w/ cavitation

Vaccinations: none
Pseudomonas aeruginosa
Morphology?
Epidemiology?
Virulence factors?
Pathogenesis?
Clinical Manifestation?
Diagnosis?
Morphology: G-, aerobic, motile bacillus (single flagellum).

Epidemiology: 1. organism is widespread in the environment (e.g., plants, moist soil). 2. Frequent or transient carriage on skin and in feces. 3. An opportunistic pathogen in the hospital environment. 4. Transmission occurs via fomites, plants, fruits, hands, etc.

Virulence factors: 1. Pili; 2. Pyoverdin (UV); 3. Pyocynin (plue pus creates ROS); 4. Exotoxin A (AB toxin, works just like diphtheria toxin) 5. Elastases (LasA and LasB); 6. Alginate (create Slime layer in lungs); 7. Adherence factor(forms Biofilm); 8. LPS

Clinical Manifestations: 1. Low virulence requires break in normal defenses (opportunistic infection of immuno suppressed);
2. Causes variety of infections (UTI, Pneumonia, Eye, Ear, skin infection, #2 infection of burn patients; Common cause of death in CF patients);
3. Toxicity and progressive cyanosis
4. Empyema

Diagnostic tests: 1. Culture; 2. Fruity smell and blue-green pigment on culture are characteristic
What are the lab testable features of Staph Aureus?
gram (+), encapsulated coccus, coagulase-positive, mannitol fermination, α hemolitic, catalase (+), optochin sensitive
How do you make a definitive diagnosis for NP?
Establish that the condition is due to an infectious
agent. Accurate diagnosis requires Gram stain and culture of microbes from
biopsy. In some cases, chest X-rays assist in discrimination between
causative organisms.
What are the lab diagnostic features of pseudomonas aurigonosa?
gram (-), encapsulated, aerobic, motile bacillus (single flagellum)
produces pyocyanin and pyoverdin
what are the virulence factors of pseudomonas aurigonosa?
1. Pyocyanin ( “blue-pus” catalyses ROS)
2. Exotoxin A (potent immunosupressor)
3. Elastases (LasA and LasB)
4. Alginate (slime layer)
5. Adherence factor (biofilm)6. Antiphagocytic glycocalyx
7. Pili (attachment to host cells)
8. Lipopolysaccharide (endotoxin)
what are the virulence factors of Staph Aureus?
Many cell surface-associated and extracellular proteins that are potential virulence factors. Therefore, the disease process is usually multifactorial.

1. Cell-associated virulence factors
a. Capsule
b. Protein A (binds to the Fc component of IgG to prevent phagocytosis and complement activation.

2. Extracellular enzymes
a. Clumping factor (bacterial aggregation)
b. Coagulase (makes fibrin clots)
c. Hyaluronidase
d. Nucleases
e. Lipases
f. Catalase
g. Staphylokinase (fibrinolysin)
h. Penicillinases (β-lactamase)

3. Toxins
a. Exfoliative toxins
b. Toxic shock syndrome toxin (TSST-1)
c. Enterotoxins
d. Cytotoxins
e. Panton-Valentine leukocidin (PVL) bicomponent cytotoxin
responsible for leukocyte destruction and tissue necrosis.
What virulence factor is severe necrotic hemorrhagic pneumonia associated with?
What type of pneumonia is this?
PVL of staph aureus.
CAP only, NOT NP
How do you diagnose NP?
Risk factors are primary key. Were they hopsitalized or in nursing home? Has previous organisms been diagnosed there recently?
After that, need to isolate organism and submit to lab for culture ID.
Treat empirically as previous organism or Staph Aureus until lab diagnostics tell you otherwise.
What are the common characteristics of all mycobacteria?
Acid-fast bacilli
Obligate aerobes (Facultative intracellular pathogens)
Nonmotile
Colonies – Ruff, Buff & Tuff
No Glycocalyx
No classical endotoxins, exotoxins or necrotizing enzymes
Describe the virulence factors of MTB?
1. Cord Factor: MA sandwich; Produces parallel growth of bacteria (cords of cells); Inhibits neutrophil migration; Damages host cell mitochondria
2. Sulfatides: Cord factor + sulfates - inhibits phagolysosome formation
3. Wax D – increases Type IV hypersensitivity RXN
4. Wax D + Cord Factor: induce granuloma formation.
5. Lipoarabinomannan (LAM): "May" do a lot of things
What is a Ghon focus; a Ghon complex?
1. Ghon Focus – from Primary infection – no viable MTB - A calcified tubercle in the middle or lower lobes/zones of the lungs

2. Ghon Complex: A Ghon Focus + perihilar lymph node calcified granulomas