1
Q
What are the two most common causes of skin and soft tissue infections as they appear on a Gram stain?
A
- Staphylococci: Gram+ cocci in clusters
- Streptococci: Gram+ cocci in chains
–> Each have thick murein layers, thus the Gram+ stain
2
Q
What are the 3 sources of skin and soft tissue infections?
A
- Exogenous: direct invasion of microbe from external environment
- Endogenous: invasion of microbe from an internal source, such as blood or infected organ
- Toxin: mediated manifestations from an infection at a distant site
3
Q
What are the most frequent transient skin flora found on humans?
A
- Staphylococcus aureus
- Streptococcus pyogenes (Group A strep)
4
Q
What are the most frequent resident skin flora found on humans?
A
- staphylococcus epidermidis
- propionibacterium acnes
5
Q
What types of skin and soft tissue infections are often caused by staphylococci?
A
Folliculitis
Carbuncles, furuncles
Impetigo
Cellulitis
6
Q
What types of skin and soft tissue infections are often caused by streptococci?
A
Impetigo
Erysipelas
Cellulitis
Synergistic cellulitis
necrotizing fasciitis
7
Q
What are the characteristics of pyogenic cocci?
A
Streptococci are:
Invasive
Produce purulent lesions
obligate extracelluar bacteria
have anti-phagocytic virulence factors
Facultative anaerobes (live w/ or w/o oxygen)
8
Q
What diagnostic criteria need to be met to confirm streptococci infection?
A
- Gram+ stain in pairs or chains
- Catalase negative
9
Q
What diagnostic criteria is used to classify streptococci?
A
- Hemolytic pattern on blood agar
- Physiological traits and biochemical reaction
- antigenic composition
10
Q
What are the three hemolytic patterns found around streptococcal blood agar colonies?
A
- alpha-hemolytic: greenish hemolysis
- beta-hemolytic:complete/clear hemolysis (bad)
- gamma-hemolytic: no hemolysis (good)
11
Q
What kind of hemolytic pattern does Group A strep (S. pyogenes) have?
A
beta-hemolysis: complete hemolysis
12
Q
What are diagnostic characteristics of Group A strep?
A
Group A strep = Strep. pyogenes:
- Gram+ cocci in chains
- beta-hemolytic
- catalase negative
- PYR positive
- bacitracin sensitive (shown by bacitracin disk in blood culture plate)
13
Q
Describe the rapid test used to detect Streptococci bacteria in a patient.
A
Control antigen and test capture antibody are fixed to test strip.
Gold-labeled (red) antibody is diffuse and not fixed to paper.
Paper is dipped in specipen w/suspect antigen and if capture antibody and control antigen show, test is positive
14
Q
What are virulence factors for S. pyogenes (Group A Strep)?
A
M Protein
Hyaluronic acid capsule
Pyrogenic exotoxins
Streptolysin O
DNAases
Streptokinase
C5a peptidase
15
Q
What are components of the streptococcal cell wall?
A
16
Q
What is M protein?
A
A virulence factor of Group A Streptococci:
Involved in binding to epidermis and is anti-phagocytic.
- Antibody to M protein is type specific; there are ~90 types
- Share sequence homology with some mammalian proteins (i.e. tropomyosin, human heart)
17
Q
Why are vaccines to M proteins dangerous?
A
If vaccine was not thoroughly screened, it could lead to autoimmunity to those vaccinated b/c of M proteins molecular mimicry of host components
18
Q
What is a hyaluronic acid capsule?
A
Group A Strep virulence factor:
identical to component in normal tissue, anti-phagocytic, antibody to capsule not protective to host
19
Q
What is pyrogenic exotoxins?
A
Virulence factor of Group A Strep:
- Fever producing toxin
- Super antigens stimulate production of cytokins
- Involved in pathogenesis of scarlet fever and toxic shock-like syndrome
- Depends on lysogeny of bacterium with temperate phage
20
Q
How do superantigens work?
A
Bind TCR to MHC; no specific peptid required
- leads to wide-spread Tcell activation:
Fever
Confusion
Hypotension
Headache and vomiting
Diarrhea
Abdominal pain/weakness
21
Q
What is streptolysin O?
A
Virulence factor for Group A Strep (S. pyogenes):
- O2 labile, antigenic, hemolytic, toxic to wide variety of cells
- antibodies to toxin basis of anti-streptolysin O test
22
Q
What are DNAases?
A
Strep. pyogenes (Group A strep) virulence factor:
- depolymerizes cell-free DNA in purulent lesions
- measure antibodies to these proteins as aid to diagnosis of recent disease
23
Q
What is streptokinase?
A
Group A Strep (S. pyogenes) virulence factor:
- lyses blood clots
- helps bacteria spread
- can be used commercially to clean wounds (surgical enzymatic debridgement)
24
Q
What are clinical presentations of suppurative streptococcal disease?
A
-Pharyngitis (uncommonly w/Scarlet Fever)
- Pyoderma: Impetigo
Ersipelas
Cellulitis
Necrotizing faciitis - Streptococcal toxic shock syndrome
25
What is Scarlet fever?
Group A strep (S. pyogenes) infection characterized by:
- strawberry tongue
- circumoral pallor around lips
- desquamation that follows rash of S.F.
26
How does Streptococcal Toxic Shock Syndrome usually occur?
Infecting strains produce pyrogenic toxins
- clinically, like staphyloccocal toxic shock syndrome EXCEPT PATIENTS ARE BACTEREMIC and many have necrotizing faciitis
- high fatality rate
27
What are clinical presentations of non-suppurative streptococcal infection?
Rheumatic Fever
Acute glomerulonephritis
28
What is rheumatic fever?
- Presents after streptococcal throat infection of 6-15 year olds after infection with certain rheumatogenic M types of Group A strep
- Autoimmune mehcanisms likely; cross reaction between anti-M protein Abs and heart tissue
29
What is acute glomerulonephritis?
After throat or skin infection with certain nephritogenic M types of Streptococci.
- Renal injury due to deposition of antigen-antibody complexes on glomeruli (Type III hypersensitivity)
30
Why is it critical to always treat Group A Strep (S. pyogenes) infections?
In order to prevent nonsuppurative disease post-infection
- The earlier the treatment, the less time the patient's immune system has to produce autoimmune antibodies resultant from infection
31
What is PANDAS Syndrome?
Pediatric Autoimmune neuropsychiatric disorder associated with group a Strep (PANDAS) characteristic of:
- Presence of OCD and/or tic disorder
- Pediatric onset
- Abrupt onset and episodic course of symptoms
- association with GAS infections
- Association with neurologic abnormalities (i.e. motoric hyperactivity, choreiform movements, tics)
32
What are characteristics of Staphylococci that can be determined by culture?
Gram+ cocci that form clusters
Facultatively anaerobic (can go w/ or w/o oxygen)
33
What factors are used to identify staphylococcus species?
34
What is the **hallmark** of staphylococcal infections?
pus (PMNs, dead tissue, bacteria)
35
What is hydradentis Suppurativa?
Staphylococcal infection infection of sweat glands
36
What is the primary treatment of cutaneous staphylococcal infections and why?
heat and drainage
- use of antibiotics only if invades subcutaneous layer b/c of antibiotic resistance
37
Why are antibiotics given to patients before surgery?
prophylaxis for hospital-acquired staph infections
38
What are some invasive, deep lesion infections caused by *Staphylococcus aureus*?
Osteomyelitis
septic arthritis
meningitis
pneumonia
39
What are some invaseive, bacteremia infections caused by *Staphylococcus aureous*?
endocarditis
meningitis
pneumonia
pyelonephritis
septicemia, septic shock
40
What are some risk factors for boils, furnuncles, carbuncles infections?
Diabetes mellitus, acne, occupational (wet conditions), poor hygiene
41
What are some risk factors for wound infections?
Diabetes mellitus, steroid therapy, obesity, malnutrition, prolonged surgery, foreign body
42
What is the #1 host defense against *S. aureous*?
Opsonophagocytosis --\> granulocytopenic or C3b subunit deficient individuals are at high risk of infection
- Staph is resistant to PMN NETs because they are Gram+; so complement is best response
43
What are virulence factors of *S. aureus*?
- Protein A
- Catalase
- leukocidin
- Ribotechoic and techoic acid
- Coagulase
- Capsule
- Hyaluronidase
- Cytotoxins
44
What virulence factors of *S. aureus* defend against phagocytes?
- Protein A
- Catalase
- Leukocidin
45
What is Protein A?
Virulence factor for *S. aureus*
- binds to Fc receptors to prevent phagocytosis
46
What is catalase?
virulence factor for *S. aureus*
- prevents breakdown in phagosome
- converts H2O2 to H2O and O2
47
What is leukocidin?
Virulence factor of *S. aureus*:
- Punches holes in PMN to prevent phagocytosis and release bacteria
48
What is ribotechoic and techoic acid?
Virulence factors for *S. aureus*:
- bind fibronectin
- techoic acid induces shock that is similar to endotoxin-mediated shock
49
What is Coagulase?
Virulence factor for *S. aureus*:
- extracellular and suface-bound
- initiates conversion of fibrinogen to fibrin
50
How is a capsule useful to *S. aureus*?
A virulence factor, it is a polysccharide that prevents complement binding
- 8 different serological types
- maximum expression *in vivo*
51
How is hyaluronidase useful to *S. aureus*?
A virulence factor, it:
- actos on hyaluronic acids in connective tissue, which facilitates dissemination through subcutaneous tissues
52
What cytotoxins are used by *S. aureus*?
**Alpha hemolysin**: potent pore-former, toxic to many cell types
**Beta toxin**: AKA sphingomyelinase C; kills cells via hydrolysis of membrane phospholipids
**Delta toxin**: cytolitic for many cells; nonspecific detergent-like action
**Gamma toxin**: pore-forming toxin; lysis of neutrophils and macrophages
**Panton-Valentine leukocidin**: same as gamma toxin
53
What in *S. aureus* causes:
Bullous impetigo
scalded skin syndrome
staphylococcal scarlet fever
Exfoliatin A, B
54
Why are *S. epidermidis* infections common with indwelling foreing devices such as:
- catheters
- peritoneal dialysis shunts
- CSF and hemolialysis shunts
etc. .
Because the coagulase(-) bacteria is good at making biofilms
55
What are common infections of *S. epidermidis*?
Urinary tract infections (hospital acquired)
Osteomyelitis
Endocarditis (native or prosthetic valve)
Bacteremia (immuneosuppressed patients)
Endophthalmitis (after ocular surgery)
Infections of indwelling foreign devices (due to biofilm)
56
What is *S. intermedius*?
- Coagulase(+) bacteria, differs from *S. aureus*
- invasive, zoonotic pathogen for humans:
Suspect if dog bite is source of wound
common oral, nasal, and skin flora in healthy dogs
57
What are toxin-mediated disease of *S. aureus*?
- bullous impetigo
- scalded skin syndrome
- staphylococcal scarlet fever
- toxic shock syndrome
- food poisoning
58
What is toxic shock syndrome?
Caused by **Toxic Shock Syndrome Toxin-1** in *S. aureus*:
- Sudden onset: fever, chills, vomiting, diarrhea, muscle pains, rash
- Later: hypotension, involvement of mucous membranes and multiple systems, desquamation
Fatality rate: 5%
Risk Groups:
- menstruating women
- women w/barrier contraceptive devices
- persons who have undergone nasal surgery
59
What is scalded skin syndrome?
Toxin-mediated disease of *S. aureus*:
Exfoliatins (serine proteases) cause splitting of desmosomes in s.granulosum epidermis
60
What makes an antibiotic bactericidal?
They kill microorganisms rapidly
61
What makes an antibiotic bacteriostatic?
They inhibit growth reversibly (prevents further replication)
62
When do bactericidal drugs have a higher efficacy than bacteriostatic?
When the body's defenses are insufficient to clear the invading agents.
i.e. bacterial endocarditis, bacterial meningitis, and infections in patients with low circulating neutrophils (agranulocytopenia)
63
Explain the tenants of selective toxicity
Characteristics of antibiotics that reduce side-effects:
- Absence of target from host
- permeability differences (effective [antibiotic] is too low to cause side effects in humans)
- structural differences in target
64
How do many antibiotics specifically target bacteria, and not humans?
They target bacterial ribosomes and inhibit protein synthesis
65
What are the main steps of bacterial protein synthesis?
1. **Amino acid activation**: "Charging" of tRNA; tRNA are attached to target AA and become activated
2. **Formation of initiation complexes**: 30S initiation complex comprised of charged fMet tRNA, mRNA and 30Sribosomal subunit+IFs+GTP;
50S complex then enters and creates the 70S complex
3. **Polypeptide chain synthesis**: recognition, peptidyl transfer, translocation and release
66
What antibiotics target the amino acid activation of bacteria?
None
- there are NO clinically significant inhibitors of AA activation
(possibly due to the fact that prokaryotic and eukaryotic processes are so similar)
67
What antibiotics target Formation of initiation complexes in bacteria?
1. Linezolid
68
What are the 4 steps of peptide chain synthesisn and which antibiotics target each step?
1. Recognition:
- Aminoglycosides
- Spectinomycin
- Tetracyclines
2. Peptidyl Transfer:
- Chloramphenicol
- Lincomycin
- Clindamycin
3. Translocation:
- Macrolides
- Ketolides
- Streptogramins
4. Release:
- None
69
What are the characteristics of Linezolid?
- Only clinically significant drug taht inhibits formation of 70S complex
- First of new class of antibiotics called **oxazolidinones**
- prevents formation of N-formylmethionyl-tRNA-mRNA-70S ribosomal ternary complex
**Activity:** Bacteriostatic for Staphylococci and enterococci
Bactocidal for Streptococci
NOT approved for catheter-related blood stream, catheter-site, or gram(-) infections
70
What antibiotics are included in the family of Aminoglycosides?
Streptomycin
Kanamycin
Tobramycin
Gentamycin
Neomycin
Amikacin
Paramomycin
71
What are the characteristics of Aminoglycosides?
Inhibitors of activated tRNA recognition:
Broad Spectrum (G+/-)
Bactericidal
Target specific proteins in the 30S ribosomal subunit
Selective Toxicity: 1. 30S vs 40S subunit
2. actively transported into bacteria, not euks.
72
What are the 3 mechanisms of action of Streptomycin?
1. **Misreading**: at low concentrations, or in case of ribosomes engaged in elongation, we see insertion of incorrect AA
2. **Cyclic Polysomal Blockade**: 70S complex forms but is unstable and falls apart; results in cell death due to inability to make proteins
3. **Faulty outer Membrane Proteins**: Translational misreading results in mutant membrane proteins that cause bacterial membrane to be leaky, thus more drug is taken into cell and acts at 30S subunit
73
What are Positive and Negative aspects of aminoglycoside therapy?
Positive: Rapid bactericidal effect
Broad spectrum
effective against *Pseudomonas* (notoriously antibiotic resistance)
Negative: Resistance
Ototoxicity and nephrotoxicity
Antagonized by anaerobiasis
low pH
ineffective against intracellular bacteria
induce biofilm production
74
How do bacteria become resistant to Aminoglycosides?
1. Altered target in 30s ribosomal subunit
2. Decreased cellular uptake
3. Enzymatic modifications of the aminoglycoside (typically by enzymes coded on transposons or plasmids)
Gentamicin specifically has:
Potential sites for acetylation
Potential sites of adenylylation or phosphorylation
- both of which alter the antibiotic activity, rendering it useless
75
What are characteristics of Spectinomycin?
Inhibitor of Recognition:
Bacteriostatic
Causes formation of unstable 70S initiation complexes (does not cause misreading or inhibit polysomal ribosomes)
Exclusively for treatment of gonorrhea caused by beta-lactamase-producing gonococci or to treat gonorrhea in patients allergic to penicillins
76
What are characteristics of Tetracyclines?
Inhibitors of recognition:
Broad Spectrum
Bacteriostatic
Hydrophobic
Used to Treat:
*Chlamydia, Mycoplasma, Rickettsia* (intracellular pathogens)
and certain G+ and G- bacterial infections
Selective Toxicity: high affinity uptake of drugs by acterial cells and increased targeting of 70S
77
What is the mechanism of action for tetracyclines?
Tetrcyclines bind to 30S ribosomal subunit and inhibit bindign of aa-tRNA to the A site
78
How do bacteria become resistant to tetracyclines?
1. Decreased uptake (often due to mutations in the OmpF porin)
2. Efflux from the bacterial cell; actively pump drug out of cell before it's able to bind to 30S ribosomal subunit
3. Elongation factor-like proteins that protect 30S subunit
79
What are characteristics of Chloramphenicol?
An inhibitor of Peptidyl transfer:
Broad Spectrum
Bacteriostatic
Mechanism:
Binds reversibly to 50S ribosomal subunit and alters the tRNA structure blocking peptidyl transfer
Selective Toxicity:
Cannot enter mitochondria
Does not bind to host 60S subunit
Resistance:
plasmid-encoded acetyltransferase that catalyze the acetylation of -OH groups; preventing 50S binding
80
What are characteristics of Lincomycin and Clindamycin?
Inhibitors of Peptidyl Transferase:
Narrow Spectrum
Bacteriostatic
Mechanism:
Similar to chloramphenicol
Selective Toxicity:
Very effective for treatment of G+ bacterial infections
Clindamycin: Very effective for staphylococcal and anaerobic G- infections
Resistance:
Methylation of 23S ribosomal RNA which prevents drug binding to 50S subunit
81
What are characteristics of Macrolides?
Inhibitors of Translocation:
Characterized by macrocyclic lactone structure
Medium Spectrum
Bacteriostatic
Treatment:
infections caused by *Mycoplasma, Legionella, Chlamydia,* and *Campylobacter*
and G+ bacteria in patients allergic to penicillins
Azithromycin and Clarithromyin: certain Mycobacteria
82
What are two common antibiotics in the Macrolide family?
Azithromycin and Clarithromycin
| (modified forms of erythromycin)
83
What is the mechanism of Macrolides?
Not entirely clear, but likely to:
1. Prevent elongation
2. prevent release of empty tRNA
3. blockage of transpeptidation
84
What contributes to Macrolide resistance?
1. Methylation of 23S RNA of teh 50S subunit; which prevents binding of drug
2. Hydrolysis of lactone ring by and esterase
3. Efflux of drug
85
What are characteristics of Ketolides?
Inhibitors of Translocation
First ketolide approved by FDA: Telithromycin
New family of antimicrobials structurally related to macrolides
Mechanism:
binding within exit tunnel of 50S subunit, thus blocking exit of nascent polypeptides
Strongly binds simultaneously to two domains of subunit (macrolides only bind to one)
Bactericidal or bacteriostatic depending on bacterium
86
What are characteristics of Streptogramins?
Inhibitors of Translocation:
Class of natural cyclic peptide antibiotics produced by certain subspecies of Streptomyces
Mechanisms:
**Dalfopristin:** binds to 50S subunit; prevents elongation and facilitates binding of quinupristin to 50S
**Quinupristin**: premature release of peptide chains from ribosome
**Synercid** (quinupristin+dalfopristin)
Alone = bacteriostatic
Together = bactericidal
87
What bacteria are treated with Streptogramins?
Staphylococci
Streptococci
*Enterococcus faecium*
(Restricted for treating vancomycin-resistant forms)
88
What are the functions of bacterial cell wall?
- Protects bacterium from osmotic shock (from inside and outside)
- Maintains shape of the bacterium
- Assists in cell division
- Mediates bacterial-host interactions
89
What is peptidoglycan?
- heteropolymer of glycan chains cross-linked by AA
- Unique chemistry of bacterial cell walls; makes enzymes in their synthesis ideal targets for antibiotics
- not found in mycoplasma
90
What are the steps in assembly of peptidoglycan?
* *Cytoplasmic:**
1. Synthesis of amino acids (GlcNAc and MurNAc)
2. Synthesis of D-amino acids (relatively rare in nature)
3. Assembly of pentapeptide component (Park nucleotide)
* *Membrane-associated:**
1. Addition of glycosyl carrier lipid
2. Addition of GlcNAc
3. Flippase to flip PG to outer cell wall
4. Transglycosylation resulting in linked dissacharides of the PG sugar backbone w/side chain
**Post-Translocation**
91
How do bacteria become resistant to beta-lactam antibiotics?
- Inactivation through beta-lactamases
- Altered PBP (*mecA*-PBP2a)
92
What do you think of when you see spaghetti and meatballs?
Pityriasis Versicolor
(AKA tinea versicolor)
93
What are the clinical categorizations of mycoses?
Superficial
cutaneous
subcutaneous
systemic
opportunistic
94
Describe a superficial mycoses (with example)
-colonization of outer keratinized surface of skin
Skin
Hair
Nails
- little to no immune response
- mostly caused by yeasts
- easily treated
Example: tinea/pityriasis versicolor, +/- dandruff
95
Describe a cutaneous mycoses (with examples)
- invasion of epidermis with inflammatory response
- primarily caused by dermatophytes
Example: Athlete's foot, jock itch, ring worm
96
Describe a subcutaneous mycoses
- invasion of subcutaneous tissue
- often slowly progressive, may require surgery
97
Describe a systemic mycoses (with example)
- systemic response
- most acquired by inhalation of spores
- typically caused by dimorphic fungi
98
Describe opportunistic mycoses
fungal infections that predominantly occur in immune compromised hosts
99
What is the clinical presentation of pityriasis versicolor?
How is it diagnosed?
How is it treated?
* *Superficial Mycoses**:
- causes hypo- or hyper-pigmented macules on chest, neck, back
- Wood's lamp exam may show yellow-green fluorescence
**Diagnosis**:
direct visualization of yeastlike cells and short, infrequently branched pseudohyphae
(spaghetti and meatballs)
Note: culture growth is enhanced by adding olive oil
* *Treatment:**
- Course: persistent, rarely self-cures
- topical therapy (azoles, selenium sulfide shampoo)
- short course/single dose oral azoles if widespread
100
What do dermatophytic fungy cause?
Cutaneous mycoses
Often: Trichophyton species
Epidermophyton species
Microsporum species
Cause: breakdown of keratin
invade skin, hair, nails
invade outermost layer of epidermis (s. corneum)
101
What is the clinical presentation of a dermatophytic fungi?
How is it diagnosed?
How is it treated?
**Cutaneous Mycoses**
* *Clinical:**
- Causes "ringworm" or "tinea infections"
- inflammatory scaling, often in the pattern of a ring
- frequent hair loss
**Transmitted by:** indirect contact (infective elements remain viable in desquamated scales and hair for long periods of time) and direct contact
* *Diagnosis:**
- often clinical
- microscopy or culture for definitive result
* *Treatment:**
- Skin only = topical agents (azole or terbinafine)
- hair or nail = oral therapy (azole, terbinafine, griseofulvin)
102
What are the common subcutaneous mycoses?
Sporotrichosis
Chromoblastomycosis
Eumycotic mycetoma
- all rare
- introduced traumatically
- infection into dermis, subcu tissue, and bone
- rarely spread to distant organs
- VERY difficult to treat
103
What is the clinical presentation of a Sporotrichosis?
How is it diagnosed?
How is it treated?
* *Subcutaneous mycoses:**
- Dimorphic
- ubiquitous in soil and decaying vegetation
- rose gardener's get this
* *Clinical:**
- Primary lesion at site of inoculation
- nodule grows, ulcerates, and becomes painful
- very little systemic illness
- 2-3 weeks later, secondary lesions along lymphatics
- lesions progress proximally
* *Diagnosed**:
- H&E shows eosinophilic granulomatous structure with starburst pattern
- culture is best tool
* *Treatment:**
- several weeks minimum
- itracanazol
- classic therapy = oral potassium iodide
104
What is the clinical presentation of a Chromomycosis?
How is it diagnosed?
How is it treated?
* *Subcutaneous mycoses****:**
- chronic local fungal infection of skin
- caused by many fungal agents
* *Clinical:**
- Causes warty and/or nodular outgrowths
- slowly progressive
- disease is mostly in tropis, on feet and legs
- Granulomatous inflammation
* *Diagnosis:**
- H&E shows muriform cells: brown cells, divided by internal septation (Medlar bodies)
* *Treatment**:
- Very difficult
- itraconazole or terbinafine
- local heat or cryotherapy to help shrink lesions
- surgery contraindicated (risk recurrence)
105
What is the clinical presentation of Eumycotic mycetoma?
How is it diagnosed?
How is it treated?
* *Subcut****aneous mycoses:**
- Deep, subcu fungal infection
- caused by soil organisms entering wounds
* *Clinical:**
- grossly see localized swelling with underlying sinus tracts
- granulomas develop with granule formation (aggregates of hyphae)
- pus and ranules can drain through skin
* *Diagnosis:**
- detection of granules by gross visualization or microscopy
- H&E shows black grain mycetoma (not req'd for diagnosis)
* *Treatment:**
- antifungal agents and local surgery can be tried, but often not effective
- frequently cure is by amputation
106
What are the different presentations of cutaneous mycoses?
Head: Tinea capitis (often ringworm)
Trunk: tinea corporis
Face: tinea barbae
Groin: tinea cruris (jock itch)
Foot: tinea pedis ("athlete's foot)
Nails: tinea unguium
107
What is the common immune response cycle for HSV and VZV?
Productive infection, controlled, virus enters latency
immune suppression or other stimulation leads to reactivation
immune deficiency due to old age, AIDS, organ transplantation, or chemotherapy can lead to virus reactivation
108
What is the structure of Herpesvirus?
Nucleocapsid surrounded by ttegumen
enveloped virus
linear dsDNA
icosahedral capsid
infects mucousal epithelial cells
replicates in nucleus
viral perticles bud through nuclear membranes and into membrane of exocytic vesicles during egress
109
What are possible presentations of HSV-1?
labial lesions (cold sores)
fever blisters
keratitis
and possibly encephalitis
110
What are possible presentations of HSV-2?
genital lesions
severe CNS disease in neonates (congenital herpes infection)
111
What are presentations of VSV?
Chicken pox
shingles
112
How are herpesvirsuses transmitted?
Most by: close contact
sex
transplants
VSV: transmitted by respiratory droplets
113
What is the herpesvirus life cycle?
1. Lytic replication
2. latency
3. reactivation
114
What happens in the lytic replication of herpesvirus?
In epithelial cells:
viruses take over cellular machineries for replication
macromolecular synthesis and virus assembly
evenutally leads to cell death
4 phases of gene expression:
1. Immediate early
2. Early
3. DNA Replication
4. Late
can produce proteins to prevent apoptosis
115
What happens in the latency step of herpesvirus life cycle?
circular viral genome (episome) maintained in neurons without replication
expresses LAT transcript whihc plays role in latency establishment
116
What happens in the reactivation step of herpesvirus?
involves limited viral replication in neurons
transport of viral capsid to axonal terminals
egress to regions innervated by specific neurons
asymptomatic reactivation facilitates virus spread
117
What can cause HSV reactivation?
Stress
sun light
trauma
menstruation
118
What can be unique about HSV-2 reactivation?
often asymptomatic
Primary HSV-2 infection preceding child birht poses great risk to neonates
119
What can lead to Varicella Zoster virus reactivation?
immune-suppresion
depressed cell-mediated immunity (age)
120
What are clinical features of HSV?
**Primary Infection**: accompanied by systemic symptoms such as fever and malaise
**Reactivation**: accompanied by prodromal symptoms such as pain, numbness, itchiness, tingling sensation
* *Acute Infection:** direct destruction of tissues or induction of immunopathologic response
- characteristic skin lesions are vesicles on an erythematous base
- usually grouped as single anatomic site
**Subclinical virus shedding:** commona nd key to transmission, poses risk for neonates
121
What are immune responses to Herpesvirus infection?
- Antibodies play minor role in recover from primary HSV or VZV
- cell-mediated immune mechanisms are most important for prevention or control of recurrent disease
- AIDS patients; transplant recipients; patients under chemotherapy; patients with leukemia are susceptible to reactivation and prolonged infection
122
What is used for the diagnosis of herpes?
Viral culture w/ or w/o immunostaining
Tzanch smear
serology
PCR
123
What are two anti-herpes therapy targets?
**Herpes Thymidine Kinase:**
(acyclovir, ganciclovir)
**Herpes DNA Polymerase**:
(Phosphonoacetic Acid (PAA))
124
What is acyclovir used for?
Treatment of HSV-2
- DNA chain terminator, specifically activated by viral TK
- incorporation into viral DNA and terminates DNA replication
125
What is ganciclovir used for?
HSV-2 treatment
-a viral protein kinase homologue involved is involved in activating ganciclovir
126
What is forscarnet used for?
A pyrophosphat analog, it is used to treat HSV and CMV retinitis in AIDS patients
Binds directly to the pyrophosphate binding sites of RNA or DNA polymerases
Does not need to be activated by cellular or viral kinasees
must be given continuously intravenously via infusion pump
renal side effects
127
What are the recommendations for the Varicella Zoster Virus vaccine?
**Recommended For:**
susceptible children entering school or daycare
susceptible persons over 13
susceptible nonpregnant women of child-bearing age
susceptible persons with humoral deficiencies
HIV+ children with age-specific CD4+ counts greater than or equal to 25%
**Not recommended for:**
pregnant women
HIV+ persons, or personsn with other cellular immunodeficiencies
persons receiving immunosuppressive therapy
128
What is the action of the Botulinum toxin.
7 toxin types.
Zn metal protease cleaves SNARE proteins inhibiting membrane fusion and Acetylcholine release.
Causes flaccid paralysis
129
What types of Clostridia make neurotoxin?
C. Botulinum
C. Tentani
130
Characterics of Clostridia
G+
Obligate Anaerobes
Spore Formers
131
Mechanism of Tetnus toxin:
Zn metal protease that inhibits release of glycene from inhibitory interneurons.
Causes Spastic paralysis
132
Treatment of Botulism
Antitoxin- heptavalent
prepared in horses
Infants treated with divalent babyBOT which is human derived.
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Treatment of tetnus
Vaccine before or after. Not effective if already symptomatic.
Antitoxin
Muscle relaxants
Ventilation
