Microbiology Flashcards
1
Q
Helicobacter Pylori
Microbiology:
A
- Slender curve Gram- Rod
- Microaerophillic
- Survives b/c ecologic niche avoids immunity & mechanical clearance
2
Q
Helicobacter Pylori
Virulence Factors:
A
- Urease: buffers H+
- Vacuolating Cytotoxin (VacA) from Pathogenicity-Associated Island (PAI)
- Cytotoxin-associated Protein (CagA) from PAI
- Pilli: important for attachment & mediated Type III
Secretion of VacA and CagA
3
Q
Helicobacter Pylori
Epidemiology:
A
- Nearly everyone becomes infected
- ↑In low SEC
- Elderly»_space; Child
4
Q
Helicobacter Pylori
Pathogenesis:
A
- Source: humans spread disease via fecal-oral (parent-kid) or oral secretions (belching w/GERD)
- Bacteria grows in gastric mucosa via urease activity
- Host immunity attempts to eliminate Hp, but cannot because bug is not invasive
- Immune response –> inflammation –> ulcer
5
Q
Helicobacter Pylori
Diseases:
A
- Duodenal Ulcers (95%) > Gastric Ulcers (70%) (other gastric ulcers from NSAID use)
- Gastric Adenocarcinoma / Lymphoma - chronic inflammation.
6
Q
Diagnosis:
A
Endoscopy with Biopsy + Urease Breath Test + Stool Serology
- Gram stain for shape: microaerophillic G- curved rod
- Culture on Campylobacter medium (looks like campylobacter)
7
Q
Helicobacter Pylori
Treatment:
A
- PPI/H2-Blockers will not cure
2. PPI/H2 + 2 Abx = Omeprazole + Metronidizole (impotence) + Clarythromycin
8
Q
Vibrio Cholerae
Microbiology:
A
- Motile (polar flagella)
- Gram-, oxidase+ curved bacilli
- Grow in ↑pH
- Found in aquatic ecosystems
9
Q
Vibrio Cholerae
Virulence Factors:
A
- Phage-encoded cholera toxin (AB Exotoxin)
- Toxin-co-regulated-pilus (TCP)
- Required for GI colonization
10
Q
Vibrio Cholerae
Epidemiology:
A
Associated with Poor Sanitation/Sewage
- 7/8 caused by O1 serogroup (O-antigen on LPS)
- 8th caused by O139 serogroup (India)
- Cholera big problem in AA refugee camps
- SEASONAL: ↑Cholera during warm months
11
Q
Vibrio Cholerae
Pathogenesis:
A
- Source: brackish water (not sea, not fresh), human-feces contaminated water, shell fish, Gulf Coast
- Vibrio Cholera attach to small intestine epithelium via TCP (Pilus)
- Cholera toxin is produced = NON INVASIVE
- A2 fragment w/ KDEL mimicks host protein –> retrograde to ER –> looks misfolded –> ejected into cytosol
- A1 fragment ADP-ribosylates GTP binding protein (Gs) by transferring ADP-ribose from NAD
- ADP-ribosylated GTP binding protein –> ↑AC –> ↑cAMP –> ↑CFTR –>↑Cl + Na/H2O Follow
- ↑Secreted ions —> ↑H2O and HCO3- “pulled” into lumen –> Osmotic Diarrhea
12
Q
Vibrio Cholerae
Disease:
A
Cholera - ABRUPT and SEVERE diarrhea (20 L/Day) & Death from Dehydration (Shock)
- Rice-Water Stool (Mucus Flecks)
13
Q
Vibrio Cholerae
Diagnosis:
A
TLBS + MacConkey special growth media (fecal material requires different growth media)
14
Q
Vibrio Cholerae
Treatment:
A
IV Fluids and Electrolytes (+ oral glucose, salts) +/- Antibiotics (Doxy, erythromycin; but not invasive!)
15
Q
Vibrio Parahaemolyticus:
A
Similar to Vibrio Cholerae but ↑association with raw shellfish & most common in Japan
16
Q
Vibrio Vulnificus
Microbiology:
A
- Free living marine vibrio
2. ↑Association with wound infection in fisherman
17
Q
Vibrio Vulnificus
Virulence Factors:
A
Fe-Sequestering: great at grabbing iron
18
Q
Vibrio Vulnificus
Epidemiology:
A
- Liver disease (Vit K) / immunocompromised = ↑Risk
2. Gulf Coast in US
19
Q
Vibrio Vulnificus
Pathogenesis / Disease:
A
- Fisherman with Vit K deficiency (liver DZ) with wound comes into contact with Vibrio Vulnificus infected water
- Infection –> Severe Septicemia
- Develops gastroenteritis ==> vomiting + diarrhea + abdominal cramps
- Develops blistering hemorrhagic bullae
20
Q
Vibrio Vulnificus
Treatment:
A
Aggressive antibiotics for septicemia & wound infection
21
Q
Campylobacter Jejuni
Microbiology
A
- Gram-, Oxidase+ spiral rods (“Seagulls”)
- Microaerophilic (grow only in ↓O2)
- Grow at 42 C (bird temperature)
- Small dose = massive death
22
Q
Campylobacter Jejuni
Pathogenesis:
A
- Source: Raw Meat / Milk with Human-Human Transmission
2. C. Jejuni infects lining of small intestine —> Systemic Spread
23
Q
Campylobacter Jejuni
Disease:
A
- Bloody Diarrhea with Pus after Fever
- Guillan Barre Syndrome: symmetric rising paralysis due to x-Reactivity of CJ-Lipo. Oligo Saccharide Abs with myelin protein
24
Q
Campylobacter Jejuni
Diagnosis:
A
Culture + Gram stain ~ “Sea Gull” Appearance
25
Campylobacter Jejuni
| Treatment:
Usually Self limiting (3-7 days) +/- Antibiotics (erythromycin); huge resistance to Fluoroquinolone
26
Campylobacter Fetus
C. Fetus: from contaminated food, rare, & more
likely to cause septicemia & disseminated
infection
27
Clostridium Perfringens
| Microbiology:
Gram+ “Boxcar” bacilli
| 1Found in colon, spores, & on surface of unrefrigerated meats.
28
Clostridium Perfringens
| Epidemiology:
Diabetics
29
Clostridium Perfringens
Pathogenesis: Based on Disease
Wound Infections =
Gas Gangrene (Myonecrosis) + Anaerobic Cellulitis
- C. Perfringens’ toxic hydrolytic enzymes = α-PLC, collagenases, protease -->
chew through tissue --> Gas
- Results in muscle necrosis (myognecrosis) & spread
30
Clostridium Perfringens
| Treatment:
(Mainly for Infected Wound): Surgery, Maggots (eat necrosis)
1. Antibiotics: Penicillin + Protein-Inhibitor (for enzymes)
2. Hyperbaric Oxygen
31
Clostridium Tetani
| Microbiology
1. G+ “tennis rackets” / “lollipops” / “drum sticks”
| 2. Found in spores / GI tract
32
Clostridium Tetani
| Virulence Factors:
1. Tetanospasmin = AB Neurotoxin (Plasmid-Encoded)
| - Single antigenic type
33
Clostridium Tetani
| Pathogenesis:
1. Spore-contaminated object (Rusty Nail) ---> Wounds Patient
- Wound = inflamed tissues = ↓O2 = ideal for anaerobic spore
- Wound location is important because can determine time for symptoms (aka time for toxin to reach CNS)
2. C. Tetani releases Tetanospasmin
- AB neurotoxin enters NMJ ---> transported retrograde to ganglia --> Clips V-Snare via Zn Metalloprotease
- No V-Snare --> no fusion of vesicle + pre-synaptic neurotransmitter membrane
- Specifically, no release of GABA + GLYCINE --> no inhibitory neurons --> constant muscular stimuli
34
Clostridium Tetani
| Presentation:
1-2 weeks post-exposure = Lockjaw + Risus Sardonicus + Respiratory Failure + Exhaustion
35
Clostridium Tetani
| Treatment and Prevention:
Antibiotics Don’t Work = Exotoxin mediated
1. Sedative Treatment: sensitive to stimuli
2. Anti-tetanus Immunoglobin (TIG)
3. Vaccine for wound management
- Even if previously immunized (>3 doses) give vaccine in minor cases if 10+ years since immunization; if severe
wound give if 5+ years since immunization
36
Clostridium Tetani
| Vaccine:
Vaccine (**Exam) = Formalin Inactivated Toxin
1. Initial Immunization (+ Booster every 10 years)
- Pt < 7 = DTaP
- Pt 10-64 = Tdap (reduced diphtheria & pertussis)
2. Wound Management
- 3 Dose Immunization: xTdap (✓if bad wound)
37
Clostridium Botulinum
| Microbiology:
1. Anaerobic Gram+ spore forming bacilli
2. Canned food, wound, honey = anaerobic!
3. 1g = 1 M deaths
4. 7 Antigenic Types (A-G)
38
Clostridium Botulinum
| Virulence Factors:
Botulinum Exotoxin
39
Clostridium Botulinum
| Pathogenesis:
1. Consumption of raw/contaminated canned foods (or honey / carpet for infant cases) / infected wound
2. Botulinum Toxin = Metalloprotease cleaves V + T-Snares --> ↓AcH Release --> Flaccid Paralysis
- Classic Food-Borne Adult Botulism (Toxin A)
- Wound Botulism (Toxin A) = rare, seen in black tar heroin users
- Infant Botulism (Toxin B > A) = Floppy Baby Syndrome (= This is an infection!)
40
Clostridium Botulinum
| Symptoms:
Classic Triad of Symmetric DESCENDING Flaccid Paralysis + NO Fever + Clear Sensorium
- Begins with CN damage (double vision, dysphagia) --> Respiratory Failure
41
Clostridium Botulinum
| Treatment:
Ventilation + Horse anti-botulism Ig + Human anti-botulism Ig
42
Clostridium Difficile
| Microbiology:
G+ Spore-former in GI normal flora
43
Clostridium Difficile
| Virulence Factors:
Toxins A and Toxin B (not AB)
1. Toxin A = Diarrhea
2. Toxin B = Kills Colon Cells
3. Mechanism: Rho-Family GTPase --> damaged
intracellular signaling --> actin/stress fibers
rearranged
44
Clostridium Difficile
| Epidemiology:
Nosocomial / Rx-Induced Diarrhea
| - Considered “superinfections”
45
Clostridium Difficile
| Pathogenesis:
1. Rx clears out normal flora / polymicrobial environmental ---> Free Reign for C. Difficile
- Rx = Clindamycin + Imipenem + Ceftaxidine + Moxifloxacin
2. C. Difficile colonizes ---> Toxin Mediated Damage (A = Diarrhea; B = kills colon cells)
3. Toxin --> Water Diarrhea ---> Bloody Diarrhea
- Progression from Watery ---> Bloody Diarrhea from pseudomembranous colitis (ulcerative lesion of colon)
46
Clostridium Difficile
| Symptoms:
Fever + Watery-->Bloody Diarrhea
47
Clostridium Difficile
| Diagnosis:
RADT for Tox A and Tox B in stool (organism rarely found in stool)
48
Clostridium Difficile
| Treatment + Prevention
1. Stop antibiotic --> give metronidazole
| 2. Prevention: soap > alcohol wipes b/c spores are resistant to alcohol
49
General Features of Enterobacteriaceae
* Gram- bacilli; faculitative anaerobes
* Ferment glucose & oxidase negative (vs. Pseudo)
* Motile/flagella (vs. non-motile Klebsiella & Shigella)
* Reduce nitrates ---> nitrites (diagnostic value with urine dipstick)
50
E. Coli
| Microbiology:
• Gram- bacilli, lac+, glucose fermenter w/H2 gas
• Does not produce H2S
• 5 Virotypes Cause Diarrhea
• Opportunists = disease elsewhere (not diarrhea)
• Strains may be inherently enterovirulent; have
additional PAI-encoded genes
51
E. Coli
| Diseases:
1. Diarrhea + Dysentery
2. #1 Cause of UTIs
3. Neonatal Septicemia + Meningitis
52
E. Coli
| Diagnosis:
1. Culture: rule out salmonella (H2S+), shigella
(H2-), KIA/TSI
• E. Coli: yellow (Glu/Lac+), no black (xH2S), bottom gap (H2)
• Shigella: red/yellow (Glu+), no black (xH2S), no bottom gap
• Proteus: black (H2S)
• Pseudo: nothing
53
Enterohemorrhagic E. Coli (EHEC)
| Microbiology:
• Has O157:H7
54
Enterohemorrhagic E. Coli (EHEC)
| Virulence Factors:
• Shiga Toxin (~Stx): phage encoded cytotoxin (AB)
that cleaves 28S RNA of Ribosome
• Locus Enterocyte Effacement (LEE) from PAI
1. Type III Secretion System
2. Intimin: outer-membrane adhesin
3. Tir: secreted receptor to bridge intimin with entero.
4. Attaching/Effacing Lesion: Δhost actin for ↑binding
55
Enterohemorrhagic E. Coli (EHEC)
| Epidemiology:
• Reservoir is cattle due to feedlot practices
• Sources of infection: ground beef, bad milk,
drinking/swimming contaminated water
• ↑Risk in childcare centers
• Occasional human-human transmission
56
Enterohemorrhagic E. Coli (EHEC)
| Pathogenesis:
1. Source: raw ground beef / milk / bad veggies or juices / person-person contact (Requires ↓Infectious Dose)
2. EHEC binds to cell and secretes toxin via LEE/Type III Secretion --> O157:H7 cleaves 28S RNA --> cell death --> Gastroenteritis ---> Diarrhea
• Diarrhea for 1-8 days
3. Toxin enters blood --> infects endothelium --> endothelial cell injury --> microthrombi --> anemia / renal failure = HUS
• Progression to HUS in Children (<5) or Elderly
• Anemia + Acute Renal Failure (+TTP, Nerve/Brain damage)
• Most common cause AKI in pediatric patients
57
Enterohemorrhagic E. Coli (EHEC)
| Presentation:
1. Sudden onset of abdominal cramps + watery diarrhea
2. Watery diarrhea ---> bloody diarrhea in 24 hours
3. +/- Fever (102 F)
58
Enterohemorrhagic E. Coli (EHEC)
| Diagnosis:
Sorbitol MacConkey Agar
• Like MacConkey; lactose replaced with sorbitol because O157:H7 is sorbitol negative and other E. Coli are positive
• Additional tests: RADT / serotypes / Nucleic Acid test for toxins.
59
Enterohemorrhagic E. Coli (EHEC)
| Treatment:
DO NOT TREAT WITH ANTIBIOTICS
| • Does not alter colitis; ↑risk for HUS because antibiotic stress simulates lysogenic phage --> ↑Stx Toxin.
60
Enterotoxigenic E. Coli (ETEC)
| Virulence Factors
* LT: heat labile enterotoxin ~ cholera toxin (AB toxin)
* ST: heat stable enterotoxin --> ↑cGMP ~ ↑cAMP
* Fimbriae: CFA I/II adhesins for SI enterocytes
* Non-invasive: secretes exotoxin
61
Enterotoxigenic E. Coli (ETEC)
| Epidemiology:
• Leading bacterial cause of diarrhea in 3rd world;
most common cause of Traveler’s Diarrhea
• Waterborne outbreaks/food-related infections
62
Enterotoxigenic E. Coli (ETEC)
| Pathogenesis:
1. Acquired via ingestion of contaminated food + water
2. Colonizes SI enterocytes via fimbriae
3. Non-invasive and secretes LT + ST
• LT (A1B5) binds GM1 gangliosides on cell surface --> ↑GTPase --> AC --> ↑cAMP --> ↑CFTR --> Secretory Diarr
• ST binds guanylyl cyclase receptor --> ↑cGMP --> ↑PKA --> ↑CFTR --> Secretory Diarrhea
63
Enterotoxigenic E. Coli (ETEC)
| Presentation:
1. Non-inflammatory + ↑↑Volume Diarrhea ~ Cholera
64
Enterotoxigenic E. Coli (ETEC)
| Treatment:
ORT
65
Enteroinvasive E. Coli (EIEC)
| Microbiology:
Non-motile, NOT lactose fermenter, NOT decarboxylator of lysine
66
Enteroinvasive E. Coli (EIEC)
| Virulence Factors:
* ↑Invade Colonic Tissue: destroys the tissue
| * Actually invasive
67
Enteroinvasive E. Coli (EIEC)
| Epidemiology:
* Underdeveloped countries; Traveler’s Diarrhea
| * Humans only known reservoir
68
Enteroinvasive E. Coli (EIEC)
| Pathogenesis
~ Shigella Toxin
1. Source: acquired via 3rd world person-person contact
• ↑Infectious dose than in children
2. EIEC penetrate and multiply within epithelial cells of colon --> widespread cell destruction
• Actually penetrates = INVASIVE
• Because non-motile, it rearranges the cytoskeleton just behind (Actin Tail) to propel it from enterocyte --> enterocyte
3. Cell death --> Symptoms / Presentation
69
Enteroinvasive E. Coli (EIEC)
| Presentation:
1. Shigella-like dysentery
| 2. Fever
70
Enteropathogenic E. Coli (EPEC)
| Virulence Factors:
1. EPEP Adherence Factor (EAF): localized binding
2. Intimin: adherence
3. LEE: mediates attachment / effacing
• Like EHEC, LEE allows pedestal formation and
Attachment / Effacement Lesion
71
Enteropathogenic E. Coli (EPEC)
| Epidemiology:
Leading cause of infantile diarrhea
• 3rd world infants
• Transmission: contaminated H2O / meat products
• DAEC: New Mexico + NA
72
Enteropathogenic E. Coli (EPEC)
| Pathogenesis:
1. Acquired via consumption of contaminated water / food
2. Moderately invasive EPEC strain --> induces inflammatory response (because not toxin-mediated)
3. Invasive --> intracellular bacterial --> ↓normal cell signaling transduction --> loss of microvilli --> Osmotic Diarrhea
73
Enteropathogenic E. Coli (EPEC)
| Presentation:
1. Profuse watery +/- bloody diarrhea
2. +/- Inflammation
3. No fever
74
Uropathogenic E. Coli (UPEC)
| Virulence Factors:
• P Fimbria: pyelonephritis associated pili (PAP); P
fimbria because P binds P blood group antigen.
Binds to galactose disaccharides on uroepithelium
• Siderophores: Fe-acquisition
• EC Hemolysin: host cell pore-former = cytotoxic
• K Antigen: ↓immunogenicity
75
Uropathogenic E. Coli (UPEC)
| Epidemiology:
90% non-obstructive UTI
| • ↑ Female Risk = shorter urethra
76
Uropathogenic E. Coli (UPEC)
| Pathogenesis:
1. Bacteria colonize from feces / perianal region ---> ascends into urinary tract --> bladder
• If in sexually active female, could be cystitis propelled up into bladder during sexual intercourse from urethra
2. Major defense against infection is urine flow
3. Can progress to Neonatal Meninges (K-Antigen Mediated)
4. Can progress to SIRS / Shock (Immunocompromised Patients)
77
Uropathogenic E. Coli (UPEC)
| Presentation:
1. Dysuria, pyuria, suprapubic pain, cramping, afebrile
78
Uropathogenic E. Coli (UPEC)
| Diagnosis:
Large number of urinary bacteria
• >10^5/mL in females
• >10^3/mL In males
79
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Microbiology:
* Gram- Frank Pathogen
| * Lac-, ferment glucose w/gas + production of H2S
80
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Virulence Factors:
PAI Type III Secretion
81
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Epidemiology:
```
Zoonosis
• Contaminated meat, dairy, poultry, pet reptiles, turtle
• Eggs = S. Enteritidis
• Dissemination rare
• ↑Risk w/AIDs + Hodgkins for Bacteremia
• Sickle Cell for osteomyelitis
• Old/Young
```
82
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Pathogenesis:
1. Improperly cooked / contaminated food ingestion --> S. Group in gut
2. Bacteria swim in mucosal layer ---> Type III Secretion System Injects M cells ---> Ruffles Membrane ---> Engulfs Bug
3. Localized infection (macrophages) in lamina propria --> Gastroenteritis
83
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Presentation:
N/V Abdominal cramps + diarrhea ~ 20-72 hours post-eating
• VOMITING*****
• Dissemination rare, but can lead to bacteremia/sepsis, osteomyelitis, endocarditis, renal problems
84
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Diagnosis:
Isolation is Mainly Important
| 1. H. Serotyping for identification
85
Salmonella Enteritidis, Typhimuium & Non-Typhi Serotype
| Treatment:
Antibiotics may be given; often best not treated
| • No vaccine
86
S. Typhi ==> Typhoid + Enteric Fever
| Microbiology:
Lac-, ferment glucose w/out gas + H2S
87
S. Typhi ==> Typhoid + Enteric Fever
| Virulence Factor:
• Vi: antigenic capsule inhibits neutrophil uptake
• 2 x Type III: one to inject protein into M-cells for
entry; one to inject proteins into macrophages for
survival.
88
S. Typhi ==> Typhoid + Enteric Fever
| Epidemiology:
Not Zoonosis
• Developing nations
• Prophylactic to traveler’s
89
S. Typhi ==> Typhoid + Enteric Fever
| Pathogenesis:
1. Parasite of humans ---> human/feces contaminated water --> migrant worker/traveler gets illness
2. Migrates to M folds of small intestine --> lamina propria --> macrophages phogocytose --> not killed
• Perforations at GI tract at necrotic Peyre’s Patches ---> Severe Hemorrhage
3. Migrates to RES organ (spleen and liver)
4. Leads to disseminated infection in blood (Sepsis) ===> Insidious Rising Fever + Headache + Abdominal Pain
• Mental confusion
• Diarrhea not common
• Skin rash ~ Rosette Spots
90
S. Typhi ==> Typhoid + Enteric Fever
| Diagnosis:
culture blood / feces
91
S. Typhi ==> Typhoid + Enteric Fever
| Treatment:
```
aggressive antibiotics (Ceftriaxone)
• Live attenuated oral vaccine
```
92
Yersinia Enterocolitica
| Microbiology:
• Gram- coccobacilli ~ Safety Pin (bipolar stain)
93
Yersinia Enterocolitica
| Epidemiology:
* Animal reservoir = PIGS
* Consumption of contaminated milk, water, food
* Children infected with pet-contact
94
Yersinia Enterocolitica
| Presentation:
* Pseudoappendicitis
* Enterocolitis w/fever, diarrhea & abdominal pain (mesenteric lymphadenitis)
* May lead to Reiter’s Syndrome
95
Shigella
| Three Speciations Based on Disease/Epidemiology
1. S. Dysenteriae
• South + Central America
• MDR
• Produce 1,000x ↑Shiga toxin than others;
mechanism dysentery unknown
2. S. Boydii
• Indian subcontinent
3. S. Flexneri
• 2nd most common in US; most common in gay men
4. S. Sonnei
• Most common cause of shigellosis in US
• Mainly dysentery in children (day care where fecaloral transmission is likely to occur)
• Next seen in mental institutions/jails/gay men (STD)
96
Shigella
| Microbiology:
Frank Pathogen
• Lac-, no gas, glucose+, non-motile, H2S-
• ~EIEC / EHEC
97
Shigella
| Virulence Factors:
* Large Invasion Plasmid: gets into lamina propria
| * Shiga Toxin: inhibits eukaryotic 28s rRNA
98
Shigella
| Pathogenesis:
1. Source: humans are only source so person-person fecal-oral transmission occurs
• Very Low Infectious Dose
• Common food-borne outbreaks do occur
2. Entry into microfold (M) cells in the gut
3. Escape from the phagocytic vesicle
4. Extension to neighboring enterocytes; rarely leaves the GI tract
99
Shigella
| Presentation:
1. Begins as water diarrhea + abdominal pain = Small Intestine Involvement
2. After +/- 1 day, colon is involved --> scant bloody diarrhea with mucus/pus; cramps + tenesmus
3. Like EHEC, Shigella Dysenteriae ---> HUS
100
Shigella
| Diagnosis:
1. Fecal leukocytes are prominent; sheets can be seen
| 2. Gut biopsy - invasion beyond epithelium is rare
101
Shigella
| Treatment:
Antibiotics & unfortunately resistance (MDR) is a problem
102
Rotavirus (Reoviridae)
| Microbiology:
```
Respiratory Enteric Orphan
• Segmented, ds-RNA
• ↑Antigen diversity (G-P serotypes)
• Non-enveloped: ↑Survival
• 2-3 Concentric icosahedral capsids
```
103
Rotavirus (Reoviridae)
| Epidemiology:
* Most important cause of diarrhea in infants/kids!
* WInter/Spring Bug (unique season**)
* Starts in New Mexico / South West
* REO = spread respiratory / enteric (Fecal/Oral)
* ↓Deaths effective fluid therapy
104
Rotavirus (Reoviridae)
| Management & Treatment:
Because only 4 G-P combinations cause majority of disease ===> Ideal for Vaccine
105
Rotavirus (Reoviridae)
| Pathogenesis
~ Transmission is Fecal / Oral ---> Infects Villus Epithelium of Small Intestine
1. Viral capsid is proteolytically processed outside enterocytes (gut) or intra-enterocyte -> Infectious Virus Particle
2. Virus taken up via endocytosis --> endosome / lysosome --> penetrates cell
3. Enzymes within core asymmetrically synthesis mRNA (only + strand is synthesized)
4. Capped +RNA strands extrude via vertices of capsid and are assembled into “Assortment Complexes”
5. Capped +RNA strands in assortment complexes serve as template for -RNA strand
6. Assembly of virus occurs in cytoplasm within Virus Factories ---> Shedding & Lysis of Enterocyte
106
Rotavirus (Reoviridae)
| Pathogenesis main point:
===> Loss of Enterocyte Lining SI / LI ---> Functional Loss of Absorption (no AC, cAMP activation like cholera)
107
Rotavirus (Reoviridae)
| Manifestation & Diagnosis:
* Nausea, vomiting, diarrhea, fever and dehydration
* 1-4 day incubation
* Death of enterocyte ---> Diarrhea ---> Dehydration ---> Death
108
Rotavirus (Reoviridae)
| Treatment:
Neutralizing antibodies develop to circulating rotavirus + 4 G-P combinations cause 90% of disease = Vaccine
• RotaTeq: live attenuated pentavalent bovine-human reassortant viruses containing G1-G4 + P8
• Rotarix: live attenuated divalent human virus containing Gi, P8
109
Norovirus (Caliciviridae)
| Microbiology:
* Non-segmented, +RNA
| * Nonenveloped
110
Norovirus (Caliciviridae)
| Epidemiology:
• Most important cause of foodborne epidemic
acute gastroenteritis in older children & adults
• “Winter Vomiting Disease”
• 50% of community-based (non-bacterial)
gastroenteritis
111
Norovirus (Caliciviridae)
| Pathogenesis:
~ Transmission is Fecal / Oral ----> Infects Villus Epithelium of Small Intestine
1. Outbreak usually due to single source (shellfish, cake frosting or Cruse Ship Outbreak)
2. Replication scheme unknown, but similar to Picornavirus Replication
112
Norovirus (Caliciviridae)
| Pathogenesis main point:
===> Loss of Enterocyte Lining SI / LI ---> Functional Loss of Absorption (no AC, cAMP activation like cholera)
113
Norovirus (Caliciviridae)
| Manifestation & Diagnosis:
* Nausea, vomiting, diarrhea, fever & dehydration
| * ~1 day incubation (shorter than rotavirus) & vomiting is more severe
114
Norovirus (Caliciviridae)
| Management & Treatment:
Capsid proteins are ↓antigenic + antigenic drift ===> no vaccine
• Wash hands, disinfect surfaces, & prepare food well
115
Enteroviruses, Coxsackie Virus & Echovirus
(Picronaviruses)
Microbiology:
Picorna ~ Pico + RNA
• Small nonenveloped +RNA viruses
• Picorn = polio, insensitive to ether, coxsackie,
orphan virus & rhinovirus
• Enterovirus different from rhinovirus because acid
stable & replication at 37C
116
Enteroviruses, Coxsackie Virus & Echovirus
(Picronaviruses)
Viruses:
1. Poliovirus: cause flaccid paralysis ~ Poliomyelitis
2. Coxsackievirus: meningoencephalitis, diarrhea,
muscle pain, myocardial / pericardial inflammation
3. Echovirus: Enteric Cytopathic Human Orphan
causing mild gastroenteritis
4. Hep A
117
Enteroviruses, Coxsackie Virus & Echovirus
(Picronaviruses)
Epidemiology:
Humans are only reservoir
| • Occur mainly in the summer and fall
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Enteroviruses, Coxsackie Virus & Echovirus
(Picronaviruses)
Management & Treatment:
1. Other than polio, no vaccines are present
• Large number of serotypes & asymptomatic
infection make it difficult to create vaccine
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Enteroviruses, Coxsackie Virus & Echovirus
(Picronaviruses)
Pathogenesis
~ All can be spread by Oral-Fecal Route (Coxsackie also from aerosol on doorknobs, toys, etc)
1. Incubates for 7-14 days
• Initially replicates inside lymphoid tissue in the URT & the gut (looks like measles but don’t be fooled!)
• Can be isolated via throat swab
2. Post-replication Viremia
• Spinal Cord + Meninges + Brain / Heart / Skin
3. Most symptoms come from direct virus-mediated cell damage & tissue necrosis from normal viral replication in a cell
• Myocarditis & nephritis may be more immune complex / cross-reactivity mediated
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Enteroviruses, Coxsackie Virus & Echovirus
(Picronaviruses)
Manifestation & Diagnosis:
Keep in Mind that Infection Period is Asymptomatic
1. Aseptic Meningitis ~ Poliovirus, Coxsackie, & Echovirus
• Fever, malaise, headache, nausea + abdominal pain ---> Meningeal Irritation + Vomiting
• Muscle aches occur & maybe confused with polio
2. Pleurodynai (Epidemic Myalgia) ~ Group B Coxsackie
• Abrupt fever + chest + abdominal pain for 2 days-2 weeks
3. Hand, Foot and Mouth ~ Coxsackie A16
• Enanthema: ulcerative lesions of the mouth (especially on tonsils and uvula ~ herpangina)
• Followed by lesions on hands/feet
4. Myocarditis --> Group B
5. Eye Disease --> Coxsackie + Echovirus
6. GI Disease ---> Diarrhea, Hepatitis, Pancreatitis
7. Skin Rashes
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Hepatitis Viruses Classification
| Hep A Virus:
Enterically transmitted “infectious” hepatitis
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Hepatitis Viruses Classification
| Hep B Virus:
Parenterally-transmitted “serum” hepatitis
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Hepatitis Viruses Classification
| Hep C Virus:
nonA, nonB PT-transmitted hepatitis
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Hepatitis Viruses Classification
| Hep D Virus:
dependent on Hep B co-infection
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Hepatitis Viruses Classification
| Hep E Virus:
nonA, nonB ET-transmitted hepatitis
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Hepatitis Viruses Classification
| Hep G Virus:
nonA, nonB PT-transmitted hepatitis
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HAV
| Microbiology:
Picornaviridae (family), Enterovirus (gen)
• ss-RNA+ non-enveloped icosahedral capsid
• Single serotype, humans known reservoir (vaccine!)
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HAV
| Disease:
Acute ET Hepatitis
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HAV
| Epidemiology:
* 33% of acute hepatitis cases in US each year
* Nationwide outbreak every decade
* Noticeable rapid decline w/vaccine (normally slow)
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HAV
| At Risk Patients:
Think Memphis Day Care!
• Household/sexual contacts of infected (recall: ET)
• International travelers
• American Indian reservations (West/Southwest)
• Outbreaks (D’s): daycare, dudes, diners, drug-users
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HAV
| Pathogenesis:
~ Acute Enterically-Transmitted Hepatitis
1. HAV spread by fecal-oral route
2. Replicates in GI tract; incubation period ~ 15-30 days
3. Transient viremia ---> Spreads to liver, kidney & spleen
4. Virus sheds ---> end of shedding signifies jaundice (start of symptoms) aka non-infectious incubation
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HAV
| Presentation:
* Jaundice (end of shedding) with ↑liver enzymes
| * ET-Transmitted = acute --> abrupt (12 weeks) icterus with sharp fever
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HAV
| Diagnosis:
Isolated from patient’s feces
| • ELISA for anti-HAV IgM (see image
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HAV
| Treatment / Control:
Hand-washing, Harvrix (killed vaccine) & gamma-globulin
| • Vaccination targeted at kids (daycares)
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HBV
| Microbiology:
~ Virion = Dane Particle
• Hepadnavirus = Hepatocyte DNA Virus
• dsDNA = L-DNA (full length) vs. S+DNA (smaller)
• Affected individuals have Dane Particle AND trillions of filaments containing HBsAg + P-lipid (no DNA)
• Why disease is chronic; immune system recognizes filaments, but actual virus (DANE) is isn’t there!
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HBV
| Encodes five proteins, key for replication
1. DNA Polymerase with R-T activity
2. HBsAg: Surface Ag, attachment protein (in filaments)
3. HBcAg: Core Ag, surface protein
4. HBeAg: secreted form of HBcAg (imp. for diagnosis)
5. X-Antigen: regulated gene expression
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HBV
| Disease:
PT-Chronic Hepatitis (“Serum” Hepatitis)
• Chronic development depends on AGE
• Younger ( HCC)
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HBV
| Epidemiology:
• Endemic to China & sub-Saharan Africa where
infection occurs earlier (not more)
• SE Asia mothers passing on to child
• ↑Incidence b/c Chinese immigration
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HBV
| At Risk Patients:
HBV makes a Dane Particle
• Hospital-Workers, Hemopheliacs (H)
• Dudes, Drug Users (D)
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HBV
| Prognosis:
25% chronic HBV die liver disease 50s-60s
| When to treat?: Liver Injury / fibrosi
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HBV
| Pathogenesis Entry:
HBV enters via parenteral-route (Present in semen & vaginal secretions)
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HBV
| Pathogenesis Replication:
Replicates primarily within the liver ~ incubation time 45-160 days
• HBV DNA --> nucleus --> completes ds-DNA circle with host machinery (b/c recall that HBV isn’t truly double stranded)
• Host DNA-dependent RNA polymerase --> pre-genomic RNA (looks ~ host mRNA)
• Core protein encapsidates pre-genomic RNA + Viral DNA polymerase (recall has RT activity)
• DNA polymerase RT pre-genomic RNA ---> L-DNA (full length)
• Original pre-genomic RNA destroyed except small piece for priming S+DNA strand (incomplete)
• Envelop acquired and virus buds from endoplasmic reticulum - NO CELL LYSIS
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HBV is opposite of retrovirus?
***HBV is opposite of retrovirus (DNA virus using RNA intermediate) except they both share a RT!
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HBV
| Pathogenesis Cellular Damage:
NOT Cytolytic --> causes immune-mediated destruction of infected cells
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HBV
| Three Stages of Disease:
~ Keep in mind that antiviral therapy can drive seroconversion of HBeAg --> HBeAb
• Immune Tolerance Phase: ↑HBV DNA, HBeAg+; long in childhood infections (no CTL/immune response); skip in adults
• Immune Clearance Phase: seroconversion (HBeAg-->HBe Abs); HBeAg causes CTL tolerance; post-seroconversion activated CTLs (with no more HBeAg) cause liver inflammation & fibrosis (ΔALT levels) ===> results in healthy carriers
• Residual Phase: Post HBeAg seroconversion, ↓HBV DNA + normal ALT; +/- confused with HBeAg mutation
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HBV
| Presentation:
Unresolved HBV infection >6 months = chronic
• Chronic cases are asymptomatic until cirrhosis or hepatocellular carcinoma appears
• Chronic HBV cause that suddenly worsens = think HDV superinfection
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HBV
| Diagnosis:
~ Screen chronic HBV patients for HBsAg, HBeAg, HBe-Ab, HBV DNA
• HBsAg: acutely infected or carriers = screening test; all chronic cases have this
• Anti-HBs: past infection (resolved) or vaccinated
• HBeAg: active infection, ↑risk of transmission; ↑DNA viral levels
• Anti-HBe: carrier with ↓risk
• Anti-HBc: past infection (notice there is no core capsid marker); this is how you distinguish past infection vs. vaccine
• IgM Anti-HBc: acute infection
• HBV DNA
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HCV
| Microbiology:
Flaviviridae -> Hepacivirus
• ss-RNA+ enveloped icosahedral capsid
• Encodes polyprotein cleaved by NS3 protease
• 6 Major Genotypes w/Subtypes (see epidemiology)
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HCV
| Disease:
nonA/B PT-Hepatitis --> Chronic Disease
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HCV
| Epidemiology:
• Subtypes 1a, 1b, 2a and 2b example of antigen var
• 45-55 year old men
• Untreated patients become chronic carriers
• Hepatocellular carcinoma (HCC) but less than HBV
Time Table
• Chronic hep (10 years), cirrhosis (20), HCC (30)
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HCV
| At Risk Patients:
Anyone born between 1945-65
• Hospital-Workers, hemophiliacs, HIV-infected
• Drug users, dialysis
• Alcoholic Liver Disease
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HCV
| Pathogenesis:
1. PT spread with incubation time ~ 7-9 weeks
• IV drug use > sexual transmission > blood transfusions
2. NOT Cytolytic --> causes immune-mediated destruction of infected cells (see immune response in HBV)
3. Cirrhosis ---> Liver Cancer --> Liver Failure --> Liver Transplant
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HCV
| Presentation:
Compare to HBV
• Patient has multiple bouts of HCV due to reinfection with same or different strains / emergence of different quasispecies
• Subsequent bouts are shorter duration, but each holds equal risk --> chronic disease
• Unlike HBV, antigenic variation facilitates immune escape (mediated by HCV hypervariable region HVR1 near E2 gene)
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HCV
| Diagnosis:
~ Screen HCV patients for HCV core antigen + RNA / determine HCV genotype via RT-PCR
• Given patient may have 10 different subtypes of genotypes, but 1 quasispecies predominates
• Difficult to grow in culture
• Screening Test of Choice: HepC Antibody ---> HCV RNA PCR ---> Biopsy (***Biopsy is to determine severity!)
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HCV
| Treatment:
Cure 2 --> 3 --> 4 --> 1 (least curable)
• Screen blood supplies for HCV RNA
• PEG-IFN + Ribavirin + Protease Inhibitors ~ contraindicate: depressed (IFN), liver failure (IFN) & TerX/hem (Ribavirin)
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HDV
| Microbiology:
Delta virus = circular ss-RNA
| • Contain Delta-Ag + HBsAg
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HDV
| Disease:
Co-Infection or Super-infection of HBV patient.
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HDV
| Epidemiology:
Only in patients with HBV infection.
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HDV
| Pathogenesis:
HDV requires HBV for transmission
• Delta-Ag (polymerase molecule) + HBsAg facilitate hepatocyte infection (replicates in liver)
• Doesn’t produce it’s own receptor; uses HBV
• Can replicate on it’s own; just no transmission
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HDV
| Presentation:
If co-infection = acute disease; if super-infection = chronic cause of HBV that suddenly get’s worse
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HDV
| How to diagnose HDV?
* Ab-HDV
| * All should have HBsAg!
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HEV
| Microbiology:
Calcivirus --> Hepevirus
• ss-RNA+ non-enveloped icosahedral capsid
• Single serotype
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HEV
| Disease:
Acute ET Hepatitis
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HEV
| Epidemiology:
* Most prevalent in developing countries***
* Pregnant women = ↑Fatality Risk***
* Swine (reservoir) may be important in industrialized countries (Japan)
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HEV
| Pathogenesis:
~ HAV ~ makes sense
| • Transmitted F/O route --> replicates in GI tract (15-30 days) --> Liver, Kidney, Spleen --> Sheds (jaundice)
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HEV
| Presentation:
Jaundice (end of shedding)
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HEV
| Diagnosis:
Isolated from patient’s feces
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HGV
| Microbiology:
Flaviviridae
| • ssRNA+
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HGV
| Disease:
nonA/B PT-Hepatitis
| • Unsure if it actually causes chronic disease
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HGV
| Epidemiology:
Common in blood-donor population
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Hepatitis Viruses
| Which cause cirrhosis?
Hepatitis B, D & C
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Hepatitis Viruses
| Which cause acute liver failure?
A, E & B
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Hepatitis Viruses
| Which can be cured?
HCV NOT HBV
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Hepatitis Viruses
| When should you always be screened for HBV?
* Cancer chemotherapy
| * HIV treatment
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Hepatitis Viruses
| What two drugs used for HBV***EXAM?
* Entacavir + Tenofovir
| * Need CT scan every 6 months b/c risk for HPC
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Hepatitis Viruses
| What should be vaccinated for?
• A & B
Screening
• All HBV should be screened for HepB
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Acute Hepatitis =
Acute Hepatitis = A, E and B
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Acute Hepatitis
| Symptoms:
Symptoms: fever, fatigue, abdominal pain
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Acute Hepatitis
| Presentation & Labs:
* Enlarged Liver
* ↑AST/ALT > 1000
* ↑PT + ↑Bilirubin
* During infection: ↑IgM; after infection: ↑IgG
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Acute Hepatitis
| Three Outcomes:
Resolution >> Progression to Chronic (HBV) >>>>>>> Fulminant Liver Failure (encephalopathy)
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Chronic Hepatitis =
C, B (+D)
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Chronic Hepatitis
| Timeframe:
> 6 months infection
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Chronic Hepatitis
| Presentayion:
* Asymptomatic with NORMAL LFTs
| * ~ 20 years for liver fibrosis; accelerated by HIV, alcohol + obesity
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Chronic Hepatitis
| Don’t forget 7-8 tests for HBV - what are they?:
IgG + IgM Ab-HBcAg, HBsAg, Ab-HBsAg, HBeAg, Ab-HBeAg, HBV DNA
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Chronic Hepatitis
| Epidemiology:
* HepB most common worldwide
| * HepC most common US (2.7 M) ~ everyone born between 1945-1965
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Chronic Hepatitis
| Testing:
* HepC test of choice: Ab-HepC ---> PCR
| * Ab-HepC+ & HCV-RNA+ = acute OR chronic; just Ab-HepC+ = resolution; just HCV-RNA+ = early/acute HCV
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Clostridium Perfringens
Pathogenesis: Based on Disease
Food Poisoning =
Non-Inflammatory Diarrhea for 8-12 Hours
- Spore germinates on unrefrigerated meats --> ↑Toxin Production
- Enterotoxin --> Non-inflammatory watery diarrhea; no Vomiting; no Fever
