Exam #2 Flashcards
1
Q
Discovery of Lobar Pneumonia
A
1882 Friedlander discovers Klebsiella
1881 Fraenkel discovers Streprococcus
2
Q
Streptococcus Genus Division
A
divided in 1919 based on blood agar hemolysis patterns
3
Q
Streptococci:
Characteristics
A
gram + spheres -pairs/chains, non-motile, catalase negative diverse group -some normal flora hemolytic pattern on blood agar -alpha/beta/gamma
4
Q
Streptococci:
Pathogenesis
A
extracellular infection
-bacteria killed within phagocytes
tend to produce purulent lesions
5
Q
Streptococci:
Major Diseases
A
bacteremia/ impetigo/ glomerulonephritis pneumonia/ wound infections/ endocarditis meningitis/ pharyngitis/ UTIs cellulitis/ necrotizing fasciitis rheumatic fever/ scarlet fever/ TSST
6
Q
Streptococcus pneumoniae:
pneumococcus
A
major respiratory pathogen -most common cause of pneumonia in US pathology (lobar pneumonia) -sudden chills, fever, pleuritic pain, rusty sputum -complications: lung abscess/ bacteremia -morbidity/mortality: 40,000 <10% cases
7
Q
Streptococcus pneumoniae:
Risk Factors
A
10-30% healthy people colonized
viral infection of upper respiratory tract
compromised pulmonary function/alcoholism
increased incidence over 50 years old
impaired immunity (sickle cell anemia, splenectomy, granulocytopenia)
males at greater risk
serotype
8
Q
Streptococcus pneumoniae:
Other Infections
A
upper respiratory -otitis media -mastoiditis -sinusitis extrapulmonary -meningitis -septic arthritis -endocarditis
9
Q
Streptococcus pneumoniae:
Pathogenesis
A
- organism colonizes pharynx
- gains access to lung (aspiration)
- bacteria move into alveoli
- bacteria multiply in edematous fluid
- exudate spills into bronchioles
- inflammatory response; air displaced
- centrifugally spreading lesion
- resolution or death
10
Q
Streptococcus pneumoniae: Virulence Factors (Polysaccharide Capsule)
A
anti-phagocytic (blocks C3b deposition)
absolute requirement for virulence
highly antigenic but variable (90 serotypes)
antibody provides type-specific protective immunity
11
Q
Streptococcus pneumoniae: Virulence Factors (Pneumolysin)
A
membrane-bound toxin (pore forming)
mutation in gene increases lethal dose in animal models
target may be pulmonary endothelium
12
Q
Streptococcus pneumoniae: Virulence Factors (Neuraminidase)
A
cleaves sialic acid in mucin, glycolipids, glycoproteins
13
Q
Streptococcus pneumoniae: Virulence Factors (Choline-Binding Proteins)
A
facilitates
- colonization of nasopharynx
- sepsis
14
Q
Streptococcus pneumoniae:
Laboratory Identification
A
alpha-hemolytic on blood agar
catalase negative
latex bead agglutination
15
Q
Streptococcus pyogenes:
Characteristics
A
‘Group A Strep’
-based on cell wall carbohydrate composition
causes majority of all streptococcal diseases
-normal flora in 5-10% of healthy humans
beta-hemolysis on blood agar
-two hemolysins; streptolysin O and S
-no hemolysis under aerobic conditions if no S
facultative anaerobe
16
Q
Streptococcus pyogenes:
Extracellular Virulence Factors
Streptolysin O
A
pore forming cytotoxin; lyses WBCs
antigenic: antibodies can be quantitated
17
Q
Streptococcus pyogenes:
Extracellular Virulence Factors
Streptolysin S
A
cell-associated and cell-free
leukocidal activity and other cells
18
Q
Streptococcus pyogenes:
Extracellular Virulence Factors
Pyrogenic Exotoxins
A
family of 9 proteins; ‘SPEs’
superantigenic properties
may enhance invasion
primary determinant of Scarlet fever and TSST
19
Q
Streptococcus pyogenes:
Extracellular Virulence Factors
Complement Protease
A
C5a peptide
disrupts chemotaxis of phagocytes
20
Q
Streptococcus pyogenes:
Extracellular Virulence Factors
Streptokinase
A
dissolves fibrin clots
21
Q
Acute Group A Strep Diseases:
Pharyngitis
A
‘strep throat’
- most common cause in kids 5-15
- very contagious- large aerosol droplets
- fomites are not a factor in transmission
- asymptomatic carrier state (<1%)
- bacteria persists 1-4 weeks post-symptomatic stage of disease
- complications: peritonsillar abscesses; scarlet fever; cervical adenitis; otitis media; TSST
22
Q
Acute Group A Strep Diseases:
Impetigo
A
different M serotype than respiratory strain
associated with insect bites
fomites are factor
23
Q
Acute Group A Strep Diseases:
Wound and Puerperal Infections
A
not very common
24
Q
Acute Group A Strep Diseases:
Streptococcal Toxic Shock-Like Syndrome
A
SPEs involved 'flesh eating' Group A Streptococcus soft tissue invasion; multi-organ involvement necrotizing fasciitis and myositis extremely rapid course
25
Non-Suppurative Sequelae:
| Rheumatic Fever
after throat infection
autoimmune mechanism
-cross-reactivity between anti-M abs and heart tissue
26
Non-Suppurative Sequelae:
| Acute Glomerulonephritis
- after throat or skin infection
| - renal injury due to deposition of antigen-Ab complexes in glomeruli
27
Group A Strep Lab ID
```
beta-hemolytic on blood agar
catalase negative
latex agglutination
PYR- pyrrolidonyl arylamidase
-test positive
bacitracin
-96-99% of strains sensitive
```
28
Treatment:
| Streptococcal pneumonia
```
penicillin drug of choice
vancomycin for resistant strains
vaccine available
-capsule from 23 most common serotypes
-recommended for >65 years, immunocompromised, chronic heart/liver/kidney conditions
```
29
Treatment:
| Group A Streptococcal Infections
penicillin or penicillinase-resistant antibiotic if mixed infection (Staph)
30
Group B Streptococcus:
| GBS
exp. S. agalactiae
first isolated from bovine mastitis
this and E. coli are most common causes of neonatal meningitis
normal flora of the gut
31
Group B Streptococcus:
| Mother to Infant Transmission
- 50% of offspring of colonized mothers will be affected
| - of those, 2% experience early onset sepsis, pneumonia, or meningitis
32
GBS:
| General
late onset, sometimes 1-3 months
risk factors: premature birth, ruptured amniotic membrane
transplancental IgG is protective
33
GBS:
| Virulence Factors
```
Capsule-Polysaccharide
-sialic acid moeity binds factor H in serum
*facilitates degradation of C3b
Component Protease
-C5a peptidase
-disrupts PMN chemotaxis
```
34
GBS:
| Virulence Factors - Blr
expressed by some GBS strains
'LRR' protein (leucine-rich-repeats)
structurally similar to internalin A-type proteins
'buried' under under the GBS capsule (in vitro)
likely functions as an adhesin
35
GBS Diseases:
| Neonatal Sepsis
fever, lethargy
CNS involvement, 5-10% of cases
20% mortality
36
GBS Diseases:
| Adults
uncommon
peripartum chorioamnionitis/ bacteremia
pneumonia, skin, soft tissue infections
37
GBS:
| Lab Identification
```
beta-hemolytic
bacitracin resistant
CAMP test
-hemolytic zone when cross streaked with S. aureus
-CAMP factor: cytolysin
serogroup typing
```
38
GBS Diseases:
| Therapeutics
```
antibiotics
-same as group A
-beta-lactam+aminoglycoside (synergy)
screen for GBS colonization
-third trimester
-prophylaxis during labor
vaccine under development
```
39
Viridans Streptococci
```
alpha-hemolytic streptococci
-many different species
normal flora-mouth, nasopharynx, URT
not typable by carbohydrate antigens
typically don't cause disease
-lack identifiable virulence determinants
-possible adhesins: glucans, other sugars
-low virulence species exist
```
40
Viridans Streptococci:
| Diseaes - Endocarditis
```
S. sanguis, S. salivarius
colonization of valves
subacute- slow progression (weeks/months)
responds well to penicillin
fatal if untreated
```
41
Viridans Streptococci:
| Diseases - Dental Infections
S. mutans
adherence+colonization= plaque formation
-pellicle: film of salivary macromolecules
42
Viridans Streptococci:
| Diseases - Dental Caries
progressive destruction of enamel --> pulp
- glycolytic end product: organic acids
* dietary monosaccharides/disaccharides
* bacterial polyglycans synth. from sucrose
43
Viridans Streptococci:
| Diseases - Gingivitis/Periodontitis
inflammation of the gums
resorption of bone and ligament
-tooth support lost
44
Group D Streptococci
```
Enterococcus spp., S. bovis, S. equinus
intestinal commensals
may be alpha, beta, gamma hemolytic
no virulence factors
-Enterococcus can kill nematode elegans
```
45
Group D:
| Diseases
- urinary tract infections
- wound and soft tissue infections
- 10-15% of all nosocomial UTIs, intra-abdominal infections and bacteremia
- pneumonia is rare
46
Group D:
| Bacteremia
most common type of strep sepsis in adults
often follows GI tract infection or manipulation
serious sequelae is endocarditis
-10-20% of all bacterial endocarditis
47
Group D;
| Treatment of Infections
- most Enterococcus spp. are resistant to penicillin
- combined antibiotics sometimes effective
- E. faecalis endocarditis is very difficult to treat
* imipenum/ciprofloxacin may be effective
48
Group D:
| Lab Identification
```
bacitracin resistant
hydrolysis of bile-esculin
-growth in 40% bile
-esculin--> esculetin
Enterococcus spp. can grow in 6.5% NaCl
-Group D Streptococcal spp. cannot
```
49
E. coli:
| History
```
1885
-Theodore Escherich isolates from infant feces
1884
-Gaffkey isolates the 'typhoid' bacillus
1898
-Kiyoshi Shiga isolate agent of bacillary dysentery
1903
-soluble toxin of one Shigella
1900-1915
-periodic epidemics of typhoid fever in NYC
1970's
-E. coli toxins characterized
```
50
Enteric Intestinal Infections:
| Watery Diarrhea
large volume, no white cells, fever, vomiting
| proximal small intestine
51
Enteric Intestinal Infections:
| Dysentery (Inflammatory Diarrhea)
small volume stools, blood, pus, fever, tenesmus
| colon is primary target
52
```
Enteric Intestinal Infections:
Enteric Fever (Systemic)
```
origin is GI tract- small bowel
| spread to biliary tract; liver; other RE organs
53
Enteric Diseases:
| Gastritis and Peptic Ulcers
Helicobacter pylori
can be asymptomatic for decades
can lead to gastric adenocarcinoma
54
Enteric Diseases:
| Extraintestinal (Opportunistic)
```
UTIs
gram negative species
meningitis
wound infections
pneumonia
```
55
Pathogenesis of Enteric Infections
```
CNS infections
entry via contaminated device
-inhalation, surgical site, ect.
bloodstream infections
entry via IV catheter/fluids
pneumonias
colonization of colon; perineum; urethra
UTIs
entry via urinary catheter
```
56
Laboratory Analysis
```
primary isolation media
-MacConkey (+lactose)
-enrichment broth, Salmonella/ Shigella
ID of isolate
-sugar fermentation, citrate
-metabolic end products (indole; ammonia)
Serotyping: agglutination w/ anti-sera
-O somatic antigen: polysaccharide LPS sidechain
-H antigen: flagella (heat liable)
capsule
```
57
Pathogenic Escherichia coli
```
produce intestinal/extraintestinal diseases
5 classes of 'diarrheagenic'
-Enterotoxigenic (ETEC)
-Enteropathogenic (EPEC)
-Enteroinvasive (EIEC)
-Enterohemorrhagic (EHEC)
-Enteroaggregative (EAEC)
evolved from commensal
grouped by serotype: O and H carbohydrates
```
58
Enterotoxigenic E. coli:
| ETEC
causes acute secretory diarrhea
-high volume fluid/electrolyte secretion into lumen
-no leukocytes, no blood
'traveler's' diarrhea, 'deli-belly', 'Montezuma's Revenge'
major cause of diarrhea in children in developing countries
transmitted by fecal contamination of food/water
59
```
ETEC Virulence Factors:
Colonization Pili (Fimbriae)
```
colonization factor antigens (CFAs)
associated with certain serotypes
can vary morphologically
60
ETEC Virulence Factors:
| Heat Labile Toxin (LT)
immunologically cross-reactive with cholera toxin
ADP ribosyltransferase
-activates adenylate cyclase--> cAMP
-mediated through modification of G protein of the membrane-bound cyclase complex
61
ETEC Virulence Factors:
| Heat Stabile Toxin 1
ST-I
low molecular weight protein
same mechanism as LT (different receptor)
-activates guanylate cyclase--> cGMP
62
ETEC Virulence Factors:
| Heat Stabile Toxin 2
ST-II
about 3x larger than ST-I
unknown mechanism of action
-might be similar to ST-I, different receptor
63
ETEC Virulence Factors
in most strains of ETEC, the CFAs and toxins are plasmid-encoded
64
ETEC:
| Treatment
improved sanitation is key!
bottled water for travelers/military
infection may provide protective immunity
-secretory IgA primary component
antibiotics may shorten duration of illness
65
ETEC:
| Prevention
licensed vaccines
- formalin-killed whole cell (oral) + CT b-subunit
* protection from immunity to CFA;s
- oral live-attenuated
* ACE527: three recombinant strains
* Phase I clinical trials completed
* human volunteer challenge study
66
Enteropathogenic E. coli:
| EPEC
- produces acute or chronic diarrhea in infants-up to 14 days; rare in adults
- accounts for diarrhea in up to 20% bottle-fed infants < 1 year old
- adults can be carriers; fecal-oral transmission
- fomites are a factor in nursery outbreaks
- watery stool; no blood; white cells
- forms 'attaching and effacing' lesions through alteration of target cell actin filaments
67
EPEC:
| Virulence Factors
```
encoded from large pathogenicity 'island'
bundle forming pili (BFP)
-plasmid-encoded adhesins
-not required for A/E lesion formation
intimin
-adhesin
-required for A/E lesion formation
exported secretion proteins (Esps)
-enzymatic ('effector') virulence proteins
-translocated into host target by TTSS
```
68
Enteroinvasive E. coli:
| EIEC
produces dysentery IDENTICAL to Shigellosis
-low volume, bloody stools; neutrophils
large virulence plasmid
-IDENTICAL to Shigella spp.
-encodes virulence proteins which induce invasion of non-phagocytic cells (epithelial)
-proteins which facilitate cell-cell spreading
world-wide distribution; developing countries
-common in kids
-person-person transmission; fecal-oral
69
Enterohemorrhagic E. coli (EHEC):
| Diseases
```
mild diarrhea
hemorrhagic colitis
-copious bloody diarrhea; no white cells
-severe abdominal cramping; no fever
-non-invasive
hemolytic uremic syndrome (HUS)
```
70
EHEC:
| Pathogenesis
A/E cytophathalogy identical to EPEC
has intimin and other similar secreted proteins
tropism different: colonic (EPEC is small bowel)
-long polar (LP) fimbrial and 'curli' adhesins
71
EHEC:
| Serotype O157:H7
```
associated with the most outbreaks
extremely low infectious dose (100-200 cells)
farm animals are carriers
contaminated food (or water)
-undercooked hamburger biggest culprit
-veggies and fruits also a source
```
72
EHEC:
| Virulence/Prevention
key virulence factor is Shiga toxin
-correlates with severity of diarrhea and HUS
vaccines are under development
73
EHEC:
| Disease Spectrum
mild diarrhea/hemorrhagic colitis
- abdominal pain
- no fever
- bloody diarrhea
- few PMNs in stools
74
EHEC:
| HUS
hemolytic uremic syndrome
- microangiopathic hemolytic anemia
- thrombocytopenia
- glomerular thrombosis
75
Enteroaggregative E. coli:
| EAEC
produces acute/chronic diarrhea in children
pathogenic mechanisms unclear
-produce a 'stacked brick' adherence pattern
76
EAEC:
| Virulence Factors
encoded on medium molecular weight plasmid
at least two different pili
at least two toxins: ST-like, LT-like
AspU- unknown function
77
Diarrheagenic E. coli:
| Laboratory Identification
Lac + (except EIEC)
serotyping -includes detection of toxin
DNA probes -virulence loci (toxins, ect.)
O157:H7 -SMAC
78
Treatment:
| ETEC, EIEC, EPEC
antibiotics may shorten duration
79
Treatment:
| EHEC
antibiotics do not alter course of HUS
-may actually enhance disease
supportive: fluid management
hemodialysis; hemopheresis
80
Uropathogenic E. coli:
| UPEC
```
commensals of the urinary tract
infections caused by
-minor trauma
-sexual intercourse
-catheterization
-prostate enlargement
-diseases (<10 serotypes)
*cystitis, pylonephritis, prostatitis
```
81
Cystitis
dysurea; frequency; urgency
| -hematuria (50%)/ turbid urine
82
Pylonephritis
flank pain; fever
| -leading cause of GNS
83
Prostatitis
lower back, perirectal, testicular pain
| -chronic form is leading cause of recurrent bacteruria in males
84
UPEC:
| Virulence Factors
alpha-hemolysin
p pili
type 1 pili
85
UPEC:
| P Pili
- primary adhesin w/affinity for uroepithelial receptor (digalactoside)
- facilitates ascending colonization/infection
86
UPEC:
| Type 1 Pili
somatic (common) pili
- ubiquitous surface structure of enterics
- difficult to express in vitro
- mannose-resistant hemmagglutination
- may be involved in colonization of the perineum and bladder
87
UPEC:
| Treatment
bacterial loads variable
-higher counts favor ascending infection (pyelonephritis)
-presence of pathogen and symptoms diagnostic
empiric treatment is common
-antibiotic sensitivity profiling recommended
-different antibiotics effective alone/in combination
-recurrent infections may be benefited by long-term, low-dose chemoprophylaxis
88
Shigella:
| Species/Serogroups
A: S. dysenteriae; rare in US; most severe
B: S. flexneri; native americans; developing countries
C: S. boydii; rare
D: S. sonnei; most common in US; developing countries
-very closely related to E. coli
-NOT normal gut flora
89
Shigella:
| Diseases
wide range: asymptomatic to bloody diarrhea
| HUS is a complication (Shiga toxin)
90
Shigella:
| Pathogenesis
transit through stomach (refractory to low pH)
transient multiplication in small intestine
invasion of colonic epithelium
cell to cell spread
91
Shigella:
| Gross Pathology
```
jejunum
-electrolyte/fluid loss
colon
-invasion of epithelium
-colitis
-electrolyte/fluid loss
```
92
Shigella:
| Cellular Pathology
1) release from dead cells into lamina propria and reinvasion through basolateral surface of epithelial cells
2) direct passage between cells w/o exposure to extracellular environment
- bacteria-generated protrusions
93
Shigella Virulence:
| Most on Large Virulence Plasmid
```
(identical in EIEC)
invasion plasmid antigens (IPAs A-D)
-induce phagocytosis in epithelial cells
-transported by a TTSS - mxi/spa genes
VirG: facilitates intercellular spread
```
94
Shigella Virulence:
| Chromosomal Determinants
```
Luc: aerobactin
-iron scavenging (siderophore)
Stx: Shiga toxin
-inhibits host protein synthesis
-binds to vascular endothelium
-expression induced by low Fe++
```
95
Shigella:
| Epidemiology...
```
no animal reservoirs
food, flies, feces, fomites
infectious dose only 10-100 organisms
17,000-30,000 cases in US a year
risk factors: 1-4 years age, poor sanitation and crowding
self-limiting, no treatment
```
96
Salmonella Diseases:
| Enteric Fever
inc. period 7-20 days
weeks duration
early constipation, then bloody diarrhea
97
Salmonella Diseases:
| Septicemia-Compromised CMI
inc. period variable; variable duration
no GI symptoms
may include 'metastatic' infection
98
Salmonella Diseases:
| Enterocolitis
inc. period 1-2 days
2-5 day duration
vomiting, diarrhea
99
Salmonella:
| Overview
only one species (S. enterica)
- sub species based on O, H, K serotypes
- typhi, typhimurium, choleraesuis, parathyphi (A/B), enteriditis
100
Salmonella:
| Groups
thyphoidal: S. typhi, S. parathyhi
-human primary host, fecal-oral
non-typhoidal: all others
-reptiles, birds, mammals
-animal fecal-human oral
101
Salmonella Virulence Factors:
| Encoded Pathogenicity Islands
virulence 'effectors' and secretion accessory proteins
| TTSS involved
102
Salmonella Virulence Factors:
| Cryptic Plasmid
large, in S. typhi
- required for virulence; gene functions unknown
- DNA homology w/ large plasmid of Yersinia pestis
103
Salmonella Virulence Factors:
| Vi Capsule
N-actyl galactosaminuronic acid
- inhibits complement-mediated lysis/chemotaxis
- antibodies against capsule protective
104
Salmonella Epidemiology:
| Typhoidal
```
-infectious dose = 10000 (low end)
humans sole reservoir
many asymptomatic carriers
persists in gall bladder
major cause of morbidity and mortality in developing countries
```
105
Salmonella Epidemiology:
| Non-Typhoidal
poultry, poultry products primary source
| 50,000 cases a year in US
106
Salmonella:
| Treatment
```
enterocolitis
-fluid/electrolyte replacement
-antibiotics not required
typhoid fever
-chloroamphenicol/ampicillin
-cephalosporins and fluoroquinolones
licensed vaccine available for typhoid
-Ty21a, live-attenuated, oral
animal vaccines for non-typhoidal strains
```
107
Yersinia Species
-Y. pestis: not GI, clonal to Y. pseudotuberculosis
-Y. enerocolitica:GI pathogen
-Y. pseudotuberculosis: GI pathogen
disease vie feces-contaminated food/water
facultative anaerobes; prefer room temp, motile
108
Yersiniae Diseases:
| Enterocolitis
mainly caused by Y. enterocolitica
| fever, diarrhea, blood and white blood cells in stool
109
Yersiniae Diseases:
| Reiter's Syndrome
'aseptic polyarthritis'
| can occur weeks to months after diarrhea
110
Yersiniae Diseases:
| Septicemia
rare
111
Yersiniae Diseases:
| Mesenteric Adenitis
mimics appendicitis
fever, lower right quadrant pain, enlarged lymph nodes
Y. pseudotuberculosis or Y. enterocolitica
112
Yersinia:
| Pathogenesis
- invasion on epithelial cells, intestinal M cells initial target
- can replicate within and destroy macrophages
- lymphotropic: can penetrate ileal mucosa to lymph nodes
- numerous virulence determinants: chromosomal and plasmid-mediated
113
Yersinia Virulence Factors:
| Chromosomal
Inv
Ail
-required for invasion
114
Yersinia Virulence Factors:
| Plasmid-Encoded
'75 kb pLcr'
low calcium response (LCR) genes
expression up-regulated by high temp and low calcium
gene products
115
Yersinia Virulence Factors:
| Yersinia Outer Proteins Effectors
enzymatic activity
- YopE
- YopH
- YopJ
- YopM
- YopN
- YpkA
- YadA (YopA)
- LcrV
116
Yersinia Virulence Factors:
| Yersinia Outer Proteins Translocators
part of a TTSS, numerous components
- Syc's: Yop effector chaperones
- YopB and YopD: docking complex
- YscC: injectisome
- YscF: injectisome
- others: injectisome
117
Yersinia Virulence Factors:
| LcrV = V Antigen
also encoded on the Lcr plasmid (pLcr)
mutants of LcrC are avirulent
required for translocation of YOP effectors into target cells
binds TLR-2 and CD-14 --> increases IL-10
binds TLR-4 --> apoptotic cascade
118
Yersinia Epidemiology and Treatment
Y. enterocolitica endemic in Europe
infections usually self-limiting
-septicemia treated w/aminoglycosides
experimental oral vaccines
119
Cholera History
1563- first outbreak described (India)
1817- first cholera pandemic
1854- mode of disease transmission identified
1883- Koch isolates etiologic agent
120
Vibrionaceae:
| Overview
'comma-shaped' rods, ferment glucose, abundant in marine and surface waters
V. cholerae O139 and O1
-endemic and pandemic cholera
V. cholerae Non-O
-diarrhea and extraintestinal infections
V. parahaemolyticus
-gastroenteritis and extraintestinal infections
other Vibrio species
-ear, wound, soft tissue, extraintestinal
121
V. cholerae
actively motile- single polar flagellum
grows well in high salt/high pH
oxidase positive
strain classification
-O1: 2 biotypes- classical, El Tor; 3 sub-types: Ogawa, Inaba, Hikojima
-O139: 'endemic' possesses a polysaccharide capsule
-O2-O138: diarrheagenic; CT-
122
El Tor
spreads at higher rate
longer post-infection carriage
longer extra-intestinal survival
123
Cholera
acute diarrheal disease
-primary effect from entertoxin CT
-non-invasive
-spectrum: asymptomatic to 'cholera gravis'
1-4 days incubation, high infectious dose
nausea, vomiting, 'rice-water' stool
-rapid fluid/electrolyte loss (1L/hr)
-death in 1-4 days due to dehydration, acidosis, shock
124
V. Cholerae Virulence Factors:
| Fimbriae
toxin co-regulated pili (Tcp)
| -facilitates colonization of small bowel
125
```
V. Cholerae Virulence Factors:
Cholera Toxin (CT)
```
```
heat labile, phage-encoded
A-B subunit structure
-binds GM1 ganglioside
-ADP-rebosylation of GTP binding protein
-increase cAMP--> increase fluid/electrolytes
25 ug purified CT = 20 L fluid loss
```
126
Cholera:
| Epidemiology
```
seven pandemics since 1817
-El Tor cause of latest
kids 2-9 years greatest risk
-no age bias in previously 'sterile' area
risk to travelers in endemic countries
endemic in US gulf coast
```
127
Cholera:
| Treatment
```
oral rehydration therapy (ORT)
intravenous fluid and electrolytes
antibiotics (tetracycline)
-shortens duration
prevention
-water sanitation
-no licensed vaccine available
```
128
Vibrio parahaemolyticus
disease: acute watery diarrhea; severe cramping; vomiting
-short incubation: 15 hours
pathogenesis: unclear, possibly toxigenic
epidemiology
-endemic in coastal waters; world-wide
-undercooked/raw seafood primary source
-very common in Japan
-U.S. outbreaks associated with shellfish
129
Vibrio Vulnificus
diseases: gastroenteritis; wound infections; bacteremia
raw oysters primary source in U.S.
possess high-affinity siderophores
-scavenge iron from lactoferrin and transferrin
higher risk host: alcoholics, iron overload disorders
130
Campylobacter Species
```
gram negative tiny 'gull-shaped' rods
microaerophilic; oxidase positive
motile- polar flagella
gut commensal in many animals
most common cause of bacterial diarrhea
-particularly in humans
```
131
C. jejuni Diseases:
| Enteritis
diarrhea, abdominal pain, fever
- stools loose, watery to dysentery-like (blood, fecal leakocytes)
- 2-4 days incubation, 5-8 days duration
- bacteremia in 1% GI infections
132
C. jejuni Diseases:
| Reiter's Syndrome
reactive arthritis
133
C. jejuni Diseases:
| Guillain Barre Syndrome (GBS)
demyelination disorder (neuromuscular paralysis)
40% have infection prior to onset of GBS symptoms
cross-reactive anti-LPS antibodies
134
Campylobacter Pathogenesis
passage through stomach
colonize upper small bowel
colon ultimate target
-invasive but remain vacuolated
135
Campylobacter:
| Virulence Factors
cytolethal distending toxin (CDT)
-arrests host cells in G2 growth phase
flagella and pili
others?
136
Camopylobacter:
| Epidemiology and Diagnosis
```
2 million cases in US
developing countries
-undercooked poultry, unpasteurized mile
special selective medium
-vancomycin, polymyxin B, trimethoprim, cephalothin
42 degrees decrease oxygen, increase CO2
stool cults positive after 48-72 hours
treatment: antibiotics reduce duration
```
137
Helicobacter pylori
```
formerly 'Campylobacter'
first isolated in 1980's
motile, spiral shaped, microaerophilic
ureases positive
cause of >90% of peptic ulcers
-early link controversial
-possible cause of duodenal ulcers
-source of infection unclear
risk factor for gastric carcinoma
```
138
Chronic Atrophic Gastritis
'CagA'
protein secreted into target epithelial cell by type IV secretion system
interacts with/inhibits SH2 phosphatase
disrupts receptor tyrosine kinase sig. pathways
-actin skeleton rearragnement
-loss of tight junction integrity
-loss of cell differentiation
-polarity, adhesion, migration inhibition
139
Helicobacter pylori:
| Epidemiology and Diagnosis
over 80% of children in developing countries colonized
-<20% in industrialized contries
large asymptomatic population
biopsy and culture of gastric mucosa
-incubated at 37 degrees
-urease detected directly from gastric fluids
serological tests: serum IggG and salivary IgA
140
Helicobacter pylori:
| Treatment
- bismuth subsalicylate + amoxycellin + metronidazole for at least 14 days
- H2 receptor antagonists (Zantac)
- do not cure, only relieve symptoms
141
Chlamydia:
| General Characteristics
```
obligate intracellular bacterium
(doesn't grow in artificial media)
contains DNA, RNA, 'normal' ribosomes
small genome
gram negative envelope (no peptidoglycan)
susceptible to antibiotics (in vivo)
harbors plasmids and phages
```
142
Chlamydia:
| Species
C. pneumonia: respiratory
C. psittaci: respiratory
C. trachomatis --> VD
trachoma
-serovars: A, B, Ba, C (cause trachoma)
-serovars: D-K (STD, urethritis, cervicitis)
lymphogranuloma venereum (LGV, urethritis, cervicitis)
143
Chlamydia:
| Elementary Body
```
small, dense
.25 uM
extracellular (infectious)
not fragile
not metabolically active
outer membrane proteins cross-linked
```
144
Chlamydia:
| Reticulate Body
```
large, homogeneous
0.6-1.0 uM
intracellular (replicative)
fragile
metabolic activity
outer membrane proteins not cross-linked
```
145
Chlamydia Pathogenesis
direct cytopathic effects
-invasion/inhibition of phagolysosomal fusion (apoptosis is inhibited)
-infected host cells vacuolate and degenerate
-De-ciliation of epithelia
-disruption of processing and packaging functions of secretory cells
immune pathology
-acute and chronic inflammation
-tissue damage: conjunctival scarring, ect.
146
Chlamydia Virulence Factors:
| Adhesins
major outer membrane protein (MOMP)
| heparin sulfate-like glucosaminoglycan (GAG)
147
Chlamydia Virulence Factors:
| Heat Shock Protein
Hsp70
| inflammatory responses
148
Chlamydia Virulence Factors:
| Cysteine-Rich Protein (CRP)
functionally equivalent to peptidoglycan
| facilitates intracellular replication and extracellular survival
149
Chlamydia psittaci:
| Psittacosis
```
'ornithosis'
primary atypical pneumonia
-bilateral interstitial pneumonia
-fever, headache, myalgia, dry couch
-occasional systemic complications
inhalation of respiratory secretions/ droppings of infected birds
zoonotic infection
-increased risk to poultry workers and pet bird owners
```
150
Chlamydia pneumonia:
| Walking Pneumonia
pharyngitis/LRT involvement w/persistent cough
clinically similar to Mycoplasma pneumoniae
human-to-human transmission via respiratory droplets
6-10% of hospital cases of pneumonia
40% of population had antibodies by 19 years
151
Chlamydia pneumonia:
| Associated w/ Coronary Heart Disease
detection of microorganism in lesions
serologic evidence
unknown cause-effect linkage
152
Chlamydia trachomatis:
| Trachoma
```
(serovars A, B, Ba, C)
conjunctival innoculum
-self-limiting or chronic infection
-pannus -superficial vascularization of cornea
-secondary infection/blindness
leading cause of preventable blindness
endemic in developing countries
problem in US Appalachia, reservations
```
153
Chlamydia trachomatis:
| Inclusion Conjunctivitis
(sero's D-K)
resembles trachoma but no pannus
copious mucopurulent discharge
newborns and adults
154
Chlamydia trachomatis:
| STDs
(serovars D-K and L1-L3)
| will include neonatal infection associated with STD's
155
Chlamydia:
| Diagnosis
growth in cell culture expensive and slow
serology: >4 fold rise in titer is positive
staining/detection of intracellular inclusion bodies
-specimens from eye or genital tract
-inclusions contain glycogen
immunofluorescence of infected tissue
156
Chlamydia:
| Detection with DNA
PCR
nucleic acid hybridization
reliability --> questionable
157
Chlamydia:
| Treatment
```
Trachoma:
-antibiotics at early stage of infection
-surgical intervention for ocular damage
-no immunity to re-infection
Psittacosis and Pneumonia:
-tetracycline and erythromycin
```
158
Neiserria Species
gram negative diplococci
many species non-pathogenic
-commensals of URT in humans
-N. gonorrhea, N. meningitidis transient flora w/o causing disease, pathogenic
159
Meningitis Species by Age:
| <1 Month Old
group B streptococci
E. coli
Lesteria monocytogenes
160
Meningitis Species by Age:
| 1-23 Months
S. pneumoniae
| N. meningitidis
161
Meningitis Species by Age:
| 2-18 Years
N. meningitidis
| S. pneumoniae
162
Meningitis Species by Age:
| 19-59 Year
S. pneumoniae
| N. meningitidis
163
Meningitis Species by Age:
| 60 Years and Up
S. pneumoniae
| L. monocytogenes
164
Neiserria:
| Characteristics
non-motile, non-spore-forming
aerobic, oxidase positive, fastidious
pathogens: don't grow at 22 degrees or on agar w/o blood, does produce CO2
non-pathogenic: grows at 22 degrees and on agar w/o blood, doesn't produce CO2
165
N. meningitidis Virulence Factors:
| Polysaccharide Capsule
```
absent on gonococcus
anti-phagocytic
13 serogroups
-group-specific antibody is protective
-group A associated with epidemics
-group B, C, and Y most common
antigen present in blood and CSF in severe infections
```
166
N. meningitidis Virulence Factors:
| LPS (LOS)
immune evasion
-structure mimics host sphingolipids found in brain
O-side chains integrate host sialic acid to inhibit complement deposition
167
N. meningitidis Virulence Factors:
| Outer membrane Proteins
'Opa' (Opacity) proteins
-may facilitate invasion
sub-divide the serogroiups
antibodies to these proteins are bactericidal
168
N. meningitidis Virulence Factors:
| Pili
adherence to nasopharyngeal epithelium
| bind CD46 glycoprotein on host cells
169
N. meningitidis Virulence Factors:
| Pili and Opa
'high level antigenic variation'
multiple gene copies
pili
-positioned downstream of different promoters by recombination 'on' (pilE) or 'off' (pilS
-pili w/ altered function, incomplete pili,ect.
opa's
-'on' or 'off' via translational frame shift in mRNA
-different combinations of proteins expressed under different conditions
170
N. meningitidis:
| Pathogenesis
pathogenesis different than gonococcus
-meningitis (ability to cross blood-brain barrier)
-toxic septicemia
possesses eight unique pathogenicity islands in its chromosome
-'region 8' required for bacteremia: encodes a siderophore receptor and a disulfide oxidoreductase
171
N. meningitidis Disease Spectrum:
| Asymptomatic Carrier State
5-25% of population (higher in closed population)
reservoir for disease
carrier state enhances immunity
172
N. meningitidis Disease Spectrum:
| Meningococcemia
```
'bacteremia'
may have cutaneous manifestations
Water-Friedrichsen syndrome
meningitis- mortality 85% w/o treatment
chronic form: associated w/ complement deficiency
```
173
N. meningitidis:
| Histopathogenesis
mucosal colonization by bacteria
bacterial invasion of and survival within bloodstream
penetration of blood-brain barrier and into CSF
local release of inflammatory cytokines in CSF
adhesion of leukocytes to brain endothelium and diapedesis into CSF
exudation of albumin through opened intercellular junctions of meningeal venules
brain, edema, increased intracranial pressure, altered cerebral blood flow
cranial nerve injury, seizures, hypoxic-ischemic brain damage, herniation
174
N. meningitidis:
| Epidemiology
```
spread human to human
asymptomatic carrier focus of infection
seasonal variation
-highest attack rate in late Winter, early Spring
age
-incidence greatest 6 months to 3 years
-correlates w/decline of maternal antibody and acquired immunity
5000,000 cases/yr
-world wide distribution, sporadic in US
```
175
N. meningitidis:
| Lab ID and Treatment
gram stain is presumptive from CSF or blood
culture on blood/chocolate, 37 degrees + 5% CO2
-can use Thayer-Martin if normal flora present
latex agglutination for capsule serotype
penicillin G drug of choice, resistance rare
rifampin, minocycline, sulfonamides used to eliminate pharyngeal carriers
176
N. meningitidis:
| Prevention
acquired immunity with age
-exposed by transient colonization w/ different capsular serogroups
vaccines available
-mixed capsular prep: A, C, Y, W-135 (not effective if under 2 years)
-serogroup B vaccine in clinical trials (outer membrane vesicles, intranasal administration)
