febrile invasive diarrhea Flashcards
most communicable bacterial diarrheal agent
Shigella
Shigella
what color on MacConkey?
G- bacilli, non-motile non-lactose fermenting (non-coliform):
white on MacConkey agar
Shigella: extra or intracellular?
intracellular: can invade and multiply in colonic epi cells–>cause inflammatory dis. of large bowel
Shigella diarrhea or dysentery?
either or both
Shigella: four species groups
S. dysenteriae Group A (most sev.)
S. flexneri, Group B
S. boydii, Group C
S. sonnei, Group D (least severe)
in US Shigella most common affects ??
what S. spp in US??
kiddos (1-4yo)
all age groups are susceptible
S. sonnei (D) and S. flexneri (B)
Shigella reservoir
carry org how long after recovery?
only humans
1 mo
Shig: low or high inf. dose?
transmitted how?
low (10^2)
secondary attack rate is high
fecal-oral route, direct person-person, vehicles (food and water), and mech. vectors (flies)
-so basically anything, sneaky Shigella
Shigella assoc. with age/gender/season
kiddos 1-4
no gender or season assoc.
Shig risk factor
poor personal hygiene
Shigella is a biphasic descending illness:
cause bacteremia?
diarrhea followed by dysentery
does NOT cause bacteremia
after ingested, Shig orgs reach ?? where they initially multiply and ?? which does what ??
small bowel
release toxin which stimulates active secretion of water and e-lytes from jejunum
Shig proceeds to the ?? where it invades/penetrate via the ?? then moves cell-cell going on to multiply in the ??
colon
penetrates via follicle associated M cells
mucosal epi cells (enterocytes) (facultative IC)
Shigella in the enterocytes results in ??
inflammatory response, bleeding, sloughing of cells, formation of abscess and ulcers
what type of Shig can cause HUS
S. dysenteriae type 1
Shig virulence factors is dependent on ??
temp reg
prod. >=37 degrees
Shig virulence factors: enterotoxins
ShET1 and ShET2
Shig virulence factors: surface Ags
induce “parasite directed” endocytosis into M cells and spread btw epi cells
Shig virulence factors: OspE proteins:
how do they increase bac. cell-to-cell spreading and promote colonization?
highly conserved among EHEC, EPEC, and Salmonella
reinforce host cell adherence to basement mem by interacting with integrin-linked kinase (ILK) –>which suppresses epi detachment
Shig vir factors: Shiga toxins (Stx)
only what Shig species?
cytotoxins
only S. dysenteriae type 1
Shig Stx acts at level of ?? causing ??
can also ??
60S ribosome causing irreversible inactivation of EF-1 and INF-y
activate apoptosis in macros (think EHEC and STEC)
Shig presentation
triad of sev. dysentery
variable: mod diarrhea to sev. dysentery:
triad of cramps, tenesmus (painful straining), and frequent small volume bloody mucoid discharge
Shig onset?
initial symptoms ??? for this spp ???
incubation for 24-72 hrs (1-3 days)
fever, systemic manifestations, cramps, vomiting, diarrhea (watery) for S. sonnei (most common in US)
Shig dysentery after initial symptoms characterized by ??
sev. cramps most common in ??
blood, mucus, PMNs in stool
fever, cramps tenesmus
kiddos and oldies
Shig causes daily loss of ?? which can result in ??
serum protein (200-300 mL) in feces–>depletion of nitrogen stores–>malnutrition, growth stunting
complications of Shig
long term carrier state!
reactive arthritis
HUS
autoimmune disease
reactive arthritis most common in ind. with ??
presents how??
what occurs ??
HLA-B27
polyarthritis: mild–>severe, may last days
polyclonal B cell activation
HUS occurs in Shig due to ?? only produced by ??
triad??
shiga toxin (Stx) S. dysenteriae, type 1 triad: microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure
Shig immunity
spp. specific
can turn off host prod. of anti-bacterial peptides
Shig dx
pres?
in feces?
bloody, mucoid stools and fever
fecal leukocytes, PMNs, and RBCs
Shig dx
Cx?
serology?
need selective media (MacConkey-white)
done to ID spp
Shig dx: ??? can be useful in ddx bacillary dysentery from amoebic dysentery
sigmoidoscopic examination
bacillary: diffuse ulcer pattern
amoebic: focal ulcers
Shig ddx
Salmonella, yersinia, EIEC, campylobacteria, amoebia
less common: EHEC and C. diff
basically all other agents of febrile diarrhea
Shig ddx EIEC: how similar?
sim. pathogenesis, virulence factors, disease manifestations
Shig vs. amebic dysentery: see ??? but no ??? with amebic
RBCs and trophozites but few if any PMNs
Shig tx
consider abx for it will ?? and ??
BUT
fluid replacement
reduce disease duration from 5-7 days to 3 days
AND eliminate carrier state
BUT abx resistants (plasmid-mediated) is a problem
Shig prevention
wash yo hands!
community recognition, participation, education on hand washing, esp for kiddos
vaccine in development
commonalities of Campy, Yersi, Salmonella
G- (only Campy ox +)
zoonosis
all invasive and can cause a bacteremia: Salm>Yersi>Campy(worst!)
virulence factor for invasiveness of Campy, Yersi, Salmonella
outer membrane component
Campy, Yersi, Salmonella are all
facultative IC pathogens in macrophages
dx Campy, Yersi, Salmonella via
if fever??
Cx and micro.examination of feces for fecal leukocytes
if fever, blood cx
Campy, Yersi, Salmonella tx
supportive unless substantive fever–>means extra intestinal disease (systemic?) so give abx
complications of Campy, Yersi, Salmonella ??
reactive polyarthritis assoc. w. HLA B27 and pseudoappendicitis Yersi>Campy>Salm (like Shig!)
Campylobacter jejuni
G- ox positive curved motile rod
Campy found in
chickens, other birds, dogs, livestock, etc
Campy infection causes
temp specificities?
diarrhea, dysentery or both
also assoc. with jejunal lesions and extra intestinal infections (bacteremia-it’s invasive!)
grows well at 42 deg. C under reduced O2 tension (microaerophilic) w. selective abx
?? used to be the leading cause of bacterial diarrheal disease ww, passed up by Salmonella
Campy
2 mil/yr in US
Campy reservoir
low or high infectious dose??
transmitted how?
risks
GIT of birds, domestic fowl, swine, cattle, sheep, dogs, etc
low infectious dose (800)
NOT usually person-person but via transmission from food sources, contaminated water
raw mild and undercooked chicken OR fecal contaminated foods
Campy age/gender/season assoc.
no age/gender
peaks in summer
Campy injures both the ???
lesions show an ??
isolates produce ??
–>resulting in ??
sm and large intestine
acute exudative and hemorrhagic inflammation
an enterotoxin and/or a cytotoxin (Stx)
diarrhea and/or dysentery
Campy virulence factors
enterotoxin: heat-labile (like LT of ETEC or CT of cholera)-seen in some strains from ppl w. acute secretory diarrhea
cytotoxin: Stx–>ulceration of mucosa
invasion factor
cytolethal distending toxin (CDT)
Campy invasion factor:??? proteins which are secreted through ?? upon contact with eukaryotic cell
Cia (Campy invasion Ags) secreted thru flagella filament
Campy invasion factor mechanism
disrupts epi cell tight junctions
allows cells to replicated IC in macros and induce apoptosis
triggers activation of NF-kB and MAPK signaling pathways
Campy Cytolethal distending toxin
mechanism?
(CDT): tripartite AB toxin where dtA and CdtC comprise the binding components and CdtB is the active subunit
CdtB is transported to the nucleus–>induces double stranded breaks in DNA and arrests the cell in G2 phase
-may play a role in malignancy
Campy immunity
Ab mediated
Campy disease often has a ??
prodrome:
fever (12-24 hrs before diarrhea) ha, myalgia, malaise
Campy onset??
most common presentation??
1-7 days
enteritis with diarrhea: loose, may be watery, may have dysentery
malaise, fever, abdominal pain (cramping)
is Campy self-limiting?
yes, improvement in several days
may also see ?? in Campy
which persists for ??
acute colitis: fever, tenesmus, sev. dysentery, sev. abd. cramps
1 wk
may also see ?? which can get bad enough to mimic ??
caused by ??
mesenteric LAD–>severe acute LRQ pain, can mimic appendicitis
Yersi>Campy>Salmy
caused by org getting to LN and causing sev. inflammation
Campy can also have extra intestinal manifests:
bacteremia
reactive arthritis in HLA-B27 peeps
Autoimmune manifests of Campy
what else can cause it?
Guillain-Barre: acute polyradiculoneuritis; AI attack on peripheral nerve myelin
Campy chief instigator–>sev. axonal form
also CMV, EBV, HIV and vaccinia virus
Pen 19, O:19, Lior 11, Lau 19 and 3/25
how Campy causes Guillain-Barre
LPS antigenic ally resembles human gangliosides Gm1 and GD1a
anti-Gm1 Abs–>cause symptoms
Campy jejuni assoc. with this malignancy
immunoproliferative small intestine disease (IPSID), a form of MALT lymphoma
responds to abx
recurrent acute Campy triggers
IBD
may carry/excrete Campy after recovery for ??
life-long??
2-3 wks
life-long in animals,
dx Campy: unique pres. features and labs
prodrome and fever
motile curved rods in feces and sea-gull shapes
+fecal leuks and RBCs
Cx feces at 42d C under microaerophilic conditions
Campy ddx
all febrile diarrhea/dysentery orgs
Campy tx
Erythromycin or other macrolide abx
and aminoglycosides
both are protein-synthesis inhibitors
Yersinia enterocolitica
G- non-coliform (white on MacConkey), motile, bipolar staining (safety pin) coccobacillus
>50 serotypes, 5 biotypes
Yersi is ?? so can multiply in ??
facultative IC, can multiply in epi cells and macros
Yersi causes ??
important cause of ??
diarrhea, mesenteric LAD, systemic disease with local abscesses
pseudoappendicitis
Yersi temp range
optimal: 22-29 C, can grow from 0-42
Yersi found in …
GIT of wild and domestic animals
agent of sporadic outbreaks
Yersi: low or high infectious dose ??
transmitted how??
high: 10^9
BUT person-person still happens
most common vehicles: milk, milk products, canned meat, meat products, blood transfusions
Yersi age/gender/season
kiddos
no gender pref.
WINTER! (think Swedes?)
Yersi virulence: orgs invade via the ???
and establish residence in ??
may extend to ??
M cells of Peyer’s patch
reticuloendothelial tissue, in LP, and muscular is mucosa
mesenteric LNs–>flamed and ulcerated nodes
complication of Yersi invasion
bacteremia, intestinal perf and peritonitis
Yersi virulence expression controlled by 2 feedback loops
temp and Ca2+
Step 1. Yersi org enters body in food/drink only produces ?? and ??
invasin: adhesion which binds to B1 integrin and induces endocytosis
ST-like enterotoxin (ETEC-guanylate cyclase)
Step 2. at 37d C synthesis of ??? stops and
synthesis of ?? begins
invasion and ST-like toxin
proteins which mediate resistance to complement-mediated killing
Step 2.2. ?? are also synthesized but only when low levels of ??
mechanism ??
other activity ??
YOPS: yersi outer membrane proteins
low levels of Ca2+
YOPS inhib. phago, INF-y activity, and macro. respiratory burst
have tyrosine phosphatase activity, mediate contact-dependent cytotoxic activity that depolymerizes actin microfilament network of target cell
Yersi onset?
presentation ??
4-7 days
fever, abd pain, vomiting, diarrhea
sev. Yersi presentations (age groups?)
fever, acute ileitis, leukocytosis (older children, adolescents)
enterocolitis (kiddos
Yersi post-inf. complications
reactive arthritis in HLA-B27’s, erythema nodosum
extraintestinal infections: high serum iron–>poor px
Yersi carriage/shedding for how long ??
weeks
Yersi Cx
requires special medium and cold enrichment
Yersi ddx
febrile diarrhea/dysentery agents
Yersi tx
maintain fluid/e-lyte balance
aminoglycosides, TMP-SMX
Salmonella serotypes highly adapted to humans
S. typhi (prototype-typhoid fever)
S. paratyphi
S. sendai
-no known reservoir outside humans
Salmonella highly adapted to specific non-human hosts
S. cholerasuis (pigs)
-can cause inf. in humans but uncommon
Salmo w. broad host range
most in this category, cause most human and nonhuman disease: S. enteritidis, S. typhimurium- “Enteritidis” Group
Salmonella is a ??
G- rod,
non-lactose fermenting (non-coliform- white on MacConkey)
facultative anaerobe, non-fastidious, non-spore forming
Salmonella is a ?? which can multiply in ??
facultative IC pathogen, multiply in macros and intestinal epi cells
is Salmo motile or non-motile?
motile, has H Ag (flagella)
>2000 serotypes based on O and H Ags
Salmonella peaks in what age groups
6 mos to 5 yrs
Salmo reservoir??
high or low infectious dose??
transmitted how??
fowl (eggs), swine, cattle, dogs, sheep, cats, turtles, rodents (NOT S. typhi)
high infectious dose: 10^5-10^9 orgs
typically ingestion of food/water
human-human has happened: closed pops, daycare, oral-anal
Salmonella may be carried for how long??
infants may shed for how long ??
5 wks
5-12 mos
Salmonella seasonality
summer/fall
Salmonella risk factors
why in industrialized countries?
other risk factors ?? may present w/ ??
use of PPIs
institutionalization
industrialized countries: bulk food processing, feed additives, food packaging/preservation, infection of chicken oviducts
Ca, AIDs, raw milk, DM, abx therapy–>may present with bacteremia
diarrhea induced in Salmonella as org ??
what virulence factor involved ??
travels thru small and large intestine via activation of adenyl cyclase–>inc. cAMP
enterotoxin, like LT toxin
Salmonella colonizes the ??? and invades the ?? (via inducing phagocytosis); invades both ?? and ??
virulence factor involved?? mechanism ?
ileum and cecum, mucosa
M cells and epi cells
Surface adhesion proteins: Type III secret. system (TTSSs) injects effector proteins into host cells
3 pathogenicity islands? result in cell apoptosis, necrosis, and excretion of IL-8
Salmonella causes ?? via what virulence factor ??
induces ??
acute inflammation via IC multiplication/prod. of Stx
release of inflamm. cytokines that cause intestinal damage (in addition to cytotoxin)–>see RBC and PMNs/macros in feces
cytokines also elicit systemic symptoms of fever, chills, and. pain
(this inflammation also contribute to diarrhea/dysentery)
orgs that have Stx (Shiga toxin)
Shigella dysenteriae (no shit)
EHEC, STEC, EIEC, EAEC
Campy
Salmonella
Salmonella causes systemic disease via this virulence factor ??
how does it spread ??
can cause??
LPS
spreads to mesenteric LNs–>then circulation–>bacteremia/endotoxic shock–>into macros (facult. IC)
causes pseudoappendicitis
what is required for Salmonella immunity/control??
CMI
Salmonella onset??
presentation??
duration ??
may affect who more severely?
12-48 hr incubation, abrupt onset
fever, chills abd. cramps, diarrhea, ha, vomiting
2-3 days normally
infants, oldies, impaired CMI
Salmonella complications
reactive arthritis in HLA-B27s, bacteremia,
pseudoappendicitis
reactive arthritis (HLA-B27s) is a complication in these infections
STEC, etc Shigella Campy Yersi Salmonella
Salmonella dx microscopic
fecal leuks and macrophages more than PMNs
FAT (fluorescent Ab test)
Salmonella dx Cx
do: feces, water, food, blood (if fever)
enhancement, selective and ddx media
serological confirmation and typing reportable
Salmonella dx
agents of febrile diarrhea/dysentery
Salmonella tx
maintain fluid/e-lyte balance
abx NOT recommended for uncomp. gastroenteritis
how to prev. salmonella
cook foods containing eggs all the way
febrile invasive food-borne agents
Vibrio parahaemolyticus, V. vulnificus
Balantidiasis coli
Vibrio parahaem. and V. vulnificus
ox +, halophilic curved rods (sim to V. cholera)
V. para normally inhabits ??
US outbreaks relate to ???
high or low dose ??
season ??
2 major outbreaks occurred where ??
marine waters- animals
eating seafood shrimp
high infectious dose 10^5-10^7
summer mos
on cruise ships
V. para can be ?? and cause ??
via what virulence factor ??
invasive and cause systemic disease
LT-like toxin
V. para onset ??
presentation ??
what typ. observed ??
> 14 hrs
diarrhea and/or dysentery, cramps, N/V and 1/3rd are bacteremic
leukocytosis
V. para dx: microscopy
direc microscopic examination of diarrheic stool:
curved rods, feca. leuks, RBCs
V. para dx: Cx
isolate feces/vomit org on high NaCl media
virulent strains are Kanagawa positive and produce beta hemolysis on human blood agar
V. para dx
any febrile diarrhea/dysentery agent assoc. with contact with marine environ.
V. para tx
rehydration
amipicillin and other abx for sev. diarrhea/fever
how to prev. V. para
don’t eat raw seafood, don’t contaminate cooked seafood
V. vulnificus
like V. para in appearance and habitat
is highly invasive
3 syndromes caused by V. vulnificus
leading cause of ??
wound infections (45%)
primary septicemia (43%)
gastroenteritis (5%)
leading cause of seafood assoc. fatalities in US
V. vulnificus sev. progession
necrotic, rapidly progressing lesions–>fulminant sepsis w. 75-90% mortality in at risk individuals (25% normal hosts w. tx)
those at risk for sev. V. vuln disease
DMs, etOHs, liver dysfunctions, hemochromatosis (Fe-overload)
don’t eat raw seafood!
Balantidium coli
ciliated protozoan
largest to infect humans
causes diarrhea/dysentery
Balantidium coli reservoir
pigs!
B. coli is ingested as ?? and migrates to ?? where it develops into ?? which do what ??
cysts, migrate to large intestine, cecum, terminal ileum
trophozoites which replicate via binary fission and conjugation while consuming bacteria
B. coli trophozoites reside primarily within the ?? but may ???
intestinal lumen
may penetrate the mucosa and cause ulcers
B. coli presentation in immunocompetents
otherwise presentation
typ. asymptomatic
bloody, mucoid diarrhea, N/V, abd. pain, anorexia, wl, fever, colitis, dehydration
B. coli dx
wet Sm of stool specimen; see trophozoites: LARGE, ciliary covering, spiraling motility
Balantidium coli tx
volume/e-lyte replacement
tetracyclin or metronidazole
