GI infections – Flashcards
Unlock all answers in this set
Unlock answersinfectious agent in the stomach? |
Helicobacter pylori |
infectious agents of the small intestine? |
Vibrio Cholerae E. Coli (ETEC) Salmonella Enteritidis Salmonella typhi Camplobacter jejuni Yersinia enterocolitica
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what are the infectious agents that live in the large intestines? |
Shigella dysenteriae E. Coli (EHEC) Vibrio parhaemolyticus Clostridium difficile |
Infectious agents that lead to intoxication only? |
clostridium perfringens Staphylococcus aureus Clostridium botulinum bacillus cereus |
enteric gram-negative bacilli |
Vibrio Campylobacter Helicobacter |
Heliobacter pylori |
Shape: slender, spirally curved rods
Type: Gram negative
Location/Habitat: human stomach mucosa (normal flora or disease)
Transmission: fecal-oral transmission (food or water-borne transmission)
Clinical manifestations: chronic gastritis and peptic ulcer dz; bacterial use flagella to invade and move below the epithelium; urease releases ammonium and protect the bacteria; colonization is most often asymptomatic, but some people develop an intense inflamm. response that leads to gastritis and peptid ulcer dz = associated with development of GASTRIC CANCER
Distinctive Properties: flagella (allows penetration into gastri mucus layer); CagA protein (kills cells and stimulates inflammation); adhesions
Exotoxins and exoenzymes: urease (neutralizes gastric acids and helps it get to base), acid-inhibitory protein, mucinase, and VacA cytotoxin (induces cell death in epithelial cells)
Diagnosis: gastric biopsies; serology; breath test and blood test; fecal antigen test
Treatment: best tx is sequential/combinational treatment with rabeprazole (proton pump inhibitor) and amoxicillin (for 5 days), THEN rabeprazole+clarithromycin+tinidazole (5 days)
Prevention: no vaccine
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epidemiology of H. pylori |
by age 50, approx. 40% of Americans will be colonized.
A person who is colonized has a 10% chance of developing ulcers
*** Under-developed countries have higher colonization rates, but they have lower disease rates! |
Clinical manifestations/pathology of H. pylori |
after ingestion, the bacteria use their flagella to move beneath the mucin layer and attach to the gastric epithelium. --> the production of urease releases AMMONIA and protects the bacteria from the acidic pH --> colonization is often ASYMPTOMATIC, but some individuals develop and intense inflammatory response that leads to gastritis and ulcer formation
vacuolating cytotoxin seems to play significant role in the inflammation
chronic gastritis is associated with development of gastric cancer!! |
CagA protein |
H. Pylori infection
surface complex injects THIS protein into host cells, killing the cell (needle-like structure injects this protein into host cell)
it is not present in all strains, but it is associated with the more VIRULENT strains
stimulates INFLAMMATION |
urease |
neutralizes gastric acids (because rxn leads to ammonia production = neutralization)
stimulates neutrophil and monocyte chemotaxis
helps H. pylori invade and tolerate the acidic environment |
VacA (vacuolating) cytotoxin |
induces vacuolation and cell death in epithelial cells stimulates inflammation (neutrophil migration) |
13C-urea --> 13CO2 tests |
diagnosis of H. pylori
formerly used breath test (less sensitive0
now use it as a blood test other methods of diagnosing H. Pylori: serology (tells you past or present infection); and fecal (stool) antigens test |
what is helicobacter similar to? |
Campylobacter, which is still more distant taxonomically to Vibrio and E. coli |
what is Vibrio most closely related to? |
E. Coli and the other enterobacteriaceae
(campylobacter and helicobacter are more distant) |
shape of Listeria? |
small gram-positive coccobacilli - short rods
NO SPORES |
organisms that live in soil-plant environments |
Listeria Bacillus Clostridium |
Listeria monocytogenes |
Shape: small coccobacilli, short rods
Type: Gram positive
Location/Habitat: widespread in nature; soil-plant environments; considered normal flora in domestic animals; in animal feces
Transmission: contaminated commercially-prepared food (remember: they are facultative anaerobes and are psychrophilic); humans must ingest; often spread through animal feces, so may be considered zoonotic; transplacental transmission from mother to fetus
Clinical manifestations: 1) Ingestion of L. monocytogenes in food 2) replication in intestinal epithelial cells with invasion into submcosa 3) replication in macrophages in submucosa 4) asymptomatic to flu-like symptoms, nausea, vomiting 5) bloodstream invasion with spread to meninges (immunocompromised or very young) (replication in macrophages) 6) Transplacental spread to developing fetus with septicemia and meningitis (replication in macrophages)
Distinctive Properties: beta-hemolysis due to listeriolysin (lyses phagosome membrane so that organism can get into macrophage cytoplasm and replicate); ActA (actin polymerization on one end of bacterium; intracell. movement)
Diagnosis: 1) monocytosis in peripheral blood and CSF (remember: elevation in MONOCYTES and not neutrophils) 2) Gram stain of CSF 3) Culture of CSF, blood = definitive (blood agar) 4) early detection is rare, esp. when you have asymptomatic individuals
Treatment: ampicillin, TMP-SMX, high-dose penicillion, erythromycin (in immunocomp., elderly, neonates)
it is CEPHALOSPORIN resistant!!!!
Prevention: 1) no vaccine 2) limit those types of foods in pregnant women and the immunocompromised 3) strict adherence to standard pathogen control programs in food industry 4) new products to kill the Listeria in the food (i.e. bacteriophage Intralytix that kills only the listeria) |
listeriolysin |
Listeria Monocytogenes
this enzyme couses β-hemolysis in blood agar
it lyses the phagosomal membrane and allows the pathogen to escape the phagosome and enter cytoplasm of macrophages
Remember: L. monocytogenes doesn't like to kill the macrophage, it just wants to get into the cytoplasm so it can replicate |
ActA |
found in Listeria monocytogenes leads to actin polymerization ON ONE END of the bacterium = intracellular movement similar process in Shigella, but Shigella is in epithelial cells spreads from cell to cell without ever exiting into the extracellular environment |
Epidemiology of Listeria monocytogenes |
major concern in the food industry outbreaks associated with: milk, cheeses, hot dogs, luncheon meats, fresh vegetables, smoked fish products READY TO EAT FOODS significant increase in hospilitization rates disease depends on dose, age, and immune status |
Listeria disease in Healthy adults |
usually asumptomatic or mild flu-like diarrheal illness ; incubation period = 1-2 days - appears to be shorter with invasive disease ; symptoms associated with eating a large dose of Listeria ; most common form of disease, but the least recognized ; referred to as listeria gastroenteritis (b/c intestinal manifestation part of presentation ; *** fever, headache, nausea, vomiting ; rarely diagnosed without multiple cases |
Listeria disease in immunocompromised, elderly adults, and neonates |
severe invasive disease ; incubation period typically 2-3 weeks and from eating a SMALL dose ; may be preceded by flu-like GI symptoms ; blood stream invasion = septicemia, encephalitis, meningitis ; AIDS patients are 300x more likely to get invasive listeriosis |
Listeriosis in pregnant women and the fetus |
mild to severe invasive disease ; pregnant women have 20x higher risk of infection ; similar flu-like disease as other healthy adults ; bloodstream invasion (non systemic symptoms in mother) ; TRANSPLACENTAL TRANSMISSION TO FETUS ; *** rarely a problem for the mother, but serious problem for the fetus: 1) first trimester spontaneous abortions 2) stillbirth or seriously ill newborn 3) third trimester - may cause premature delivery |
bacteria transmitted transplacentally and cause infection in utero |
Listeria monocytogenes - listeriosis ; Treponema pallidum - congenital syphilis ; Borrelia burgdorferi - Lyme disease |
Listeriosis in Neonates |
*** Severe invasive disease - meningitis ; 1) Early onset (;2days postpartum) = acquired transplacentally; septicemia, pneumonia, meningitis; granulomas; 80% mortality rate ; 2) Late onset (1-2 weeks postpartum) = acquired at or soon after birth (not sure from where: birth canal or transmission from other babies); blood stream invasion = meningitis; good evidence for hosptial acquired infections |
What antibiotic is Listeria resistant to? |
cephalosporin |
spore forming bacteria? |
anaerobic: Clostridium aerobic: Bacillus |
Clostridium perfringens |
Shape: spore forming rods; large non-motile with square, "box-car" ends ; Spores: subterminal spores; do not form spores in clinical specimens (in vitro or in tissue); they do sporulate in the intestines and in some foods ; Type: anaerobic Gram-positive ; Location/Habitat: soil; intestinal tract of humans and animals; isolated from intestinal tract and female genital tract ; Transmission: 1) Traumatic infections: a) exogenous: contamination with dirt/dust b) endogenous: escape of intestinal bacteria (stabbing and gunshot wounds) ; 2) non-traumatic infections: ENDOGENOUS, simultaneous or idiopathic; spreads from intestinal tract WITHOUT OBVIOUS TRAUMA ; ; Clinical manifestations: 1) Anaerobic cellulitis - traumatic or non-traumatic; Remember: ***localized to dead tissue, with little invasion of healthy tissue *** lots of gas production *** little alpha-toxin production * common in patients with diabetes and/or poor circulation ; 2) Myonecrosis - gas gangrene; traumatic or simultaneous *** major alpha-toxin production; necrotizing invasion of healhty muscle *** gas formation *** may progress to bloodstream invasion, septicemia, intravascular hemolysis - fatal ; ; ; Distinctive Properties: moderate anaerobes (more aerotolerant than C. tetani, for example); common in soil, intestinal tract of humans and animals; large nonmotile rod with square, "box-car" ends; subterminal spores (sporulate in intestines and in some foods); large amounts of gas production during growth (CO2 + H2 plus foul smelling volatile amines such as putrescine and cadaverine); produces several lethal toxins (but only a few have definitive roles in disease); C. perfringens in 80-90% of clostridial infections ; Toxins: responsible for serious disease in humans and animals; strain typing based on toxinc profiles for ;,;,;,;-toxins ; Diagnosis:; rapid diagnosis is crucial; Lab: Anaerobic culture (24 hrs) - Look for beta-hemolysis (double zone: alpha-toxin and theta-toxin); gram stain ; Treatment:; debridement of necrotic tissue; ancillary measure - high doeses of penicillin; hyperbaric oxygen (alos effective against MRSA and invasive asperillgus); wound dressing with charcol for bad smell ; ;Prevention: no vaccine; treat wounds to preven infection ; Enterotoxin:; 3rd most common cause of food poisoning (but these strains are uncommon); requires ingestion of contaminated food (esp. gravy, stews, and meat products) - they contain mixture of the organism and the preformed enterotoxin - -; LEADS to DIARRHEA and fever (look at another slide) ; |
different exotoxins lead to different diseases. What are they? |
neurotoxic: 1) botulism (C. botulinum) 2) tetanus (C. tetani) ; histotoxic: 1) gas gangrene (C. perfringens, novyi, C. septicum, C. histolyticum, others) 2) pseudomembranous colitis (C. difficile) ; enterotoxic: food poisoning (C. perfringens) |
;-toxin (alpha toxin) |
C. perfringens =phospholipase C (lecithinase) - most important toxin in humans!! ; ; ; ; ; ; ; ; ; ; ; ; beta hemolytic rxn in blood agar ; Nagler rxn on egg yolk agar ; Widespread tissue destruction |
;-toxin (theta toxin) |
C. perfringens produced by most strains (human and animal)
; oxygen-labile hemolysin called perfringolysin O-in humans ; similar to tetanolysin (C. tetani) and streptolysin O (S. pyogenes) ; kills and lyses phagocytic cells |
Enterotoxin |
C. perfringens ; may be produced by all toxin-type strains FOOD POISONING Fluid secretion, diarrhea ; (1-5% of all type A strains produce this toxin) |
Transmission of C. perfringens |
1) Traumatic infections: a) exogenous: most common as contamination of a wound with dirt/dust from environment b) endogenous: escape of intestinal bacteria to other body sites following trauma (stabbing and gunshot wounds) ; 2) non-traumatic infections: ENDOGENOUS, simultaneous or idiopathic; spreads from intestinal tract to tissue, peritoneal cavity, and bloodstream WITHOUT OBVIOUS TRAUMA |
Epidemiology of C. perfringens |
1) traumatic infections: typical trauma includes surgery, compound fractures, motor vehicle crashes, pressure sores, thermal or electrical burns, frostbite, injection of illicit drugs ; (studies of war wounds show that 90% of contaminated wounds contain clostridial organisms, but only 2% develop disease) ; 2) Non-traumatic infections: associated with over or occult malignancy (colorectal or hematologic); ***frequently mixed infections with C. perfringens, C. septicum, C. novyi *mortality rates approaching 100% |
Compare and contrast anaerobic cellulitis and myonecrosis |
[image] |
enterotoxin in C. perfringens |
3rd most common cause of food poisoning (but these strains are uncommon); ; requires ingestion of contaminated food (esp. gravy, stews, and meat products) - they contain mixture of the organism and the preformed enterotoxin - -; LEADS to DIARRHEA ; Can also be formed in SMALL BOWEL; noninvasive - incubation period is wide: 8-16 hours - shorter period: if large amount of toxin is ingested - longer period: if bacteria is ingested and toxin is produced in intestines ; Diarrhea with fever, rare vomiting - SHORT DURATION |
Clostridium difficile |
Shape: longer and thinner rods ; Type: Gram positive; spore forming ; Spores: sporulate well in INTESTINES ; Location/Habitat: normal flora, but can be acquired during hospitalization; found in soil, water, and intestines of various animals ; Transmission: 1) Classical Dz: overgrowth of normal flora, but may be recent acquisition (from another person or the environement); induced by antibiotic treatment; person-environment-person transmission (rectal thermometers) ; 2) Severe dz: new anti-biotic resistance - person-to-person (via fecal contamination containing cells or spores); person-environment-person transmission (rectal thermometers) ; Clinical manifestations: adherence to mucosa, growth, and toxin production IN COLON; mild to severe diarrhea; severe inflammation with destruction of colonic epithelial cells; ***yellow pseudomembrane in colon; ulceration of colon ; Distinctive Properties: Toxin A and Toxin B - lead to fluid secretion, inflammation, and cell death.; New NAP1 severe strains produce 20x more of these toxins; non-toxigenic C. diff (used prophetically); binary toxin (highly associated with NAP1 strains that cause more severe disease) ; Diagnosis: clinical presentation of diarrhea; yellow pseudomembrane on colonoscopy; C. diff antigen detection in stool sample (includes antigen detection of toxins A;B and glutamate dehydrogenase (GDH); Xpert C difficile PCR ; Treatment: metronidazole, vancomycin, fidaxomicin; re-establish normal flora via probiotics and fecal transplantation and non-toxigenic C. diff ; Prevention: no vaccine; non-toxigenic C. diff; WASH YOUR HANDS (gels don't work as well) |
Toxin A and Toxin B |
Clostridium difficile
A= enterotoxin; B= cytotoxin
mechanism of action on intestinal epithelial cells
Covalent glycosylation of RhoGTPase = interferes with intracellular signaling:
Toxin B is 100x more cytotoxic than A (but can be avirulent) |
NAP1 |
Clostridium difficile
SEVERE STRAINS produce 20x more of A and B toxins
This is a hypertoxin |
NTCD |
non-toxigenic C. difficile
isolated from diarrhea along with toxigenic C difficile
it is just normal flora
now use it prophylactically |
Binary toxin |
C. difficile
highly associated with NAP1 strains that cause more severe disease
has 2 components
actin-specific ADP ribosyltransferase toxin
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C. diff transmission induced by antibiotic treatment very commonly related to . . .? |
1) Very commonly related:
clindamycin, ampicillin/amoxicillin, cephalosporins, fluroquinolones
(especially new severe NAP1 strains) |
C. diff transmission is less commonly related to . . .? |
2) other penicillins, TMP-SMX, cotrimoxazol, macrolides
3) uncommonly related to: vancomycin, metronidazole (these are the two often used for treatment) |
Classical C diff disease |
Nosocomial diarrhea to severe, fatal, diarrhea, and colitis
Susceptible populations: 1) recent antimicrobial use (look at transmission) 2) length of stay (in healthcare facility) 3) Increasing age (primarily older people - ave. 60 yr) 4) serious underlying illness
Primarily in hospitalized patients, undergoing antibiotic theraby (antibiotic-associated) |
Severe C diff disease |
new-antibiotic resistant - nocosmial or community-acquired diarrhea
increased cases with: 1) increased severity (higher mortality) 2) fluroquinolone resistance 3) higher amounts of A and B toxin production 4) new toxin not found in classical strains
2003 increased cases in Quebec hospitals
isolated outbreaks in US and around the world with this new increased severity (high toxin producers), antibiotic resistance patterns (single epidemic strain -B1/NAP/027)
Community associated cases now observed (20% of total, half with no prior antibiotic use and in younger populations
another risk factor: proton pump inhibitors (omeprazole and esomeprazole) |
Human members of the reovirus family |
Genus orthoreovirus Genus rotavirus Genus coltivirus |
Orthoreovirus genus? |
respiratory- enteric- orphan virus Three antigenic serotypes transmitted by respiratory and fecal- oral routes Infections are asymptomatic and not important for disease (also called orphan - - without disease) |
Coltivirus genus |
named for Colorodo tick fever virus
arbovirus transmitted by ticks |
Rotavirus |
2 shells: Naked outer icosahedral and inner icosahedral capsid
Segmented, double stranded RNA genome = this segmented genome allows for reassortment
Associated with viral RNA dependent RNA polymerase
Multiple genotypes/serotypes
Transmitted by the fecal oral route (which is most important), but also transmitted by vomit |
what is the importance of the segmented genome of Rotavirus?? |
segmented genomes allow for "genome reassortment" within cells infected with 2 distinct strains
Repeated infections = greater immunity
also allows for production of "live"-oral reassortant vaccines based upon naturally-attenuated animal rotavirus and important human serotypes of rotavirus |
what age groups are most affected by rotavirus? but norovirus? |
R= little children, especially those under 5 years of age
N= everyone else |
lab analysis of Rotavirus?? |
antigen-capture ELISA of a FECAL specimen
usually done on infants who present to the ER with severe dehydration during the virus' peak time |
speculated pathogenesis of Rotavirus? |
virus infects cells at the villus tip and then spreads quickly --> viral particles get released into lumen --> infected cells are damaged and lost and immature cells have reduced absorptive capacity = fluid accumulation in lumen = DIARRHEA another theory: non structural protein 4 is an enterotoxin that affect Ca2+ homeostasis |
Rotavirus vaccines!!! |
reassortant virus isolate containing 10 bovine virus dsRNA segments plus 1 human virus segment
encodes for either the major outer capsid protein : G1,G2, G3, G4 or for one major P protein serotype
bovine vaccine is safe; rhesus rotavirus vaccine was associated with greater rates of intussusception |
RotaTeq® |
pentavalent "live" vaccine for rota virus
3 doses
perviously licensed rheusus-human tetravalent reassortant vaccine was removed after rare intussusception complications |
Rotarix® |
live attenuated vaccine, containing a single attenuated human rotavirus with the major G1 serotype
2 doses (admission) |
other causes of viral gastroenteritis |
noroviruses - no evidence of compound immunity - genus is caliciviridae; it is major cause of viral fastroeneritis in older children and adults astroviruses - less severe dz in infants and young children (less severe than rota) adenoviruses: serotypes 40,41, and 31 - replicate in GI tract (but minor cause of dz in infants) enteroviruses (ex: polio) - members of genus Picornaviridae - rarely symptomatic because of lytic infection in small intestine, but can cause some symptoms in infants (they replicate in the GI, but usually asymptomatic) |
norovirus |
major infectious cause of FOODBORNE ILLNESS OUTBREAKS, but associated with less mortality and morbidity it is environmentally stable - virons are resistant to inactivation by chlorine and heating compared to other naked icoshedral viruses multiple genotypes/serotypes with lack of long lasting immunity typical incubation period = 24-48 hrs predominant symptom : acute onset EMISIS other symptoms: watery, non-bloody diarrhea
occurs ALL YEAR LONG
tx: replace fluids (no specific antiviral)
no routine lab assays/diagnosis, but use RT-PCR for ID in epidemilogical studies or use electron microscopy
NO LISCENCED VACCINE |
general features of the enterobacteriaceae |
enteric gram-negative bacilli; gram-negative rods
found widely distributed on plants, in soil, and in the intestines of animals and humans
rapid growth under both aerobic and anaerobic conditions
differentiation based on fermentation of various carbohydrates (ALL SPECIES FERMENT GLUCOSE) can be motile (flagella) or nonmotile associated with many different types of human infections, including: intestinal, urinary, respiratory, wound, bloodstream, and meningeal infections They are the major cause of NOSOCOMIAL INFECTIONS |
all enterobac. ferment what?? |
GLUCOSE |
enterobact. pathogens |
major pathogens: Escherichia, Shigella, Salmonella
Opportunistic pathogens: Klebsiella, Proteus, Enterobacter, Serratia, Providencia, others |
bacteria that are rapid lactose fermenters? |
Escherichia, others (coliforms) |
lactose non-fermenters |
Shigella
salmonella |
antigenic analysis (serotyping) |
O-antigen: somatic antigen (carbohydrate repeat of LPS)
H-antigen: flagella (if present)
K-antigen: polysaccharide capsule (if present)
fimbriae (may have more than one type - not for serotyping)
(these are virulence factors, but they are also used for serotyping) |
Escherichia coli |
Shape: bacilli, rods
Type: Gram negative
Location/Habitat:
Transmission:
Clinical manifestations:
Distinctive Properties:
Diagnosis:
Treatment:
Prevention:
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