Vibrio Cholerae

E. Coli (ETEC)

Salmonella Enteritidis

Salmonella typhi

Camplobacter jejuni

Yersinia enterocolitica

Shigella dysenteriae

E. Coli (EHEC)

Vibrio parhaemolyticus

Clostridium difficile

clostridium perfringens

Staphylococcus aureus

Clostridium botulinum

bacillus cereus

Vibrio

Campylobacter

Helicobacter

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

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!

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!!

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

neutralizes gastric acids (because rxn leads to ammonia production = neutralization)

stimulates neutrophil and monocyte chemotaxis

helps H. pylori invade and tolerate the acidic environment

induces vacuolation and cell death in epithelial cells

stimulates inflammation  (neutrophil migration)

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

E. Coli and the other enterobacteriaceae

(campylobacter and helicobacter are more distant)

small gram-positive coccobacilli - short rods

NO SPORES

Listeria

Bacillus

Clostridium

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)

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

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

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

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

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

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

Listeria monocytogenes - listeriosis

Treponema pallidum - congenital syphilis

Borrelia burgdorferi - Lyme disease

*** 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

anaerobic: Clostridium

aerobic: Bacillus

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 α,β,ε,ι-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)

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)

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

C. perfringens

produced by most strains (human and animal)

beta-hemolysis - blood agar

oxygen-labile hemolysin called perfringolysin O-in humans

similar to tetanolysin (C. tetani) and streptolysin O (S. pyogenes)

kills and lyses phagocytic cells

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)

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

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%

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

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)

Clostridium difficile

A= enterotoxin; B= cytotoxin

mechanism of action on intestinal epithelial cells

Covalent glycosylation of RhoGTPase = interferes with intracellular signaling:

• inhibition of actin polymerization
• disruption of tight junction
• increased permeability = fluid loss
• apoptosis
• leads to fluid accumulation, cell death, and inflammation

Toxin B is 100x more cytotoxic than A (but can be avirulent)

Clostridium difficile

SEVERE STRAINS produce 20x more of A and B toxins

This is a hypertoxin

non-toxigenic C. difficile

isolated from diarrhea along with toxigenic C difficile

it is just normal flora

now use it prophylactically

C. difficile

highly associated with NAP1 strains that cause more severe disease

has 2 components

actin-specific ADP ribosyltransferase toxin

1) Very commonly related:

clindamycin, ampicillin/amoxicillin, cephalosporins, fluroquinolones

(especially new severe NAP1 strains)

2) other penicillins, TMP-SMX, cotrimoxazol, macrolides

3) uncommonly related to: vancomycin, metronidazole (these are the two often used for treatment)

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)

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)

named for Colorodo tick fever virus

arbovirus transmitted by ticks

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

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

R= little children, especially those under 5 years of age

N= everyone else

antigen-capture ELISA of a FECAL specimen

usually done on infants who present to the ER with severe dehydration during the virus' peak time

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

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

pentavalent "live" vaccine for rota virus

3 doses

perviously licensed rheusus-human tetravalent reassortant vaccine was removed after rare intussusception complications

live attenuated vaccine, containing a single attenuated human rotavirus with the major G1 serotype

2 doses (admission)

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)

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

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

major pathogens: Escherichia, Shigella, Salmonella

Opportunistic pathogens: Klebsiella, Proteus, Enterobacter, Serratia, Providencia, others

Shigella

salmonella

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)

Shape: bacilli, rods

Type: Gram negative

Location/Habitat:

Transmission:

Clinical manifestations:

Distinctive Properties: 

Diagnosis:

Treatment:

Prevention: