Cross - ID Flashcards
1
Q
What are the 7 causes of inflammatory diarrhea?
A
- EHEC (enterohemorrhagic E. coli)
- EIEC (enteroinvasive)
- Shigella
- Salmonella: enterica and enteritidis
- Campylobacter jejuni
- Clostridium difficile
- Yersinia enterocolitica
2
Q
What are the 6 causes of non-inflammatory diarrhea?
A
- ETEC (enterotoxigenic)
- EAEC (enteroaggregative)
- EPEC (enteropathogenic)
- Vibrio: cholera, parahemolyticus, and vulnificus
- S. aureus
- Bacillus cereus
3
Q
What are th 5 anaerobes?
A
- Bacteroides fragilis
- Prevotella
- Clostridium perfringens
- Tetani
- Botulinum difficile
4
Q
What is the MCC of infectious diarrhea?
A
- 90% of infectious diarrheas are caused by VIRUSES
5
Q
What should you think about when a pt presents with persistent diarrhea (>10-14d)? Chronic?
A
- PERSISTENT: more likely to be a parasite, rather than a bacterial or viral cause
- CHRONIC: start considering HIV status
1. Diarrhea is a big problem with AIDS pts: can get HIV-associated diarrhea w/or w/o other opportunistic infection
2. Mycobacterium avium intracellulare, CMV
6
Q
What are the definitions of acute and chronic diarrhea?
A
- ACUTE: 3 or more loose stools/day lasting <2 wks
- CHRONIC: persists greater than 4 weeks
7
Q
What is inflammatory diarrhea?
A
- BLOODY diarrhea, aka dysentery
1. WBCs and RBCs seen in stool
2. Fever is common
3. Small volume diarrhea
4. Colon is commonly affected, but not always just the colon
8
Q
What is non-inflammatory diarrhea?
A
- WATERY diarrhea
1. No cells in stool
2. Usually afebrile
3. Large volume diarrhea
4. Small intestine is commonly affected
9
Q
What are the general characteristics of Shigella, E. coli, and Salmonella?
A
- G(-), facultative, anaerobic rods
1. Ferment glu w/acid production
2. Oxidase (-)
3. Reduce nitrates to nitrites (dipstick test)
4. Motile (except Shigella) - Antigenic structures used in serotyping: H (flagellar) Ag’s & O Ag’s -> O-side chain (polysaccharide) of LPS
- E. coli are part of normal flora: most do NOT cause disease b/c lack pathogenicity associated island (PAI)
10
Q
What are the 3 types, and transmission of Shigella?
A
- G(-), non-motile, non-lactose fermenting, does not produce H2S
1. S. dysenteriae: Central/S. America epidemics
2. S. sonnei: 70% of US cases (mostly kids)
3. S. flexneri: 2nd most comm in US (most comm worldwide) - Highly transmissible (very low infectious dose) via fecal-oral or contaminated water/food
1. Daycare centers, migrant workers, travelers to developing countries, nursing homes
11
Q
What is the pathogenesis of Shigella?
A
- Resistant to acidic environment of stomach, and taken up by epithelial cells (M cells) in the intestine
- Proliferate IC, escape into lamina propria, and are phagocytosed by macros that then apoptose
- Inflam response damages epi and allows bac to gain access to colonic epi cells -> invasion
- Spreads into adjacent cells via bacterium-induced, membrane-bound protrusions from the surface of the host cell -> formation of these protrusions depends on cellular actin polymerization proteins called formins (F-actin polymerization b/c non-motile bac)
1. Bacterium lyses membranes that surround it, freeing itself into the cytoplasm of the new cell
12
Q
What are the clinical manifestations (and complications) of Shigella? Tx?
A
- CLINICAL: 1-wk incubation period
1. Self-limited diarrhea, fever, & abdominal pain lasting about 1 week
2. Initially watery diarrhea, but progresses to dysentery (bloody) in 50%
3. Some adults will have a subacute course that lasts several weeks (less common) - COMPLICATIONS: reactive arthritis, urethritis, conjunctivitis (Reiter’s)
1. Hemolytic uremic syndrome (HUS) may occur after infection with S. dysenteriae that produces Shiga toxin (AB toxin) - TX: Ceftriaxone, Ciprofloxacin, Azithromycin -> AB’s shorten the course and reduces duration of organism shedding in stools
13
Q
What is unique about Enterohemorrhagic E. coli? Causes?
A
- Aka, STEC: Shiga toxin producing E. coli
1. Produce Shiga-like toxins – clinical symptoms similar to Shigellosis (S. dysenteriae)
2. Hemorrhagic colitis - Can’t ferment sorbitol (can be differentiated from other E. coli)
- Categorized as 0157:H7 and non-0157:H7 (both may cause severe illness)
- Caused by ingesting inadequately cooked meat (hamburgers), contaminated vegetables and milk; also human-to-human
1. Low infectious dose
2. Hospitalization required in 25-50% of patients
14
Q
What are the 2 key pathogenetic mechs of EHEC?
A
- Locus of Enterocyte Effacement (LEE):
1. PAI
2. Type III secretion system that delivers E. coli receptor to host cell
3. Pedestal formation 4 attachment -> attaching and effacing lesion
4. Responsible for the diarrhea - Shiga toxin acts by removing an adenine from large (28S) ribosomal RNA, stopping protein synthesis
15
Q
What is the clinical presentation of EHEC?
A
- Little fever, acute onset cramps, + watery diarrhea
- Diarrhea becomes bloody (hemorrhagic colitis) w/in 24 hours, and lasts up to 8 days (quite a long time)
1. O157:H7 strains more likely to cause large outbreaks, bloody diarrhea, hemolytic uremic syndrome, and ischemic colitis
16
Q
What 2 bacteria can cause HUS? How? Clinical manifestations?
A
- Shigella and more commonly, EHEC (6-9% of EHEC cases -> accounts for >90% of HUS in children)
1. One of the main causes of AKI in children <3 - HOW: shiga toxin absorbed from inflamed GI mucosa into circulation, and alters endo cell function of sm blood vessels and kidney epithelium -> platelet activation and aggregation + damaged RBC’s that are lysed (schistocytes)
- CLINICAL: microangiopathic hemolytic anemia and thrombocytopenia 5-10 days after onset of diarrhea
1. AKI w/dialysis required in >50% pts (most regain kidney function)
2. Neuro sxs (seizures, somnolence): 25%
3. Mortality rate of about 5%
17
Q
How is EHEC diagnosed and treated?
A
- DIAGNOSIS: Sorbitol-MacConkey agar
1. 0157:H7 strain does NOT ferment sorbitol: colonies will be white/translucent (image)
2. Other EHEC/E. coli colonies will be red/pink
3. PCR or ELISA can detect Shiga toxin (in stool) - TX: supportive care + monitoring for complications
1. Avoid anti-diarrheals (INC risk of systemic cxs)
2. AB’s are NOT beneficial, and may predispose to HUS by inducing more Shiga toxin release -> basically CONTRAINDICATED
18
Q
How is EIEC transmitted? Pathogenesis?
A
- Similar to Shigella: causes similar disease
1. NO toxins produced - Transmitted via food/water and person-to-person contact
- PATHOGENESIS: invades intestinal cell, multiplies IC, and extends into adjacent intestinal cells
- Most common in young children in developing countries
19
Q
What are the basics of Salmonella? Subtypes?
A
- G(-) bacilli, non-lactose fermenting, produces H2S (unlike shigella)
- Salmonella enterica serotype Typhimurium (formerly S. typhi) and nontyphoid Salmonella
1. S. enterica is the causative agent of typhoid fever, and does NOT cause gastroenteritis
2. S. paratyphi is another species that can cause illness similar to Typhoid fever (also does NOT cause gastroenteritis)
3. Non-typhoid Salmonella, most commonly S. enteritidis, causes salmonellosis, a significant source of gastroenteritis from food poisoning
20
Q
What are the sources of S. enteritidis?
A
- Dairy products
- Meat
- Poultry and eggs
- Pet turtles, lizards, other reptiles
- Human-to-human
21
Q
What is the pathogenesis of S. enteritidis?
A
- Organisms attach to M cells, and are endocytosed through a complex pathway
1. Virulence genes encode a type III secretion system capable of transferring bacterial proteins into M cells and enterocytes
2. Bacterial proteins trigger endocytosis and allow bacterial growth within endosomes - Bacteria cross basal membrane and enter lamina propria -> inflammatory response occurs
1. S. enteritidis also kills macrophages
22
Q
What is the clinical presentation of Salmonellosis? Dx?
A
- CLINICAL: incubation period 1-3 days
1. N/V, diarrhea (can be bloody), crampy abdominal pain + fever in 50%
2. Illness lasts 3-4 days
3. 5% devo invasive disease: bacteremia, endo-vascular infections, endocarditis, osteomyelitis (SICKLE CELL) -> predilection for aortic plaques, bone prostheses (likes to cling to, infect these)
a. Note: Shigella does NOT do this
4. Can also develop reactive arthritis - DX: routine stool culture
23
Q
What is the tx for Salmonellosis? Who is it indicated for?
A
- Not required for healthy people between 2 and 50 years (self-limited, and will resolve on its own)
- Tx INDICATED FOR those at-risk of disseminated or invasive disease:
1. Immunocompetent patients w/severe infection requiring hospitalization
2. Those w/known or suspected atherosclerotic plaques and endovascular/bone prostheses
3. Immunocompromised (HIV, those on steroids or o/immunosuppressants), sickle cell disease - TX: Flouroquinolones -> susceptibility testing should be performed
24
Q
What is the causative agent of Typhoid fever? Transmission and epi?
A
- CAUSATIVE AGENT: S. enterica serotype Typhi
1. S. paratyphi can cause a similar illness - Humans are sole reservoir; TRANSMISSION occurs person-to-person (fecal-oral, infected food handler) or via contaminated food/water
- EPI: more common in children and young adults than older patients
1. Most prevalent in impoverished, overcrowded areas with poor access to sanitation
2. 80% US cases in travelers to countries where typhoid fever is endemic (South-central Asia)
3. Outbreaks in the U.S. most often foodborne
25
Q
What is the pathogenesis of Typhoid fever?
A
- Orgs taken up by, invade M cells in sm intestine -> bacteria then engulfed by macros in lymphoid tissue
- Can disseminate to lymph nodes and RES (reticuloendothelial system), then spread to blood
1. Sepsis can occur - Proliferate in submucosa -> hypertrophy of Peyer’s patches due to influx of inflammatory cells
1. Hypertrophy + subsequent necrosis of sub-mucosal tissues can cause GI tract perforation - Chronic carriage can occur in the biliary tract
- NOTE: pts may devo “2o” bacteremia w/o/bugs due to micro or macro breach in intestinal mucosal barrier
26
Q
What is the clinical presentation of Typhoid fever (by week)?
A
- Incubation period 5-21 days (variable)
- 1st wk of illness: rising fever/chills develop; pts are bacteremic, and relative bradycardia is possible
- 2nd wk: adominal pain + “rose spots” (faint salmon-colored macules on trunk/abdomen) may appear (see attached image)
-
3rd wk: hepatosplenomegaly, GI bleed, perforation, 2o bacteremia
1. Septic shock or altered mental status possible - In the absence of death or severe complications, symptoms resolve over weeks to months
27
Q
How can Typhoid fever be dx’d? Tx’d? Prevented?
A
- DX: blood cultures (+) in 50-80% of pts, but may require several days (up to 5) of incubation
- TX: Ceftriaxone, Azithromycin, or Ciprofloxacin (unless the pt has been in an area with high rates of flouroquinolone resistance like South Asia)
- PREVENTION: vaccine
28
Q
What are the basics of Campylobacter jejuni? Transmission?
A
- Thin, spiral shaped G(-) rods
1. C. coli is another species that can cause enterocolitis - Most common bac enteric pathogen in developed countries (important cause of traveler’s diarrhea)
- TRANSMISSION: eating improperly cooked chicken; o/sources: unpasteurized milk, contaminated H2O
1. Reservoirs: sheep, cows, chickens, birds, dogs
2. Highly transmissible – very low ID
29
Q
What is the clinical presentation of C. jejuni?
A
- Incubation period 1 week
- Watery diarrhea (10+ BMs/day) that becomes bloody in 15% of adults and >50% of children
- Fever
- Crampy, periumbilical abdominal pain
- Self-limited over 3-7 days
31
Q
What are the potential complications w/C. jejuni?
A
- MCC of Guillain Barre syndrome, but devo in only 0.1% or less of those infected w/C. jejuni
1. Molecular mimicry: serum Ab’s to C. jejuni LPS cross-react with peripheral & CNS gangliosides
2. Ascending paralysis that begins 1-2 weeks post-GI infection - Erythema nodosum: inflam condition w/inflam of fat cells under skin -> tender, red nodules or lumps that are usually seen on both shins (attached image)
-
Reactive arthritis (used to be called Reiter’s): more common with HLA-B27 phenotype
1. Can also be seen with Salmonella, Shigella, and Yersinia
32
Q
Yersinia enterocolitica
A
-
G(-) coccobacilli w/bipolar staining (more common in Europe)
1. Infection preferentially involves ileum, right colon, appendix
2. Multiplies in lymphoid tissue -> regional lymph node and Peyer’s patch hyperplasia - SOURCES: pork, raw milk, contaminated water, pet feces
- CLINICAL: abdominal pain is main feature (Peyer’s patch, mesenteric lymph node hyperplasia can mimic acute appendicitis in teens/young adults; RLQ pain)
1. N/V common, and fever/diarrhea can occur
2. Extraintestinal sxs frequent: pharyngitis, arthralgia, erythema nodosum (image attached) - DX: stool culture
- TX: most cases do not warrant treatment
34
Q
What is the pathogenesis of C. diff?
A
- AB’s suppress normal flora, allowing C. diff to multiply and produce exotoxins A and B
1. Exotoxins A and B cause glucosylation of small GTPases like Rho, involved in cytoskeleton structure and signal transduction - Toxin A (enterotoxin) disrupts colonic mucosal cell adherence to colonic basement membrane and damages villous tips; inflammation leads to fluid secretion
- Toxin B (cytotoxin) causes depolymerization of actin, resulting in loss of cytoskeletal integrity, apoptosis and death of enterocytes
- Both toxins (A>B) stimulate monocytes and macrophages, which release IL-8 resulting in tissue infiltration with neutrophils; both cause disruption of epithelial tight junctions
39
Q
What is this? Associated infection?
A
- Pseudomembranes (on sigmoidoscopy)
- C. diff
40
Q
What do you see here? Associated infection?
A
- Colonic dilatation
- C. diff
- NOTE: toxic megacolon possible too (see attached)
43
Q
What is EPEC? Epi and pathogenesis?
A
-
Enteropathogenic E. coli: most commonly assoc. with illness in children <6 months to 2 years of age in developing countries (diarrhea has been described in adults, though uncommon)
1. Profuse, watery diarrhea; can be severe, with vomiting and dehydration - PATHOGENESIS: characterized by ability to produce attaching and effacing lesions and formation of pedestal like structures (LEE; attached image)
1. No Shiga toxin produced
46
Q
What are the Vibrio basics? Types?
A
- Curved (comma-shaped), G(-) rods
- Motile, polar flagellum; oxidase positive
- Commonly found in saltwater, disease in warm months
- Significant human pathogens:
1. V. cholerae
2. V. parahaemolyticus
3. V. vulnificus
47
Q
Transmission and epi of V. cholerae?
A
- TRANSMISSION: primarily via fecally contaminated drinking water, and less often food
1. Natural/man-made disasters (Haiti earthquake)
2. Other factors predisposing to epidemics: poor sanitation, malnutrition, overcrowding, inadequate medical services
3. Humans are carriers and envo reservoirs; main animal reservoirs marine shellfish (eating without adequate cooking can cause disease) - EPI: endemic in Asia, Africa, S. America, Indian subcontinent
1. Marked seasonal variation in incidence in most climates b/c rapid growth in warmer temps
2. >200 serogroups based on the O antigen, but O1 and O139 responsible for epidemic and pandemic cholera
a. O1 has 2 biotypes: E1 Tor and Classic
48
Q
What is the pathogenesis of V. cholerae?
A
- Dependent on colonization of small intestine and secretion of AB toxin -> lg #s of bac must be ingested for colonization to occur (sensitive to stomach acid; high infectious dose)
- Adherence to cells of brush border of gut related to secretion of bacterial enzyme mucinase that dissolves glycoprotein covering the intestinal cells
- Multiplies and secretes cholera toxin –> AB toxin
1. 5 B (binding) subunits: binds to ganglioside receptor on the surface of the enterocyte
2. 1 A (active) subunit: inserted into cytosol and catalyzes add’n of ADP-ribose to Gs (stimulatory G) protein, causing persistent stimulation of adenylate cyclase
a. cAMP overproduced, activates cAMP-dependent protein kinase that phosphorylates ion transporters in cell mem, leading to loss of water and ions
b. Watery efflux enters the lumen of the gut and massive watery diarrhea ensues
49
Q
What is the clinical presentation of V. cholerae?
A
- Incubation period 1-3 days
- Watery diarrhea in large volumes: up to 20 L/day
1. No RBCs or WBCs in stool -
Rice water stools: watery stool w/flecks of mucous and often has a fishy odor -> very large # of orgs in the stool
1. Vomiting and dehydration common
2. Abdominal pain usually absent - DEHYDRATION: loss of fluid and electrolytes leads to cardiac and renal failure
1. Acidosis and hypokalemia also occur b/c loss of bicarb and K in the stool - 40% mortality rate without treatment
50
Q
How is V. cholerae diagnosed? Tx?
A
- DX: most cases dx’d based on clinical suspicion
1. Organism can be isolated from stool using selective media like: Thiosulfate citrate bile sucrose (TCBS) agar, Taurocholate tellurite gelatin agar (TTGA), or MacConkey agar (colonies will be colorless) - TX: mainstay is aggressive volume repletion
1. AB’s adjunctive therapy for pts w/cholera and moderate-severe vol depletion: Tetracycline, Erythromycin, Azithromycin, Ciprofloxacin
2. Reduced osmolar ORS DEC stool output, vomiting, and need for supplemental IV fluids
51
Q
How can V. cholerae be prevented?
A
- Clean water supply, appropriate sanitation
1. About 760 million people still lack access to clean water sources - WHO recommends oral cholera vaccine in cholera control programs in endemic areas: Asia, Africa, S. America, Indian subcontinent
53
Q
V. vulnificus: epi, clinical, dx, tx
A
- Marine organism; most common foodborne illness in Japan
- CLINICAL: diarrhea, severe skin and soft tissue infections (see attached image)
1. Shellfish handlers who often sustain hand wounds are at risk of skin infection
2. Can cause rapidly fatal septicemia in immuno-compromised pts who eat raw shellfish w/org
a. Pts most at-risk are those w/underlying liver disease, alcohol abuse, and some chronic disease (diabetes, rheumatoid arthritis) -> 39% mortality rate, and bullous skin lesions are characteristic - DX: culture
- TX: Doxy + Cefotaxime or Ceftriaxone
54
Q
Bacillus cereus: epi, transmission, clinical presentation
A
- Spore-forming, G+ bacilli abundant in soil, fresh H2O
- Can survive in envo for extended periods and withstand extremes of temp; can also survive in food processing environments
1. Has been recovered from rice, dairy products, spices, bean sprouts; fried rice important cause of emetic-type food poisoning - 2 enterotoxins: diarrheal enterotoxin & emetic toxin
- CLINICAL: diarrheal or emetic syndrome
1. Diarrheal syndrome: abdominal cramps, copious diarrhea, 8-16 hours after ingestion, resolves within 24 hours; vomiting uncommon
1. Emetic syndrome: caused by direct ingestion of the toxin cereulide (heat stable); abdominal cramps, N/V (diarrhea in 1/3 of people) w/onset in 1-5 hours of ingestion, resolve in 6-24 hours
a. Rice dishes: cooling fried rice dishes overnight at room temperature, then reheating the next day
58
Q
What is Bacteroides fragilis? Pathogenesis?
A
-
G(-) bacillus: predominant orgs in human colon (1011/g of feces) + found in vagina of 60% of women
1. MCC of serious anaerobic infections - PATHOGENESIS: usually arises from a break in a mucosal surface -> predisposing factors: surgery, trauma, chronic disease
1. Polysaccharide anti-phagocytic capsule important virulence factor
2. Host response to the capsule actually plays important role in abscess formation
61
Q
What is going on here? Describe the pathogen and other possible clinical findings.
A
- Prevatella melaninogenica: formerly Bacteroides melaninogenicus
- G(-) coccobacillus commonly found in oral cavity, GI tract, vagina, nasopharynx
- Opportunistic pathogen
- CLINICAL FINDINGS: oral/periodontal abscesses
1. Pulmonary abscesses/empyemas
2. Chronic otitis
3. Sinusitis: image on front of card
64
Q
How is C. tetani transmitted? Pathogenesis?
A
- TRANSMISSION: spores found in soil, and portal of entry usually a wound site (e.g., nail penetrates foot)
1. Also can be introduced during “skin-popping”
2. Neonatal tetanus a major problem in developing countries -> org enters through contaminated umbilicus or circumcision wound - PATHOGENESIS: tetanus toxin (tetanospasmin), an AB neurotoxin (metalloprotease)
1. Enters at NM junction and is transported by motor neurons (via retrograde axonal transport) to ganglia in brain and spinal cord
2. Toxin binds tightly and irreversibly to ganglioside receptors and blocks release of INH neurotransmitters (glycine and GABA) by its cleaving action on membrane proteins (SNARE) involved in neuro-exocytosis
3. Net effect is disINH of neurons that modulate excitatory impulses from motor cortex, resulting in INC muscle tone, painful spasms, widespread autonomic instability
65
Q
What is the clinical presentation of tetanus?
A
- Characterized by strong muscle spasms/spastic paralysis
- Trismus (lock jaw) first; characteristic grimace known as risus sardonicus
- Exaggerated reflexes
- Opisthotonos: pronounced arching of the back due to spasm of the strong extensor muscles of the back
- Respiratory failure can occur
- High mortality rate
71
Q
What is H. pylori? Clinical importance? Virulence factors?
A
- Cause of ulcers that is spread human-to-human by fecal-oral route or gastric secretions
1. Associated with 95% of duodenal ulcers and 70% of gastric ulcers
2. Also assoc with gastric adenocarcinomas and lymphomas - Slender, curved G(-) rods that are motile with polar flagella and microaerophilic
1. VacA: vacuolating cytotoxin
2. PAI encoding Type III secretion system
3. Cag: rearranges cytoskeleton
4. Urease
72
Q
What is the pathogenesis of H. pylori?
A
- Combination of cell destruction leads to ulcers via:
1. VacA: vacuolating cytotoxin
2. Cag: rearranges cytoskeleton
3. Immune response
