Cross - ID Flashcards

Question

What is the pathogenesis of Typhoid fever?

Answer 1

- 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 _"2^o" bacteremia_ w/o/bugs due to micro or macro breach in intestinal mucosal barrier

Answer 2

- 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**, 2^o bacteremia 1. Septic shock or altered mental status possible - In the absence of death or severe complications, symptoms _resolve over weeks to months_

Answer 3

- 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

Answer 4

- 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_

Answer 5

- 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

Answer 6

- DX: stool culture - TX: only warranted for those with _severe disease_ or at-risk of severe disease (bloody stools, high fever, worsening symptoms) 1. _Azithromycin or Cipro_ are DOC; resistance rates to flouroquinolones are rising, however

Answer 7

- 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

Answer 8

- _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

Answer 9

- Anaerobic, spore-forming _G(+) rod_ - Carried in GI tract in 3% of pop and 30% of pts in the hospital - TRANSMISSION: fecal-oral 1. Hands of hospital personnel are important intermediaries - EPI: most comm nosocomial cause of diarrhea and most common cause of antibiotic-associated diarrhea - NOTE: may be hard to get under control and pts can have serious disease

Answer 10

- 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

Answer 11

- _Watery diarrhea is the cardinal symptom_, but can progress to bloody diarrhea 1. SPECTRUM of manifestations incl. carrier state to fulminant disease with toxic megacolon - C diff associated diarrhea (**CDAD**) w/colitis: watery diarrhea (10-15 BM/day), mild lower abdominal pain and cramping, low grade fever, leukocytosis - **Pseudomembranous** colitis: present similarly + sigmoidoscopy shows pseudomembranes (adherent layer of inflam cells + debris at sites of colonic muscle injury) - **Fulminant** colitis: severe disease (severe abdominal pain, abdominal distention, fever, hypovolemia) 1. _Toxic megacolon_: colonic dilatation \>7 cm with severe systemic toxicity - Hypervirulent strains emerging: more severe, lower clinical cure rates, higher relapse rates (**NAP-1/027**)

Answer 12

- Advanced age - Hospitalization - Antibiotic treatment

Answer 13

- _PCR_ can detect A & B toxins -\> highly sensitive and specific - _EIA_ for A & B toxins: high false (-) rate (75% sens) - **Cell culture cytotoxicity assay**: gold standard 1. Stool sample is added to a monolayer of cultured cells -\> if C diff toxin is present, exerts cytopathic effect in tissue culture 2. Labor intensive: takes 2 days

Answer 14

- _Metronidazole_ usually 1st line usually 1. If severe, _PO Vancomycin_ indicated as 1st line - 1st recurrence: Metronidazole; 2nd recurrence: PO Vancomycin extended course - _Fidaxomycin_ new, and superior clinical response + less recurrences compared head-to-head with Vanc - _Fecal transplants_ hot new thing

Answer 15

- Pseudomembranes (on sigmoidoscopy) - C. diff

Answer 16

- Colonic dilatation - C. diff - NOTE: toxic megacolon possible too (see attached)

Answer 17

- _Enterotoxigenic_ E. coli: contaminated food/water 1. Major cause of _traveler’s diarrhea_ - Clinical presentation: 1. Watery diarrhea, ranges from mild to severe 2. Duration of _1-5 days_

Answer 18

- Produces heat-labile (LT) and heat-stable toxin (ST) 1. **LT**: like Cholera toxin; stimulates adenylate cyclase and INC IC _cAMP_, leading to secretion of Cl- from intestinal crypt cells + INH of absorption of NaCl at villous tips = secretion of free water into intestinal lumen (watery diarrhea) 2. **ST**: activates enterocyte _cyclic GMP_, also leading to stimulation of Cl- secretion and INH of NaCl absorption -\> end result again secretion of free water into intestinal lumen

Answer 19

- **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

Answer 20

- **Enteroaggregative E. coli**: cause of diarrhea in kids and adults in both developed and developing countries (_uncommon in adults_) 1. Also can affect HIV+ patients in developing countries (and probably developed countries) 2. Can cause traveler’s diarrhea - Pathogenesis not well understood

Answer 21

- **Hospital-acquired** infections: in many hospital labs, E. coli is the most commonly isolated organism 1. Sepsis - **Neonatal meningitis**: encapsulated strains (K1-Ag) - **Uropathogenic E. coli** (UPEC): cause 90% of urinary tract infections (UTI) 1. More common in females than males 2. _Symptoms_: freq, dysuria, pyuria, suprapubic pain, cloudy urine, cramping, afebrile or low-grade fever 2. _Diagnosis_: bacteria in urine a. \>10⁵ per ml in females b. \>10³ per ml in males 3. _Virulence factors_: P fimbriae (also called PAP pili), and a capsule (K antigen)

Answer 22

- 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

Answer 23

- 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_

Answer 24

- 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

Answer 25

- 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**

Answer 26

- 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

Answer 27

- 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

Answer 28

- Marine organism transmitted by ingesting _raw or undercooked seafood_, especially shellfish (oysters). - Major cause of diarrhea in _Japan_ (raw fish eaten in large quantities) 1. Relatively rare in US, but can be seen in the Gulf and Pacific Coasts in warm months - CLINICAL: incubation period about 1 day 1. Mild to severe WATERY diarrhea, N/V, fever, abdominal cramps 2. _Self-limited_ of about 3 days’ duration 3. Bacteremia can occur in those w/underlying conditions, such as liver disease 4. Also causes _wound infections_: assoc with marine recreational activities and handling of seafood (generally mild, but can get severe cellulitis in those with liver disease, diabetes, alcoholism, etc.) - DX: culture - TX: _volume repletion_ 1. AB's in severe cases: Doxycycline

Answer 29

- 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

Answer 30

- 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

Answer 31

- _Enterotoxin_ is heat-stable: acts as a _superantigen_ within the GI tract to stimulate release of IL-1 and IL-2 - Consumption of _foods prepared by a food handler_ like dairy, produce, meats, eggs, and salads (potato salad at a picnic) 1. Food handler contaminates the product 2. Food left at room temp and orgs multiply and can produce substantial quantity of toxin - Symptoms begin within 1-6 hours of ingestion with _N/V and abdominal cramps_ 1. Fever and/or diarrhea in a minority of patients - Lasts _24 hours or less_, but can be longer

Answer 32

- Each individual harbors at least 160 different gut microbes 1. 57 shared by 90% of Europeans 2. 75 shared by 50% 3. Two phyla account for 90% of the species - Evidence that our core gut microbiome influences our _body weight, CV health_ and tendency to develop of _type II diabetes_ - Anaerobes (Bacteroides, Clostridia) are major contributors to the gut microbiome

Answer 33

- _Lack SOD (superoxide dismutase) and catalase_, so their growth is INH by O₂-\> these enzymes eliminate the toxic compounds H₂O₂ and superoxide that are formed during production of energy by the organism - Anaerobic infections _STINK_: odor caused by metabolic end-products (mostly organic acids) 1. Lack of putrid smell does NOT rule out anaerobic infection - _Special transport and culture_ required - Anaerobic flora cause disease (abscesses) when introduced into normally sterile sites or when _balance of orgs upset_ and pathogenic orgs overgrow 1. Species found in abscesses often reflect the normal flora in that site 2. Anaerobic infections often polymicrobial (mixed anaerobic + facultative aerobic bacteria) - _Environmental anaerobes_ also cause disease: tetanus, botulism, gas gangrene

Answer 34

- _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_

Answer 35

- Most frequently cause _intra-abdominal infections_, e.g., abscesses or peritonitis - Pelvic or peri-rectal abscesses, bacteremia, infected decubitus ulcers can occur - In general, causes disease below the diaphragm (lung abscess being the exception -\> found in 25%) - Enterotoxin producing strain _can cause diarrhea_

Answer 36

- DX: anaerobic cultures - TX: resistant to Penicillin, but universally susceptible to metronidazole, carbapenems, combination beta-lactam and beta-lactamase inhibitors

Answer 37

- **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

Answer 38

- G(+), spore-forming rods - The _only anaerobic, endospore-forming bacteria_ 1. Resistant to high heat 2. Resistant to harsh environment - Exotoxins and secreted hydrolytic enzymes responsible for pathogenesis - Found in the _colon and soil_ (spores)

Answer 39

- Large, “boxcar” G(+) bacilli found in soil and colon - CLINICAL SYNDROMES: gas gangrene and **f****ood poisoning** 1. 3rd most common foodborne illness in the U.S. -\> watery diarrhea 2. _Heat-resistant spores survive cooking_, then spores can germinate in foods such as meats, poultry or gravy at lower temps 3. Following ingestion of large quantity of organisms, _enterotoxin_ produced in the GI tract 4. Outbreaks in psych inpatient facilities 5. 8-16 hr incubation period with watery diarrhea + cramps + minimal vomiting; _resolves in 24 hrs_

Answer 40

- 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_

Answer 41

- 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**

Answer 42

- Wound _debridement_ to eradicate spores - Human tetanus immune globulin (**HTIG**) used to neutralize the toxin - AB's probably play minor role, but universally recommended -\> DOC _Metronidazole_; Penicillin is an acceptable alternative - Tetanus _does NOT confer immunity_ after recovery from acute illness 1. All pts should receive active immunization with 3 doses of tetanus toxoid spaced at least 2 wks apart and _1st dose given immediately at dx_

Answer 43

- Causes botulism of different forms: 1. _Foodborne_ (classic) botulism: home-canned foods like fruits, vegetables; and fish 2. _Infant_ botulism: inhalation or ingestion of spores in carpet or raw honey 3. _Wound_ botulism: rise in incidence in CA due to black tar heroin users 4. _Inhalational_: would be an act of bioterrorism 5. _Iatrogenic_ - 110 cases/year reported in the U.S.: _72% infant_, 25% foodborne, 3% wound

Answer 44

- Spores resistant to heat; germinate after cooking and release toxin 1. _Subsequent heating will inactivate toxin_ (heat-labile) - CLINICAL: acute, symmetric _descending flaccid paralysis_ 1. Symptoms begin 12-36 hours post-ingestion 2. Nausea, dry mouth, dysphagia, diarrhea, blurred vision 3. Paralysis descends to respiratory muscles, trunk and extremities -\> possible death by respiratory failure - NOTE: _AB's NOT recommended_ for infant botulism or adults w/suspected GI botulism bc lysis of intra-luminal bac could INC toxin available for absorption

Answer 45

- “**Floppy baby syndrome**:" infants _1 wk-12 mos_ - Infection first, then intoxication: inhale or ingest spores (environmental dust) or honey - CLINICAL: presentation and severity _variable_ 1. Constipation followed by weakness, feeding difficulties, _descending global hypotonia_, drooling, anorexia, irritability, weak cry

Answer 46

- TX: mechanical ventilation 1. _Horse anti-toxin_ for those over 1 year of age 2. Human-derived botulism immune globulin (_BIG-IV_) for infants \<1 year of age 3. AB therapy unproven, but recommended for WOUND botulism only (DOC penicillin, but metronidazole a possible alternative) a. Not recommended for infant botulism bc lysis of intraluminal bac could increase the amount of toxin available for absorption - PREVENTION: proper cooking/canning

Answer 47

- 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

Answer 48

- Combination of cell destruction leads to ulcers via: 1. VacA: vacuolating cytotoxin 2. Cag: rearranges cytoskeleton 3. Immune response

Answer 49

- DX: endoscopy with biopsy and culture 1. Stool antigen 2. Urea breath test 3. Serology - TX: triple/quadruple therapy covered in GI lecture

Cross - ID Flashcards

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