GI Bacteria Flashcards

(76 cards)

1
Q

H. pylori

Morphology and Characteristics

A

Helicobacter pylori

  • Gram helical-shaped rod
  • Catalase
  • Oxidase
  • Highly motile with corkscrew motility
  • Causes a persistent infection with long-term low-level inflammation
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2
Q

H. pylori

Transmission and Epidemiology

A
  • Spreads via human-human contact
    • fecal-oral or oral-oral contact
    • Humans are the natural reservoir
  • Infects 50% of the world population early in life
    • Highest carriage rates in developing countries
    • Majority of population infected by age 10
    • In developed countries, ~ 40% carriers
  • Risk factors for infection: low socioeconomic class & over-crowding
  • Risk factors for disease development: smoking, alcohol, NSAIDs
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3
Q

H. pylori

Virulence Factors

A
  • Flagella and adhesins⇒ colonization and adherence to stomach wall
  • LPS ⇒ incites and maintains inflammatory response to persistent infection
  • Urease ⇒ produces ammonia and neutralizes gastric acids ⇒ supports long term survival
  • Vacuolating cytotoxin (VacA) ⇒ damages cells by producing vacuoles
  • Cytotoxicity associated gene (CagA) ⇒ 30 genes on a pathogenicity island
    • Encodes syringe like structure that injects Cag A protein into host epithelial cells
      • Interferes with normal cytoskeleton structure
      • Induces IL-8 ⇒ attracts PMNs ⇒ release proteases and ROS ⇒ tissue damage
    • Not all strains are CagA ⊕
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4
Q

H. pylori

Clinical Disease and Pathogenesis

A
  1. Gastritis
    • Chronic inflammation of the stomach
    • Infiltration into gastric mucosa by PMNs and MΦ
    • Sx include feeling of fullness, N/V
    • Can evolve into a gastric ulcer or duodenal ulcer
  2. Gastric adenocarcinoma
    • Chronic gastritis → destruction of normal mucosa by inflammatory and oxidative damage
    • ↑ risk of mutation
    • Replacement with fibrosis
    • Proliferation of intestinal-like epithelium
    • Risk ∆ by host immune system & strain of H. pylori
  3. MALT lymphoma
    • B cell lymphoma
    • Arises due to infiltration of lymphoid tissue into the gastric mucosa
    • Can be cured w/ treatment of H. pylori
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5
Q

H. pylori

Diagnosis

A
  • Noninvasive
    • Urea breath test
      • Ingest radiolabeled urea
      • If H. pylori present ⇒ urea → ammonia and CO2
      • Radioactive CO2 detected in breath samples
      • Very high sensitivity
    • Serology
    • EIA: sensitive but cannot monitor tx b/c titers fall very gradually
    • HpSA: detection of helicobactor Ab in feces, can be used for initial dx and monitoring
  • Invasive
    • Biopsy
      • Test for urease
      • Culture for organisms
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6
Q

H. pylori

Treatment

A
  • Asymptomatic infections not treated
  • Presently, H. pylori disease is tx when pt c/o abd pain or ass. signs and sx
  • Pt w/ active duodenal or gastric ulcers tx if infected w/ H. pylori
  • Triple or quadruple therapy:
    Triple therapy recommended for eradication of organisms and control of sx
    • PPI + β-lactam + macrolide
      • Usu. 2 abx to prevent resistance
      • Clarithromycin + Amoxicillin or Metronidazole
      • Successful in ~90% of cases but antimicrobial resistance ↑
    • H2 Blocker and/or bismuth subsalicylate
      • H2 Blocker ⇒ ⊗ histamine which triggers stomach acid
      • Bismuth subsalicylate ⇒ coats stomach and protects it from acid
  • No known immunity
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7
Q

H. pylori

Prevention

A

Prevention is limited

No chemoprophylaxis or vaccine

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8
Q

Non-invasive, Toxigenic

Enteric Bacteria

A
  • Escherichia coli
  • Vibrio cholera
  • Clostridium difficile
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9
Q

Enterobacteriaceae

Characteristics

A

E. coli, Salmonella, Shigella, Yersinia

  • Enteric bacilli ⇒ reside or cause infections in the GI tract
    • Gram ⊖ rods
    • Facultative anaerobes
    • Oxidase negative
    • All ferment glucose
  • Commonly found in soil and GI tract of man and lower animals
  • Opportunistic or primary (strict) pathogens
  • Serological classification based on 3 groups of Ag:
    • O polysaccharides
    • Capsular K antigens
    • Flagellar H proteins
  • Specific Ab develop in systemic infections but unclear if significant immunity persists
    • Secretory IgA ⇒ ⊗ attachment to intestinal mucosa
  • Cultivated on ordinary laboratory media
  • Kits available for rapid, biochemical ID
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10
Q

Enterobacteriaceae

Lab Identification

A

Selective and differential media commonly used include:

  • MacConkey’s Agar
    • Contains lactose, Neutral Red (pH indicator) and bile salts (⊗ gram-⊕ organisms)
    • Lactose fermenters (i.e. E. coli, Klebsiella, Enterobacter) ⇒ pink to red colonies
    • Non-lactose fermenters (i.e. Salmonella, Shigella) ⇒ colorless colonies
  • Eosin-Methylene Blue Agar
    • Contains lactose, eosin and methylene blue
    • Aniline dyes ⇒ ⊗ some gram-⊕ and fastidious gram-⊖ bacteria; also form a precipitate at acidic pH
    • Strong lactose fermenters (i.e. E. coli) ⇒ green-black w/ a metallic sheen
    • Other lactose fermenters (i.e. Klebsiella, Enterobacter) ⇒ pink-purple colonies
    • Non-lactose fermenterscolorless transparent colonies
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11
Q

Non-Enterobacteriaceae

A

Curved gram-__⊖ rods:

Helicobacter, Vibrio, Campylobacter

Anaerobic, gram-__⊕ rods:

Clostridium difficile

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12
Q

E. Coli

Overview

A
  • Most common facultative, GNR in normal flora of large intestine
  • Lactose & glucose fermenter
  • Indole ⊕
  • Commonly associated w/ endogenous, opportunistic infections
    • UTI
    • Neonatal meningitis
    • Nosocomial infections, wound infections, secondary PNA, sepsis
  • Certain strains may be strict pathogens
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13
Q

Pathogenic E. Coli

Classification

A
  • Serological classification:
    • O antigens of LPS (serogroup)
    • H antigens of flagellum (serotype – O+H)
    • Capsular polysaccharide
  • Pathogenicity (pathotype, virotype)
    Based on pathogenic capabilities, epidemiology and clinical manifestations of GI disease
    • Main types:
      • Enterotoxigenic E. coli (ETEC)
      • Enteropathogenic E. coli (EPEC)
      • Enterohemorrhagic E. coli (EHEC)
        • Shigella toxin-producing E. coli (STEC)
    • Rarer types:
      • Enteroaggregative E. coli (EAEC) / Diffuse adherent E. coli (DAEC)
      • Enteroinvasive E. coli (EIEC)
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14
Q

E. Coli

Virulence Factors

A
  • Colonization factors, adhesion factors, fimbria, pili
    • Attachment to epithelial lining of GI and urinary tract
    • May be antiphagocytic
  • Enterotoxins
  • Cytotoxins
  • Capsule
    • Antiphagocytic
    • Important in neonatal meningitis due to the K1 strain of E. coli
  • Type III Secretion System
  • Endotoxin
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15
Q

Enterotoxigenic E. coli (ETEC)

Virulence Factors

A

Enterotoxins:

  • LT-1 and LT-2 (heat labile) [A-B toxin]
    • B subunit → binds GM1 gangliosides
    • A subunit → ADPR transferase
    • Adenyl cyclase ⇒ cAMP ⇒ secretion of K+, Na+, HCO3- and Cl- ions ⇒ loss of large amounts of water
  • ST toxin (heat stabile)
    • Small peptide, proteolytically processed during secretion
    • Methanol-soluble (STa) and methanol-insoluble (STb)
    • STa ⇒ guanyl cyclase ⇒ ↑ cyclic GMP ⇒ ↓ net absorption of Na+ and Cl- ions ⇒ fluid loss
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16
Q

Enteropathogenic E. coli (EPEC)

Virulence Factors

A
  • Initial loose attachment mediated by bundle forming pili (Bfp)
    • Plasmid encoded
  • Type III Secretion System
    • Active secretion of virulence factors into epithelial cells
    • LEE ⇒ genetic locus for enterocyte effacement
    • Pathogenicity island shared by A/E pathogens (E. coli, Salmonella, Shigella, Yersinia)
    • Adhesion/attachment molecules, syringe-like injection apparatus, chaperones, effector molecules
    • Specific effectors differ between organisms
  • E. coli:
    • Attachment/Effacement lesions (A/E lesions)
    • Tir (translocated intimin receptor) inserted into epithelial cell membrane
    • Tir binds intimin (outer membrane bacterial adhesin on E. coli) → tight binding → signal transduction cascade
    • Secreted effectors:
      • Disrupt normal microvillus structure
      • Mediate rearrangement of host cell actin in the vicinity of adherent bacteria → pedestal formation
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17
Q

Enterohemorrhagic E. coli (EHEC)

Virulence Factors

A
  • Type III Secretion System
    • A/E lesions ⇒ destruction of intestinal microvillus ⇒ ↓ absorption in large intestine
  • Cytotoxins
    • Cytotoxic hemolysins
    • Shiga-like toxins (Stx-1 and Stx-2) [A-B toxin]
      • B subunit → binds globotriaosylceramide (GB3) on intestinal villi and renal endothelial cells
      • A subunit → cleaved by host furin & calpain upon translocation
      • A1 fragment deadenylates a specific 28S rRNA nucleotide
      • Protein synthesis (chain elongation) by blocking AA-tRNA binding to acceptor site on rRNA
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18
Q

E. Coli

Diagnosis

A
  • Culture and isolation on differential/selective media
    • MacConkey’s Agarpink to red colonies
    • Eosin-Methylene Blue Agargreen-black w/ a metallic sheen
  • Identification by biochemical reactions
  • Key characteristics: gram-⊖ rod, lactose fermenter, indole ⊕
    • Of the KEE organisms, only E. coli is indole ⊕
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19
Q

E. Coli

Treatment, Transmission, and Prevention

A
  • Tx:
    • Rehydration therapy (oral, IV) for gastrointestinal infections
    • Abx used in the very young, pts w/ extra-intestinal infections and pts w/ chronic infections irrespective of location
  • Transmission: fecal-oral route, food-borne, endogenous infections
  • Prevention: proper sanitation and food handling
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20
Q

Vibrionaceae

A
  • Vibrio species are common in surface, coastal waters around the world
  • Three medically important species: V. cholerae, V. parahemolyticus, V. vulnificus
  • All are curved, gram-rods
  • Easily cultivated on ordinary lab media
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21
Q

Vibrio cholera

Overview

A
  • V. cholerae O1 and 0139 ⇒ Classic epidemic cholera
    • Biotypes El Tor and classic
    • El Tor ⇒ major cause of human pandemic infection
  • Non-O1 V. cholerae ⇒ isolated cases of cholera and small outbreaks of diarrhea
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22
Q

Vibrio cholera

Epidemiology and Transmission

A
  • V. cholerae caused major pandemics of cholera
  • Epidemic disease in South East Asia (esp. India), Northern Africa, Peru, and Brazil
  • In the USA, a small endemic focus of disease exists along coastal areas of Louisiana and East Texas
  • Transmission is primarily by contaminated water under poor conditions of sanitation
    • Infectious dose: 105 organisms
  • Carriers important in maintaining and transmitting the organism in the absence of epidemic outbreaks
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23
Q

Vibrio cholera

Virulence Factors

A
  • Cholera toxin (“Choleragen”) [A-B toxin] ⇒ potent enterotoxin
    • B subunit → bind to the GM1 ganglioside receptor on intestinal mucosal cells
    • A subunit → active ADPR-transferase
      • ADP ribosylation of GTP-binding protein that regulates adenyl cyclase activity
      • Persistent ⊕ of adenyl cyclase ⇒ ↑ cAMP ⇒ hypersecretion of electrolytes and fluid loss
    • MOA is the same as E. coli LT
    • Enters cells via endosome → Golgi → ER → cytosol → plasma membrane
  • Adhesion factors
    • Exact mechanism by which V. cholera adhere to the microvilli of the small bowel is unclear
    • Specific adhesins and a mucinase likely involved
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24
Q

Vibrio cholera

Pathogenesis and Clinical Disease

A
  • Cholera is an acute and severe diarrheal disease
    • Extensive fluid and dehydration
    • Little or no tissue damage
  • Initiates infection in the ileum
    • Penetrates mucus
    • Adheres to mucosal epithelium
    • Replicates extracellularly
    • May then spread and grow throughout small and large intestines
  • Pathology and symptomatology due exclusively to action of cholera toxin
    • “Rice-water stool” ⇒ hallmark
      • Non-bloody watery diarrhea in large volumes
      • Contains mucus, epithelial cells and large # of Vibrios
    • Loss of fluid and electrolytes ⇒ ± cardiac and renal failure
    • If untreated, mortality 40-60%
      • Due to profound dehydration and electrolyte imbalanc
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25
Vibrio cholera Diagnosis
**Fecal specimens** * Culture and isolation on _differential/selective media_ * **TCBS agar** * ID by biochemical reactions and agglutination assays w/ specific antisera * Key characteristics: **gram-****⊖****, comma-shaped rods, oxidase** ⊕**, motile** * All Enterobacteriaceae are oxidase ⊖ ⇒ distinguishing feature of Vibrio
26
Vibrio cholera Immunity
* Natural infection → high degree of **resistance to reinfection by homologous strains** but not to a heterologous strain * **Bactericidal, antitoxin and agglutinating Ab** produced but exact role unclear * Local immunity due to **IgA antibodies** associated w/ immune state * Current vaccines provide some short-term protection
27
Vibrio cholera Treatment and Prevention
* **Fluid and electrolyte replacement** * Serious cases ⇒ **tetracycline, azithromycin, and ciprofloxacin** * _Current vaccines in development but not commercially available in the US_ * **Oral: heat-killed and genetically attenuated vaccines** * Current vaccines provide some short-term protection * Ongoing work on subunit vaccines, combinations * **Water purification, sanitation, and elimination of carriers**
28
Vibrio parahemolyticus
**Halophilic marine organism** * **Major cause of diarrheal disease** in _Japan_ * **Outbreaks of diarrhea** in the _coastal areas of the USA and on cruise ships_ * Ass. w/ ingestion of **raw or undercooked seafood** * _Clinical disease:_ * Varies from **mild to severe watery diarrhea, N/V, abdominal cramps and fever** * Diarrhea is **occasionally bloody** * Self-limiting, lasts **~3 days**
29
Vibrio vulnificus
**Halophilic marine organism** * Common in shellfish _along Gulf of Mexico coast_ * Less common along Atlantic and Pacific * **Severe skin and soft tissue infections** in _shellfish handlers_ * **Rapidly fatal septicemia** in _immunocompromised hosts_ * Chronic liver disease predisposes to severe infection * 50% fatality rate
30
Clostridium difficile Characteristics
* **Large, gram-**⊕**, spore-forming rod, obligate anaerobe** * Found in **soil** * Present in the colon of **2-4%** of **normal healthy individuals** * Carriage rate for hospital personnel up to 30%
31
Clostridium difficile Clinical Disease
* Major cause of **antibiotic-associated diarrhea** * Severe inflammation * Occasionally lethal * Almost always ass. w/ intense **antibiotic therapy** ⇒ imbalance in normal intestinal flora ⇒ overgrowth of resistant organisms (endogenous or exogenous) * **Mild, watery or bloody** **diarrhea** w/ abd cramping * May progress to **pseudomembranous colitis** * Pseudomembrane composed of fibrin, leukocytes and necrotic colonic cells * Can result in **perforations**
32
Clostridium difficile Virulence Factors
Two exotoxins (**glucosyltransferases**) ⇒ ⊗ Ras GTPase (Rho, Rac, Cdc42) ⇒ cell death * **Toxin A (TcdA)** ⇒ _enterotoxin_ * Causes **fluid secretion** and **hemorrhagic necrosis** * **Chemotactic** for PMNs, additional release of cytokines * **Toxin B** (**TcdB**) ⇒ _cytotoxin_ * Induces actin depolymerization/condensation ⇒ **disruption of cellular cytoskeleton** * Loss of cell shape, adherence and tight junctions ⇒ **cell rounding** * Subsequent **interference w/ protein synthesis**
33
Clostridium difficile Diagnosis
* **Detection of toxins in stools** * Toxin B by tissue culture cell cytotoxicity assay * Toxins A and B by ELISA * **Endoscopy** * Culture and isolation (not routine)
34
Clostridium difficile Treatment
* Mild cases ⇒ **discontinue implicated abx therapy** * Severe cases ⇒ **metronidazole or vancomycin** * **15-30% relapse or reinfection rate**
35
Invasive Enteric Bacteria
**“Facultative pathogens”** Enterobacteriaceae family ⇒ **Salmonella, Shigella, Yersinia** Vibrionaceae ⇒ **Campylobacter** * Attach to and invade epithelial cells * Can replicate intracellular & extracellularly * Most do not cause disseminated disease * Some exceptions
36
Shigella Overview
* **Enterobacteriaceae** family * Facultative intracellular pathogens * **True human pathogen** ⇒ no animal reservoir * 2° attack rates in families up to 40% * ***S. dysenteriae, S. boydii, S. flexneri, S. sonnei*** * 15-20k cases of Shigellosis/yr in US * Developed nations ⇒ ***S. sonnei*** and ***S. flexneri*** most common * **S. sonnei** ⇒ young children and adolescents * **Bacillary dysentery** * Acute diarrheal disease marked by mucous, blood and tenesmus
37
Shigella Virulence Factors
* **Shiga-toxin** [A-B toxin] * Heat labile, _cytotoxic_ S. dysenteriae _exotoxin_ * **⊗** **Protein synthesis** (chain elongation) by blocking AA-tRNA binding to acceptor site on rRNA * Affects **gut**, **renal endothelial cells**, and **CNS** * Similar to EHEC verotoxin (Shiga-like toxin) * Encoded by **lysogenic bacteriophage** * **Invasion plasmid antigens** * **Type III Secretion System** * Mediate attachment, penetration, escape from phagocytic vesicles, cell-to-cell spread via actin filaments, host cell apoptosis * **Endotoxin**
38
Shigella Pathogenesis
* Infectious dose: **100 bacteria** * Infection of _small intestine_: 1-4 days * invasion of _large intestine_: 3 to 4 weeks * Invasion and penetration of epithelial cells of mucosa * Penetration into lamina propria * Can invade resident MΦ * ⊕ Cytokine secretion or MΦ apoptosis * **Microabscesses and shallow, crater-like ulcers** * Can cause actin rearrangement ⇒ contiguous spread to adjacent epithelial cells * Invasion into the bloodstream and beyond lamina propria rare
39
Shigella Clinical Disease
* Sx begin w/ **fever and abdominal cramps** * **Diarrhea** common during _first 2-3 days_ * Afterwards **stools are low volume** * _In severe cases:_ **frequent, mucoid and bloody stools** w/ **tenesmus** (pain and strain on defecation) * Except for *_S. dysenteriae_* infection, **shigellosis** is self-limiting w/ low case fatality rates in untreated cases * Can be acute or chronic * Can be associated w/ sign. morbidity * Usu. tx w/ abx
40
Shigella dysenteriae
* Found in developing countries * Produces a potent exotoxin * **Toxic megacolon**, intestinal perforation, hemolytic uremic syndrome, severe metabolic alterations
41
Shigella Diagnosis
* Non-specific **methylene blue stain** for fecal leukocytes * Culture and isolation on **differential/selective media** * MacConkey’s agar * Eosin methylene blue agar * Salmonella/Shigella agar * ID by biochemical reactions * _Key characteristics:_ * **Gram-⊖ rod** * **Lactose non-fermenter** * Differentiate from E. coli which is a lactose fermenter * **Urease ⊖** * **H2S ⊖ and non-motile** at both 25°C and 37°C * Differentiate from Salmonella which are H2S ⊕ and motile
42
Shigella Treatment and Prevention
* _Supportive therapy_: **fluid and electrolyte replacement** * Abx may be given, particularly to young patient to shorten the duration of disease and carrier state * **Ciprofloxacin, ampicillin, tetracycline, trimethoprim-sulfamethoxazole** * **Sanitation and personal hygiene** to interfere w/ fecal-oral transmission
43
Salmonella Classification
* **Enterobacteriaceae** family * _Historically 3 species recognized_ * ***Salmonella typhi****, **Salmonella choleraesuis, Salmonella enteritidis*** * Numerous named serotypes of *Salmonella enteritidis* * Undergo **antigenic variation** ⇒ mosaics of genes * Recombination, ∆ in length, gene duplications, point mucations * _2 species now recognized based on DNA:_ * ***Salmonella enterica*** (divided into 6 subspecies or serovars, medically relavent group) * ***Salmonella bongori*** * _Recommended nomenclature:_ * Salmonella enterica ser Typhi * Salmonella enterica ser Enteritidis * In practice, _named serotypes/subspecies referred to as species:_ * *S. typhi, S. paratyphi A, S. paratyphi B, S. typhimurium, S. enteritidis*
44
Salmonella Virulence Factors
* **Facultative intracellular pathogens** ⇒ able to survive in phagocytic cells * **Invasins** * Adherence and penetration of intestinal epithelial cells * **Vi (virulence) antigen** * Antiphagocytic _capsular polysaccharide_ of S. typhi * **Endotoxin** * LPS w/ specific O polysaccharide chains that contribute to virulence * **Type III Secretion System**
45
Salmonella Pathogenesis and Clinical Disease
* 1° enter via **oral route** * Infective dose: **106-108 bacteria** * Initiate infection by **attaching to epithelium of small intestine** * _Three main types of disease in humans:_ 1. **Typhoid fever** * S. typhi, S. paratyphi A, and S. paratyphi B ⇒ **enteric fever** (less severe form) 2. **Enterocolitis** 3. **Bacteremia w/ focal lesions**
46
Typhoid Fever
Caused by ***Salmonella enteric ser Typhi*** *(S. typhi)* Severest form of the disease Restricted to humans * Organisms acquired by **fecal contamination of water, food or fomites** * Replication starts within **salmonella containing vacuoles (SCV)** * Taken up by MΦ and PMNs * S. typhi penetrates lamina propria → submucosal and serosal layers of intestinal wall → **systemic infection** * _First week:_ * **Lethargy, malaise, fever, aches, pain, constipation** * Multiply in **Peyer's patches** in small intestines * Disseminate to **regional lymph nodes, RES, bloodstream, liver and spleen** * _Second week:_ * **High fever, tender abdomen** and ± **rose spots** on the skin * ± **Diarrhea** * **Seeding of bloodstream** from different foci of infection * _Third week:_ * **Diarrhea**; **bloody stools** may develop * **Infection of biliary system**, **re-infection of intestines** from bloodstream * _Complications_**:** * Generalized infection w/ **metastasis to bone, joints, liver, and meninges** * **Carrier state** may develop w/ _excretion of organisms in feces for long periods_
47
Salmonella Enterocolitis
* Caused most frequently by **S. enteritidis** and **S. typhimurium** * *Salmonella enterica ser Enteritidis, Salmonella enterica ser Typhimurium* * Associated w/ contaminated **poultry or poultry products** * Infects ovaries of healthy appearing hens and contaminate eggs before shells are formed * Enter via **oral route** * Infectious dose: **105-108 bacteria** * Organisms **invade mucosa of small and large intestines** * **Facultative intracellular pathogen** * Remains within a membrane bound vacuole ⇒ **salmonella containing vacuole (SCV)** * Bloodstream invasion is rare * **Nausea, vomiting and diarrhea** occur _8-48 hrs_ after ingestion * ± **Fever** and other constitutional sx * Organisms may be **isolated from stools** * ⊕ Fecal leukocytes, not usually bloody * **Self-limiting,** sx last ~**1-4 days** * Not usually treated * Similar presentation to Enteroinvasive E. coli (EIEC)
48
Salmonella Bacteremia w/ Focal Lesions
* 5-10% of Salmonella infections * Associated w/ *S. choleraesuis* (**Salmonella enterica ser Cholerasuis)** but may involve any NTS serotype * Oral ingestion → **early invasion of the bloodstream** * **Osteomyelitis**, **PNA, and meningitis** most common manifestations * **Sickle cell patients** at ↑ risk * Intestinal symptoms _often absent_ * **Blood cultures ⊕**
49
Salmonella Diagnosis
* _Specimens:_ * **Enterocolitis** * Stool * **Typhoid fever** * Blood (1st and 2nd weeks) * Stool (2nd and 3rd weeks) * Urine (4th week) * Bone marrow cultures may be useful in certain circumstances * Culture and isolation on **differential/selective media** * ID by **biochemical reactions** and **agglutination tests** w/ specific sera * _Key characteristics:_ * **Gram-⊖ rod** * **Lactose non-fermenter** * **H2S ⊕, motile** * Differentiates from Shigella which is H2S ⊖, non-motile * **Widal test** * Agglutination test for **anti-Salmonella Ab** in serum * Paired serum samples must demonstrate rise in titer
50
Salmonella Treatment and Prevention
* **Enterocolitis** * _Tx_: **supportive therapy**, fluid and electrolyte replacement * _Prevention_: adequate sanitation, immunization of domestic livestock and the proper cooking of poultry products and meat * **Typhoid fever** * _Tx_: **chloramphenicol, ampicillin or trimethoprim-sulfamethoxazole** * Replapses problematic * Chronic carrier rates high * _Prevention_: proper sanitation and personal hygiene * **S. typhi killed and attenuated vaccines** available but protection limited * Used as traveler’s vaccines * Boosters required * Potential for vaccination of hens vs non-typhi Salmonella
51
Campylobacter jejuni Characteristics
* **Causes 5-10% of all infectious diarrheas** * _Bimodal peak incidence:_ * **Infants \< 1 y/o** * Adolescents and young adults (**15-29 y/o**) * Found in **GI tract of wild and domestic animals** * Abx resistant infectious ass. w/ abx used in raising cattle, restricted by FDA * Transmitted by **contaminated food/drink** and **contact w/ infected animals** * Causes **chronic diarrhea** in up to _20% of HIV pts_ * Two other species: ***C. fetus*** and ***C. intestinalis*** implicated as a rare cause of **systemic infections** in _immunocompromised hosts_
52
Campylobacter jejuni Pathogenesis and Clinical Disease
* _Infectious dose:_ **several hundred bacteria** * _Incubation period_: **2-6 days** * **Enterocolitis** * Begins as **watery, foul smelling diarrhea** * Followed by **bloody stools**, **fever and abdominal pain** * **Locally invasive** ⇒ ⊕ for fecal leukocytes * No known enterotoxins or exotoxins * **Self-limiting** after **5-8 days** but sometimes continues for longer * Not usu. tx w/ abx unless severe or prolonged disease
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Campylobacter and Autoimmunity
* **Guillain-Barré Syndrome** * Autoimmune **acute demyelinating neuropathy** * Symmetical weakness over several days w/ recovery over weeks to months * Frequently _preceded by infection_ * CMV, Coxsackievirus, echovirus, Flu A, Zika virus, and Camplylobacter * **~40% of pts have culture or serologic e/o Camplyobacter infection** @ onset of neurologic sx * MOA: Ab vs _C. jejuni LPS core oligosaccharide_ **cross-react w/** _gangliosides of peripheral nerves_ * Molecular mimicry, type II hypersensitivity
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Campylobacter jejuni Diagnosis
* **Short, curved, gram-⊖ rods** * **Microaerophilic** (5-10% O2) * **Grows at 42°C** on special media * Extended culture period (3-4 days, up to 1 wk) * **Oxidase ⊕** * All Enterobacteriaceae are oxidase ⊖ * Vibrio cholera oxidase ⊕ but have more episodes of diarrhea
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Yersinia Overview
_Three species of medical importance:_ * **Yersinia pestis** * Bubonic plague * ***Yersinia enterocolitica*** and ***Yersinia pseudotuberculosis*** * GI infections * Typhoid fever-like syndromes
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Enteric Yersinia Characteristics
***Yersinia enterocolitica*** and ***Yersinia pseudotuberculosis*** * **Enterobacteriaceae** family ⇒ **gram ⊖ rods** * Found in a wide variety of **wild and domestic animals** * Transmission by **contaminated water, food, and milk** or by **entry via skin break** * *Y. enterocolitica* affects **mostly children**
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Enteric Yersinia Pathogenesis and Clinical Disease
***Y. enterocolitica*** and ***Y. pseudotuberculosis*** * Initial infection of the **ileum** * **Gastroenteritis** (more typical infection) * **Fever, abd pain and diarrhea** * Clinically indistinguishable from Shigella or Salmonella gastroenteritis * **Enterotoxin** similar to _ST toxin_ of E. coli * May be responsible for fluid loss * Usually **self-limiting** * **I****nvasive infection** (less common) * **Mucosal destruction, enlargement of regional mesenteric lymph nodes,** **±** **ulceration** * _Complications:_ * **Extraintestinal infection of liver, joints** * **Generalized septicemia**
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Enteric Yersinia Diagnosis and Treatment
* _Diagnosis:_ * Definitive dx by isolation of Yersinia from **stool cultures** * ID by **biochemical tests** * Can grow at **4****°C** * _Treatment:_ * Y. enterocolitica usually self-limiting ⇒ **supportive tx** * Disease caused by either species ⇒ Tetracycline, ampicillin, cephalosporins or chloramphenicol
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Staphylococcus Introduction
* **Gram-⊕ cocci** in **grape-like clusters** * _3 species of Staphylococcus of clinical importance:_ * **S. epidermidis** * Most commonly associated w/ infections related to cardiovascular and orthopedic prostheses, CSF shunts, vascular grafts and catheters * **S. saprophyticus** * Cause 10-20% of urinary tract infections in young, sexually active women * **S. aureus** * Normal flora of skin and nares in ~30-40% * May cause disease in nearly any tissue * _Staphylococcal disease divided into 3 general groups:_ 1. **Skin infections** 2. **Infections of hard and soft tissue** 3. **Toxic syndromes** * _Virulence factors varied and include:_ * **Surface antigens** (protein A) * **Extracellular enzymes** (coagulase, lipases, staphylokinase) * **Exotoxins** (enterotoxins, exfoliatin, TSST-1)
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Staphylococcus aureus Characteristics
* **Gram-⊕ Cocci in Grape-Like Clusters** * **Catalase ⊕** * Differentiates staph (catalase ⊕) from strep (catalase ⊖) * **Coagulase ⊕** * Differentiates S. aureus (coagulase ⊕) from all other staph (coagulase ⊖) * Routinely cultured on blood agar plates * **Beta-hemolytic, yellow or golden colonies**
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Staphylococcus aureus Virulence Factors
**Enterotoxins** * **18 serologically distinct types of enterotoxin (A-R)** * **A-D** associated w/ food poisoning * Heat stable and can resist boiling * Resistant to gastric enzymes and acidity * **Cytokine release, PMN infiltration, mast cell degranulation** * **Loss of brush border** * **⊕** **Intestinal peristalsis and diarrhea** * **⊕** **Vomit reflex** by interacting w/ neural receptors in upper GI tract * **±** **Superantigen activity** similar to Staph TSST-1 ⇒ excessive cytokine release
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Staphylococcal Food-Poisoning
* Fairly common food borne illness * Caused by **ingestion of enterotoxin produced by S. aureus** * Enterotoxins produced by ~ ½ of all coagulase ⊕ S. aureus strains * Ham, processed foods, chicken salad, cottage cheese, etc. * Sx onset within **1-6 hours** s/p ingestion * **Nausea, abdominal cramps, vomiting, watery and non-bloody diarrhea, profuse sweating, headache** * Self-limiting, **recovery within 24-48 hours** * _Treatment:_ **fluid replacement; abx not indicated**
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Bacillus Overview
_2 medically important species in the genus Bacillus:_ * ***Bacillus anthracis*** ⇒ anthrax (1° a disease of sheep and cattle) * Man acquires disease accidentally, usu. in an agricultural or industrial setting * ***Bacillus cereus*** ⇒ food poisoning in man
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Bacillus cereus Characteristics
* **Aerobic, large gram-⊕ rods** * **Spore-formers (endospores)** * Resistant to adverse chemical and physical environmental changes, withstand dry heat and certain disinfectants * Survive on **grain foods** (ex. rice) and in **some meat dishes** * Spores germinate when food is kept warm * *B. cereus* produces a **heat-stable** and a **heat-labile** **enterotoxin**
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Bacillus cereus Emetic-type Food Poisoning
* _Resembles staph food poisoning_ * Short incubation period (**~ 4 hrs**) * **Nausea, vomiting, abdominal cramps and occasional diarrhea** * Mediated by a **heat-stable enterotoxin** * **Contaminated rice and grain dishes** * Usually self-limitin
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Bacillus cereus Diarrheal-type Food Poisoning
* _Resembles clostridial gastroenteritis_ * Incubation longer, **up to 24 hrs** * Colonization of GI tract * **Profuse diarrhea, abd pain and cramps** * Mediated by **heat-labile enterotoxin** ⇒ ↑ cAMP production * Similar to E. coli and Vibrio cholera * **Contaminated meat, vegetables and gravy/sauces** * Generally self-limiting * Symptomatic treatment
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Clostridium Overview
**Anaerobic, gram-⊕, spore-forming rods** _Most commonly associated w/ human diseases:_ * **C. tetani:** causative agent of tetanus * **C. botulinum**: food-borne botulism, infant botulism, wound botulism * **C. perfringens**: myonecrosis, gas gangrene, anaerobic cellulitis, food poisoning * **C. difficile**: abx-associated diarrhea, pseudomembranous enterocolitis
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Clostridium botulinum Morphology and General Characteristics
* **Gram-⊕, spore-forming rod** * **Obligate anaerobe** * Found in **soil, pond and lake sediments** * Germination of spores and growth of vegetative form occur in **alkaline foodstuffs** (usually home canned) _when conditions are anaerobic_ * Also found in **Alaska** following **ingestion of home preserved fish**
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Clostridium botulinum Virulence Factors
**Neurotoxic exotoxin (botulinum)** _⊗_ _Release of ACh_ @ peripheral synapses ⇒ **flaccid paralysis** 8 antigenically distinct subtypes **(A-G)** of botulinum toxin [A-B toxin]
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Food-Borne Botulism
* **Ingestion of preformed toxin** in _home canned alkaline vegetables_ (string beans, mushrooms) * Not cooked enough to inactivate the toxin * Acidic foods do not support growth of C. botulinum * **Incubation 12-36 hrs** * **Nausea, vomiting, diarrhea or constipation** followed by **descending paralysis** * Ocular, pharyngeal, and respiratory muscles involvement → extensive voluntary muscle involvement * Mortality rate 60% untreated, 10% w/ treatment
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Wound Botulism
* Occasionally organism can **multiply in wounds** * Same clinical picture food-borne **w/o GI sx** * **Incubation 4-14 days**
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Infant Botulism
* **Most common form of botulism in the US** * Some ass. w/ feeding infants **honey containing C. botulinum spores** * In many cases, spores from **unknown environmental sources** * Incubation **3-30 days** * Organism grow in GI tract * _Produce toxins_ absorbed through intestinal wall into circulation * Babies w/ **constipation, weakness and flaccid paralysis** (**floppy infant syndrome**) * **Infants 1-8 months of age**, prior to establishment of normal GI flora
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Clostridium botulinum Diagnosis
* **Clinical dx** (disease usually an **intoxication**) * **Serum and stool samples** from all suspected cases * Stool cultured anaerobically for organism * Toxin may be identified in serum * **Samples from suspected contaminated foodstuffs** * Test for both organisms and toxin
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Clostridium botulinum Treatment
* Supportive care: **nutritional and respiratory** * _Assisted respiration_ most important determinant of outcome * **Penicillin is abx of choice**, only if organisms present * Abx not recommended for infant botulism b/c autolysis of organisms ⇒ ↑ [toxin] * **Equine antitoxins** * Trivalent (A, B, and E) and heptavalent (A-G) * For **food-borne and wound botulism** * Hypersensitivity rxn in 20% * Not recommended in infant botulism * **BabyBIG®, Botulism Immune Globulin IV (BIG-IV)** * Human-derived botulism antitoxin Ab for tx of infant botulism types A and B
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Clostridium botulinum Prevention & Control
* Education to improve home canning methods, but cases are also restaurant acquired * All canned food should be **cooked at 100°C for 10 min** to inactivate toxin * **Bulging food containers** may contain gas produced by C. botulinum and should be discarded * **honey should not be given to children under 12 months of age**; however most cases of infant botulism are caused by unidentified sources * Anti-toxin is not recommended prophylactically in cases of suspected exposure
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Clostridium perfringens
Notable cause of **myonecrosis** and **gas gangrene** in contaminated wounds **_Food poisoning_** * Ingestion of **meat dishes (stew, soup, gravy) contaminated w/ spores** of C. perfringens * Spores germinate in GI tract * Organisms **colonize ileum and large intestine** * Production of **heat-labile enterotoxin** * Onset of sx **within 18 hours** of ingestion * **Watery diarrhea w/ abd cramps and little vomiting** * Usually self-limiting * Supportive treatment