Table Of Contents
Helicobacter
- Briefly describe Helicobacter
- Previously classified under campylobacter
- Encompasses and enterohepatic species
- Gastric
- Helicobacter pylori
- Helicobacter heilmanni
- Enterohepatic
- Helicobacter hepaticus
- Gastric
- Helicobater pylori infects humans, primates, and pigs, and is associated with:
- gastritis
- peptic ulcers
- gastric adenocarcinoma, and
- MALT B-cell lymphomas.
- Helicobacter cinaedi affects humans and hamsters and causes:
- gastroenteritis
- septicemia and
- proctocolitis.
- Helicobacter fenneliae affects humans and causes:
- gastroenteritis
- septicemia and
- proctocolitis
- Briefly describe Helicobacter pylori
- Helicobacter pylori is a GN curved rod.
- It is spiral shaped, micro-aerophilic, highly motile (cockscrew motility) with lophotrichious flagella (2-6 sheathed unipolar flagellar).
- It colonizes the stomach in around 50% of the population and is spread via the fecal-oral route. It is the main risk factor for Gastric and duodeal ulcers, Stomach cancer, Gastric MALToma. It produces oxidase, catalase and urease (positive)
- Helicobacter pylori has the highest incidence of carriage in developing countries (70-90%) of the population and most <10 years of age.
- Humans are the primary reservoir and colonization is believed to persist for life – Unless the host is specifically treated
- Transmission is by the fecal-oral route.
- It is found in 70-100% of patients with gastritis, gastric ulcers or duodenal ulcers.
- Colonization appears to offer protection from GERD and adenocarcinomas of the lower oesophagus and cardia of the stomach.
- Helicobacter pylori produces NH3 in more neutral microenvironment.
- Vacuolating cytotoxin A(VacA) causes apoptosis in eukaryotic cells by producing large cytoplasmic vacules.
- Cytotoxin-associated gene (cagA) resides in pathogenicity island and encodes a syringe-like structure (Type IV secretion system) that injects CagA protein in host epithelium.
- CagA activates signal transduction molecules causing morphological and neoplastic changes (actin remodelling, host cell growth and inhibition of apoptosis).
- CagA-negative strains are significantly less associated with gastric adenocarcinoma.
- Cag genes also induce IL-8 production causing neutrophil chemoattraction and ROS production.
- List the virulence factors associated with Helicobacter pylori
- Multiple unipolar flagellae: motility and chemotaxis
- Urease: neutralizes gastric acid, mucosal injury by ammonia
- Outer membrane proteins (BabA, BabB, sabA): adhesion to gastric epithelial cells
- VacA Exotoxin: promotes inflammation and gastric mucosal injury
- Cytotoxin-associated gee (cagA): codes Type IV secretory system for Cag Proteins
- Cag(A) proteins: promotes inflammation (Il-8) and carcinogenesis (actin remodelling, host cell growth and inhibition of apoptosis)
- Protease: modifies gastric mucus reducing ability of acid to diffuse through
- Mucinase: breaks down gastric mucus allowing the organism to penetrate and adhere to the epithelial cells
- Briefly describe the pathogenesis Gastritis and Gastric Ulcers caused by Helicobacter pylori
- Initial colonization is facilitated by:
- Blockage of acid production (by bacterial acid-inhibotory proteins)
- Neutralization of gastric acid (ammonia produced by urease activity)
- Passes through gastric mucus
- Adheres to gastric epithelial cells via multiple surface adhesion proteins (BabA, BabB, sabA)
- Adhesion proteins aid with immune evasion
- Localized tissue damage (urease byproducts, mucinase, phospholipases, and activity of VacA)
- CagA stimulates IL-8 production and subsequent neutrophil chemoattraction
- Release of proteases and ROS by neutrophils
- Gastritis (Type B) and Gastric ulcers
- Initial colonization is facilitated by:
- Briefly describe the clinical features of Helicobacter Pylori
- Gastritis: Inflammation of stomach lining with associated mucosal ijury; infiltration of neutrophils and mononuclear cells into the gastric mucosa
- Acute gastritis: feeling of fullnes, N, V, and hypochlorhydria +/- recurrent upper abdominal pain, heart burn, anorexia
- Chronic gastritis (Type B): Confined to the gastric antrum or pangastritis. Approximately 10-15% of chronic gastritis patients progress to PUD. Chronic gastritis also leads to replacement of normal gastric mucosa with fibrosis and proliferation of intestinal-type epithelium
- Gastric and duodenual ulcers
- Ulcers occur at sites of intense inflammation commonly at the junction between the corpus and antrum (in gastric ulcert) and proximal duodenum (duodenal ulcers)H.pylori is responsible for 85% of gastric and 95% of duodenal ulcers.
- Gastric cancer
- H.pylori increases te patient’s risk for gastric cancer by almost 100-fold. It is influenced by the strain of H.pylori (cagA positive), and the host’s response (Increased IL-1 production)
- MALT Lymphoma
- Monoconal population of B cells may deveope and evolve into a MALToma in a small subset of individuals. Not considered a cancer per se.
- Gastritis: Inflammation of stomach lining with associated mucosal ijury; infiltration of neutrophils and mononuclear cells into the gastric mucosa
- Briefly describe the laboratory features of Helicobacter pylori
- Specimen: Stool, Blood, Biopsy
- Non-invasive procedures
- Microscopy: GN comma shaped rods (difficult to visualize + non-pathogenic organisms may be present)
- Stool Antigen test: positive (95% specificity and sensitivity, easy, inexpensive, active infection, monoclonal is useful before and after treament, polyclonal is done for only a few studies)
- Blood Antigen test: positive (Is qualititave and quantitative IgG, Widely available, inexpensive, not useful after treatment. Note that IgM disappears rapidly, IgA and IgG can persist for months to years)
- Urea breath test: positive (Patients drinks urea radio-labelled solution {13C or 14C small radiation tube} then blows into a tube, Detection of CO2 is positive. It is relatively expensive {cost of detection instruments})
- PCR: expensive, not widely available or standardized
- Invasive procedures
- Endoscopy and biopsy: 100% sensitivity and specificity, is considered diagnositc
- Biopsy in urea solution: alklaline byproduct detected may change wthin miniute-2hours, specificity is 100%
- Histology (Warthin-starry silver stain): 100% sensitivity and specificity, diagositic
- Culture: Difficult to isolate in culture and identified by biochemical testing and nonculture techniques
- Specimen is gastric biopsy. Complex media supplemented with blood, serum, charcoal, starch, or egg yolk in microaerophilic (low O2, High CO2) for up to 2 weeks), temperature range is 30-37 degree.
- Endoscopy and biopsy: 100% sensitivity and specificity, is considered diagnositc
- Biochemical tests
- Oxidase: Positive
- Catalase: Positive
- Urease: Positive
- How is Helicobacter pylori infection treated ***treatment is conserved for symptomatic individuals since 2.3 or 50% of population has H.pylori commensals
- Triple therapy: PPI (osemeprazole) + Clarithromycin + Amoxicillin/Metronidazole. 10-14 days. Compliance is important. OR PPI + metronidazole + tetracycline
- Quadruple therapy: PPI + Bismuth subsalicylate + Metronidazole + Tetracycline
- Antibiotic resistant bacteria: associated with clarithromycin resistance +/- metronidazole
Campylobacter
- Briefly describe Campylobacter
- Campylobacter is derived from the word “kampylos” meaning curved rod.
- It is a small (0.2-0.5um wide, 0.5-5um long), curved, gram negative rod that is comma or S-shaped or Cigar shaped.
- It is non-sporing and motile and exhibits rapid motility (darting, in cork-skrew fashion) due to its flagella (1-2)
- It is microaerophilic (candle extinction jar of CO2) and oxidase positive.
- The cell wall has LOS instead of LPS endotoxin.
- The major pathogens are:
- Campylobacter jejuni (80-90% illnesses, >50 capsular serotypes)
- Campylobacter festus (Systemic infections – bacteremia, septic thrombophlebitis, arthritis, septic abortion, and meningitis),
- Campylobacter coli (Gastroenteritis),
- Campylobacter upsaliensis (incidence unknown, GI infection)
- Campylobacter shares similarities with Vibrio and Helicobacter (cork-screw motiliy, microaerophilic)
- Campylobacter is found in the GIT of poultry, cattle, sheep, pigs, birds, dogs, and cats (on illnesses)
- Transmission to humans is through contaminated food (water and milk), contaminated poultry (>50% infections in developed countries) and fecal-oral (fecal material from infected animals), food handlers (uncommon).
- It is common in infants and young children with a 2nd peak in 20-40y adults. 1.4-2 million infection are estimated to occur anually in the US (more common than Salmonella and Shigella infections)
- Incidence is higher in developing countries and it is the most common bacterial cause of diarrhea.
- List the virulence factors associated with Campylobacter jejuni
- S proteins (proteinaceous, capsule-like, prevents complement-mediated killing and opsonisation – phagocytosis)
- Heat-labile enterotoxin (Cholera-like enterotoxin that causes diarrhea)
- Briefly describe the pathogenesis of enteritis caused by Campylobacter jejuni
- Risk of disease influenced by infectious dose
- Ingestion (Contaminates milk, water, or Fecal-oral)
- Colonization
- Infection of Jejunum +/ ileum, colon, rectum
- Ulcerated mucosal surfaces, edematous, bloody w/crypt abscesses in epithelial glands and inlitration of the lamina propria with neutrophils, mononuclear cells and eosinophils (C.jejuni infection)
- Involvement of mesenteric nodes and transient bacteremia
- Outline the clinical features of Campylobacter jejuni
- Acute enteritis: Diarrhea, Fever + Severe abdominal pain. ≥10 bowel movements per day during the pek of the disease. Stool may be bloody. Self—limited. Symptoms may last > a week or longer
- Bacteremia: (secondary to diarrhea), Risk is associated with pregnancy, HIV, Extremes of age, alcoholism ,post-splenectomy status and other immunosuppressive status
- Cholecystitis
- Arthritis
- Deep abscesses
- Osteomyelitis
- Meningitis
- C.festus: affinity for genital tract and tropism for fetal tissue. Causes perinatal infection, abortion, still birth, and premature labour.
- List the immune-related complication associated with Campylobacter jejuni
- Guillain-Barre Syndrome: Rare (1 in 1000 infections) Campylobacter jejuni serotype O:19 has antigen cross-reactivity between surface LOS and peripheral nerve gangliosides. Causes an ascending paralysis.
- Reactive arthritis (Reiter’s syndrome): Joint pain, swelling of the hands, ankles, knees; persisting from 1 week to several months, unrelated to the severity of diarrheal disease, More common in individuals with HLA-B27 phenotype
- Hemolytic uremic syndrome
- Toxic megacolon
- Cholecystitis
- Meningitis
- Briefly describe the laboratory features of Campylobacter jejuni
- Specimen: stool
- **Direct (**phase contrast or darkfield) microscopy: Darting motility like vibrio (on Phase contrast or dark-field microscopy)
- Culture: ***On campylobacter special media. Microaerophilic (5-7% O2 and 5-10% CO2) and elevated incubation temperatures (42C) on selective agar. Slow growing (incubate 48H or longer) ***differentiate from vibrio by temperature, atmospheric conditions and media used
- Skirrows media (BA with antibiotics vancomycin, trimethroprim, cephalothin, polymyxin, amphotericin B to inhibit other enteric organisms): Non-hemolytic, spreading, droplet-like colonies
- Butzlers medium
- Campy BA
- Brucella antigen base with sheep blood
- Gram stain: Gram ngative comma or S-shaped or Cigar shaped bacilli
- Biochemical tests
- Oxidase: Positive
- Catalase: Positive
- Serotpying
- Biotyping
- Phage typing
- Antibody detection: IgG and IgM for epidemiological surveys
- Nucleic acid based tests: For Campylobacter jejuni and Campylobacter coli
- How is infection with Campylobacter jejunitreated
- Self-limiting: rehydration
- Severe dysentery: erythromycin, azithromyin, ciprofloxavin
- Severe disease and septicemia: macrolides, tetracyclines, aminoglycosides, CAF, FQs, clindamycin, amoxicillin/clavulanic acid, and imipenem
- Resistance: Penicillins, cephalosporins, sulfonamides +/- FQs
- Systemic infections: aminoglycoside, chloramphenicol, imipenem
- C.coli: TMP-SMX
- Antimotility drugs: not recommended
