7. Vibrio, Campylobacter, Helicobacter

VIBRIO, CAMPYLOBACTER, HELICOBACTER

Global Cholera Cases 2024

  • Time Frame: January 1 to September 29, 2024

  • Reported Cases: 439,724 cholera cases worldwide

  • Mortality Rate: 3,432 deaths

  • Trends:

    • Cases: 16% lower than previous year

    • Deaths: 126% increase, concerning trend

VIBRIO Genus

  • Species Diversity: Over 60 species

  • Clinically Important Species:

    • V. cholerae

    • V. parahaemolyticus

    • V. vulnificus

  • Growth Conditions:

    • Temperature range: 14-40°C

    • Halophilic (salt tolerant)

    • Alkaline pH tolerance: 6.5-9.0

  • Habitat: Primarily found in water, associated with phyto- or zooplanktons (copepods)

Vibrio cholerae

  • Serogroups: Over 140 known O serogroups

  • Key Serotype:

    • O1: Major cause of cholera outbreaks

    • O139: Significant outbreak in 1992, Bangladesh

  • Diarrheal Diseases: Non-O1 and non-O139 V. cholerae cause various forms of diarrhea

  • Biotypes in O1 Serogroup:

    • Classical

    • El Tor: Currently predominant, better environmental survival, more asymptomatic carriers

Virulence Factors of Vibrio cholerae

  • Key Toxins:

    • Cholera Toxin (CT) (phage-coded)

    • Toxin-coregulated pilus (TCP)

  • Additional Toxins:

    • Zot: Zonula occludens toxin

    • Ace: Accessorial cholera toxin

  • Other Factors:

    • Motility

    • Mucinase

    • Neuraminidase

    • Protease

Mechanism of Cholera Toxin

  1. Binding: Toxin binds to GM1 ganglioside on epithelial cells via B subunits

  2. A Subunit Activation:

  • A subunit splits into A1 and A2

  • Active A1 enters the cell and activates adenyl cyclase by transferring an ADP ribose group from NAD to GS regulator protein

  1. Activation Mechanism:

  • GTP binds to adenyl-cyclase, initially activating it

  • Gi protein eventually removes GTP, inactivating adenyl-cyclase

  1. Continuous Activation: After ADP ribosylation, adenyl cyclase remains active

  • Result: Increased intracellular cAMP concentration

  • Effects on Secretions: Enhanced secretion of ions (Na+, K+, Cl-, HCO3-) and water into the gut lumen

Clinical Picture of Cholera toxin

  • Symptoms:

    • Characteristic "rice-water stool"

Diagnosis of Vibrio Cholerae Infections

  • Methods:

    • Microscopy

    • Culture (Alkaline enrichment of fecal specimens)

    • Selective Medium: TCBS (Thiosulfate – Citrate - Bile salts – Sucrose)

    • Agglutination to identify serogroups (i.e., O1 or O139)

  • Therapy:

    • Rehydration (Oral Rehydration Solution)

    • Antimicrobials: Doxycycline or Azithromycin in cases of high resistance

  • Vaccines:

    • Single-dose live oral cholera vaccine

    • Killed whole cell vaccines with or without Toxin B subunit

Vibrio parahaemolyticus and Vibrio vulnificus

Vibrio parahaemolyticus

  • Symptoms: Watery diarrhea or dysentery

  • Transmission: Mostly through raw seafood consumption

  • Common Regions: Japan and Far-East

Vibrio vulnificus

  • Infection:

    • Develops after contact with seafood or seawater

    • Clinical Course:

      • Fulminant bacteremia

      • Cellulitis

    • High Fatality Rate: Particularly in individuals with iron storage diseases and alcoholics

Case Study 1

  • Patient Profile: 46-year-old Caucasian male physician from central Serbia

  • Initial Symptoms: Nausea, fever, watery diarrhea (self-limiting)

  • Subsequent Symptoms: Muscle weakness in limbs, proximal, and distal muscle weakness leading to disability

CAMPYLOBACTER Overview

  • Shape: S-shaped, curved rods

  • Gram Stain: Negative

  • Locomotion: Motile with bipolar flagella

  • Oxygen Requirements: Microaerophilic (lower O2, higher CO2) for growth

Spectrum of Disease Caused by Campylobacter spp.

  • Gastrointestinal Disorders:

    • Enteritis

    • Toxic megacolon

    • Perforation

    • Hepatitis, pancreatitis, cholecystitis, gastric ulceration

    • Peritonitis and splenic rupture

  • Rheumatological Complications:

    • Reactive arthritis

    • Reiter's syndrome

    • Septic arthritis

    • Vertebral osteomyelitis, Henoch-Schönlein purpura

  • Neurological Disorders:

    • Guillain-Barré syndrome (GBS)

    • Meningitis, meningoencephalitis

Campylobacter Enteric Infections

  • Common Species: C. jejuni, C. coli, C. fetus

  • Symptoms Spectrum: Ranges from mild diarrhea to severe dysentery with abdominal pain and blood in stool

Campylobacteriosis as a Zoonosis

  • Reservoir Hosts:

    • C. jejuni: Poultry, cattle, sheep

    • C. coli: Pigs, poultry, sheep, birds

    • C. fetus: Cattle, sheep

    • C. upsaliensis: Dogs, cats

Pathogenic Mechanisms of Campylobacter

  • Cytolethal Distending Toxin (CDT):

    • Prevents cell replacement in intestinal epithelium

    • Induces IL-8 production leading to inflammation

Post-infectious Sequelae of Campylobacter jejuni Infections

  • Recurrent Conditions:

    • Reactive arthritis

    • Guillain-Barré syndrome

    • Acute ascending flaccid paralysis in 1:1000 cases of C. jejuni enteritis

    • Related to cross-reactivity between C. jejuni and nerve gangliosides

Systemic Infections of Campylobacter

  • Common Species: C. fetus, C. jejuni, C. coli

  • Serum Resistance: C. fetus shows resistance with tropism to the vasculature

    • Associated conditions: Endocarditis, pericarditis, thrombophlebitis

Diagnosis of Campylobacter Infections

  • Methods:

    • Stool and/or blood culture

    • NAAT (PCR)

    • Culture under microaerophilic conditions

  • Therapy:

    • Generally not required for enteric diseases

    • In severe cases, Macrolides and Fluoroquinolones (increasing resistance)

Case Study 2

  • Background: Australian scientist Neil Noakes’ self-experimentation with bacteria for research on ulcers

  • Outcome: Resulted in significant findings leading to the Nobel Prize for Barry Marshall

HELICOBACTER PYLORI Overview

  • Characteristics: Highly motile, curved Gram-negative rod

  • Oxygen Requirements: Microaerophilic

  • Growth Rate: Grows slowly, culture requires 5-7 days in rich medium

  • Significance: Class I carcinogen, associated with gastric infections

Epidemiology of Helicobacter pylori

  • Transmission: Feco-oral route, from human to human

  • Carrier Status: Common, higher in older populations or areas with poor hygiene

  • Pathogenetic Factors: Adhesins, motility, urease production, cytotoxins

Clinical Manifestations of H. pylori

  • Acute Infection: Gastritis

  • Chronic Infection: Chronic diffuse superficial gastritis, which may be asymptomatic

    • Potential development into peptic ulcers, atrophic gastritis, gastric adenocarcinoma, MALTomas

Diagnosis of Helicobacter pylori

Invasive Tests

  • From Biopsy Samples:

    • Histology (silver, Gram, Giemsa stains)

    • Rapid Urease Test (CLO test)

    • Culture (requires microaerophilic conditions)

Non-invasive Tests

  • Breath Test: Labeled urea measurement

  • Serology: Cannot differentiate between chronic and acute infections

  • Fecal Antigen Test

Treatment of H. pylori

  • Indications: Treatment only for symptomatic individuals

  • Eradication Regimen:

    • Proton pump inhibitor + antibiotics (clarithromycin, amoxicillin) for 10 days

    • Failure Management: Biopsy and culture for antibiotic susceptibility testing

Enterohepatic Helicobacter spp.

  • Zoonotic Species: Helicobacter pullorum, Helicobacter cinedi, Helicobacter fennelliae

  • Associations: Gastroenteritis in immunocompromised patients, potential links to inflammatory bowel diseases

Questions?

  • Contact: Pal.agnes@pte.hu