Vibrio Cholera

Aka: Vibrio Cholera, Cholera, Vibrio Cholerae

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II. History

  1. Various modern outbreaks
    1. Yemen as of 2016-2017 has the largest Cholera outbreak in history
    2. Bangladash (1993 post-monsoon potable water contamination)
    3. Latin America and South America (1991 improper sewage processing)
    4. Indonesia had onset in the 1960s of an ongoing Cholera epidemic
    5. Cholera was limited to Asia until 1817, when it spread to India and then globally
  2. London Physician John Snow (1813-1858)
    1. Famous role in public health history
    2. Linked Cholera outbreak to Broad Street Pump in 1854
      1. Proved Cholera to be a Waterborne Illness
      2. Ghost Map is a literary account of his epidemiological investigation
        1. https://en.wikipedia.org/wiki/The_Ghost_Map
      3. Concurrent epidemic in Italy in 1854
        1. Lead to identification of Vibrio Cholera organism by Filippo Pacini, a florence physician
    3. Snow was also a proponent of Anesthesia in childbirth
      1. Knighted by Queen Victoria on birth of seventh child

III. Pathophysiology

  1. Characteristics
    1. Vibrio Cholera is a facultative Anaerobic Gram Negative Rod in Vibrionaceae family
    2. All Vibrio genus Bacteria are curved (crescent shaped) and motile with a single polar flagellum
  2. Organism survival
    1. Not viable in pure water (stable in salt water)
    2. Survives up to 24 hours in sewerage
    3. Survives in impure water with organics for 6 weeks
    4. Withstands freezing for 3-4 days
    5. Readily killed by drying, heat, or disinfectants
  3. Pathogenesis
    1. Incubation: 4 hours to 5 days (average 1-2 days)
    2. Causes Toxigenic, Secretory Diarrhea (similar but more severe than Enterotoxigenic E. coli or ETEC)
      1. Enterotoxin adheres to intestinal epithelial cell (but does not invade)
      2. Severe fluid loss occurs in Small Bowel
      3. Large Intestine is overwhelmed by large fluid volume
        1. Unable to reabsorb majority of fluid losses
        2. Results in profuse, rice-water Diarrhea (up to 1 Liter/hour)
    3. Cholera Enterotoxin (Choleragen)
      1. Similar to Heat Labile (LT) toxin of Enterotoxigenic E. coli (ETEC)
      2. B-Subunits (5)
        1. Bind GM1 gangliosides on intestinal cell membranes
      3. A-Subunits (2)
        1. Acts at GTP-binding Protein (ADP-ribosylation)
        2. Activates membrane associated adenylate cyclase, converting ATP to cAMP
        3. Increased cAMP levels induce Sodium chloride (NaCl) secretion, and inhibit its reabsorption
        4. Results in osmotic water losses (as well as Electrolytes, e.g. bicarbonate and Potassium)
  4. Transmission
    1. Large infectious dose needed to cause disease
    2. Fecal contamination of food or water
      1. Waterborne Illness (most common)
      2. Foodborne Illness
    3. Heavily soiled hands or utensils
    4. Biological Weapon
      1. Infective aerosol dose: 10-500 organisms

IV. Symptoms

  1. Asymptomatic to severe sudden onset
    1. Only 1 symptomatic patient for every 400 infected
  2. Vomiting
  3. Headache
  4. Intestinal cramping
  5. Low grade fever or afebrile
  6. Painless voluminous Diarrhea
    1. Rice water stools
  7. Fluid losses: 5-10 liters per day (up to 15 liters per day)

V. Signs

  1. Severe Dehydration
  2. Hypovolemia to shock
  3. Manifestations of Electrolyte disturbance (e.g. Hypokalemia, Hypomagnesemia)

VI. Course

  1. Usual duration: 1 week
  2. Death may occur due to severe Dehydration if untreated
    1. Mortality rates approach 50% from Dehydration without aggressive Fluid Replacement
    2. Mortality 0.2% with aggressive rehydration (see below)

VII. Labs

  1. See Acute Diarrhea
  2. Enteric Pathogens Nucleic Acid Test Panels
  3. Stool microscopy
    1. Darting, motile short curved Gram Negative Rods
    2. No or minimal Fecal Occult Blood
    3. No or minimal Fecal Leukocytes
    4. Other microscopy modalities
      1. Darkfield microscopy
      2. Phase contrast microscopy

VIII. Management: General

  1. See Oral Rehydration Therapy
  2. Cholera has a high mortality, not via invasive disease, but via severe Dehydration
  3. Fluid and Electrolyte replacement
    1. Aggressive fluid and Electrolyte replacement is the key to effective management (drops mortality from 50% to 0.2%)
    2. Lactated Ringers is preferred crystalloid if IV hydration is required
    3. Replace Electrolytes (e.g. Potassium)

IX. Management: Antibiotics

  1. Indication: Moderate to severe disease
    1. May shorten the duration of Diarrhea
    2. Reduces Bacterial shedding
  2. Adult Preparations
    1. Tetracycline 500 mg four times daily for 3 days
    2. Doxycycline 300 mg x1 dose or 100 mg bid for 3 days
    3. Azithromycin 500 mg orally daily for 3 days (or 1 g for 1 dose)
    4. Erythromycin 250 mg orally three times daily for 3 days
    5. Ciprofloxacin 1 g orally for 1 dose
  3. Child Preparations
    1. Azithromycin 10 mg/kg/day orally daily for 3 days
    2. Erythromycin 30 mg/kg/day orally divided three times daily for 3 days
  4. References
    1. Gilbert (2016) Sanford Guide, accessed 9/12/2016

X. Prevention

  1. Water Disinfection
    1. Dry heat at 117 degrees C (steam or boiling)
    2. Short exposure to disinfectants
    3. Water chlorination
  2. Good Hygiene
    1. Frequent Hand Washing
    2. Exclusive use of safe water and food
  3. Licensed killed Cholera Vaccine
    1. Indicated during epidemics
    2. Efficacy: 50-86% protection lasts only 6 months
    3. Vaccine schedule
      1. Initial Doses: 0 and 4 weeks
      2. Booster Doses: every 6 months
    4. References
      1. Luquero (2014) N Engl J Med 370(22): 2111-20 +PMID: 24869721 [PubMed]

XI. Prognosis: Indicators of severe disease and worse outcomes

  1. Difficult access to medical services
  2. Blood Type O (45% of U.S. persons)
  3. Low gastric acidity
    1. Antacid therapy
    2. Partial gastrectomy

XII. Resources

  1. CDC Cholera
    1. http://www.cdc.gov/cholera/index.html
  2. WHO Cholera
    1. http://www.who.int/cholera/en/

XIII. References

  1. Harris (2012) Lancet 379(9835): 2466-76 +PMID:22748592 [PubMed]
  2. Lippi (2016) Microbiol Spectr 4(4) +PMID: 27726771 [PubMed]

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