Vibrio cholerae

• Causes cholera, a severe diarrheal illness that is transmitted with the fecal-oral route (food or water), and specifically associated with improper sanitation

Microbiology

• Curved, motile Gram-negative bacillus
• Serogroups O1 and O139 cause epidemic cholera, others cause mild gastroenteritis

Pathogenesis

• Can grow in salt water with organic material
• Human are only known hosts
• Ingestion of contaminated water leads to small intestine colonization mediated by TCP (toxin coregulated pili)
  • Vibrio is non-invasive
• Severe secratory diarrhea cause by cholera toxin (CT)
  • CT causes severe secretory diarrhea
  • It enters epithelial cells by binding to a glycosphingolipid, GM1
  • Inside the cell, it increases activity of adenylyl cyclase, causing an increase in cAMP, which causes chloride ion secretion
  • CT is encoded by ctxAB genes, which were added to TCP-positive V. cholera by a bacteriophage

Epidemiology

• 3-5 million people affected annually
• 100-120,000 deaths annually, but likely underestimated
• Typically in poor countries with poor sanitation
• Seven pandemics described since 1817
  • The seventh and current pandemic started in Indonesia in 1961, and is currently still circulating
    • The current strain is called El Tor

Risk Factors

• Limited access to clean water and sanitation
• In endemic countries, Very young less than four
• In newly affected countries, everyone is at risk

Clinical Manifestations

Cholera

• 6h to 5d onset requiring very low innoculum
• Profuse painless watery diarrhea with rice-water stools
  • Up to 1 L/h
• Abdo cramping and nausea
• Only rarely associated with fever, as it is non-invasive
  • More likely to be hypothermic from severe dehydration

Severe cholera (cholera gravis)

• Severe, life threatening dehydration occurs in 10-20%
  • Profuse diarrhea, leading to shock from profound fluid losses, and, eventually, death
• Signs are those of severe dehydration:
  • Lethargy or loss of consciousness
  • Sunken eyes
  • Low skin turgor
  • Low blood pressure and weak pulse
  • Unable to drink

Asymptomatic carriage

• 90% of colonized patients are asymptomatic but still infectious [CITATION NEEDED]
• Among those who are symptomatic, they can shed it for months after illness (though most stop 2-3 days after symptom resolution)

Diagnosis

• Usually clinical diagnosis in low-resource settings
• Stool culture
  • Helpful for determining resistance during outbreaks, but not routinely done
• Rapid stool tests, requiring dark field microscopy to see "shooting star" appearance of vibrios
• Serology, sometimes

Treatment

• Isolation
• Rehydration is the main way to reduce mortality
  • Mild: alert with normal exam
    • Oral rehydration at home, guided by thirst
    • Should be observed until they are reliably replacing their losses, then can be discharged home
  • Moderate: alert to restless, with some abnormalities on exam to suggest dehydration
    • Oral or IV rehydration in hospital
    • Bolus 75 mL/kg over 3-4 hours
    • Replace losses
    • Observe until signs of dehydration resolves and patient peeing
  • Severe: cholera gravis, as described above
    • Aggressive IV rehydration in hospital
    • Bolus >100 mL/kg as rapidly as possible until circulation is restored, then the remainder over 3 hours
    • Replace losses
• Replace electrolytes as needed, but laboratory assistance is not required in most cases
• Antibiotics decrease duration and volume of diarrhea, and are indicated in cases of moderate or severe cholera
  • Doxycycline 300 mg po once, avoided in pregnant women and children <8 years
  • Azithromycin 1 g po once
  • Ciprofloxcin used previously, but increasing resistance
• Avoid antiemetics and antimotility agents
• Consider zinc supplementation in children 10-30 mg daily x5-7 days
• Can use a cholera cot

Choice of fluids

• D5/lactated Ringer's (D5LR) is the preferred IV fluid, though D5-NS can be used if D5LR is not available
  • "Dhaka solution" has more potassium, bicarbonate, and glucose, and is optimal
• NS can be used for circulatory support
• Oral rehydration solutions (ORS) have salt and glucose
  • In an emergency, can add 1/2 tsp salt with 6 tsp sugar in 1 L of clean water

Vaccination

• Dukoral and Shanchol are both killed Vibrio vaccines
• Immunity lasts 6 months to a few years, not approved in children
  • Boosters every 2 years
• Both vaccines are well-tolerated but only 60-80% effective
• During outbreaks, they have about 80% effectiveness

Prognosis

• Depends on context (rich vs poor)

Further Reading

• Cholera Outbreak Training and Shigellosis (COTS) Program: information and tools for managing cholera