Vibrio cholerae

Background

• 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 within the class Gammaproteobacteria, family Vibrionaceae, and genus Vibrio
• Oxidase positive and facultatively anaerobic
• Serotypes differ in O-specific polysaccharide (OSP) chains of lipopolysaccharide (LPS), and are grouped into more than 200 serogroups
  • Serogroups O1 and O139 cause epidemic cholera, while other serogroups cause mild gastroenteritis
  • Serogroup O1 is divided into serotypes Inaba and Ogawa
  • El Tor is a specific biotype of serotype O1
• Halophylic, can grow in salt water with organic material

Pathophysiology

• Ingestion of contaminated water leads to small intestine colonization mediated by TCP (toxin coregulated pili)
• Vibrio is non-invasive but rather causes toxin-mediated disease
• VP1 pathogenic island is associated with pandemic strains of cholera and confers severity
• Severe secratory diarrhea cause by the virulence factor cholera toxin (CT)
  • CT causes severe secretory diarrhea
  • CT comprises 1 A subunit and 5 B subunits
  • It enters epithelial cells by binding of B subunit 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

• Fecal-oral transmission, with humans being only known host
  • Survives in brackish water
• 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 biotype El Tor within serotype O1

Risk Factors

• Limited access to clean water and sanitation
• In endemic countries, those less than 4 years of age
• In newly affected countries, everyone is at risk

Clinical Manifestations

Cholera

• Incubation period Usual incubation period::2 hours to 5 days, depending on the size of the inoculum
• Profuse painless watery diarrhea with rice-water stools, up to 1 L/h when severe
• Abdominal 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
  • Up to 1 L of diarrhea per day, with death occurring in as little as one day
• 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
• Can see significant electrolyte abnormalities due to the secretory diarrhea

Cholera Sicca

• Fluid builds up in abdomen and can cause dehydration and death even without significant bowel movements

Asymptomatic Carriage

• Colonized patients are asymptomatic but still infectious
• Among those who are symptomatic, they can shed it for months after illness (though most stop 2-3 days after symptom resolution)

Differential Diagnosis

• Refer to diarrhea in the returned traveller

Diagnosis

• Usually clinical diagnosis in low-resource settings
  • Essentially all patients 5 years of age and older who present with acute watery diarrhea causing severe dehydration
• 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, with a sensitivity and specificity anywhere from 60 and 100%
• PCR also exists

Management

• 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
  • Ciprofloxacin 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

Rehydration 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 solution (ORS) has salt and glucose
  • In an emergency, can add 1/2 tsp salt with 6 tsp sugar in 1 L of clean water

Prevention

• Improved water hygiene and sanitation is the backbone of long-term prevention, but is expensive and slow to set up

Infection Prevention and Control

• Routine precautions
• Needs contact precaution if:
  • Pediatric patient
  • Incontinent
  • Stool not contained
  • Poor hygiene
  • Patient is contaminating the environment
• Continue until 48 hours after symptoms have resolved

Immunization

• All vaccines in use are based on killed Vibrio cholerae
  • Dukoral is killed whole-cell serotype O1, classic and El Tor biotypes, with additional recombinant cholera toxin subunit B (CtxB)
  • Shanchol (India) is bivalent, including a number of O1 strains as well as O139, without the addition of CtxB
  • Euvichol (South Korea) similar to Shanchol
  • mORCVAX (Vietnam) is similar to Shanchol, but only available locally in Vietnam
• For children, Dukoral is approved for people aged 2 years and older while the others are for ages 1 and older
• Dukoral needs boosters every 2 years (or every 6 months for children younger than 5 years)
• All vaccines are well-tolerated but only 60-80% effective within 6 months (Dukoral) to 5 years (Shanchol and Euvichol)
  • During outbreaks, they have about 80% effectiveness and vaccine rates of at least 50% are needed to interrupt transmission

Further Reading

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