Vibrio cholerae: Difference between revisions

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Vibrio cholerae
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== Background ==
* Causes '''cholera''', a severe diarrheal illness that is transmitted with the fecal-oral route (food or water), and specifically associated with improper sanitation
 
   
  +
*Causes '''cholera''', a severe diarrheal illness that is transmitted with the fecal-oral route (food or water), and specifically associated with improper sanitation
== Microbiology ==
 
   
  +
===Microbiology===
* Curved, motile Gram-negative bacillus
 
* Serogroups O1 and O139 cause epidemic cholera, others cause mild gastroenteritis
 
   
  +
*[[Shape::Curved]], motile [[Stain::Gram-negative]] [[Shape::bacillus]] within the class [[Class::Gammaproteobacteria]], family [[Family::Vibrionaceae]], and genus [[Genus::Vibrio]]
== Pathogenesis ==
 
  +
*Oxidase [[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===
* 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
 
   
  +
*Ingestion of contaminated water leads to small intestine colonization mediated by TCP (toxin coregulated pili)
== Epidemiology ==
 
  +
*''Vibrio'' is non-invasive but rather causes toxin-mediated disease
  +
*Severe secratory diarrhea cause by the virulence factor 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
 
   
  +
*3-5 million people affected annually
== Risk Factors ==
 
  +
*100-120,000 deaths annually, but likely underestimated
  +
*Human are only known hosts
  +
*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, Very young less than four
 
* In newly affected countries, everyone is at risk
 
   
  +
*Limited access to clean water and sanitation
== Clinical Manifestations ==
 
  +
*In endemic countries, those less than 4 years of age
  +
*In newly affected countries, everyone is at risk
   
  +
==Clinical Manifestations==
=== Cholera ===
 
   
  +
===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
 
   
  +
*Incubation period [[Usual incubation period::6 hours to 5 days|Usual incubation period::2 hours to 5 days]], depending on the size of the inoculum
=== Severe cholera (cholera gravis) ===
 
  +
*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
 
   
  +
*Severe, life threatening dehydration occurs in 10-20%
=== Asymptomatic carriage ===
 
  +
**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)
 
   
  +
*Colonized patients are asymptomatic but still infectious
== Diagnosis ==
 
  +
*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
 
   
  +
*Usually clinical diagnosis in low-resource settings
== Treatment ==
 
  +
**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
 
** 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
 
   
  +
*Isolation
=== Choice of fluids ===
 
  +
*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
   
  +
===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
 
   
  +
*D5/lactated Ringer's (D5LR) is the preferred IV fluid, though D5-NS can be used if D5LR is not available
== Vaccination ==
 
  +
**"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 ==
* 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
 
   
  +
* Improved water hygiene and sanitation is the backbone of long-term prevention, but is expensive and slow to set up
== Prognosis ==
 
   
  +
===Immunization===
* Depends on context (rich vs poor)
 
   
  +
*All vaccines in use are based on killed ''Vibrio cholerae''
== Further Reading ==
 
  +
**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==
* [http://www.cotsprogram.com/ Cholera Outbreak Training and Shigellosis (COTS) Program]: information and tools for managing cholera
 
  +
  +
*[http://www.cotsprogram.com/ Cholera Outbreak Training and Shigellosis (COTS) Program]: information and tools for managing cholera
   
 
{{DISPLAYTITLE:''Vibrio cholerae''}}
 
{{DISPLAYTITLE:''Vibrio cholerae''}}

Revision as of 20:30, 18 November 2020

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"Curved" is not in the list (coccus, bacillus, coccobacillus, diplococcus, spirochete, curved, pleomorphic, yeast, mold) of allowed values for the "Shape" property., 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
  • Severe secratory diarrhea cause by the virulence factor 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
  • Human are only known hosts
  • 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
  • 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

  • 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)

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
  • 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 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

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