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 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 diseaseVP1 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 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 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
