Contents
Cholera is an acute secretory diarrheal illness caused by the bacteria Vibrio cholerae.
Microbiology
Epidemiology:
There are about four million cases of cholera worldwide annually, with over 140,000 deaths attributed to the disease. Nearly 1.8 million people worldwide obtain their drinking water from sources contaminated with human feces that may act as a reservoir for the cholera bacteria. Outbreaks are known to occur, specifically in the developing world where sanitation and water filtration standards may not exist. Currently, cholera is known to be endemic in approximately 50 nations, mostly throughout Asia and Africa. The incidence is tied to a seasonal distribution, depending on the timing of the region’s rainy season. Epidemics can be more widespread, however, involving other parts of the world, including South and Central America. The introduction of the species to a new region with a collapse of hygiene and health services has been known to lead to the propagation of epidemics.
- V. cholerae is found in food (classically shellfish) and poorly sanitized water.
- Large dose is required to develop infectivity.
- Spread: Fecal-oral route and is thus endemic to areas associated with inadequate food and water hygiene
- Factors that increase susceptibility include:
- Proton-pump inhibitors (PPIs) and antihistamine use
- Type O blood
- Poor sanitation
- Overcrowding
- Prior vagotomy
- Helicobacter pylori infection

Vibrio cholerae:
Facultative, gram-negative, comma-shaped, oxidase-positive rod that is prevalent in developing countries.
Cholera toxin-producing (toxigenic) strains:
- O1 serogroup: Responsible for all recent outbreaks
- The O1 serogroup is subdivided into two phenotypically distinct biotypes, El Tor and classical, the second of which is associated with earlier pandemics.
- Both biotypes can be further subdivided into two serotypes, Inaba and Ogawa7. In the past 20 years, El Tor has replaced the classical biotype
- O139 serogroup: First appeared in 1992, as a result of a multi-gene substitution in the O antigen-coding region of a progenitor O1 El Tor strain. Although the O139 serogroup caused devastating outbreaks in the 1990s especially in Asia, the El Tor strain remains the dominant strain globally

Virulence factors:
- Cholera toxin (secreted AB-subunit toxin): The B subunit pentamer binds monosialotetrahexosylgangliosides on absorptive epithelial cells, triggering endocytosis of the enzymatic A subunit, whereupon it ADP ribosylates a subunit of the G protein that controls adenylyl cyclase activity.
- Toxin co-regulated pilus (TCP): Self-binding pilus that tethers bacterial cells together, possibly to resist shearing forces in the host small intestine.
- Lysogenic bacteriophage: Carries genes for cholera toxin and the SXT element that harbours antibiotic resistance genes

Presentation
High-volume fluid loss with electrolyte derangements that can progress to hypovolemic shock and ultimately death characterizes this gastrointestinal disease. The infection is transmitted via the fecal-oral route and can vary in severity.
Clinical manifestations of cholera can range from asymptomatic to profuse diarrhea.
- Common symptoms: Diarrhea, abdominal discomfort, and vomiting
- Stools: Characteristic “rice water” consistency, which can be laced with bile and mucus
- Adult output can reach as high as one liter per hour whereas, in children, it can reach up to 20 cc/kg/hr.

Cholera gravis (severe cholera):
Severe cholera can be distinguished clinically from other diarrheal illnesses due to the profound and rapid loss of fluid and electrolytes. The resulting hypovolemia results in the characteristic manifestations of fluid loss.
- Hypovolemia: Dry oral mucosa, cool skin, and decreased skin turgor
- Poor perfusion → Lactic acidosis (hyperventilation and Kussmaul breathing)
- Electrolyte abnormalities (hypokalemia and hypocalcemia): Generalized muscle weakness and cramping
- Non-anion gap metabolic acidosis
Diagnosis
The diagnosis of cholera can be based on clinical suspicion. The characteristic high volume diarrhea and travel to an endemic area can be sufficient for a diagnosis. As such, laboratory testing is often not required before initiating treatment. The diagnosis can be confirmed, however, by the isolation and culture of V. cholerae from stool isolates.
Differential diagnosis:
- Escherichia coli infection
- Salmonellosis
- Shigellosis
- Typhoid fever
- Rotavirus infection
Management
Fluid resuscitation
The mainstay of treatment of cholera is prompt fluid resuscitation based on the degree of volume depletion. If an estimated 5% to 10% of body weight has been lost, oral rehydration solution should be used. Prompt treatment of severe cholera with fluids can reduce the mortality from over 10% to less than 0.5%.
- Severe cases (hypovolemic shock or > 10% loss of body weight): IV fluids
Antibiotic therapy:
Once an appropriate volume status has been achieved, antibiotic therapy can be initiated.
- Tetracyclines (M/C used class) or doxycycline
- Alternative therapies: Macrolides (erythromycin/azithromycin), or fluoroquinolones (ciprofloxacin)