Cholera

Etiology

Vibrio cholerae is a facultative, gram-negative, comma-shaped, oxidase-positive rod that is prevalent in developing countries. Two serotypes have been identified to cause outbreaks. O1 is responsible for all recent outbreaks, whereas O139 causes sporadic outbreaks, specifically in Asia. There is no etiologic difference between the two. V. cholerae is found in food (classically shellfish) and poorly sanitized water. The bacteria is known to spread via the fecal-oral route and is thus endemic to areas associated with inadequate food and water hygiene.[4][5]

The organism is acquired via the fecal-oral route and a large dose is required to develop infectivity. Factors that increase susceptibility include:

• Use of proton-pump inhibitors (PPIs) and antihistamines
• Having type 0 blood
• Poor sanitation
• Overcrowding
• Prior vagotomy
• Helicobacter pylori infection

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.[6][7]

Pathophysiology

Ingestion of V. cholerae can lead to colonization of the small intestine. Its flagella allow the organism to swim through mucus and arrive at the intestinal wall. There, toxigenic V. cholerae produces toxin-coregulated pilus that attaches to gangliosides receptors in the mucosal wall. Cholera toxin is produced, which ADP-ribosylates the Gs subunit of the G protein complex in the gut epithelium. This leads to constitutive action of adenylate cyclase, thereby increasing cAMP intracellularly. As a result, increased secretion of chloride, bicarbonate, sodium, and potassium is observed. The secretion of these electrolytes pulls water out of the intestinal cells osmotically, thereby causing diarrhea.

Host susceptibility is affected by previous exposure to the organism which can result in immunity, although this is dependent on the biotype and serotype of the previous organism encountered. Since it is a labile acid organism, a large inoculation dose is required to cause infection in a healthy adult. This can explain why lowered gastric acidity (as seen in cases of achlorhydria) can lower the threshold needed for the bacteria to cause infection. Interestingly, blood type O has also been associated with an increased likelihood of infection. The mechanism of this increased susceptibility to disease is not yet clear.[8][9]

The use of proton pump inhibitors and antihistamines can increase the risk of infection and make the patient susceptible to more severe symptoms. The fluid losses typically occur from the duodenum, whereas the colon is insensitive to the toxin. Because the enterotoxin has a local effect and is not invasive, in most cases no neutrophils are observed in fecal specimens.

History and Physical

Clinical manifestations of cholera can range from asymptomatic to profuse diarrhea. Common symptoms include diarrhea, abdominal discomfort, and vomiting. Severe cholera can be distinguished clinically from other diarrheal illnesses due to the profound and rapid loss of fluid and electrolytes. The stools are often described to have a “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.

The resulting hypovolemia results in the characteristic manifestations of fluid loss, including dry oral mucosa, cool skin, and decreased skin turgor. Poor perfusion of body tissue can result in lactic acidosis, thereby causing hyperventilation and Kussmaul breathing. In addition, electrolyte abnormalities such as hypokalemia and hypocalcemia can be responsible for generalized muscle weakness and cramping.

Evaluation

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. Culture can be enhanced via the use of selective media with a high pH that suppresses the growth of intestinal microflora while allowing V. cholerae to multiply. Likewise, rapid tests can be employed to identify the O1 or O130 antigen in stool samples. Dipsticks and darkfield microscopy of the stool are available methods that can be used to identify or visualize the organism rapidly.[1]

Treatment / Management

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. Clinical trials have shown that rice-based oral rehydration solution can shorten the duration of diarrhea and the amount of stool loss. In an emergency, a solution can be made, consisting of one liter of water, mixed with six teaspoons of sugar and a half teaspoon of salt. For patients in hypovolemic shock or greater than 10% loss of body weight, intravenous fluids should be administered. Approximately 100 mL/kg of lactated ringers should be administered during the first three hours. Prompt treatment of severe cholera with fluids can reduce the mortality from over 10% to less than 0.5%.[7][10][11](A1)

Once an appropriate volume status has been achieved, antibiotic therapy can be initiated. Tetracyclines are the most commonly used class. A single 300 mg dose of doxycycline or 500 mg of tetracycline every 6 hours for 2 days has been shown to reduce disease duration. However, resistance is common in certain areas, and thus alternative therapies include macrolides such as erythromycin and azithromycin, or fluoroquinolones such as ciprofloxacin.

Differential Diagnosis

• Escherichia coli infection
• Salmonellosis
• Shigellosis
• Typhoid fever
• Rotavirus infection

Prognosis

Without hydration, mortality rates in excess of 50% have been reported. The mortality rates are higher in children, pregnant women, and the elderly. Overall, the mortality rates have decreased because of better access to healthcare, improved sanitation, and education.

Complications

• Dehydration
• Acute tubular necrosis
• Renal failure
• Severe hypotension
• Death