Continuing Education Activity

Cholera is an acute secretory diarrheal illness caused by the bacteria Vibrio cholerae. It is estimated to cause upwards of four million cases per year, worldwide. High-volume fluid loss with electrolyte derangements that can progress to hypovolemic shock and ultimately death characterizes this gastrointestinal disease. This activity describes the evaluation and management of cholera and highlights the role of the interprofessional team in improving care for affected patients.

Objectives:

• Describe the pathophysiology of cholera.
• Outline the typical presentation of a patient with cholera.
• Describe the management considerations for patients with cholera.
• Outline the importance of collaboration and coordination among the interprofessional team to enhance the management of cholera and associated acute secretory diarrheal illnesses in order to improve patient outcomes and prevent spread.

Introduction

Cholera is an acute secretory diarrheal illness caused by the bacteria Vibrio cholerae. It is estimated to cause upwards of four million cases per year, worldwide. High-volume fluid loss with electrolyte derangements that can progress to hypovolemic shock and ultimately death characterizes this gastrointestinal disease.[1][2][3] The infection is transmitted via the fecal-oral route and can vary in severity. The key is replacing the fluid and electrolytes lost as soon as possible.

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]

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

Deterrence and Patient Education

In endemic areas, the patient and the family need to be educated about personal hygiene, boiling water, and improving sanitation. The prevention of cholera rests on improving public health measures like proper sewage disposal and ensuring clean water for drinking. Much of the contaminated water is used to wash the fruits and vegetables, and also to fertilize crops, which creates a never-ending cycle of cholera. Food handlers must be educated on personal hygiene and proper handwashing.

Regarding the prevention of illness in travelers, the centerpiece of counteracting transmission is adequate sanitation and water filtration. They should be educated to avoid undercooked seafood and raw fruits and vegetables. Tap water should be avoided but can be filtered or boiled to reduce the risk of transmission of V. cholerae. In the United States, a live attenuated oral cholera vaccine is licensed for use in adults ages 18 to 64 who travel to an area of active cholera transmission. A single dose is taken, ideally 10 days before travel to an endemic area. It should be administered separately from systemic antibiotic use, which can alter the effectiveness of the vaccine. Efficacy was shown to be 80% after 3 months of vaccination. Worldwide, three killed whole-cell oral vaccines are also available for use.

Enhancing Healthcare Team Outcomes

Cholera usually occurs in epidemics and thus is best managed by an interprofessional team. Many guidelines have been established to manage cholera outbreaks. The most important feature of cholera outbreaks is to be aggressive and proactive in rehydration. This infectious disorder can quickly lead to death if not diagnosed early. Rapid identification of the infected patient is vital as prompt treatment will prevent further cases.

Patient education is key. Water should be boiled before consumption. Since contamination via food is common, all foods and fruits should be washed with clean water. Personal hygiene should be improved and hand washing is essential. In many countries, there are now established surveillance and prompt reporting systems set up to contain the cholera epidemic. There is usually a team of nurses and other healthcare workers who provide an alert to outbreaks so that a coordinated response is initiated. The key feature to prevent outbreaks is to modify human behavior and control environmental conditions. Education is key. [Level 5][12][13]

For travelers to the tropics where cholera outbreaks have occurred, the pharmacist should educate them on basic hygiene, washing food with clean water, and only drinking bottled water. Even though vaccines are available, the risk of a traveler acquiring cholera is low. The pharmacist should be aware of the recommendations for use of the cholera vaccine and who should not receive it. [Level 5][6][14]

Outcomes

Today the morbidity and mortality of cholera are much lower than in past eras. The key reason is that healthcare workers are aware of the importance of hydration and replenishing electrolytes. In the past, without hydration, the mortality was close to 50%, but today the mortality rates are less than 5%. The key element of treatment is to start rehydration at the onset of symptoms. [Level 5][15]