Vibrio cholerae Case File

Vibrio cholerae Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 23

A 35-year-old woman presents to the emergency room with a 2-day history of severe diarrhea and vomiting. Her symptoms started shortly after returning from a mission trip that she took with her church to a rural area in central Africa. She recalls eating shrimp that seemed undercooked. Her symptoms started abruptly, with watery diarrhea followed by vomiting. She has not had a fever and denies abdominal pain. On examination, her temperature is 37.2°C (98.9°F), pulse is 115 beats per minute, and blood pressure is 80/50 mm Hg. Her mucous membranes are dry, and her eyes appear sunken. Her skin is dry and tents when lightly pinched. Her abdomen has hyperactive bowel sounds but is soft and nontender. Her stool is watery and tests negative for blood. A complete blood count shows an elevated white blood cell count and an elevated hematocrit. A metabolic panel shows hypokalemia, low serum bicarbonate, and prerenal azotemia. You assess this patient to be in hypovolemic shock and metabolic acidosis, and institute appropriate therapy.

◆ What organism is most likely to be identified on stool culture?

◆ What is the cause of this patient’s diarrhea?

ANSWERS TO CASE 23: Vibrio cholerae

Summary: A 35-year-old woman recently traveled to Africa and developed diarrhea causing hypovolemic shock and metabolic acidosis. She remembers eating undercooked shrimp.

◆ Most likely etiologic agent: Vibrio cholerae

◆ Cause of the diarrhea: Hypersecretion of water and electrolytes into the intestinal lumen caused by cholera toxin

CLINICAL CORRELATION

The first priorities as with any patient are the ABCs: airway, breathing, circulation. This patient is in hypovolemic shock, meaning insufficient circulation to maintain tissue perfusion needs. The most important step in intervention is volume repletion, usually with intravenous isotonic saline solution. A likely therapy would be 3 L of normal saline intravenously.

Vibrio species are found in saltwater and infections usually occur in the spring and summer. Transmission is by either consumption of contaminated shellfish or traumatic injury associated with infected water. The disease cholera is caused by toxigenic strains of V. cholerae (01 and 0139 serotypes). Vibrio cholerae is spread by ingestion of contaminated water or food. The organism is sensitive to gastric acid; therefore, the dose required to cause an infection is high. Conditions that reduce gastric acid, such as antacid medications or achlorhydria, increase the risk of infection.

The hallmark of cholera is severe watery diarrhea with mild to severe dehydration because of production of toxin by the organism. In cases of severe dehydration, patients have a nonpalpable pulse and very low blood pressure. Fever is usually not present. Patients may become obtunded with sunken eyes and dry mucous membranes.

Vibrio parahaemolyticus is associated with gastroenteritis that is selflimited even though patients present with explosive watery diarrhea, with abdominal pain and fever. The disease rarely progressed to the severity of dehydration of V. cholerae. Vibrio vulnificus is more often associated with wound infections, that is, cellulitis, rather than gastroenteritis. In alcoholic patients or those with other underlying liver disease, the organism can become disseminated and be associated with a high mortality rate.

APPROACH TO SUSPECTED Vibrio INFECTION

Objectives

1. Know the structure, physiology, and virulence factors of V. cholerae.
2. Know the reservoirs and mechanisms of spread of V. cholerae and the mechanism of action of the cholera toxin in causing disease.

Definitions

Azotemia: Buildup in the blood of nitrogenous end-products of protein metabolism.

Obtunded: Loss or dulling of sensations.

DISCUSSION

Characteristics of Vibrio

Vibrio species are motile, curved, gram-negative bacilli with a single polar flagellum. They are facultative anaerobic organisms. Their natural environment is saltwater, where they can multiply freely, and it has been found in shellfish and plankton. The major human pathogens are V. parahaemolyticus, V. vulnificus, and Vibrio cholerae.

Over 200 serotypes of V. cholerae have been identified, based on their O antigen serogroup. Serotype O1 has been responsible for the major cholera pandemics of the past 200 years, but serotype O139 has been identified as contributing to disease since 1992.

The major virulence of this organism is its enterotoxin. The toxin consists of five B subunits, which bind to mucosal cell receptors and allow for release of the single A subunit into the cell. The A subunit activates adenyl cyclase, resulting in the hypersecretion of water, sodium, potassium, chloride, and bicarbonate into the intestinal lumen.

Bacteria that survive transit through the stomach can colonize the upper small intestine. Colonization pili facilitate attachment to the intestinal mucosa. The volume of the secreted fluid and electrolytes can overwhelm the gastrointestinal tract’s ability to reabsorb them, resulting in large volumes of watery diarrhea. The loss of an isotonic, bicarbonate-containing fluid results in dehydration, hypovolemia, metabolic acidosis, hemoconcentration, and hypokalemia.

Diagnosis

The presumptive diagnosis of Vibrio disease can be made after history of association with saltwater, either involving trauma or consumption of raw shellfish. The watery diarrhea associated with V. parahaemolyticus cannot be easily distinguished clinically from other forms of bacterial gastroenteritis. Cellulitis caused by V. vulnificus should be diagnosed rapidly to avoid mortality. History of recent exposure to seawater is helpful in making a presumptive diagnosis.

The diagnosis of cholera should be suspected in those with severe diarrheal illness who live in or have traveled to an endemic area. Diagnosis of Vibrio infection can be confirmed by culturing stool or wound samples. Gram stain of wound or blood cultures may demonstrate a characteristic curved appearance to the gram-negative bacilli.

Most of the Vibrio species require salt for growth and therefore specialized media, such as thiosulfate citrate bile salts sucrose (TCBS) agar. Most of the Vibrio species will grow on blood agar and may appear β-hemolytic, but poor growth is seen on MacConkey agar. Vibrio cholerae appear as yellow colonies, and V. parahaemolyticus and V. vulnificus appear as green colonies on TCBS agar.

Treatment and Prevention

The treatment of cholera involves volume replacement with isotonic, bicarbonate-containing fluids, either using oral rehydration solutions in mild to moderate dehydration or IV fluids, such as Ringer lactate, in the profoundly dehydrated or those unable to tolerate oral intake. Oral antibiotics can be given to kill the bacteria and decrease the duration of the illness, but do not take away the need for appropriate rehydration therapy. Most commonly administered antimicrobial is doxycycline.

Treatment with antimicrobials is not usually needed for gastroenteritis caused by V. parahaemolyticus. Wound infections or bacteremia caused by V. vulnificus require rapid administration of antimicrobials such as tetracycline or a quinolones. Prevention of cholera includes improvement of

hygienic practices including treatment of the potable water supply with either heat or chlorine and ensuring thorough cooking of seafood. Research is ongoing to perfect a vaccine to prevent cholera.

COMPREHENSION QUESTIONS

[23.1] An individual experiences diarrhea after eating raw shellfish in San Francisco. What is the most probable cause of the problem?

A. Campylobacter jejuni

B. Salmonella choleraesuis

C. Shigella dysenteriae

D. Vibrio parahaemolyticus

E. Yersinia enterocolitica

[23.2] Which of the following statements is true of cholera enterotoxin?

A. Appears to produce its effect by stimulating adenyl-cyclase activity in mucosal cells

B. Causes destruction of the intestinal mucosa allowing for invasive infection

C. Causes a net efflux of ions and water from tissue into the lumen of the large intestine

D. Is a protein with a molecular weight of approximately 284,000 daltons

[23.3] Fever, leukopenia, disseminated intravascular coagulation, and hypotension caused by members of the Enterobacteriaceae family are most strongly associated with which of the following structures?

A. H antigens

B. K antigens

C. Lipid A

D. Polysaccharides

E. R antigens

[23.4] A 50-year-old man recently visited India and developed diarrhea before returning to the United States. Vibrio cholerae O1 (El Tor, Ogawa) was isolated from his stool. Which of the following is the biotype of the V. cholerae strain?

A. Classical

B. El Tor

C. 10

D. Ogawa

Answers

[23.1] D. Vibrio parahaemolyticus is a halophilic bacterium that causes acute gastroenteritis following ingestion of contaminated seafood such as raw fish or shellfish. After 12–24 hours, the patient develops nausea and vomiting, abdominal cramps, fever, and watery to bloody diarrhea. It is usually self-limited in 1–4 days, requiring only restoration of water and electrolytes. All other answer options could produce episodes of gastroenteritis, but the halophilic nature of V. parahaemolyticus and seafood is recognized as a classic combination.

[23.2] A. The clinical correlation section of this case study summarizes the action of the V. cholerae enterotoxin quite well. It can be the cause of 20–30 L/day diarrheal output, resulting in dehydration, shock, acidosis, and death. It is antigenically related to the LT of Escherichia coli, has a molecular weight of approximately 84,000 daltons, does not damage the mucosa, and affects the small intestine.

[23.3] C. The lipopolysaccharide (LPS) of gram-negative cell walls consists of a complex lipid, lipid A, to which is attached a polysaccharide made up of a core and a terminal series of repeat units. LPS is attached to the outer membrane by hydrophobic bonds and is required for the function of many outer membrane proteins. LPS is also called endotoxin. All the toxicity resides in the lipid A component. Endotoxin (lipid A) can activate complement, resulting in inflammation and the clinical features referred to in the question.

[23.4] B. The O antigen of Vibrio species has been given numbers to indicate biotype, a form of subdivision for strains of cholera organism. Vibrio cholerae serogroups O1 and O139 have long been recognized as strains responsible for epidemic and pandemic cholera. There have been six pandemics from 1817 to 1923, most likely caused by the O1 subtype. A new pandemic caused by the El Tor biotype started in Asia in 1961 and spread to Central and South America by 1991. The disease and biotype is rare in North America, but it does have an endemic focus on the Gulf of Mexico coastal areas (Louisiana and Texas).

MICROBIOLOGY PEARLS ❖ The A subunit of the Vibrio enterotoxin activates adenyl cyclase, resulting in the hypersecretion of water, sodium, potassium, chloride, and bicarbonate into the intestinal lumen. ❖ The predominant clinical presentation of Vibrio gastroenteritis is watery diarrhea. ❖ The Vibrio organism appears as gram-negative, curved, motile bacilli. Vibrio gastroenteritis or cholera is associated with consumption of contaminated seafood or water. ❖ Vibrio vulnificus is associated with cellulitis caused by trauma incurred in a seawater environment and carries a high mortality rate if not treated rapidly. ❖ Vibrio species require salt for growth and can be differentiated from other organisms by growth on TCBS agar.

REFERENCES

Murray PR, Rosenthal KS, Pfaller MA. Vibrio, Aeromonas, and Plesiomonas. In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:339–45. 

Neill MA, Carpenter CCJ. Other pathogenic vibrios. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed. Philadelphia, PA: Churchill Livingstone, 2005:2544–48. 

Seas C, Gotuzzo E. Vibrio cholerae. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed. Philadelphia, PA: Churchill Livingstone, 2005:2553–44.

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