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Cholera
Updated: Feb 26, 2010
Introduction
Background
The word cholera is derived from a Greek term that means "flow of bile." Cholera
is caused by Vibrio cholerae, the most feared epidemic diarrheal disease because
of its severity. Dehydration and death can occur within hours of infection.
Robert Koch discovered V cholerae in 1883 during an outbreak in Egypt. The
organism is a comma-shaped, gram-negative aerobic bacillus whose size varies
from 1-3 µm in length by 0.5-0.8 µm in diameter. Its antigenic structure consists of
a flagellar H antigen and a somatic O antigen. The differentiation of the latter
allows for separation into pathogenic and nonpathogenic strains. V cholerae O1
and V cholerae O139 are associated with epidemic cholera.
Classification of V cholerae includes more than 200 serogroups; only a few of
these have been demonstrated to possess the cholera gene.1
V cholerae O1 is classified into 2 major biotypes: classic and El Tor. Currently,
El Tor is the predominant cholera pathogen. Organisms in both biotypes are
subdivided into serotypes according to the structure of the O antigen, as follows:

• Serotype Inaba - O antigens A and C

• Serotype Ogawa - O antigens A and B
• Serotype Hikojima - O antigens A, B, and C

Pathophysiology
The infectious dose of bacteria required to cause clinical disease varies by the
mode of administration. If ingested with water, the infectious dose is 103 -106
organisms. When ingested with food, fewer organisms (102 -104 organisms) are
required to produce disease.
The use of antacids, histamine receptor blockers, and proton pump inhibitors
increases the risk of cholera infection and predisposes patients to more severe
disease as a result of reduced gastric acidity. The same applies to patients with
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chronic gastritis secondary to Helicobacter pylori infection or those who have

undergone a gastrectomy.
V cholerae O1 and V cholerae O139 cause clinical disease by producing an
enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of
the small intestine. The enterotoxin is a protein molecule composed of 5 B subunits
and 2 A subunits. The B subunits are responsible for binding to a ganglioside
(monosialosyl ganglioside, GM1) receptor located on the surface of the cells that
line the intestinal mucosa.
The activation of the A1 subunit by adenylate cyclase is responsible for the net
increase in cyclic adenosine monophosphate (cAMP). cAMP blocks the absorption
of sodium and chloride by the microvilli and promotes the secretion of chloride
and water by the crypt cells. The result is watery diarrhea with electrolyte
concentrations isotonic to those of plasma.
Fluid loss originates in the duodenum and upper jejunum; the ileum is less
affected. The colon is usually in a state of absorption because it is relatively
insensitive to the toxin. However, the large volume of fluid produced in the upper
intestine overwhelms the absorptive capacity of the lower bowel, resulting in
severe diarrhea.
The enterotoxin acts locally and does not invade the intestinal wall. As a result,
few neutrophils are found in the stool.
Frequency
United States
Among the millions of Americans who travel to endemic areas in foreign
countries, only 42 imported cases of cholera were reported from 1965-1991.
However, in August 1986, 4 cases of cholera were acquired in Louisiana and 1
case was acquired in Florida. These patients were hospitalized with severe diarrhea
and had stool cultures that yielded toxigenic V cholerae O1 Inaba. Although the
vehicle of transmission was not specifically identified, the patients had consumed
seafood within 5 days prior to symptom onset. Toxigenic V cholerae O1 El Tor
Inaba appears to have an environmental reservoir on the US Gulf Coast. Of note,
none of the toxigenic V cholerae strains associated with the US Gulf Coast (01,
0141, and 075) have caused more than sporadic cases and small outbreaks of
diarrhea in the United States.1
Between January 1, 1995, and December 31, 2000, 61 cases of cholera were
reported in 18 states and 2 US territories. Thirty-seven were travel-associated
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cases; the other 24 cases were acquired in the United States.2 Individuals living in
the United States most often acquire cholera through travel to cholera-endemic
areas or through consumption of undercooked seafood from the Gulf Coast or
foreign waters.
In 2005, 12 cases were reported to the World Health Organization (WHO), and, of
these, 8 were imported. In October 2005, toxigenic V cholerae infection due to the
consumption of contaminated and improperly cooked seafood was reported from
Louisiana after Hurricanes Katrina and Rita.3
From 2003-2007, V cholerae serogroup 075 strains possessing the cholera toxin
were isolated from 6 patients (3 in Georgia, 2 in Alabama, and 1 in South Carolina)
with severe diarrhea.1
International
Since 1817, 7 cholera pandemics have occurred. The first 6 occurred from 1817-
1923 and were probably the result of V cholerae O1 of the classic biotype. The
pandemics originated in Asia, with subsequent spread to Europe and the Americas.
The seventh pandemic was caused by V cholerae O1 El Tor, which was first
isolated in Egypt in 1905. The pandemic originated from the Celebes Islands,
Indonesia, in 1961; this pandemic affected more countries and continents than the
previous 6 pandemics. The last extension of this pandemic was into Latin America.
The total number of cases officially reported from 1997 through March 26, 1998,
was 120,867; 89% of these cases were reported in Africa.
In 2002, all regions of the world continued to report cholera caused by V cholerae
O1 El Tor; that year, 142,311 cases and 4564 deaths were reported to the WHO by
52 countries. Compared with 2001, the number of reported cases almost doubled.
Between 2002 and 2004, the number of cases reported to the WHO decreased
worldwide. In 2005, however, the number reported increased 30% to a total of
131,943 cases in 52 countries. In 2007, 53 countries reported 177,693 cholera
cases and 4,031 cholera deaths. Areas poor in resources continued to report the
vast majority of cases.
In October 1992, an epidemic of cholera emerged from Madras, India, as a result
of a new serogroup, O139 (also known as Bengal). This Bengal strain has now
spread throughout Bangladesh and India and into neighboring countries in Asia.
Some experts regard this as an eighth pandemic. Thus far, 11 countries in
Southeast Asia have reported isolation of this Vibrio serogroup.
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Mortality/Morbidity
If untreated, the disease rapidly results in dehydration and can result in death in
more than 50% of infected individuals. The mortality rate is increased in pregnant
women and children.
Age
People of all ages are susceptible, although infants are protected through
maternally transmitted antibodies during breastfeeding. An attack of the classic
biotype of V cholerae usually protects against recurrent infection by either biotype,
but El Tor cholera does not protect against further attacks.
Clinical
History
After a 24- to 48-hour incubation period, symptoms begin with the sudden onset
of painless watery diarrhea that may quickly become voluminous and is often
followed by vomiting. The patient may experience accompanying abdominal
cramps. Fever is typically absent. The diarrhea has a "rice water" appearance and a
fishy odor. In patients with severe disease, the stool volume can exceed 250 mL/kg
in the first 24 hours. Without replacement of fluids and electrolytes, hypovolemic
shock and death ensue.
However, most V cholerae infections are asymptomatic, and mild to moderate
diarrhea due to V cholerae infection may not be clinically distinguished from other
causes of gastroenteritis. An estimated 5% of infected patients will develop cholera
gravis, ie, severe watery diarrhea, vomiting, and dehydration.
Physical
Clinical signs of cholera parallel the level of volume contraction. The amount of
fluid loss and the corresponding clinical signs of cholera are as follows:

• With 3-5% loss of normal body weight - Excessive thirst

• With 5-8% loss of normal body weight - Postural hypotension, tachycardia,
weakness, fatigue, and dry mucous membranes or dry mouth
• With greater than 10% loss of normal body weight - Oliguria; glassy or
sunken eyes; sunken fontanelles in infants; weak, thready, or absent pulse;
wrinkled "washerwoman" skin; somnolence; and coma
• Pediatric patients
o In pediatric patients, the primary signs are similar to those in adults.
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o Children with severe cholera may present with signs that are rarely
seen in adults. A child with cholera is usually very drowsy, and coma
is not uncommon.
o In addition, pediatric patients may have convulsions that appear to be
related, in part, to hypoglycemia because patients exhibit some
response to intravenous dextrose.
o Another significant difference from the adult presentation is that
children are often febrile.

Causes

• Cholera is transmitted via the fecal-oral route. Owing to the relatively large
infectious dose, transmission occurs almost exclusively via contaminated
water or food. Toxigenic V cholerae O1 has been shown to survive in crabs
boiled for 8 minutes, but not in crabs boiled for 10 minutes. Transmission
via direct person-to-person contact is rare.
• V cholerae is unable to survive in an acidic environment. Therefore, any
condition that reduces gastric acid production increases the risk of
acquisition. In addition, although the pathophysiology is not understood,
individuals with blood group O are at increased risk of developing El Tor
cholera.