CHOLERA
Cholera is an acute infection of the small bowel by the gram-negative bacterium Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria, and circulatory collapse. Infection is typically through contaminated water or shellfish. Diagnosis is by culture or serology. Treatment is vigorous rehydration and electrolyte replacement plus doxycycline.
The causative organism, V. cholerae serogroups O1 and O139, is a short, curved, motile, aerobic, gram-negative bacillus that produces enterotoxin, a protein that induces hypersecretion of an isotonic electrolyte solution by the small-bowel mucosa. Humans are the only known natural host for V. cholerae. After penetrating the mucus layer, these organisms colonize the epithelial lining of the gut and secrete cholera toxin. These organisms do not invade the intestinal wall; thus, few or no white blood cells are found in stool.
Both the El Tor and classic biotypes of V. cholerae O1 can cause severe disease. However, mild or asymptomatic infection is much more common with the currently predominant El Tor biotype and with non-O1 and non-O139 serogroups of V. cholerae.
HOW CHOLERA CAN BE TRANSMITTED
Cholera is spread by ingestion of water, shellfish, or other foods contaminated by the excrement of people with symptomatic or asymptomatic infection. Household contacts of patients with cholera are at high risk of infection, which probably occurs through shared sources of contaminated food and water. Person-to-person transmission is less likely to occur because a large inoculum of organism is needed to transmit the infection.
Cholera is endemic in portions of Asia, the Middle East, Africa, South and Central America, and the Gulf Coast of the US. In 2010, an outbreak started in Haiti and lasted until 2017. It later spread to the Dominican Republic and Cuba. During this outbreak, over 820,000 people became ill, and nearly 10,000 died. Cases transported into Europe, Japan, and Australia have caused localized outbreaks. An outbreak in Yemen started in 2016 and has not yet ended. This outbreak has had even greater devastating effects. Over 2.5 million people in Yemen have become ill, and almost 4,000 have died. It is thought to be the largest, fastest-spreading cholera outbreak in modern history.
In endemic areas, outbreaks usually occur during warm months. The incidence is highest in children. In newly affected areas, epidemics may occur during any season, and all ages are equally susceptible.
A milder form of gastroenteritis is caused by noncholera V. cholerae strains O1 and O139, which do not produce cholera toxin.
Susceptibility to infection varies and is greater for people with blood type O. Because vibrios are sensitive to gastric acid, hypochlorhydria and achlorhydria are predisposing factors.
People living in endemic areas gradually acquire a natural immunity.
SYMPTOMS AND SOGNS OF CHOLERA
The incubation period for cholera is 1 to 3 days.
Cholera can be subclinical, a mild and uncomplicated episode of diarrhea, or a fulminant, potentially lethal disease.
Abrupt, painless,
watery diarrhea and vomiting are usually the initial symptoms.
Significant nausea is typically absent.
Stool loss in adults may exceed 1 L/hour but is usually much less. Often, stools consist of white liquid void of fecal material (rice-water stool).
The resultant severe water and electrolyte depletion leads to intense thirst, oliguria, muscle cramps, weakness, and marked loss of tissue turgor, with sunken eyes and wrinkling of skin on the fingers. Hypovolemia, hemoconcentration, oliguria and anuria, and severe metabolic acidosis with potassium depletion (but normal serum sodium concentration) occur. If cholera is untreated, circulatory collapse with cyanosis and stupor may follow. Prolonged hypovolemia can cause renal tubular necrosis.
Most patients are free of V. cholerae within 2 weeks after cessation of diarrhea; chronic biliary tract carriers are rare.
DIAGNOSIS OF CHOLERA
- Stool culture and serogrouping/subtyping
- Diagnosis of cholera is confirmed by stool culture (use of selective media is recommended) plus subsequent serogrouping/subtyping. Tests for V. cholerae are available in reference laboratories;
- polymerase chain reaction (PCR) testing is also an option.
- Rapid dipstick testing for cholera is available for public health use in areas with limited access to laboratory testing, but specificity of this test is suboptimal, so dipstick-positive specimens should be confirmed by culture if possible.
Cholera should be distinguished from clinically similar disease caused by enterotoxin-producing strains of Escherichia coli and occasionally by Salmonella and Shigella.
- Serum electrolytes, blood urea nitrogen, and creatinine should be measured.
TREATMENT OF CHOLERA
- Fluid replacement
- Doxycycline, azithromycin, furazolidone, trimethoprim/sulfamethoxazole (TMP/SMX), or ciprofloxacin, depending on results of susceptibility testing
Fluid replacement
Replacement of fluid loss is essential. Mild cases can be treated with standard oral rehydration formulas. Rapid correction of severe hypovolemia is lifesaving. Prevention or correction of metabolic acidosis and hypokalemia is important. For hypovolemic and severely dehydrated patients, IV replacement with isotonic fluids should be used (see oral rehydration). Water should also be given freely by mouth.
To replace potassium losses, potassium chloride 10 to 15 mEq/L (10 to 15 mmol/L) can be added to the IV solution, or oral potassium bicarbonate 1 mL/kg of a 100-g/L solution can be given 4 times a day. Potassium replacement is especially important for children, who tolerate hypokalemia poorly.
Once intravascular volume is restored (rehydration phase), amounts for replacement of continuing losses should equal measured stool volume (maintenance phase). Adequacy of hydration is confirmed by frequent clinical evaluation (pulse rate and strength, skin turgor, urine output). Plasma, plasma volume expanders, and vasopressors should not be used in place of water and electrolytes.
Oral glucose-electrolyte solution is effective in replacing stool losses and may be used after initial IV rehydration, and it may be the only means of rehydration in epidemic areas where supplies of parenteral fluids are limited. Patients who have mild or moderate dehydration and who can drink may be rehydrated with the oral solution (about 75 mL/kg in 4 hours). Those with more severe dehydration need more and may need to receive the fluid by nasogastric tube.
The oral rehydration solution (ORS) recommended by the World Health organization (WHO) contains 13.5 g glucose, 2.6 g sodium chloride, 2.9 g trisodium citrate dihydrate (or 2.5 g potassium bicarbonate), and 1.5 g potassium chloride per liter of drinking water. This solution is best prepared using widely available, premeasured, sealed packets of glucose and salts; one packet is mixed with 1 L of clean water. Using such prepared ORS packets minimizes the possibility of error when untrained people mix the solution. If ORS packets are not available, a reasonable substitute can be made by mixing half a small spoon of salt and 6 small spoons of sugar in 1 L of clean water. The ORS should be continued ad libitum after rehydration in amounts at least equal to continuing stool and vomitus losses.
Solid food should be given only after vomiting stops and appetite returns.
Antimicrobials
Early treatment with an effective oral antimicrobial eradicates vibrios, reduces stool volume by 50%, and stops diarrhea within 48 hours. The choice of antimicrobial should be based on the susceptibility of V. cholerae isolated from the community.
Doxycycline is recommended as first-line treatment for adults (including pregnant women) and children. If resistance to doxycycline is documented, azithromycin and ciprofloxacin are alternative options for the Use of Antibiotics for the Treatment of Cholera) for susceptible strains include
Doxycycline: For adults, including pregnant women and children ≥ 12 years old, a single dose of 300 mg; for children < 12 years old, a single dose of 2 to 4 mg/kg
Azithromycin: For adults, including pregnant women and children ≥ 12 years old, a single dose of 1 g; for children < 12 years old, a single dose of 20 mg/kg (maximum 1 g)
Ciprofloxacin: For adults, including pregnant women and children ≥ 12 years old, a single dose of 1 g; for children < 12 years old, a single dose of 20 mg/kg (maximum 1 g)
PREVENTION OF CHOLERA
For control of cholera, human excrement must be correctly disposed of, and water supplies purified. In endemic regions, drinking water should be boiled or chlorinated, and vegetables and shellfish cooked thoroughly.
Antibiotic prophylaxis for household contacts of patients with cholera is not recommended because data supporting this measure are lacking. In addition, antibiotic resistance emerged in previous epidemics when antibiotic prophylaxis was given to household contacts of cholera patients.
CHOLERA VACCINES
Several oral cholera vaccines are available.
A live-attenuated, single-dose, monovalent vaccine, lyophilized V. cholerae CVD 103-HgR, is available in the US for adults ages 18 to 64 years who are traveling to cholera-infected areas. It protects against disease caused by V. cholerae O1. The effectiveness of this vaccine beyond 3 to 6 months is unknown.
Three killed whole-cell oral vaccines are available for use in children and adults internationally but not in the US:
A monovalent vaccine (travelers' diarrhea and cholera vaccine [Dukoral®]) contains only V. cholera O1 and El Tor bacteria plus a small amount of nontoxic b subunit cholera toxin; before taking, it must be mixed into buffer fluid (buffer packet is dissolved in 150 mL [5 oz] of cool water).
Two bivalent vaccines (ShanChol® and Euvichol®) contain both O1 and O139 serogroups of V. cholera and have no added components, eliminating the requirement for fluid ingestion at the time of vaccination.
These three vaccines provide 60 to 85% protection for up to 5 years. They require 2 doses, and booster doses are recommended after 2 years for people with ongoing risk of cholera.
Injectable vaccines provide less protection for shorter periods of time with more adverse effects and are not recommended when an oral vaccine is available.
Key Points
V. cholerae serogroups O1 and O139 secrete an enterotoxin that can cause severe, sometimes fatal diarrheal illness that often occurs in large outbreaks caused by mass exposure to contaminated water or food.
Other V. cholerae serogroups can cause milder, nonepidemic disease.
Diagnose using stool culture and serotyping; a rapid dipstick test is helpful in identifying outbreaks in remote areas.
Rehydration is critical; oral rehydration solution is adequate for most cases, but patients with severe volume depletion require IV fluids.
Give infected adults doxycycline or azithromycin (for pregnant women and children) pending results of susceptibility testing.
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