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What is cholera?

Cholera is an acute infectious disease caused by a bacterium, Vibrio cholerae (V. cholerae), which results in a painless, watery diarrhea in humans. Some affected individuals have copious amounts of diarrhea and develop dehydration so severe it can lead to death. Most people who get the disease ingest the organisms through food or water sources contaminated with V. cholerae. Although symptoms may be mild, approximately 5%-10% of previously healthy people will develop a copious diarrhea within about one to five days after ingesting the bacteria. Severe disease requires prompt medical care. Hydration (usually by IV for the very ill) of the patient is the key to surviving the disease.

The term cholera has a long history (see history section below) and has been assigned to several other diseases. For example, fowl or chicken cholera is a disease that can rapidly kill chickens and other avian species rapidly with a major symptom of diarrhea. However, the disease-causing agent in fowl is Pasteurella multocida, a gram-negative bacterium. Similarly, pig cholera (also termed hog or swine cholera) can cause rapid death (in about 15 days) in pigs with symptoms of fever, skin lesions, and seizures. This disease is caused by a pestivirus termed CSFV (classical swine fever virus). Neither one of these animal diseases are related to human cholera, but the terminology can be confusing.

What are cholera symptoms and signs?

The symptoms and signs of cholera are diarrhea, vomiting, rapid heart rate, loss of skin elasticity (washer woman hands sign; see figure 2), dry mucous membranes, low blood pressure, thirst, muscle cramps, restlessness or irritability (especially in children).

People require immediate hydration to prevent these symptoms from continuing because these signs and symptoms indicate that the person is becoming or is dehydrated and may go on to develop severe cholera. People with severe cholera (about 5%-10% of previously healthy people; higher if a population is compromised by poor nutrition or has a high percentage of very young or elderly people) can develop severe dehydration, leading to acute renal failure, severe electrolyte imbalances (especially potassium an sodium), and coma. If untreated, this severe dehydration can rapidly lead to shock and death. Severe dehydration can often occur four to eight hours after the first liquid stool with death in about 18 hours to a few days in undertreated or untreated people. In epidemic outbreaks in underdeveloped countries where little or no treatment is available, the mortality (death) rate can be as high as 50%-60%.

What causes cholera, and how is cholera transmitted?

Cholera is caused by the bacterium V. cholerae. This bacterium is Gram stain-negative and has a flagellum (a long, tapering, projecting part) for motility and pili (hairlike structures) used to attach to tissue. Although there are many V. cholerae serotypes that can produce cholera symptoms, the O groups O1 and O139, which also produce a toxin, cause the most severe symptoms of cholera. O groups consist of different lipopolysaccharides-protein structures on the surface of bacteria that are distinguished by immunological techniques. The toxin produced by these V. cholerae serotypes is an enterotoxin composed of two subunits, A and B; the genetic information for the synthesis of these subunits is encoded on plasmids (genetic elements not in the bacterial chromosome). In addition, another plasmid type encodes for a pilus (a hollow hairlike structure that can augment bacterial attachment to human cells and facilitate the movement of toxin from V. cholerae into human cells). The enterotoxin causes human cells to extract water and electrolytes from the body (mainly the upper gastrointestinal tract) and pump it into the intestinal lumen where the fluid and electrolytes are excreted as diarrheal fluid. The enterotoxin is similar to toxin formed by bacteria that cause diphtheria in that both bacterial types secret the toxins into their surrounding environment where the toxin then enters the human cells. The bacteria are usually transmitted by people drinking contaminated water, but the bacteria can also be obtained in contaminated food, especially seafood such as raw oysters.

What is the history of cholera?

Cholera has likely been with humans for many centuries. Reports of cholera-like disease have been found in India as early as 1000 AD. Cholera is a term derived from Greek khole (illness from bile) and later in the 14th century to colere (French) and choler (English). In the 17th century, cholera was a term used to describe a severe gastrointestinal disorder involving diarrhea and vomiting. There were many outbreaks of cholera, and by the 16th century, some were being noted in history. England had several in the 18th century, most notable being in 1854, when Dr. John Snow did a classic study in London that showed a main source of the disease (resulting in about 500 deaths in 10 days) came from at least one of the major water sources for London residents termed the "Broad Street pump." The pump handle was removed, and the cholera deaths slowed and stopped. The pump is still present as a landmark in London. Although Dr. Snow did not discover the cause of cholera, he did show how the disease could be spread and how to stop a local outbreak. This was the beginning of modern epidemiologic studies.

V. cholerae was first isolated as the cause of cholera by Filippo Pacini in 1854, but his discovery was not widely known until Robert Koch (who also discovered the cause of tuberculosis), working independently 30 years later, publicized the knowledge and the means of fighting the disease. The history of cholera repeats itself. The U.S. National Library of Medicine houses original documents about multiple cholera outbreaks in the U.S. from the 1820s to the 1900s, with the last large outbreak in 1910-1911. Since the 1800s, there have been seven cholera pandemics (worldwide outbreaks).

Multiple outbreaks worldwide continue into the 21st century with outbreaks in India, Iran, Vietnam, and several African countries in the last 10 years (most recent outbreaks occurred in Haiti and Nigeria in 2010-2011). Why is cholera history repeating itself? The answer can be traced back to Dr. Snow's studies that show a source (water or occasionally food) contaminated with V. cholerae can easily and rapidly transmit the cholera-causing bacteria to many people. Until safe water and food is available to all humans, it is likely cholera outbreaks will continue to happen.

Who is at risk for cholera, and where do outbreaks occur?

Everyone who drinks or eats food that has not been treated to eliminate V. cholerae (liquids need to be chemically treated, boiled, or pasteurized, and foods need to be cleaned and cooked), especially in areas of the world where cholera is present, is at risk for cholera. The CDC says in regard to cholera risk as of November 2010, "There has been an ongoing global pandemic in Asia, Africa, and Latin America for the last four decades." Outbreaks occur when there are disasters or other reasons for a loss of sanitary human waste disposal and the lack of safe fluids and foods for people to ingest. Haiti, a country that had not seen a cholera outbreak in over 50 years, had such circumstances develop in 2010 after a massive earthquake destroyed sanitary facilities and water and food treatment facilities for many Haitians. V. cholerae bacteria eventually contaminated primary water sources, resulting in over 4,100 deaths from cholera as of February 2011. There is some evidence that V. cholerae can survive in saltwater and have been isolated from shellfish; eating raw oysters is considered a risk factor for cholera, especially in underdeveloped countries and occasionally even in developed countries. A few people are diagnosed with cholera every year in the U.S. Most of the individuals diagnosed are travelers who were exposed to cholera outside the country, but occasionally, isolated cases are traced to contaminated seafood, usually from states that border the Gulf of Mexico.

It takes about 100 million bacteria to infect a healthy adult. Because of this high number, significant contamination of food or water is required to transmit the disease and person-to-person transmission is thought to be uncommon.

Some individuals are at higher risk to become infected than others. People who are malnourished or immune-compromised are more likely to get the disease. Children ages 2-4 seem more susceptible than older children, according to some investigators. In addition, researchers have noted that patients with blood type O are twice more likely to develop cholera than others. The reason for this blood type susceptibility is not completely understood. People with achlorhydria (reduced acid secretion in the stomach) and people taking medicines to reduce stomach acid (H2 blockers and others) are also more likely to develop cholera because stomach acid kills many types of bacteria, including V. cholerae.

How is cholera diagnosed?

Preliminary diagnosis is usually done by a caregiver who takes a history from the patient and observes the characteristic rice-water diarrhea, especially if a local outbreak of cholera has been identified. The diarrhea fluid is often teeming with motile, comma-shaped bacteria (presumptively V. cholerae). The definitive diagnosis is made by isolation of the bacteria from diarrhea fluid on a selective medium thiosulfate-citrate-bile salts agar (TCBS). Reagents for serogrouping Vibrio cholerae isolates are available in all state health department laboratories in the U.S. Readers may see terms like serotypes Inaba, Ogawa, and Hikojima to describe V. cholerae; they simply indicate which O antigens (O antigens designated A, B, or C) are found on these strains of V. cholerae. PCR tests have also been developed to detect cholera but currently they are not as widely used as other tests based on type-specific antiserum.

Definitive diagnosis helps to distinguish cholera from other diseases caused by other bacterial, protozoal, or viral pathogens that cause dysentery (gastrointestinal inflammation with diarrhea).

What is the treatment for cholera?

The CDC (and almost every medical agency) recommends rehydration with ORS (oral rehydration salts) fluids as the primary treatment for cholera. ORS fluids are available in prepackaged containers, commercially available worldwide, and contain glucose and electrolytes. The CDC follows the guidelines developed by the WHO (World Health Organization) and are as follows:

WHO Fluid Replacement or Treatment Recommendations (as per the CDC)

                     *Repeat once if radial pulse is still very weak or not detectable

In general, antibiotics are reserved for more severe cholera infections; they function to reduce fluid rehydration volumes and may speed recovery. Although good microbiological principals dictate it is best to treat a patient with antibiotics that are known to be effective against the infecting bacteria, this may take too long a time to accomplish during an initial outbreak (but it still should be attempted); meanwhile, severe infections have been effectively treated with tetracycline (Sumycin), doxycycline (Vibramycin, Oracea, Adoxa, Atridox and others), furazolidone (Furoxone), erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Ilosone), or ciprofloxacin (Cipro, Cipro XR, Proquin XR) in conjunction with IV hydration.

What is the prognosis of cholera?

The prognosis (outcome) of cholera can range from excellent to poor, depending on the severity of the dehydration and how quickly the patient is given and responds to treatments. Death (mortality) rates in untreated cholera can be as high as 50%-60% during large outbreaks but can be reduced to about 1% if treatment protocols (see above treatment section) are rapidly put into action. In general, the less severe the symptoms and the less time people have dehydration symptoms, the better the prognosis; in many people, if dehydration is quickly reversed, the prognosis is often excellent.

Can cholera be prevented?

Yes, cholera can be prevented by several methods. Developed countries have almost no incidents of cholera because they have widespread water-treatment plants, food-preparation facilities that usually practice sanitary protocols, and most people have access to toilets and hand-washing facilities. Although these countries may have occasional lapses or gaps in these methods, they have prevented many disease outbreaks, including cholera.

Individuals can prevent or reduce the chance they may get cholera by hand washing, avoiding areas and people with cholera, drinking treated water or similar safe fluids and eating cleaned and well-cooked food. In addition, there are vaccines available that can help prevent cholera, although they are not available in the U.S. and their effectiveness ranges from 50%-90%, depending on the studies reported. The vaccines are oral preparations as injected vaccines have not proved to be very effective. Two vaccines (Shanchol and mORC-VAX) are composed of killed V. cholerae bacteria and without the enterotoxin B subunit. Unfortunately, both offer protection for only about two years. Both vaccines are given in two doses, about one to six weeks apart. Unfortunately, the vaccines have limited availability; their recommended use is for people going to known areas of outbreaks with the likely possibility the person may be exposed to cholera. Some researchers suggest this limited oral vaccine availability should be changed and cite data that oral vaccine may help limit outbreaks, even after they have begun.

Where can people find more information about cholera?

The following links can provide additional information about cholera:

"Cholera," CDC

http://www.cdc.gov/cholera/index.html

"Cholera," Travelers' Health - Yellow Book, CDC

http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-5/cholera.aspx

"Cholera Online," National Institutes of Health

http://www.nlm.nih.gov/exhibition/cholera/timeline.html

"Cholera Epidemiology and Risk Factors," CDC

http://www.cdc.gov/cholera/epi.html

"Cholera," eMedicine.com

http://emedicine.medscape.com/article/214911-overview

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