Risk Factors (Genetics & Inherited Conditions)
In the poorer nations of the world, cholera is still widespread and occurs where sanitation is inadequate. In the United States and other industrialized nations, where sanitation is generally good, only a few cases occur each year. These usually result from the return of afflicted travelers from regions where cholera is endemic.
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Etiology and Genetics (Genetics & Inherited Conditions)
The disease occurs when cholera toxin binds to intestinal cells and stimulates the passage of water from the blood into the intestine. This water depletion and resultant cardiovascular collapse are major causes of cholera mortality. Study of the genetics and the biochemistry of cholera has shown that the toxin is a protein composed of portions called A and B subunits, each produced by a separate gene. When a bacterium secretes a molecule of cholera toxin, it binds to a cell of the intestinal lining (an intestinal mucosa cell) via B subunits. Then the A subunits cause the mucosal cell to stimulate the secretion of water and salts from the blood to produce diarrhea. Lesser amounts of the watery mix are vomited and exacerbate dehydration.
The use of bacterial genetics to compare virulent V. cholerae and strains that did not cause the disease helped in the discovery of the nature of the cholera toxin and enabled production of vaccines against the protein. These vaccines are useful to those individuals who visit areas where cholera is endemic, ensuring that they do not become infected with it during these travels. Unfortunately, the vaccines are effective only for about six months.
The basis for the operation of cholera toxin is production of a hormone substance called cyclic adenosine monophosphate (cAMP). The presence of excess cAMP in intestinal mucosa cells causes movement of water and other tissue...
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Symptoms (Genetics & Inherited Conditions)
Infection is almost always caused by consumption of food or water contaminated with the bacterium. It is followed in one to five days by watery diarrhea that may be accompanied by vomiting. The diarrhea and vomiting may cause the loss of as much as a pint of body water per hour. This fluid loss depletes the blood water and other tissues so severely that, if left unchecked, it can cause death within a day.
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Screening and Diagnosis (Genetics & Inherited Conditions)
The signs and symptoms of cholera are usually evident in areas where the disease is endemic. However, the only way to confirm this diagnosis is to test a patient’s stool sample for V. cholerae. Health care providers in remote parts of the world conduct rapid cholera dipstick tests that enable them to confirm quickly if a patient has the disease. Polymerase chain reaction (PCR) assays or other genetic tests can also to confirm a diagnosis.
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Treatment and Therapy (Genetics & Inherited Conditions)
Treatment of cholera combines oral or intravenous rehydration of afflicted individuals with saline-nutrient solutions and chemotherapy with antibiotics, especially tetracycline. The two-pronged therapy replaces lost body water and destroys all V. cholerae in infected individuals. Antibiotic prophylaxis, which destroys the bacteria, leads to the cessation of production of cholera toxin, the substance that causes diarrhea, vomiting, and death.
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Prevention and Outcomes (Genetics & Inherited Conditions)
Cholera has, for centuries, been a serious threat to humans throughout the world. During the twentieth century, its consequences to industrialized nations diminished significantly with the advent of sound sanitation practices that almost entirely prevented the entry of V. cholerae into the food and water supply. In poorer nations with less adequate sanitation, the disease flourishes and is still a severe threat.
It must be remembered that dealing with cholera occurs at three levels. The isolation and identification of cholera toxin, as well as development of current short-term cholera vaccines, were highly dependent on genetic methodology. Vaccine protects most travelers from the disease. However, wherever the disease afflicts individuals, its treatment depends solely upon rehydration and use of antibiotics. Finally, current cholera prevention focuses solely on adequate sanitation. Medicine seeks to produce a long-lasting vaccine for treatment of cholera to enable prolonged immunization at least at the ten-year level of tetanus shots. Efforts aimed at this goal are ongoing and utilize molecular genetics to define more clearly why long-term vaccination has so far been unsuccessful. Particularly useful will be fine genetic sequence analysis and the use of gene amplification followed by DNA fingerprinting.
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Further Reading (Genetics & Inherited Conditions)
Chadhuri, Keya, and S. N. Chatterjee. Cholera Toxins. Berlin: Springer, 2009. Offers comprehensive information about the Vibrio cholerae toxins, including their physical and chemical structures, biosynthesis and genetic regulation, physiology, and role in the development of a cholera vaccine.
Colwell, Rita R. “Global Climate and Infectious Disease: The Cholera Paradigm.” Science 274, no. 5295 (1996): 2025-2031. An analysis of the role climate change might play in the spread of cholera. Includes a good overview of the history of cholera.
Gotuzzo, E., and C. Seas. “Cholera and Other Vibrio Infections.” In Cecil Medicine, edited by Lee Goldman and Dennis Ausiello. 23d ed. Philadelphia: Saunders Elsevier, 2008. Describes these pathogens and the diseases they cause.
Heidelberg, John F., et al. “DNA Sequence of Both Chromosomes of the Cholera Pathogen Vibrio cholerae.” Nature 406, no. 6795 (August 3, 2000): 477-483. Presents the results of a report revealing the complete genome sequence of the bacteria responsible for cholera and describes how this sequencing may improve treatment of the disease.
Holmgren, John. “Action of Cholera Toxin and Prevention and Treatment of Cholera.” Nature 292 (1981): 413-417. Clearly describes both the composition and bioaction of the cholera toxin.
Keusch, Gerald, and Masanobu Kawakami,...
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Web Sites of Interest (Genetics & Inherited Conditions)
Centers for Disease Control and Prevention. http://www.cdc.gov/nczved/dfbmd/disease_listing/cholera_gi.html. Offers information about cholera and what the United States is doing to treat it.
Food and Drug Administration. http://vm.cfsan.fda.gov. The FDA’s “Bad Bug Book” provides information on Vibrio cholerae, the bacterium that causes cholera.
Mayo Clinic.com. http://www.mayoclinic.com/health/cholera/DS00579. An overview of the causes, symptoms, treatment, and prevention of cholera.
Medline Plus. http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/000303.htm. A concise, “user-friendly” article about cholera, describing its causes, symptoms, diagnosis, and treatment.
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Causes and Symptoms (Magill’s Medical Guide, Sixth Edition)
The comma-shaped bacterium Vibrio cholerae causes the life-threatening disease cholera. The organism is spread when people ingest water or raw food contaminated with fecal matter. Studies have shown that the bacterium can live in both oceanic salt water and freshwater. In the ocean, it adheres to a type of zooplankton called copepods, which are eaten by certain types of shellfish. Therefore, people who consume shellfish grown in contaminated water can ingest the cholera organism. Also, people eating crops fertilized with human feces can ingest the organism.
Cholera affects particularly underdeveloped nations with poor sewage disposal and sanitation practices. It is endemic in Africa, Southeast Asia, the Indian subcontinent, and Central and South America. Even in developed nations, however, cholera may emerge after major disasters, such as hurricanes and earthquakes. Fewer than 250 cases were reported in the United States from 1996 to 2006, primarily around the Gulf Coast. Most of those cases were caused by the ingestion of contaminated raw shellfish.
After a person ingests contaminated food or water, between twenty-four and seventy-two hours elapse before the symptoms of cholera develop. Normally, between ten million to a billion V. cholerae bacteria must be present to cause infection, due to the large number that die in stomach acid. If an individual has taken antacids to neutralize stomach acid,...
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Treatment and Therapy (Magill’s Medical Guide, Sixth Edition)
The best method for controlling cholera is prevention. Societies with adequate sanitation and sewage treatment are normally protected, except for contaminated seafood. Underdeveloped nations should be encouraged to improve their sanitation and sewage treatment practices and to cease using human feces as crop fertilizer. Also, especially in infected areas, raw foods and unpurified water should be avoided.
Although different vaccines have been developed, the immunity that they produce appears to be short-lived and not effective against all strains. Prophylactic antibiotic treatment for travelers entering affected areas has not been shown to be effective. Given the large number of bacteria needed for the disease to occur, however, proper hygienic practices alone should provide sufficient protection.
Treatment for cholera patients is primarily supportive, with rehydration and restoration of the electrolyte balance being paramount. Secondary treatment with antibiotics may reduce the presence of organisms and their production of toxin, thus ameliorating the symptoms. Because of the high volume of watery diarrhea, the antibiotic tends to be released from the body very rapidly. Doxycycline is usually the preferred drug, but trimethoprim-sulfamethoxazole or tetracycline have also been used. Unfortunately, certain strains of V. cholerae have been discovered to be resistant to the latter two antibiotics. Using...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
Historically, cholera has been a very important epidemic pathogen credited with causing seven different pandemics. These pandemics have affected various areas, including Asia, the Middle East, and Africa. Between 1832 and 1836, two pandemics (the second and fourth) affected the North American continent, resulting in 200,000 American deaths. While studying and trying to limit the effects of the 1854 cholera epidemic in London, physician John Snow founded the science of epidemiology and introduced techniques that are still in use today. The seventh pandemic occurred in 1961, starting in Indonesia and spreading to South Asia, the Middle East, and portions of both Europe and Africa.
In 1991, Peru suddenly reported new cases after being free of cholera for more than a century. Contaminated bilge water discharged from a freighter into the Peru harbor has been hypothesized as being responsible for the disease’s reappearance. The water supply in the capital city of Lima was not chlorinated, and the organism rapidly multiplied and infected the inhabitants. In two years, more than 700,000 cases and 6,323 deaths were recorded in South and Central America, and spread of this cholera strain continues today.
The 1961 pandemic strain has caused over five million cases of cholera and more than 250,000 deaths. In 1992, a genetic variant of this strain appeared in Bangladesh, causing an epidemic. This cholera strain spread...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Ezzell, Carol. “It Came from the Deep.” Scientific American 280 (June, 1999): 22-24.
Pennisi, Elizabeth. “Infectious Disease: Cholera Strengthened by Trip Through Gut.” Science 296 (June, 2002): 1783-1784.
Reidl, Joachim, et al. “Vibrio cholerae and Cholera: Out of the Water and into the Host.” FEMS Microbiological Reviews 26 (June, 2002): 125-139.
Wachsmuth, Kaye, et al. “Vibrio cholerae” and Cholera: Molecular to Global Perspectives. Washington, D.C.: American Society for Microbiology, 1994.
Zimmer, Carl. “Infectious Diseases: Taming Pathogens—An Elegant Idea, but Does It Work?” Science 300 (May, 2003): 1362-1364.
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Cholera (Encyclopedia of Medicine)
Cholera is an acute illness characterized by watery diarrhea that is caused by the bacterium Vibrio cholerae. Cholera is spread by eating food or drinking water contaminated with the bacteria. Although cholera was a public health problem in the United States and Europe a hundred years ago, modern sanitation and the treatment of drinking water have virtually eliminated the disease in developed countries. In third world countries, however, cholera is still common.
Cholera is spread by eating food or drinking water that has been contaminated with cholera bacteria. Contamination usually occurs when human feces from a person who has the disease seeps into a community water supply. Fruits and vegetables can also be contaminated in areas where crops are fertilized with human feces. Cholera bacteria also live in warm, brackish water and can infect persons who eat raw or undercooked seafood obtained from such waters. Cholera is rarely transmitted directly from one person to another.
Cholera often occurs in outbreaks or epidemics. The World Health Organization (WHO) estimates that during any cholera epidemic, approximately 0.2% of the local population will contract the disease. Anyone can get cholera, but infants, children, and the elderly are more likely to die from the disease because...
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Cholera (Encyclopedia of Public Health)
Cholera is an acute diarrheal illness caused by a bacterium, Vibrio cholerae. There are several environmental strains of Vibrio cholerae, which are found mainly in brackish waters and marine environments, but only two strains are responsible for cholera epidemics in humans, serogroups O1 and O139.
The first described cholera pandemic was in Europe from 1817 to 1823. However, the disease was known in Asia prior to that, with the first possible descriptions dating back as far as 2,000 years ago in India and China. Since that first pandemic there have been a total of seven pandemics. The cholera outbreaks that occurred in London, England in 1849 and 1854 are important in the history of the disease. John Snow, a physician, recognized that cholera was spread via water contaminated with human waste when he identified the source of the London outbreak as the Broad Street water pump. This discovery stimulated the future development of adequate water and sewage systems, which led to the control of many infectious diseases.
The seventh pandemic started in Sulawesi, an island in Indonesia, in 1961 and then spread rapidly through Asia and the Middle East. In 1970, for the first time in over one hundred years, cholera was found in West Africa. In 1991, cholera appeared in Peru and quickly spread throughout the remainder of South and Central America. As was the case with Africa, cholera had not been seen in the western hemisphere for over one hundred years. As of 2001, the seventh cholera pandemic showed no signs of abating.
Cholera is acquired by ingestion of V. cholerae in water, seafood, or other foods that have been contaminated by human excrement. The incubation period can range from a few hours to five days, depending on the inoculum size and the underlying health of the person. Cholera can cause a spectrum of disease, from no clinical symptoms to a mild diarrheal illness or a severe fulminant illness resulting in death. The diarrhea is caused by an enterotoxin produced by the V. cholerae that stimulates the small intestine to secrete large volumes of fluid and electrolytes. Some factors that predispose to severe disease include having blood group O, low gastric acid levels, and malnutrition. The very young and the very old are at particular risk for severe disease. Persons living in endemic areas appear to develop some natural immunity to the infection.
In symptomatic infections, there is an abrupt onset of copious diarrhea, often accompanied by abdominal cramps and vomiting. The diarrhea is typically watery and clear with mucous flecksoften described as "rice water stools." It is unusual for fever to develop. Uncomplicated cholera is a self-limited disease that resolves in three to six days. In more severe cases, fluid losses from diarrhea can amount to over 20 liters a day and can lead to profound dehydration that produces weakness, muscle cramping, loss of skin turgor, and sunken eyes and cheeks. If the fluid losses are not rapidly corrected, death results. The fatality rate can be over 50 percent in cases of severe cholera; however, with prompt and adequate rehydration the death rate may be as low as 1 to 2 percent.
The infection is diagnosed by identification of V. cholerae bacteria in stool. The organism can be grown in the laboratory on special alkaline culture media. It appears microscopically as curved, gramnegative rods. A clinical diagnosis can be made in severe cases if a patient presents with profuse, watery diarrhea in an endemic region. There are few other illness that cause such copious diarrhea.
The mainstay of treatment is fluid replacement, either intravenously or orally. In very severe cases, intravenous fluid replacement should be used. When fluids are administered by mouth, it is important to use an oral rehydration solution that contains the correct mix of sugars and electrolytes.
Antibiotics can be used to shorten the duration of illness by several days. Tetracycline, furazolidone, or doxycycline are all effective.
Prevention of cholera depends upon good sanitation and hygiene, including treatment of water supplies, adequate sewage control, and strict hygiene in food preparation. Good food preparation involves hand washing before contact with food, thorough cooking of food, eating food while it is still hot, and not allowing cooked food come into contact with raw foods or with water or ice.
There are several vaccines currently available to prevent cholera. The original cholera vaccine was a parenteral-killed preparation that provided about 50 to 60 percent protection and was only effective for a period of three to six months. This vaccine is no longer recommended for use. The World Heath Organization currently advocates the use of a killed whole cell V. cholerae O1 vaccine (WC/rBS), which is combined with one of the toxin subunits and is given in two doses one week apart. This newer vaccine has been shown to confer 85 to 90 percent protection for six months. The vaccine can be used to prevent a cholera outbreak in a population felt to be at high risk of an out-break, such as the inhabitants of refugee camps. It can also be offered to travelers going to high-risk regions. Another recently developed effective vaccine is the oral, single dose, live attenuated V. cholerae strain, devoid of the A toxin subunit (Mutachol), that provides from 62 to 100 percent protection for about six months. The level of protection varies for different cholera biotypes.
A concern about future cholera outbreaks is the possible emergence of new biotypes. Until 1992, the only strain of cholera identified as causing epidemics in humans was V. cholerae O1. That year a new serotype, O139, emerged in India. Neither previous exposure to O1 cholera, nor vaccination with current vaccines, confers protection against O139. Because V. cholerae exists naturally in brackish waters, and because of the possibility of new biotypes emerging, it is unlikely that cholera will ever be eradicated as a human pathogen. Good hygiene and sanitation are the best strategies we have for control of this disease.
(SEE ALSO: Communicable Disease Control; Epidemics; Waterborne Diseases)
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(2000). Fact Sheet 107: Cholera. Geneva: WHO.