Cholera

Cholera
Cholera
Specialty	Infectious diseases, emergency medicine

Cholera (also called Asiatic cholera) is a water-borne disease caused by the bacterium Vibrio cholerae, which are typically ingested by drinking contaminated water, or by eating improperly cooked fish, especially shellfish. It was first described in a scientific manner by the Portuguese physician Garcia de Orta in the 16th century.

Pathology

Susceptibility

Cholera produces potentially lethal secretory diarrhea through a pathway that involves the cystic fibrosis transmembrane conductance regulator, CFTR (Gabriel 1994). This discovery led to the hypothesis that carriers for cystic fibrosis, who have lower levels of functional CFTR, are protected from the severe effects of cholera because they don't lose water as quickly as other people. This might explain the high incidence of cystic fibrosis among populations which were formerly exposed to cholera. However, no evidence of resistance in vivo has been observed in humans, and studies in mice have produced conflicting results (Gabriel 1994, Cuthbert 1995, Hogenauer 2000).

Recent genetic research has determined that a person's susceptibility to cholera (and other diarrheas) is affected by their blood type. Those with type O blood are the most susceptible. Those with type AB are the most resistant, virtually immune. Between these two extremes are the A and B blood types, with type A being more resistant than type B.

About one million Vibrio cholerae bacteria must be ingested to cause cholera in normally healthy adults, although increased susceptibility may be observed in those with a weakened immune system, individuals with decreased gastric acidity (as from the use of antacids), or those who are malnourished.

Transmission

Cholera is transmitted through ingestion of feces contaminated with the bacterium. The contamination usually occurs when untreated sewage is released into waterways, affecting the water supply, any foods washed in the water, and shellfish living in the affected waterway  it is rarely spread directly from person to person. The resulting diarrhea allows the bacterium to spread to other people under unsanitary conditions.

Symptoms

Symptoms include those of general GI tract upset: profuse diarrhea (eg 1L/hour), abdominal cramping, fever, nausea and vomiting. Also those of the resulting dehydration: thirst, muscle cramps, weakness, loss of tissue turgor, sunken eyes and wrinkled skin, severe metabolic acidosis with potassium depletion, anuria, circulatory collapse and cyanosis. Death is through circulatory volume shock (massive loss of fluid and electrolytes), and can occur within hours.

The root causes of these symptoms are the enterotoxins that V. cholerae produces. The main enterotoxin, known as cholera toxin, interacts with G proteins and cyclic AMP in the intestinal lining to open ion channels. As ions flow into the intestinal lumen, water follows through osmosis.

History

Origin and Spread

Cholera was originally endemic to the Indian subcontinent, with the Ganges River likely serving as a contamination reservoir. It spread by trade routes (land and sea) to Russia, then to Western Europe, and from Europe to North America. It is now no longer considered an issue in Europe and North America, due to filtering and chlorination of the water supply.

1816-1826 - First pandemic: Previously restricted, the pandemic began in Bengal, then spread across India by 1820. It extended as far as China and the Caspian Sea before receding.
1829-1851 - Second pandemic reached Europe, London and Paris in 1832 (in London, it claimed at least 3000 victims according to a 1832 article; in Paris, 20 000 on a population of 650 000, and 100 000 in all of France [1]), Russia (Cholera Riots), Quebec, Ontario and New York in the same year, and the Pacific coast of North America by 1834.
1849 - Second outbreak in Paris. An outbreak in North America took the life of U.S. President James K. Polk
1852-1860 - Third pandemic mainly affected Russia, with over a million deaths.
1863-1875 - Fourth pandemic spread mostly in Europe and Africa.
1866 - Outbreak in North America.
1899-1923 - Sixth pandemic had little effect in Europe because of advances in public health, but Russia was badly affected again.
1961-1970s - Seventh pandemic began in Indonesia, called El Tor after the strain, and reached Bangladesh in 1963, India in 1964, and the USSR in 1966. From North Africa it spread into Italy by 1973. In the late 1970s there were small outbreaks in Japan and in the South Pacific.
January 1991 to September 1994 - Outbreak in South America, apparently initiated by discharged ballast water. Beginning in Peru there were 1.04 million identified cases and almost 10,000 deaths. The causative agent was a non-O1, nonagglutinable vibrio (NAG) named O139 Bengal. It was first identified in Tamilnadu, India and for a while displaced El Tor in southern Asia before decreasing in prevalence from 1995 to around 10% of all cases. It is considered to be an intermediate between El Tor and the classic strain and occurs in a new serogroup. There is evidence as to the emergence of wide-spectrum resistance to drugs such as trimethoprim, sulfamethoxazole and streptomycin.

Research

The scientists with major contributions to fighting cholera were John Snow, who found the link between cholera and drinking water in 1854, and Robert Koch, who identified V. cholerae as the bacillus causing the disease. The bacterium was originally isolated thirty years earlier by Italian anatomist Filippo Pacini, but his results were not widely known around the world.

Other historical information

In the past, people travelling in ships would hang a yellow flag if one of the crews suffered from cholera. Boats with a yellow flag hung would not be allowed to disembark at any harbor. (See Love in the Time of Cholera)

Treatment

Treatment typically consists of aggressive rehydration and replacement of electrolytes, since the death rate is generally high due to the serious dehydration caused by the illness.

Prevention

Although cholera can be life-threatening, it is easily prevented. In the United States and Western Europe, because of advanced water and sanitation systems, cholera is not a major threat. The last major outbreak of cholera in the United States was in 1911. However, everyone, especially travelers, should be aware of how the disease is transmitted and what can be done to prevent it.

Simple sanitation is usually sufficient to stop an epidemic. There are several points along the transmission path at which the spread may be halted:

Sickbed: Proper disposal and treatment of waste produced by cholera victims.
Sewage: Treatment of general sewage before it enters the waterways.
Sources: Warnings about cholera contamination posted around contaminated water sources.
Sterilization: Boiling, filtering, and chlorination of water before use.

Filtration and boiling is by far the most effective means of halting transmission. Cloth filters, though very basic, have greatly reduced the occurrence of cholera when used in poor villages in Bangladesh that rely on untreated surface water.

In general, education and sanitation are the limiting factors in prevention of cholera epidemics.

Sources

FDA "Bad Bug Book" entry: http://vm.cfsan.fda.gov/~MOW/chap7.html
Cholera and the Cholera Toxin, by Elizabeth Cronenwett

References

Cholera facts from the United States FDA website: http://vm.cfsan.fda.gov/~MOW/chap7.html
Gabriel, S.E. et al; Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model; Science: 1994, v 266, 5182; pp 107-109
Cuthbert, A.W. et al; The genetic advantage hypothesis in cystic fibrosis heterozygotes: a murine study; J Physiol: 1995, v 482; pp 449-454
Hogenauer, C. et al; Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion; Am J Hum Genet: 2000, v 67, i 6, pp 1422-1427
Cholera in 19th century,London: John Snow: website:

www.ph.ucla.edu/epi/snow.html

External links