Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period of one to five days and produces a toxin that causes painless, watery diarrhoea and vomiting that can quickly lead to severe dehydration and death.
The genus Vibrio consists of Gram-negative straight or curved rod-like bacteria, with a single polar flagellum. Vibrios are capable of both respiratory and fermentative metabolism. Most species are oxidase-positive. V. cholerae and V. parahaemolyticus are pathogens of humans. V.parahaemolyticus is an invasive organism affecting primarily the colon, while V. Another species, Vibrio vulnificus is another emerging pathogen of humans that causes cholerae is noninvasive affecting the small intestine by producing an enterotoxin. wound infections, gastroenteritis or a syndrome known as “primary septicaemia.”
HISTORY
During the 19th century cholera spread repeatedly from the Ganges delta in India to the rest of the world before receding to South Asia. Six epidemics were recorded that killed millions of people across Europe, Africa and the Americas. Cholera is mainly transmitted through contaminated water and food and is closely related to unhygienic conditions of surrounding environment.
The absence or shortage of safe drinking water and insufficient sanitation, combined with an unhygienic environmental status are the main causes of spread of the disease. Cholera still remains a global threat to public health and one of the key indicators of social development. While the disease is no longer an issue in countries where minimum hygiene standards are met, it remains a threat in almost every developing country where populations are large.
The number of cholera cases reported to WHO during 2006 rose dramatically, reaching the level of the late 1990s. A total of 236 896 cases were notified from 52 countries, including 6311 deaths, an overall increase of 79% compared with the number of cases reported in 2005.
CHOLERA TOXIN
Cholera toxin activates the adenylate cyclase enzyme in cells of the intestinal mucosa leading to increased levels of intracellular cAMP, and the secretion of H20, Na+, K+, Cl–, and HCO3– into the lumen of the small intestine. The effect is dependent on a specific receptor, monosialosyl ganglioside (GM1 ganglioside) present on the surface of intestinal mucosal cells.
The bacterium produces invasin, neuraminidase, during the colonization stage which has the interesting property of degrading gangliosides to the monosialosyl form, which is the specific receptor for the toxin. Once it has entered the cell, the A1 subunit enzymatically transfers ADP ribose from NAD to a protein (called Gs or Ns), that regulates the adenylate cyclase system which is located on the inside of the plasma membrane of mammalian cells. Enzymatically, fragment A1 catalyzes the transfer of the ADP-ribosyl moiety of NAD to a component of the adenylate cyclase system. Adenylate cyclase (AC) is activated normally by a regulatory protein (GS) and GTP.
TRANSMISSION
The highly liquid diarrhea during cholera infection is loaded with bacteria that can spread under unsanitary conditions to infect water used by other people. Cholera is transmitted from person to person through ingestion of faeces-contaminated water.
The sources of contamination are typically other cholera patients whose diarrhoeal discharge is allowed to get into waterways or into groundwater or drinking water supply. Any infected water or food washed in such water and fish and shellfish living in the affected waterways can cause infection. Cholera is rarely spread directly from person to person. V. cholerae occurs naturally in the planktons of fresh, brackish, and salt water, attached primarily to copepods. Both toxic and non-toxic strains exist. Coastal cholera outbreaks typically follow zooplankton blooms.
COLONIZATION OF INTESTINE
There are several characteristics of pathogenic V. cholerae that help it in the colonization process, namely, adhesins, neuraminidase, intestinal motility, chemotaxis and toxin production. V. cholerae is resistant to bile salts and can penetrate the mucus layer of small intestine, possibly aided by secretion of neuraminidase and proteases (mucinases). They also withstand the propulsive gut motility by their own swimming ability and chemotaxis directed against the gut mucosa.
Two other possible adhesins in V. cholerae are a surface protein that agglutinates red blood cells (hemagglutinin) and a group of outer membrane proteins which are products of the acf (accessory colonization factor) genes. acf mutants have been shown to have reduced ability to colonize the intestinal tract. It has been suggested that V. cholerae might use these nonfimbrial adhesins to mediate a tighter binding to host cells than is attainable with fimbriae alone
VACCINES
The oral vaccines are made from a live attenuated strain of V. cholerae. The ideal properties of such a vaccine of the bacterium would be to possess all the pathogenicity factors required for colonization of the small intestine but not to produce toxin molecules. Ideally it should produce only the B subunit of the toxin which would stimulate formation of antibodies that could neutralize the binding of the native toxin molecule to epithelial cells.
A new vaccine has been developed to combat the Bengal strain of Vibrio cholerae that has started spreading in epidemic fashion in the Indian subcontinent and Southeast Asia. The Bengal strain differs from previously isolated epidemic strains in that it is sero group is 0139 rather than 01, and it expresses a distinct polysaccharide capsule. Since previous exposure to 01 Vibrio cholerae does not provide immunity against 0139, populations suffer from the Bengal form of cholera.
The noncellular vaccine is relatively nontoxic and contains little or no LPS and other impurities. The vaccine will be used for active immunization against Vibriocholerae O139 and other bacterial species expressing similar surface polysaccharides. In addition, human or other antibodies induced by this vaccine could be used to identify Vibriocholerae Bengal for the diagnosis of the infection and for environmental monitoring of the bacterium.
TREATMENT
Cholera can be simply and successfully treated by immediate replacement of body fluids and salts lost through diarrhoea and vomiting. Patients can be treated with Oral Rehydration Solution, a mixture of sugar and salts to be mixed with water and taken in large amounts but patients who become severely dehydrated must be given intravenous fluids. With prompt rehydration, less than 1% of cholera patients die.
In severe cases, an effective antibiotic can reduce the volume and duration of diarrhoea and the period of Vibrio excretion. Tetracycline is the usual antibiotic of choice, but resistance to it is increasing. Other antibiotics that are effective include, cotrimoxazole, erythromycin, doxycycline, chloramphenicol and furazolidone.
Antibiotics used to treat cholera
Doxycycline, a single dose of 300 mg tablet
Tetracycline, 12.5 mg/kg or 500 mg tablet, 4 times per day
for 3 days.
Trimethoprim/sulfamethoxazole (TMP/SMX), TMP 5 mg/kg and
SMX 25 mg/kgc TMP 160 mg and SMX 800 mg twice a day for 3 days.
Furazolidone, 1.25 mg/kg or 100 mg tablet, 4 times per day for 3 days.
Erythromycin or chloramphenicol may be used when the antibiotics recommended above are not available, or where Vibrio cholerae O1 is resistant to them.
Doxycycline is the antibiotic of choice for adults but not for pregnant women.
TMP-SMX is the antibiotic of choice for children.
Tetracycline is equally effective in all age groups.
Furazolidone is the antibiotic of choice for pregnant women.