Cholera

Cholera is a water borne disease caused by the bacteria Vibrio cholerae. V. cholerae causes a rapid onset of diarrhoea which leads to severe dehydration. The severity of the illness is shown in the occurrence of deaths to be approximately 50-70% in cases which have not been medically treated.

History

Cholera is a relatively modern disease in terms of our understanding of it: our awareness developed during the early part of the 1800s when a worldwide pandemic occurred that started 1817. However, it is apparent that Hippocrates (466-377 BC) and Galen (129-316 AD), two Greek physicians and philosophers, both described diseases which were synonymous to cholera.

Data from the World Health Organisation (WHO) that the most recent outbreak of the disease began in 1961 in Indonesia. Within a few years it had spread across eastern Asia and by 1970 has reached western Africa where cholera has not been prevalent in approximately a century. Since then there has been outbreaks of the devastating disease in Latin America and it is estimated that there are over 100,000 deaths per year as a result of cholera.

Symptoms & Causes

Cholera is very virulent disease, however sometimes contractions of cholera will show no symptoms. The majority of the population whom show symptoms will only show mild versions, though approximately 20% will display harsh symptoms. These symptoms will start to show approximately within 2 to 3 days after infection.The main issue with regards to cholera is "rice-water" diarrhoea. This is caused by movement of electrolytes from the epithelial cells in the intestine into the lumen of the gut, subsequently followed by water. It causes the loss of a large amount of fluid in a short time, and can lead to death in less than 48 hours.

The cholera toxin consists of 2 subunits: A and B. The B subunit is a pentameric ring with properties enabling the cholera toxin to bind to cell surfaces; the A subunit presents the catalytic properties within the infected cell.

The Cholera toxin increases the activity of adenylyl cyclase by catalysing the transfer of ADP ribose from intracellular NAD+ to the alpha subunit of stimulatory G protein (Gs), so the alpha subunit can no longer hydrolyse the GTP to GDP bound to it, resulting in adenlyly cylase remaining in an indefinately active state. This results in greater production of cyclic AMP (cAMP) and cAMP activates Protein Kinase A (PKA) in Cystic fibrosis transmembrane conductance regulator (CFTR) cells.

In the CFTR cell PKA leads to the opening of chloride channels and chloride ions move from the cell into the lumen. Chloride ions are negatively charged and create an electrochemical gradient.
Positively charged sodium ions also move into the lumen via ENaC in the apical membrane in order to balance this electrochemical gradient. Cholera toxin increases the expression of ENaC in the apical surface of the membrane and consequently sodium absorption is intensified. 

The movement of sodium increases the osmolarity in the lumen and water then moves from the intracellular fluid into the extracellular fluid resulting in diarrhoea. Oral rehydration therapy should be commenced promptly to prevent dehydration which if untreated could be fatal.

Other symptoms include vomiting and cramps in the individuals legs. People with weaker immune systems are more likely to die from cholera once infected as they cannot fight off any other infections due to the damaging effects caused by the loss of water and vital electrolytes.

Treatment

Fundamental treatment for any type of watery diarrhoea is to replace the water and electrolytes that have been lost. Therefore, fluids can be introduced back into the body intravenously though this is difficult to do and expensive. Water and electrolytes can be replaced back into the blood via a method of oral rehydration treatment (ORT). The composition of the oral rehydration solution (ORS) given to patients is calculate on average electrolyte contents of the diarrhoea. The standard ORS contains: 30 mmol/l bicarbonate, 80 mmol/l cholride, 90 mmol/l sodium, and finally 111 mmol/l glucose. This standard composition is recommended by UNICEF and WHO. If a patient receives treatment in the early stages of contraction the chance of mortality can be reduced down to below 1%.

Additionally, in areas of high risk of a cholera outbreak, vaccinations are being administered in order to provide a short term solution until more permanent fixes can be made. These long term fixes include improved sanitation and water filtering systems. There are two types of safe vaccine currently available, both of which are administered orally. The patient receives the vaccine in two doses, given one and then a second between one week up to six weeks later.

Zinc supplements have also been of some use to reduce the symptoms of the disease. A study conducted in Bangledesh showed that they are able to reduce the severity of the diarrhoea however this alone is not sufficient to completely cure the disease and they should be taken in small quantities of 10-20mg each day.