Cholera

Cholera is caused by infection with the bacterium Vibrio cholerae. Vibrios are one of the most common organisms in surface waters of the world. Although the reservoir has always been assumed to be humans, there is some evidence of an aquatic reservoir.

It can produce watery diarrhoea that is very profuse and this can rapidly lead to severe dehydration and death. Transmission is usually from contaminated water and direct person to person transmission is rare.

Over 100 serotypes of V. cholerae exist but only two cause disease. V. cholerae O1 has 2 variants called classical and El Tor. The other pathogen is O139 that emerged in 1992.

• The disease is not endemic to the United Kingdom and is rarely imported from abroad.
• Most of the recent pandemics have been due to El Tor but O1 classical and O139 are endemic in India and Bangladesh.
• Cholera occurs where sanitation, food and water hygiene are poor.
• It may also arise where there is no clean water or adequate sewage disposal as after natural disasters or within displaced populations in war zones and it can spread very quickly.
• The main areas where cholera is prevalent are in Africa, Asia, the Middle East, Peru and some countries of Central America.
• Research suggests that levels of cholera relate to rainfall level and river levels in Bangladesh. The exact mechanism of this remains to be elucidated.¹

In 2002, the World Health Organisation was officially notified of 142,311 cases of cholera including 4,564 deaths but this is almost certainly an underestimate. 97% of reported cases were from Africa. Large outbreaks occurred in Malawi, Mozambique and Zambia, accounting for 44% of the African cases. Vibrio cholerae O1 El Tor was responsible for the majority of cases.

V. cholerae O139, which emerged in the Bay of Bengal in 1992, is confined to south east Asia and is responsible for approximately 15% of laboratory-confirmed cases of cholera reported from cholera-endemic countries in Asia. 5 cases were reported in Australia in 2002 of which 2 were imported and 3 were locally acquired. In Australia non-pathogenic forms of V. Cholerae are occasionally isolated.

• Short-term travel has an extremely low risk and is in the order of 2 or 3 cases per million travellers.²
• For long-term travellers in areas of outbreaks the rate may be as high as 5 cases per 1,000 persons and when routine screening for V. cholerae is done in all returned travellers with diarrhoea the rate is in the order of 5 cases per 100,000.
• Drinking untreated water or eating poorly cooked seafood in endemic areas carries a high risk.
• Travellers living in unsanitary conditions, such as humanitarian relief workers in disaster areas, are also at risk.

Most people who are infected with cholera do not become ill although they may be excreting the organism for 7 to 14 days.

History

A number develop a moderate form of diarrhoea that is clinically indistinguishable from other forms of gastroenteritis. No more than 10% develop the very profuse diarrhoea that is regarded as characteristic of the disease.

• The incubation period is 6 to 72 hours.
• Severe illness - sudden onset of profuse, watery diarrhoea with nausea and vomiting.
• The volume of fluid lost can be up to 20 litres a day.
• If not replaced, heavy fluid loss rapidly leads to serious dehydration and circulatory collapse.

Examination

The severely dehydrated patient will look very unwell with sunken eyes and possibly impaired level of consciousness. Skin will be dry and lacking turgor. Pulse will be fast but weak with a low blood pressure indicating haemodynamic instability.

• Stool specimen to identify organism.
• U&E as likely to be significantly dehydrated and to monitor IV fluid replacement. Creatinine may rise if kidneys fail with circulatory collapse.
• FBC will show a high Hb with haemoconcentration.
• WCC is likely to be raised but will not aid diagnosis or management.

A good way of estimating net fluid loss or gain if changes are large is to weigh the patient daily. 1kg of weight represents 1 litre of fluid.

Resuscitation

• The basis of treatment is the replacement of lost fluid.
• This may be done orally if not very severe or if there is no access to facilities for IV replacement but the latter is required in severe fluid loss.

Antibiotics

• It used to be taught that antibiotics had no place in the management of cholera.
• However, if fluid loss is profuse, antibiotics may help. Tetracycline, doxycycline, norfloxacin, ciprofloxacin and furazolidone may be used. They reduce the rate of stool output and this shortens the duration of hospital stay, stops excretion of vibrios in the stool and minimises the requirement of fluids.
• Resistance to many of these drugs has been observed and is a matter of concern.³

Antidiarrhoeals and antisecretory drugs

• Antidiarrhoeals are not recommended.
• Many antisecretory drugs have been tried as an adjunct therapy but none has been found useful.

Feeding

• Feeding during and after cholera is emphasised.

Between 1975 and 1981, 129 cases of cholera were notified to the WHO in travellers from Europe and North America. The incidence per journey to Africa or Asia was around 2 in a million and the death rate was less than 2%.⁴ Epidemics in unprepared communities can have a mortality in excess of 50%.

All travellers should take sensible precautions about food and water hygiene. An oral cholera vaccine is now available in the UK. The vaccine is not required by most travellers but may be suitable for those who are unable to take adequate precautions in highly endemic or epidemic settings. This would include aid workers assisting in disaster relief or refugee camps, and more adventurous backpackers who do not have access to medical care.

The old cholera injection vaccine was of dubious value and lasted just 6 months but a new oral, killed whole cell vaccine is much better. It appears safe and effective for up to 2 years with a single dose and 3 or 4 years with a booster at 1 year.^5,6 In endemic areas it has been used in older children and adults and studies suggest that targeting these groups, especially women, leads to herd immunity and protection of those too young for the vaccine.⁷

• Cholera comes from the Greek meaning flow of bile.
• A dehydrating, diarrhoea-like death is described in both Sanskrit and Hippocrates writings from 500-300 BC.
• The first recorded cholera epidemic occurred in 1563. For the history of cholera epidemics see the WHO reference above.
• Cholera became a worldwide problem in the early 19th century, with the first major pandemic of 1817-1820, spreading out of India to Europe and the Americas.
• It had long been endemic in India but in 1817, India's traditional, great Kumbh festival at Hardwar in the Upper Ganges led to vast numbers of people coming together. The disease spread rapidly and when they returned to their villages the pilgrims took it with them. That epidemic killed 10,000 British troops in India, and so the number of Indians who died was probably in the hundreds of thousands. After the festival, cholera raged along the trade routes to Iran, Baku and Astrakhan and up the Volga into Russia, where merchants gathered for the great autumn fair in Nijni-Novgorod. When the merchants went back to their homes in inner Russia and Europe, they took the disease with them. Steam ships were improving the ease of international travel and the disease was spread from port to port, becoming the most feared disease in the world. The speed of the disease was such that the victim may be well in the morning and dead by nightfall.
• Cholera hit England in Sunderland in 1831. The death of William Sproat was concealed as the merchants and port authorities wished to avoid a 40 days quarantine of the port.
• John Snow witnessed the great cholera epidemic in London in 1831-2 when he was working as a colliery surgeon and unqualified assistant. He later became a student at the Hunterian School of Medicine in Great Windmill Street, London and 2 years later qualified as MRCS. He graduated MD from the University of London in 1844. In 1849 he published a small pamphlet "On the Mode of Communication of Cholera", proposing that the "Cholera Poison" reproduced in the human body and was spread through the contamination of food or water. This was opposed because the current theory was that Cholera, like all infectious diseases, was transmitted through inhalation of contaminated vapours. In 1854, cholera struck England again and Snow was able to test his hypothesis that cholera was spread through contaminated food or water. He began plotting the location of deaths from cholera. London was supplied by two water companies. One company pumped its water out of the River Thames upstream of the main city while the other took its water from the river downstream from the city. A higher concentration of cholera was found in the region supplied by the water company that drew its water form the downstream location. This water was contaminated by the city's sewage. He found that near the intersection of Cambridge Street and Broad Street in Soho, up to 500 deaths from cholera occurred within 10 days. He convinced the authorities to remove the handle from the water pump in Broad Street and the infection rapidly subsided.
• The opponents of Snow argued that he had not identified the cause of the disease and it was not until some time after Snow's death that the organism was discovered by Robert Koch in 1884 during an epidemic in Egypt.
• However it was the Italian anatomist Filippo Pacini (1812-1883) who first stated that cholera was a contagious disease, caused by the microorganisms he drew from his microscopic studies, and which he called "vibrions", during the Florence epidemics of 1854-55, predating Koch by 30 years.
• The use of intravenous fluids as treatment dates back to 1831, when Dr William O'Shaughnessy first proposed the idea, with Dr Thomas Latta undertaking the first experimental treatment the next year. The full story of the first use of intravenous fluid replacement is discussed in the article by B.A. Foëx above.
• It was understood that the remains of those who had died from cholera could spread the disease and so cholera graves were often kept apart. In York cemetery there is a specific area for cholera graves. In most cemeteries and graveyards the graves may be re-used after 50 years if there is no objection from any living relative of the interred but for cholera graves the time is 150 years.