1. Summary, 580
2. Introduction, 580
3. Pandemics, 580
3.1. The seven pandemics, 581
3.2. The beginning of the eighth pandemic? 586
4. Treatment, 590
5. References, 590
1. Summary, 580
2. Introduction, 580
3. Pandemics, 580
3.1. The seven pandemics, 581
3.2. The beginning of the eighth pandemic? 586
4. Treatment, 590
5. References, 590
Cholera is a disease which can strike in any community where sanitary conditions deteriorate or where it is possible for a few people to transport the organism from infected areas to new communities. The historical background of the seven major pandemics and the discovery of the causative organism are provided from 1800 to 1995. With the procedure of oral rehydration therapy few patients should succumb to the disease if clean water is available. The problem is that large-scale floods in many places often lead to a breakdown in clean water supplies and sewerage treatment so it will not pay to be complacent, cholera has not disappeared!
The history of cholera still provides important lessons for our society, in terms of the role of politicians, clergy and medics in the provision of clear and sensible information about infectious disease. It also reveals the jealousies and prejudices which exist in all strata of modern society. In natural disasters or in war one of the first fears expressed in the media is the onset of cholera; 80 000 Rwandan refugees died in Zaire in 1994 from the disease. The underlying threat has existed in recent major floods in Mozambique, Australia and the UK where raw sewage has seeped out into the flood water.
The pathogenesis of cholera involves the ingestion of contaminated water or food. Before 1 × 103 organisms can reach the small intestine and exert their effect they must survive the acidic conditions of the stomach, because of this it has been estimated that some 1 × 1011 organisms are required as an infective dose. Once in the small intestine the organisms multiply and form colonial mats on the epithelial surface where they release a toxin. This creates an imbalance that affects normal fluid exchange across the epithelial layer and essential salts and fluid are drawn out of the tissues; the rice-water stools that are clear and nonfoul smelling. This net loss of body fluid and electrolytes leads to hypovolaemic shock and death of the patient in 10–18 h. Further details of the molecular basis of cholera pathogenesis may be found in Mekalanos et al. (1997) and Lencer et al. (1995).
There have been seven major pandemics and some authors have proposed that the eighth pandemic commenced after the outbreak in Peru in 1991. Nevertheless, the origins of cholera are probably lost in antiquity but according to Baron (1958) the earliest records indicate that the disease has been endemic in India from at least 400 BC, where prayers to the goddess of cholera, Oola Beebee, were unable to prevent the deaths of countless worshippers. Translations of ancient Greek and Chinese literature, as well as a Sanskrit document of 802 AD, provide clear accounts of the disease. An outbreak in 1325 was first recognized as a cause of many deaths in Delhi and subsequently Europeans became aware of cholera in 1502 with the invasion of Goa by the Portuguese when 20 000 Calcuts were stricken with the disease. There was an epidemic in Juggernaut, India in 1781 that caused many deaths. India is noted for its pilgrimages and as many as 20 × 106 people travelled long distances to visit insanitary shrines each year (Rogers and Megaw 1952). Such pilgrims to a Juggernaut festival were housed in primitive temple huts with no windows, little ventilation and a sewage hole in the floor leading to an open cesspool. Then there was often incessant rain, dead cholera victims lay in the fields and filth from bodies contaminated the water. The pilgrims were fed ‘holy food’ prepared in the temples; much of this quickly putrefied but they were obliged to consume it. So many of the 100 000 succumbed to cholera that it was impossible for them to continue to pull the huge carriage, bearing the statues of the god Juggernath, a form of the Hindu god Krishna, and his brother and sister, around the town. The appalling state of the pilgrims on the ‘death’ march was recorded by Peters (1875); festering bodies were all around, and as the numbers diminished they were unable to pull the heavy Juggernaut. It is interesting that a quick calculation does not relate the beginning of a pandemic of cholera to the Kumbh Mela festival which is held every 12 years in India.
The scheme proposed by Pollitzer (1959) with seven defined pandemics starting from 1817 is accepted now although the boundaries between each one tends to be indistinct. The disease was almost a continuum from 1817 to 1975 with peaks of activity which defined the pandemics. Early accounts by different authors provided variable periods for each pandemic (Haeser 1882; Hirsch 1883; Sticker 1912) with some overlap between the cited dates. In general, the disease retreats to the endemic regions of India, in particular to the deltas of the Ganges and Brahmaputra rivers in the Bay of Bengal. A high proportion of the world’s population live in or near the endemic area and with modern modes of travel cholera can spread rapidly if control measures are not observed. From the 1860s this disease has played an important role in the development of modern international health and sanitation laws and has led to the provision of the clean water supplies and sewage disposal schemes that many countries expect today.
The origins of the first major pandemic were traced to the town of Jessore on the river Ganges, some 50 miles from Calcutta, where in 1817 (Fig. 1a) the outbreak of Vibrio cholerae O1 rapidly spread to Delhi, Bombay in the west and southwards to Puri in east India where the Juggernaut festival was held. By 1819 the disease had spread eastwards to Burma and Siam, where religious rites were held to placate the monster which spewed its disease upon their shores. Thence by merchant shipping the disease spread to China, Malaya, the Philippines and Japan and westwards to Iran and Iraq by 1822. By land the disease extended into Syria and on into southern Russia.
During the first pandemic it was not uncommon to quarantine ships, the crews were sometimes confined in lazarets, disease hospitals for the poor, and cargoes destroyed if there were cases of cholera on board during the voyage. The Master of an infected ship would be expected to swear an oath that his ship was free from infection and his ship’s Bill of Health would be handled with iron tongs and doused in vinegar before inspection by the port Health Officer. Any letters from the sick on board were thrown 10 paces, retrieved with long-handled tongs and doused in vinegar before passing through the smoke of ignited gunpowder.
The second pandemic began in 1829, although it commenced in 1826 in Bengal and spread to China through Mongolia and onwards to Moscow. By 1829 the disease was rampant in Iran (Persia) from where it spread northwards by camel caravan into south-east Russia, an epidemic occurred there and the disease spread into north-west Europe. From 1829 to 1832 more than 290 000 Russians died, for a detailed account see McGrew (1965).
The role of shipping troops and emigrants, as well as merchant shipping, led to the transfer of the disease; and most ports through which British ships traded were infected, e.g. Baltic and Indian ports. By 1831, cholera appeared in Sunderland, Newcastle, Edinburgh and London and by 1832 in Hull, Liverpool, York and Leeds; ˜14 796 known cholera cases and 5432 deaths occurred nationwide.
The Committee of the Lords of His Majesty’s most honourable Privy Council in London were concerned by the effects of cholera in the nation and on 20 October 1831 they set up the first Board of Health. However, they had little success in persuading the Board that ships’ cargoes were not the cause of cholera. The Board insisted that there should be a period of ‘airing of the goods’ before release to merchants, this was unpopular as it caused long delays and hence cost to the merchants. The complete history of cholera in Exeter in 1832 by Thomas Shapter, reprinted as part of the Urban History Series in 1971 (Shapter 1971), exposed the tensions in both the government, local authority and the public. Separate burial grounds were provided and nurses lived apart from the rest of the community. The public were incensed that coffins were wrapped in brown paper, tarred and for the first time ‘carried underhand’ on cords to prevent pallbearers coming into direct contact with the coffin (Fig. 2). An infected town was isolated and, if necessary, ‘troops or a strong body of police’ could be used to enforce this. The clergy were not to be left out –‘Who are most likely to fall victims to this fatal disorder? – persons addicted to drinking spirituous liquors and to indulgence in irregular and sensual habits!’ One preventative measure against cholera was flannel belts worn round the body. The prayer against the cholera in England, quoted by Longmate (1966) seems curiously ironic today:
‘O Almighty God, who hast visited the nations near us with the sudden death of thousands, spare, we beseech Thee, this Thy favoured land, the wrath which to our sins is justly due’.
The outbreak in Hull was due to the arrival of Russian emigrants, who then travelled overland to Liverpool, embarked on ships to North America where soon after the disease appeared in New York, and later in the same year the disease reached Quebec. Similar emotions were evident in America and churchmen used cholera as a means of castigating their congregation –‘Drunkards and filthy wicked people … are swept away in heaps as if the Holy God could no longer bear their wickedness’ (Rosenberg 1962). The disease was the ‘poor man’s plague’ in Paris because so few deaths occurred in the upper classes the poor regarded the epidemic as a poison plot of the rich executed by doctors. Of 1400 prostitutes in Paris 1300 died, and the Governor of New York stated ‘an infinitely wise and just God has seen fit to employ pestilence as one means of scourging the human race for their sins, an appropriate one for the sins of uncleanliness and intemperance’. Cholera was apparently exported from England on a troop ship to Portugal, with consequent spread to Spain. The Spanish re-exported cholera to Mexico and from there it spread to Peru and Chile. Similarly, French troops sent to Algeria carried the disease from Marseilles where 1500 had died in two days in one outbreak.
The pandemic continued to fluctuate in severity for several years in different countries and no continent was spared, e.g. 880 000 people died in Russia between 1846 and 1849. This was caused by a second incursion from Iran along the Caspian shore and upwards along the river Volga; muskovites were affected in the summer of 1847. The death toll in 1846 among pilgrims to Mecca was 15 000 and during 1848–9 in England it was 53 293. Epidemics continued in America, Poland and North Africa through to 1852 and some believed that Poland was the source of the organism that started the third pandemic in 1852. Pollitzer (1959) believed that a resurgence of the disease in India between 1848 and 1849 resulted in a further spread through Iran to Russia and led to the third pandemic which reached England, Canada, the USA, Mexico, Colombia and the Caribbean. Troop transportation to the Crimean War (1854–6) once again showed the importance of war in the transmittance of disease as cholera appeared in Greece and Turkey.
Dr John Snow in London gathered evidence in 1855 that cholera was transmitted by faecally contaminated water. Sanitary conditions in London at this time were appalling and as early as 1838 a Commissioner under the Poor Law Amendment Act described a survey carried out in the poor areas of Bethnal Green (Fig. 3). Punderson’s Gardens was narrow with an open gutter in the centre of the street into which filth of every kind was found and fever constantly broke out in the houses. The houses had no underfloor and the contents of the gutter overflowed into the houses in wet weather. Mape’s Street also had a large open sewer running along its front and the contents of privies of the houses, close to the street, were poured into this sewer. Some of the houses were of good description with neat gardens but mains sewerage systems were absent. These examples give some idea of life in London when chamber pots were emptied from windows into the street with the familiar cry of ‘Gardez l’eau’ (Russell and Goodman 1972). The first International Sanitary Conference took place in 1851 in Paris (see Howard-Jones 1974). It was with this background that Snow noticed there were some 500 deaths from cholera within a 250-yard radius of the local water pump in Broad Street in the Soho area of London. Nearby there was a brewery with its own water supply and there were fewer cases among the 70 workers who drank the brewery water, or more likely the ale. The local authorities were unconvinced by Snow’s demand to remove the handle of the pump but they finally agreed reluctantly and the outbreak abated. Many of the patients were taken in 1853 to the nearby Middlesex Hospital where Florence Nightingale cared for them and later realized the dangers in the Crimean War. Nevertheless, the Board of Health were still reluctant to accept his findings and in their report on the Broad Street outbreak they stated: ‘We do not find it established that the water was contaminated in the manner alleged; nor is there before us any evidence to show whether inhabitants of the district, drinking from the well, suffered in proportion more than other inhabitants of the district who drank from other sources’ (cited from Gale 1959).
In a previous example, Snow had indicated the importance of water as the carrier of the disease. In the Cholera Fields of South London 1849 and 1854 he showed there were noticeable differences in the companies providing water. The Southwark and Vauxhall Co. drew its water, containing the sewage of London, from the river Thames at Battersea. On the other hand, the Lambeth Co. realized that it would be more advisable to draw their supply from the less polluted water up-river near Thames Ditton in the suburbs. There were 286 deaths from the former company water in contrast with 15 from the latter company. Snow published his views in 1849 in a pamphlet entitled ‘On the mode of communication of cholera’. At about the same time Dr William Budd (1849) in Bristol believed that there was an association between water and soil and supported Snow’s view in a book entitled ‘Malignant cholera: its mode of propagation and its prevention’ but did not show conclusively the importance of faecal involvement; he described the germ as a large fungus. There was a high incidence in the Whitechapel district where the death rate was 80% of admissions at the London Hospital. Dr Thomas Barnado, a young doctor working at the London, became familiar with the real poverty in the area and this concerned him so much that he founded a boys’ home for the poor of Stepney – the rest has become part of the UK social history.
Alternative theories about the cause of cholera hampered a real advance in the fight against the disease; atmospheric pollution, intemperance, contagion still attracted the attention of some but this annoyed those who had published their incorrect assessments. In America, one elderly physician, Richard Arnold (1929) could not conceal his criticism for ‘some of our young medical men, who take their medical opinions from the last London periodicals, as the chameleon his hues from the colour of the last branch on which he has basked’ (Rosenberg 1962).
The route of spread of the fourth pandemic of 1863–75 was by a different route, through Arabia, Egypt to Istanbul (Constantinople) in 1865, to southern France, 10 000 cases, and into Italy, with 130 000 deaths in 1868; the precise detail of the movement from the Bay of Bengal to Arabia is uncertain. Nevertheless, from Arabia there was spread to Mecca where 30 000 Moslems from the subcontinent had cholera at the Hadjiz. On their return pilgrims carried the disease to numerous places in the Middle East, and from Turkey it spread again to Russia where 90 000 died. There were comparatively few cases in England, 5596 deaths in London and 1170 in Scotland. In 1866, the death rate was high in areas supplied with water from the Old Ford reservoirs and lower in water pumps supplied from the Lea Bridge filter beds. The incidence in the latter group was due to an error that allowed unfiltered water from the river Lea, which contained sewerage from a house with a known cholera case, to enter the distribution system before filtration. The spread southwards into Africa from Ethiopia led to outbreaks along the various trade routes along the rivers and across the lakes. Similar sea routes led to outbreaks in 1866 in America with 50 000 deaths and on to the Caribbean. In China, there were more than 80 000 deaths in 1879. For a more detailed account see Pollitzer 1959).
One of the more significant events during this pandemic was the description of the causative organism, Vibrio cholerae, by Filippo Pacini (1812–83) in Florence, where he published ‘Microscopic observations and pathologic deductions on Asiatic cholera’ in 1854. He described vibrios in the intestinal contents of cholera victims and he was amazed by the large numbers occurring in the mucus and desquamated epithelial cells. He termed the organism ‘vibrio cholera’ and emphasized that the contagion was ‘an organic living substance of a parasitic nature which can reproduce itself and thereby produce a specific disease’. The contributions of Snow and Pacini should have been recognized for their importance but they were virtually ignored.
Various historical accounts still accord Dr Robert Koch with the discovery of Vibrio cholerae during the fifth pandemic that began in 1881. In 1884, when he was working among patients during the outbreak in Egypt, he noted the disease was a specific gastro-intestinal infection caused by a comma-shaped bacillus which he isolated in the laboratory and named Vibrio cholerae. It was not until 1965 that the Judicial Committee on Bacteriological Nomenclature ruled that the organism should be known as Vibrio cholerae Pacini 1854.
The disease had not disappeared from Asia and Egypt after the fifth pandemic, for example between 1892 and 1894 800 000 Russians died from cholera, and there was a resurgence in Calcutta and Bombay in 1899, the start of the sixth pandemic. The disease spread by ship transportation of pilgrims en route for Mecca, where 4000 died in one week during 1902. After the work of Koch, the Sanitary Administration of Egypt had created a sanitary and quarantine service in the area around the Red Sea, and in 1867 a quarantine centre was established at El Tor. The El Tor strain was isolated by Gotschlich (1905, 1906) at the El Tor Quarantine station from the dead bodies of pilgrims. The disease rapidly spread and within three months there were 34 000 cases in Egypt and by 1908 the outbreak claimed 25 000 victims at the Hadjiz. An obligatory stool examination of all pilgrims was introduced at El Tor in 1911 regardless of clinical symptoms.
Once again there were outbreaks in Russia, with 110 000 deaths in 1910. During the 1912 epidemic in Japan, Kabeshima (1913) isolated serologically different classical strains – the Inaba and Ogawa serovars, the family names of patients from whom he isolated the strains. Nobechi (1923) found strains which existed between these two, the Hikojima strain. During this period the Indian people suffered greatly; in 1905 there were 439 439 deaths, in 1906, 682 649 deaths, in 1908, 579 814 deaths, in 1918, 556 533 deaths and in 1919, 565 166 deaths. World War I intervened in 1914 and cholera took its toll, although the number of deaths attributed to the disease and not to the warfare was difficult to gauge, but generally the pandemic peaked in 1921 and then began to retreat to the endemic areas.
The causative organism of the seventh pandemic was V. cholerae El Tor which caused an outbreak in 1937–8 on the island of Sulawesi in Indonesia. However, this was limited and it was only in 1961 that local boats carried infected people to other islands (Fig. 1b). There was spread to Korea and other countries in south-east Asia and by 1965 the classical V. cholerae had been replaced by El Tor in India. Successive waves of the disease brought the disease to Europe and by the 1970s 40 countries were reporting cases of cholera. The last outbreak in Europe was recorded in Portugal in 1974 and after this time the disease retreated, although isolated cases in other countries were due to importation by travellers. The 2467 cases in Portugal were caused by El Tor serovar Inaba and there were 48 deaths. The outbreak was caused by the consumption of raw or poorly cooked cockles and latterly by spring water that supplied a spa and from bottled mineral water (Blake et al. 1977a, b ); it reached the UK via a tourist who only drank bottled spring water. The disease may have been introduced by troops returning from Angola, Mozambique or Portuguese Guinea.
In January 1991, a serious outbreak occurred in the port of Lima, Peru. A Chinese freighter discharged the ship’s bilges into the harbour. The population living around the port regularly eat a dish known as ‘ceviche’ prepared from local fish and shellfish and soon cases of cholera appeared. It was concluded that the V. cholerae serovar Inaba biovar El Tor had entered filter-feeding shellfish and before long the organism was also found in the water supply. It was ironic that chlorination of local water supplies had been abandoned after a report was published by the US Environmental Protection Agency which reported a slight risk due to drinking chlorinated water (Anderson 1991). At a later stage cases appeared among people living in houses on the cliffs overlooking the port and before long the epidemic had spread to Equador, Colombia, Chile, Brazil and Central America with 340 000 cases and some 3600 deaths, Fig. 4a. There were signs that travellers could carry the disease further afield; a conference delegate in Lima ate a cold crab appetizer and carried the infection into the USA. Another outbreak involved eight people in the USA after they had eaten imported crab from Equador and colleagues who had eaten oysters.
Until 1992, only V. cholerae serovar O1 and El Tor were involved in previous pandemics. In that year large outbreaks occurred in India and Bangladesh caused by a previously unrecognized serovar V. cholerae O139, now known as the Bengal strain (Fig. 4b, c). This organism has now been isolated in countries in south-east Asia. As in previous pandemics, there were initial epidemics in the endemic areas a few years prior to the main spread of the disease. It should not be forgotten that there are excreters of V. cholerae in the community. In the 1980s Dr S. Sanyal (personal communication) collected faecal samples himself from residents living around a water pump in Benares, from 200 people positive for V. cholerae only four residents showed clinical signs of cholera. In addition, Azurin et al. (1967) described a long-term carrier of cholera in the Philippines named ‘Cholera Dolores’. This person suffered from El Tor cholera and was still harbouring the organism in her biliary tract four years later when the duodenal intubation study ceased.
It will be necessary to maintain vigilance to ensure that the spread is limited to sporadic outbreaks where insanitary conditions exist mainly due to poverty or the vicissitudes of the weather causing extensive flooding. Without effective food hygiene, the thorough cooking and consumption of cooked food while hot, to prevent contamination of stored cooked food, an adequate clean water supply and the hygienic disposal of human faeces, there could be further spread. In the USA they use the slogan ‘Boil it, Cook it, Peel it or Forget it!’
Early treatments are on record and one in 1648 prescribed ‘the patient to drink three glasses of cow’s urine, tobacco smoke enema or electric shocks’. Comatose patients could be revived by throwing pepper in the eyes or by holding red-hot irons to the soles of the feet – enough to waken anyone. In 1832, the Scot Dr Thomas Latta published the method of fluid replacement by intravenous injection of a saline solution (Latta 1831–2, 1832–3a, b). Even the War Office ‘Memoranda on Medical Diseases’ prepared under War conditions recommended fairly primitive treatments for cholera: ‘treat the promonitory diarrhoea by giving half an ounce of castor oil with a teaspoonful of brandy … as it clears the bowel of irritating material’ and ‘keep the patient warm and apply turpentine stupes to the abdomen’ (HMSO 1941). They obviously had not heard of Latta. Longmate (1966) described some rather humorous treatments, including one by a Dr Shute in Gloucester who persuaded a patient to drink 17 gallons of water. A more detailed account may be obtained in the article by Carpenter (1976) although one doubts whether ‘plugging the anus with beeswax or oilcloth or with a tapering cork, smooth, oiled and secured with a T-bandage to check the diarrhoea’ would have been welcomed by the patient.
During the initial use of rehydration therapy, the rice-water stools were collected and measured in a vessel strategically placed under a cholera cot. An equal volume of a balanced maintenance solution (110 mM glucose, 72 mM NaCl, 48 mM NaHCO3, 25 mM KCl) was administered intravenously. Phillips (1964a) reported the i.v. administration of 60 l to a 50-kg patient over 5 d. The difficulties associated with the preparation of such fluids on a large-scale, see Pollitzer (1959), made it almost impossible to use the technique in a major outbreak.
There were numerous other attempts made to treat patients with fluid after this time, but it was not until Phillips (1964a, b) suggested the inclusion of glucose in oral solutions might replace the use of intravenous injections that oral rehydration therapy (ORT) became a regular treatment (Nalin et al. 1968, Pierce et al. 1968). Some 90% of patients experienced bouts of vomiting and such patients were given 1–1·5 l of fluid to drink per hour (Nalin and Cash 1970). Difficulties in providing large quantities of such sterile solutions led to the use of ORT with clean water; there was one example where a Bengali man drank 56 l of water in 48 h and soon left his hospital bed to go home. The latest recommendations provide for a combination of intravenous and/or oral rehydration solution, ORS. The standard WHO/UNICEF (1983) formula consists of 3·5 g NaCl, 2·5 g Na(HCO3)2, 1·5 g KCl and 20·0 g glucose dissolved in 1·0 litre of clean drinking water. The ORS is administered together with an oral antibiotic, to which strains of V. cholerae in the area are known to be sensitive, such as tetracycline, doxycycline, cotrimoxazole, erythromycin and chloramphenicol (WHO 2000).