Cholera – Characteristics and History
Cholera is an acute diarrheal disease usually accompanied by vomiting and resulting in severe dehydration or water loss and its consequences. The disease is caused by a comma-shaped bacterium, Vibrio cholerae, first isolated in Egypt and Calcutta in 1883. Mortality rates have reached up to 70 percent of infected individuals during epidemics. Cholera has long been endemic in India and Bangladesh, from where it has spread in periodic epidemics to other parts of Asia and eventually to much of the rest of the world. Most of this spread has occurred since 1817, when the modern history of the disease outside India begins; it is now generally agreed that some seven pandemics have occurred since its initial spread. The most re-cent began in 1961 and is only now receding. The bacterium is disseminated by the so-called fecal-oral route as a consequence of sewage and fecal contamination of water supplies and food-stuffs. This indirect transmission long made its spread difficult to understand.
In the course of history, the term “cholera” has been variously applied. The word first appears in the Hippocratic corpus and there refers to sporadic diarrheal disease. Later classical writers including Celsus, Aretaeus, and Caelius Aurelianus used the term as well. By 1669, Thomas Sydenham employed it in describing an epidemic in London. “Cholera” was also widely used to describe endemic or sporadic diarrhea throughout the nineteenth century and ear-lier in Western Europe and the Americas. This is sometimes specifically designated as cholera nostras.
The term cholera morbus, today limited to the disease caused by V. cholerae, can cause confusion because in the past it meant either epidemic or endemic forms of such illness. Synonyms include cholera asiatica, cholera epidemica, malignant cholera, cholera asphyxia, and cholera spasmodica. It is now generally accepted that all cholera in the West prior to the nineteenth century epidemics was endemic or sporadic and not caused by V. cholerae.
The cholera bacterium, V. cholerae, was seen in the excreta and intestinal contents of cholera victims by Filippo Pacini and described and named by him in a report published in Florence in 1854. The bacterium can be grown in the lab-oratory in an alkalinity greater than that tolerated by most other bacteria. This characteristic is of significance for its growth in the human small intestine. V. cholerae survives and multi-plies outside the human body in any relatively uncontaminated alkaline environment. It does not regularly infect animals; its host range is limited to humans, who can also act as asymptomatic carriers. The bacteria produce a toxin, which causes the symptoms of the disease.
Cholera is spread solely by infected humans, whose excreta may contaminate drinking water and food. This is not a direct-contact infection as expected from such diseases as smallpox, and communicability was initially a highly controversial matter.
The spread of cholera in a community depends first on the appearance of a person, either ill or well, who is discharging the cholera vibrio from his or her intestinal tract, and second on the state of hygiene, water supply, and sewage disposal in promoting or impeding the transmission of the bacteria to potential victims. unsatisfactory sanitary facilities were a necessary condition for cholera outbreaks in Europe and the Americas. Indeed, the history of the control of cholera is the history of improved sanitation.
Current distribution of epidemic cholera is largely limited to areas in India and the tropical Far East, where it persists and occasionally breaks out in areas with contaminated water and sewage. Since World War II, it has made sporadic forays into the Middle East and other Asian regions. In the 1970s, cholera appeared briefly in Europe, with outbreaks in Naples (more than 30 deaths), Barcelona, and Lisbon (more than 2,000 cases). One small area of persistent infection ap-pears to be the lower bayou country outside of New Orleans.
The bacterial infection is limited to the intestinal tract; no microbes are found to invade the body tissues. The low bacterial population normally in the small intestine as well as its high alkalinity contribute to the cholera vibrio’s ability to survive and grow there, usually in massive numbers. The bacteria adhere to the intestinal wall and secrete a toxin that inhibits the absorption of water and electrolytes (salts) from the intestine into the circulation. Failure of this absorption results in the loss and excretion of many liters of fluid in the course of a single day. This loss presents as a massive, debilitating diarrhea, which is the major clinical feature of cholera. All other symptoms of the disease are attributable to water and salt depletion. These include weakening and finally loss of pulse, thickening of the blood, suppression of urination, loss of tissue fluids giving the face a sunken appearance, cyanosis, muscular spasms, and a disastrous fall in blood pressure leading to profound shock, which represents the fatal conclusion of the disease.
Modern therapy consists simply of replacing the lost water and salts. Thus cholera is essentially curable. Antibiotics play only a minor role, in that they may shorten the duration of disease and reduce the massive amounts of necessary fluid replacement.
In India, a relatively sparse literature on the dis-ease serves as a prelude to the modern history of true cholera. Modern literature on cholera starts slowly in 1817 and accelerates with its ap-pearance in Russia in 1829, Eastern Europe in 1831, and Western Europe and North America in 1832.
Portuguese explorer Gaspar Correia stated that in the spring of 1503, many soldiers of Cali-cut died of a “disease, sudden-like, which struck with pain in the belly, so that a man did not last out eight hours time.” Correia also met cholera in an epidemic form in the spring of 1543 in Goa, where the mortality was so great that it was difficult to bury all of the dead. The dis-ease was marked “by vomiting, with drought of water accompanying it, as if the stomach were parched up, and cramps that fixed the sinews of the joints.”
The disease was repeatedly described by Europeans in Goa in 1563, 1584, and 1585. Re-ports followed through the rest of the 1500s and 1600s, including that of the well-known physician Jacobus Bontius in the earlier 1600s, who extended his observations to Indonesia. Notices of the disease continued to appear into the eighteenth century, when they were supplemented by reports by English medical men (including famed naval doctor James Lind), who provided good descriptions of cholera cases and symptoms in the 1750s and 1760s.
In 1781, cholera ravaged British troops in the Ganjam district of India, requiring the hospitalization on March 22 alone of no less than 500 men of a division of 5,000. A report of the incident calls the disease a “pestilential disor-der” and does not name it cholera, although later writers assumed that it was. This outbreak is reported to have reached Calcutta. In April of 1783, “cholera burst out at Hurdwar, and in less than eight days is supposed to have cut off 20,000 pilgrims.” Fragmentary observations continued to appear, depicting the “terrible ferocity” of the disease, which “destroyed an enormous number of people,” and further ravages occurred at Arcot and Vellore in October 1787.
Cholera, or cholera-like disease, continued to be observed during the rest of the eighteenth and into the nineteenth century. Then, in the year 1814, outbreaks of cholera occurred in a number of Indian provinces, including the crowded barracks of Fort William at Calcutta among recruits just arrived from England.
It may well be that “it was nothing new for cholera to spread over India in an epidemic form prior to 1817 and 1819.” But at this point, some-thing drastically “new” did occur, as cholera es-caped the bounds of India and initiated the waves of pandemics that were to engulf the world. This change in cholera’s pattern of activity has led a few to conclude that a new disease arose in Bengal in 1817, a contention that was much debated. More recently, it has also been suggested that a genetic modification in the microbe was responsible for this supposed change in cholera’s nature.
In any event, in March 1817, a death from cholera took place in Fort William, but because it was a solitary case no notice was taken of it. By July, however, outbreaks occurred in several districts in the Province of Bengal. In July and the following months, Calcutta was affected; 25,000 of its inhabitants were under medical treatment for the disease, of whom 4,000 died. Thus be-gins the modern history of Asiatic or epidemic cholera, although none of the documents immediately surrounding the event makes reference to the name “cholera,” until a letter dated September 16 specifically refers to cholera morbus.
Within 3 months the disease had spread throughout the Province of Bengal, and in November it reached the camp of the Marquis of Hastings in Bundelcund. During 1818, it moved over the greater part of India including Delhi and Bombay, with estimated attack rates of up to 7.5 percent of the exposed population. It continued to rage through 1819 and 1820, extending into Ceylon and Burma, Siam, Malacca and Singapore, and the Philippines. By 1821, it had invaded Java, Batavia, and China to the east and Persia to the west, reaching Baghdad with a besieging Persian army, and extending from there to Aleppo. By 1823, it was in Egypt, Astrakhan, and the Caspian shores and throughout Syria along the shores of the Mediterranean. But it receded for a number of years, thereby terminating the First Pandemic.
By 1824, cholera had retreated to its endemic area in Bengal, where it remained active in the Ganges Delta through 1826. But in 1827, it spread out again in the so-called Second Pandemic into the Punjab, and by 1829 extended through Persia to the shores of the Caspian Sea. Reaching Orenburg in August 1829, it soon expanded north and west into Russia. By September of 1830, cholera was in Kharkov and Moscow, and began spreading west into Bulgaria. During the winter of 1830–31, it persisted in the Russian army in Poland, and then in the spring invaded Warsaw and, soon after, Riga. Meanwhile, cholera was also rag-ing through Mecca and Turkey, reaching Constantinople and Alexandria by July and August. On August 3, it entered Berlin and Vienna, and reached Hamburg by the beginning of October. Around the end of October, if not before, it appeared in England at Sunderland, supposedly imported from Hamburg or Riga. Late fall and early winter brought a brief respite; observers were sent to infected areas, and efforts were made to prepare for the coming onslaught amid much argument about such matters as quarantine, sanitation, contagiousness, and treatment.
The opening of the year 1832 was soon fol-lowed by a reawakening of cholera. In February, it appeared in Newcastle, Edinburgh, and London, as well as places in between. Next it reached France, bursting on Paris on March 24, and soon engulfing all districts of the city. Within 18 days no fewer than 7,000 persons were dead. Next, cholera hurdled the Atlantic Ocean to appear on June 8 in Quebec and on June 19 in Montreal. Presumably, it arrived with emigrants on the brig Carricks, which left infected Dublin in April and lost 42 of its 173 passengers before reaching Quebec on June 3. On June 23, cholera invaded the United States, appearing in New York on that date and in Philadelphia on July 5. From these ports of entry, it marched westward across both North American countries.
Entry into Spain, Portugal, the Caribbean, and Latin America was delayed until 1833, and into Italy until 1835. Havana lost 8,253 persons in a population of 65,000 between February 26 and April 20, 1833, and by August no less than 15,000 had perished in Mexico.
Yet by 1834, the disease was beginning to recede, and while it persisted in a number of Mediterranean and Central American areas for a few more years, it retreated once again in 1837 to its Indian homeland. For much of the world, this pandemic was the first modern experience with the disease, and subsequent epidemics or pandemics were to follow much the same route. Popular and governmental response to subsequent appearances was largely based on experience gained during this pandemic.
During the following decade, cholera continued to plague India, and it entered with British troops into Afghanistan in 1839 and China in 1840, where it remained into 1841 and 1842. In 1844–45, it extended into Persia and Central Asia, reaching the Arabian coast as well as the Caspian and Black seas in 1846–47. Constantinople was attacked on October 24, 1847. In the spring of 1848, it broke out with renewed vigor, advancing as far as a line drawn through Arabia, Poland, and Sweden, reaching Berlin in July and Hamburg and Holland by September, and then London and Edinburgh in short order. After a short period of comparative rest, it renewed its activity in the spring, reach-ing Paris in March and by now covering much the same ground as the earlier epidemic. Mean-while, in December 1848 cholera had crossed the Atlantic to invade New York and New Or-leans, and spread rapidly across the continent from these centers. In 1850, it reached California with wagon trains as well as by ship from Panama. In that year it was reported in North Africa, Europe, and both North and South America. In many of these regions, it continued through 1851 and 1852.
The year 1854 found cholera widely spread in Europe, the Near East, and the Americas to produce one of the worst cholera years on record. It was during this pandemic that John Snow made his observations in London that in 1855 led to the publication of his critical, if not immediately appreciated, study on cholera transmission by contaminated water. In 1855 and after, the dis-ease died down in much of the West, but it continued in a few spots there as well as in much of the East.
The Fourth Pandemic is generally dated from 1863 and lasted 10–12 years. In 1865, an estimated one-third of 90,000 pilgrims at Mecca succumbed. As before, cholera reached Constantinople and spread around the Mediterranean, reaching northern Europe in 1866 and 1867, and the United States and Latin America in 1866. It raged over its old grounds until 1874.
The Fifth Pandemic is said by many to have begun in 1881 and lasted until 1896. It was during this epidemic that the studies of Robert Koch in Alexandria and Calcutta in 1883-84 led to the isolation and identification of the causative microbe. The epidemic was at first largely limited to the Mediterranean shores of Africa and Europe, although it later became widespread in Russia and in Germany, where it was marked by the explosive outbreak in Hamburg in 1892. Importation into New York in 1887 was arrested, but outbreaks did occur in Latin America. The disease was also widely prevalent in the Far East – in China and Japan.
The Sixth Pandemic ran from 1899 through 1923. It followed much the pattern of the fifth – largely affecting India, the Near and Far East, Egypt, western Russia, and the Balkan Peninsula. Sporadic outbreaks occurred in southern Europe and Hungary in the West and China, Japan, Korea, and the Philippines in the East. But this time cholera did not reach the Western Hemisphere.
The Seventh Pandemic dates from about 1961 and followed much the pattern of the previous epidemic. It was particularly important in providing an opportunity for significant advances in cholera pathogenicity and therapy in studies carried out in Egypt, India, Bangladesh, and the Philippines by several U.S. teams.
This brief sketch provides only the barest out-line of the history of cholera. Historians do not always agree on the chronology of the pandemics. In fact, it is sometimes not entirely clear why or when one pandemic is said to have terminated and another to have begun.
Earlier, thoughts on the causes of cholera were embedded in notions of disease causation going back to Hippocrates, such as weather, sea-sons, geographic environment, bad air and miasmas, and dietary indiscretions. If an infecting agent was even envisioned, it was as a vague poison or miasma.
By the middle of the nineteenth century, how-ever, ideas of a microbial etiology were gaining ground. In 1849, William Budd and two associates described microscopic bodies in cholera excreta and published their findings with illustrations. French botanist Charles Robin reproduced the illustrations in 1853. These were seen by the German botanist Ernst Hallier, who at-tempted to grow microbes from cholera excreta. He published his findings in 1867.
T. R. Lewis tried to confirm Hallier’s work in Calcutta in 1870, but failed. In the meantime, as already described, Pacini made his correct but at the time largely ignored observations of the actual V. cholerae in 1854. Thus it was left to the genius, persistence, and technical elegance of Koch in 1883 to isolate and identify the microbe and to introduce the modern phase of understanding of the disease. It was not, however, until 1959 that the toxin produced by the microbe was discovered, along with its role in dis-ease causation.
The question of the “contagiousness” of cholera was a matter of heated debate through-out most of the nineteenth century. The contagionists were viewed by contemporaries as archaic, conservative, and even antisocial, whereas the anticontagionists were seen as modern, bourgeois, mercantile, and socially responsible. Most of the debate focused on the question of quarantine which, of course, was anathema to mercantile interests, and the anticontagionists gained ground as the nineteenth century progressed. The demonstration by Snow of the waterborne nature of cholera was slow to gain acceptance, but this development, coupled with Koch’s discoveries, finally proved the “contagion” of the disease, albeit allowing for the intermediary roles of infected excreta, water or food, and of individuals who can act as carriers but do not develop the disease.
Sanitation has always played a major role in efforts to understand and control the propagation of cholera. As a consequence, a large body of literature has been generated on the role and influences of cholera epidemics on the development of public-health policies, public-health organizations, and sanitation procedures and techniques.
The definitive treatment – intravenous fluid and salt replacement – was a long time in developing. As early as 1830, German chemist R. Hermann demonstrated that the change in the blood’s fluid balance was reflected in the contents of the cholera excreta. A colleague injected 6 ounces of water into his terminally ill patients, a treatment that produced a quick, temporary return of the pulse, although death nonetheless occurred 2 hours later. In October 1831, Berlin surgeon J. F. Dieffenbach took the premature step of injecting several ounces of whole blood into three patients. They died 6 minutes, 2 hours, and 6 hours later, respectively, the first during violent convulsions. In Britain in late 1831 and early 1832, W. B. O’Shaughnessy published papers suggesting the intravenous replacement of salt and water. This led Thomas Latta to try the treatment on patients; he subsequently re-ported that 5 of 15 survived. Other attempts followed, with some success, during the 1830s. Sporadic trials continued through the century, but the treatment was not successful until Leonard Rogers perfected it in Calcutta in the early 1900s. There were a number of technical problems to be solved first, such as effective sterilization. But with these difficulties re-solved, the definitive treatment of cholera was established.