Cholera and Calcutta (Kolkata)

 Cholera and Calcutta (Kolkata)

          PKGhatak,MD

In 1964, I disembarked at the international terminal of the Cairo Airport in Egypt as a transit passenger. The instant, the officer saw Calcutta address on my passport, he asked me to produce a cholera inoculation certificate and his body language told me as if I was going to give him cholera at that moment. Until that moment, I did not know that a stigma was attached to Calcutta as the birthplace of the cholera pandemic.

The first pandemic originated in 1817 in a town called Jessore (যশোর) near Calcutta, which now belongs to Bangladesh. Since then, five more pandemics of cholera followed and all those pandemics began in and around Calcutta. The seventh cholera pandemic, however, started in Indonesia.

It is also fitting that a fundamental understanding of the parthenogenesis of cholera and an effective treatment modality also came from Calcutta. Pathology professor Dr. Subhunath Dey of Calcutta University discovered cholera toxins in 1951. The endotoxin not only prevents sodium chloride absorption but also destroys the enterocytes of small interstice, resulting in pouring into the gut lumen, a massive amount of water, electrolytes and bicarbonate from the blood and intestinal tissues. That amount of blood volume loss in the small intestine results in “Rice water” diarrhea and severe dehydration. Dehydration leads to shock and death. Professor Dey also found another cholera toxin called exotoxin which was antigenic, heat labile, and had no enzymatic action. He used rabbits as the animal model to study cholera. Recent advances in molecular biology made it possible to define clearly how endotoxin acts on the intestinal cells and opens up pores that pump out water and electrolytes into the intestinal lumen. Endotoxin activates the adenylate cyclase enzyme which then increases cAMP, resulting in the opening of pores.

Dr. Hemendranath Chatterjee of Chittyaranjan Hospital in Calcutta developed the Oral rehydrating solution for combating dehydration which cut down the death rate of cholera to 3% from 30%. His oral rehydration solution contains 1000 ml of sterile water, 2.6 gm of sodium chloride / common salt substitution allowed, and 25 gm of glucose /sugar if glucose is not available. The current oral rehydrating powder has a different formulation with the addition of citrates/ bicarbonate, potassium and a balanced osmolarity matching the human tissue.

A typical case of cholera.

Cholera is an infectious diarrheal disease. Children are specially vulnerable because of the lesser amount of acid present in their stomachs; adults on gastric acid blocking drugs or antacids, are susceptible to infection. Contaminated drinking water is a common source of cholera but eating contaminated raw fruits and vegetables, and undercooked shrimps, crabs, prawns, lobsters, oysters, etc. are common in endemic areas. The number of V. cholerae ingested, in an epidemic, maybe as high as 100,000/ ml. If the bacteria survive the gastric acid bath in the stomach and enter the small intestine then the vibrio quickly moves past the mucus layer of the small intestine by the flagellar movement and gets attached to the intestinal cells. Once the V.choleare enters inside the cells, the endotoxin quickly produces symptoms. Symptoms usually start within a few hours but may be delayed 24 to 48 hrs. The first symptom is the onset of watery diarrhea, which quickly turns into frequent voluminous rice water looking stools, often have a mild fishy odor and patients begin to vomit. Patients become dehydrated, weak and prostrated; the color of the skin turns yellowish pale to light blue. If treatment is not available immediately, shock soon follows.  Patients usually do not have a fever and may complain of abdominal cramps from the distended small intestine with watery fluid accumulation. Death comes early and in earlier times, it was called Blue Deaths. Mortality without treatment is over 50 % or higher. Diagnosis is easy in an outbreak, if in doubt a stool examination reveals numerous Vibrios, a rapid test kit- Crystal VC dipstick is available and the confirmation requires stool culture.

In Indian Sanskrit literature, Sushruta Samhita, written at the time of Buddha, a disease was recorded called Visuchika, now we call the same disease as cholera. Hippocrates, 460-377 AD, described the illness as cholera, the word derived from the Greek word bile. In Calcutta, cholera was called Olautha (an act of vomiting and purging). Portuguese sailors who sailed between Gujarat ports in west India and Europe learned the name Mordezin from the locals. Arabs called it Haida and the Chinese it Huo Luon.

Important events in cholera pandemics.

The name Asiatic Cholera was introduced at the time of the second pandemic which raged between 1829 and 1837. The 3^rd pandemic of 1852 killed 1 million Russians. The pandemic of 4^th between the years 1865 - 1866, that pandemic hit Zanzibar very hard and 70,000 people perished. Zanzibar is now in Tanzania. In the years between 1881 and 1896, the 5^th pandemic, cholera reached South America for the first time. India suffered the most deaths, about 800,000, during the years 1899 and 1923 during the 6^th pandemic. The last pandemic began in 1961 in Indonesia and is still going on. Following the earthquake in Haiti, a cholera epidemic began in crowded shelters and killed 10,000 people and in Yemen, during the civil war in 2015 about 2000 refugees died of cholera.

Other milestones in combating the cholera pandemic.

In 1832 Dr. Thomas Latta of Scotland introduced an I.V. saline solution to combat dehydration. Filippo Pacini of Italy in 1854 detected and demonstrated Cholera organism – Vibrio cholerae. Dr. John Snow of London, England documented the origin of the Cholera epidemic of 1954 in Soho, London from raw sewage contamination of drinking water wells, and initiated control of cholera by supplying safe water. Dr. Robert Koch isolated Vibrio cholerae from the stool of cholera victims of the Egyptian cholera epidemic in 1883 and established Vibrio cholerae as the causative organism of cholera. In 1879 an effective cholera vaccine for chicken was developed by Louis Pasture of France. The first human cholera vaccine was introduced in Valencia, Spain in 1885 by Jaume Ferran. A virulent new biotype cholera Vibrio called El Tor was identified in 1935 in Celebes, Indonesia. In 1948 antibiotic Tetracycline was demonstrated to kill Vibrio cholerae and introduced for the treatment of cholera. Subsequently, Erythromycin and doxycycline were approved for cholera treatment in 1952 and 1967 respectively. Bactrim proved to be equally effective in controlling cholera in 1968. Currently, no antibiotic is required for the treatment of cholera. Ondansetron, an antagonist to Serotonin was used to control diarrhea in cholera effectively. An oral cholera vaccine, Dukoral was approved in 1991. Another serotype of El Tor O139 cholera was detected in Bangladesh. (O stands for somatic antigen). In 2007 Japan incorporated a cholera gene in the rice grains and used engineered rice to control cholera. In 2009 Indian Stantha Biotech company introduced a vaccine named Sanchol which incorporated both O1 and O139 stereotypes of Vibrio cholerae.

Some special features of Vibrio cholerae.

 Vibrio cholerae is a gram negative, curved shaped rod, measuring 1 to 3 micrometers by 0.5 micrometers, having a single flagellum from one pole, and is very mobile in liquid medium. It is a marine and brackish river water organism. Humans are the only known reservoir but shellfish, crabs, shrimps and vegetation in coastal mangrove forests are heavily contaminated with vibrio. Vibrio belongs to the vibrionaceae family and also exhibits some features of pseudomonas and Enterobacteriaceae. Vibrio is a facultative anaerobe. Since vibrio is a marine organism, they require 2 to 3 % sodium chloride for growth in artificial media. In solid medium V. cholerae develops numerous lateral flagella and becomes much less mobile. Vibrio does not produce spores and reacts positively to oxidase. Vibrio is the most abundant bacteria in water. Only V. cholerae and V. parahaemolyticus are pathogenic to humans. V. vulnificus can cause wound infection, gastroenteritis and septicemia in humans. V. fetus, now called Campylobacter jejune may cause dysenteries like gastroenteritis and CNS infection. Helicobacter pylori are closely related to vibrio and H.pylori is often the cause of duodenal, gastric ulcers, and gastric cancer.

The classic V. cholerae is serologically O1. El Tor subspecies subsequently morphed into a new stereotype O139 in Bangladesh in 1992. Gradually El Tor O139 became the main vibrio responsible for cholera in the Indian subcontinent, Philippines and Indonesia. Antigenically O139 is completely different from the O1 serogroup. People in the endemic area have no immunity against O139. El Tor O139 is more virulent and prevalent in humans as carriers at a rate of 1: 30 -100. Whereas, the carrier ratio in V.cholerae O1 is 1: 2-3. The El Tor also survives longer in extraintestinal sites.

Calcutta.

Today Calcutta is a megacity in India. But it had a very humble beginning. The British East India Company arrived at the Mughal court in Delhi in 1608. Job Charnock, an employee of the East India Company came to Calcutta in 1690. Then Calcutta was a sleepy little village called Sutanatti. East India Company established a trading post on the east bank of the Hugli River 120 miles upstream from the Bay of Bengal. A pristine Mangrove Forest, Sundarbans (beautiful forest), was present along the entire Bengal coastal area of the Bay of Bengal. That mangrove forest was also the habitat of Vibrio Cholerae. In between the Surdarban and Calcutta, there were mainly swamps. The East India Company obtained “Letters of Patent” in 1698 from the Mughal emperor that gave them the authority to collect revenue from the local population. In 1756 a war broke out between the East India Company and the Bengal province Mughal ruler Siraj-al-Dawlah. In 1757 Siraj-al-Dawlah was defeated, in a so-called war, and he was assassinated while in custody. Subsequently, the British took over the administration of the entire Bengal province. In 1772 Calcutta became the capital of British India.

As local people started to settle in and around Calcutta, swamps were drained for agricultural use and other parcels of swamps were covered by fisheries. The king of Sundarban was the Royal Bengal Tiger. Local people did not venture into the forest because of fear of tigers except, during the fishing season, at the time of Shad running upriver for spawning. Gangetic shad (গঙ্গা ইলিশ) is a local delicacy and in high demand in Bengal. 

British hunting parties used to employ Sepoy (local foot soldiers) to scare the tigers by beating drums and driving the tigers toward the hunters sitting with their guns on a high platform built for the occasion. A single hunting party killed 100 or more tigers. As the tiger population decreased, the chance of encountering tigers became less; and more locals began to invade the forest frequently. Now, humans began to come in contact with Vibrio cholerae in higher numbers. Local people had acquired immunity but the new people that came to the area had no immunity and local outbreaks of cholera became an annual event.

In 1817 outbreak of cholera in Jessore, a town not far from Calcutta got out of hand and cholera became a Pandemic.

Chlorination of Calcutta water supply.

Calcutta corporation began chlorinating water in 1905 for residential and business uses but also continued to supply unfiltered and unchlorinated water for cleaning streets and fire hydrants. Yes, the streets of Calcutta and the pavements (footpaths) were washed clean, at the crack of dawn, each morning and gaslights were turned off at the same time. Each summer cholera broke out locally until a team of experts from the WHO arrived in Calcutta in 1952. They recommended chlorinating unfiltered water; and after chlorination of the unfiltered water was implemented, the local outbreak of cholera nearly completely disappeared from the slumps (baste) of Calcutta. Calcutta being known as a Cholera city, the Indian Council of Medical Research set up its Cholera Research Centre (later named as National Institute of Cholera & Enteric Disease). In recognition of the excellence in research, the W.H.O. established its WHO-International Reference Centre for Vibrio.

 The advances in medical science in the last 50 years are nothing but spectacular and the degradation of the environment is nothing but disastrous. Many have pointed out covid-19 pandemic is a wake-up call. There have been many wake-up calls before and the covid is not going to be the last one. The special interest groups, those who have degraded the environment, are not going to fade away easily. Progressive human encroachment in forested areas, wetlands and seas has disturbed the balance between plants and the animal kingdom and diseases unknown to humans are exploding disastrously. The cholera pandemic is just one such incidence.

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