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Cholera

Cholera is a bacterial disease transmitted in water or food contaminated with Vibrio cholerae bacteria and has existed since at least 500 B.C. Symptoms typically include diarrhea and vomiting and can be mild or fatal.

The earliest discovery of the bacterium was in 1854 by Italian Filippo Pacini. His work went mostly unnoticed.

In mid-1800s London, an anesthesiologist named John Snow conducted a series of field investigations that have earned him the title the “founder of field epidemiology.” Snow conducted studies of cholera outbreaks and discovered the cause of disease and prevented its recurrence. In 1854, there was a cholera epidemic in the Golden Square neighborhood of London. He began his investigation by determining where in the area people with cholera lived and worked. He marked each residence on a map. Because Snow believed that water was a source of infection for cholera, he marked the location of water pumps on his map, then looked for a relationship between the distribution of households with cases of cholera and the location of pumps. Even with no knowledge of the existence of microorganisms, Snow demonstrated through epidemiologic studies that water could serve as a vehicle for transmitting cholera and that epidemiologic information could be used to direct prompt and appropriate public health action as recourse and prevention.

inside cover of a book from 1854 by Dr. John Snow on his report of a cholera epidemic in London

The inside cover of Cholera and the Water Supply in the South Districts of London, in 1854 by Dr. John Snow. National Library of Medicine

an etching showing people in the countryside getting inoculated against cholera

Image from Harper’s Weekly 1885 of Dr. Ferran inoculating for cholera in Spain. He accompanied the cholera commission from Barcelona, Spain to Marseille, France. National Library of Medicine

In the 1880s, Dr. Robert Koch discovered cholera bacteria, traveling from Germany to Egypt and India during outbreaks. They confirmed the bacteria during autopsies and concluded it was linked to infected water supplies. Koch also discovered that people infected with cholera were protected from it afterwards.

In 1885, Spanish doctor Jaime Ferran, who studied under Louis Pasteur (Koch’s rival), created the first cholera vaccine from working with live bacteria. He did a mass vaccination (50,000 people) during an outbreak in Spain.

Two scientists, Sawtschenko and Sabolotny, experimented with a killed cholera bacteria “broth” in 1893, which prevented cholera but was impractical because it required many doses.

Video produced by Byron Motion Pictures of the U.S. Navy in Calcutta, India to do a controlled experiment using chemotherapy against cholera, c. 1946. (Link to video)

Several cholera vaccines were invented worldwide, including Haffkine’s vaccine trials in India in 1893, and his heat-killed vaccine in 1911. In 1927, Alexandre Besredka’s oral bilivaccine was tested in India and China alongside an injected vaccine. At the National Institutes of Health (NIH) from 1943 until her retirement in 1971, Dr. Margaret Pittman worked to assess the efficacy of and establish national and international standards for the production of the cholera vaccine.

There was an epidemic of cholera in Thailand in May 1958, and the World Health Organization, and Philippine and American officials sent vaccines and other aid to Thailand. The King and Queen of Thailand, Their Majesties King Bhumibol Adulyadej and Queen Sirikit, were invited to attend the dedication ceremony of the NIH's Building 29, the newly built home of the Division of Biologics Standards (DBS), in June 1960 because of his majesty’s active role in the South East Asia Treaty Organization (SEATO) Cholera Research Project. The SEATO Cholera Research Project formed in the wake of the epidemic.

Dr. Pittman was active with SEATO and traveled to the cholera research laboratory in Dacca, East Pakistan (now Bangladesh). For five years she was the SEATO Cholera Research Project director at the NIH. Pittman helped design the laboratory, the equipment, and the research that would take place at SEATO. With Pittman leading the team their findings demonstrated that the effectiveness of a cholera vaccination directly relates to its potency assay. This research project also verified the importance of IV restorative fluids in treatment procedures for victims of cholera. Today SEATO has been replaced by the International Center for Diarrhoeal Disease Research, Bangladesh.

The 1980s and 1990s brought increased research and understanding of the complexity of the cholera bacteria, leading to many more vaccines around the world. Trials around the world expanded knowledge on the theory of herd immunity or herd protection. Vaxchora, approved by the FDA in 2016 and which is the vaccine currently in use, is a single-dose vaccine taken before traveling to at-risk areas.

People are gathered around a lab bench stacked high with large vaccine bottles

Interior of a Philippine government laboratory where officials are checking an initial shipment of 200,000 doses of cholera vaccine. There was an epidemic of cholera in Thailand in May 1958. Millions of doses of vaccines, along with technical advisors, and other medical equipment were airlifted to Thailand. World Health Organization (WHO)