Cholera: the Broad Street Pump and beyond

I was struck by three original observations of Snow's. The first was that he was not content to merely document that deaths occurred clustered in space around the Broad Street pump. He also investigated areas which were significantly low in deaths... The second observation that intrigued me was in the following passage. "I had an interview with the Board of Guardians of St. James's parish, on the evening of Thursday, 7th September, and represented the above circumstances to them. In consequence of what I said, the handle of the pump was removed on the following day." I have heard the story of the pump handle removal many times, including classes in Medical School, but each time I was told that Dr. Snow had removed the handle himself. It is interesting to me that in fact he worked through channels... The third observation continues to diverge further from the urban myth that I was taught. John Snow allowed himself to doubt that the removal of the pump handle was critical to terminating the epidemic...

I especially like the first of these, because it's a reminder of the vitally important Sherlock Holmes story ("Silver Blaze") in which the Curious Incident of the Dog in the Night-time appears:

Inspector Gregory: "Is there any point to which you would wish to draw my attention?"
Holmes: "To the curious incident of the dog in the night-time."
Inspector: "The dog did nothing in the night-time."
Holmes: "That was the curious incident."

The UCLA site on John Snow is a lovely and rich summary of his life and work. See also The making of an epidemiologist: John Snow before the Broad Street pump (from Communicable Disease and Public Health, December 2002; 5(4): 265-348)

From Harvard Medical School Focus:Until 1817, when people began tracking the disease globally, Vibrio cholerae seemed to confine its destruction mostly to Asia. Since then, some of the many pathogenic strains lurking in the brackish waters along the coasts of Asia, Africa, Europe, and the Americas have flared into six pandemics. Waves of cholera afflicted U.S. populations in 1832, 1848, and 1866. By 1900, cholera had disappeared from the Americas and most of Africa and Europe. By 1950, it again was found primarily in Asia.

Then came the seventh pandemic in 1961, when the El Tor 01 biotype apparently spread out of Indonesia to other countries in Asia and the Middle East. In the 1970s, carried in the ballast water of ships or by zooplankton in ocean currents, El Tor invaded Africa, southern Europe, and several Pacific islands. In 1991 it gained a foothold in South America. El Tor may live longer in aquatic ecosystems than previous pandemic strains, and it appears to have developed antibiotic resistance.
(http://focus.hms.harvard.edu/2002/Feb22_2002/microbiology.html)

1817: India, Persia, Turkey 1831: the first Cholera Outbreak in Britain (BBC program[me] on Sunderland
1832: It is Enough, Stay Now Thine Hand! (The 1832 Cholera Outbreak in Wantage)
1848-49: Rotherham "In the first edition of his now famous book On the Mode of Transmission of Cholera, published in 1849, Snow had already implicated contaminated water as a major contributor to cholera transmission." (http://www.sph.unc.edu/courses/john_snow/prologue.htm)
1853-54: Bermondsey, Potterspury
1865-1875: 4th global pandemic
1881-1896: 5th global pandemic
1899-1923: 6th global pandemic
1961: beginning of 7th global pandemic (first case in Celebes, Indonesia)

from Yellow Fever, Black Goddess Christopher Wills (RA649 .W55 1996)

(Vibrio cholerae) only recently crossed species boundaries to inflict damage in human populations ...first recorded outbreak in 1817, which began in the river deltas of Bengal near Calcutta... swept across the world in seven successive pandemics

...the seventh, beginning in the 1960s, was due to a slightly different strain called El Tor ...(which) in 1991 leaped its way to Peru and then to almost all the countries of Central and South America. And there may soon be an eighth pandemic, sparked by a new strain called 0139 Bengal that was first found in Vellore in 1992... (106)

Normally, water and salts can pass freely through the intestinal wall in both directions, with a net inward flow of about 200 cc a day. This is just enough to keep the faecal matter in the bowels moist, but not enough to be much of a drain on the body's resources of liquid. The toxin secreted by the cholera bacillus, however, upsets this gentle process dramatically. Specific parts of this large and complex molecule bind to receptors on the surface of cells. This causes an enormous overproduction of the enzyme adenyl cyclase, which in turn produces large quantities of a molecule called cyclic AMP. This important compound acts as a messenger that can penetrate the interior of the cells, causing them to switch on a number of processes full blast. As a result, chloride and bicarbonate ions are excreted, and the cells are unable to take up sodium ions.

The cells that are most dramatically affected by the toxin are not those that line the gut, but rather the nerve cells that control them. Recent experiments have shown that if these toxin-treated nerve cells are prevented from functioning, they trigger a violent expulsion of water into the gut's interior. The loss of salts also causes the nerves leading to the muscles of the abdomen and the legs to misfire, resulting in convulsions. (118)

It is not a coincidence that cholera, which was apparently a rare disease in ancient times, started to explode into pandemics as the human population began to grow and sewage from human and domesticated animals began to run off the land into estuaries in greater and greater quantities. It was in the vast and complex delta of the River Ganges in India that these ecological changes first began to ahve a dramatic effect. (122)

...a transposon, a piece of DNA that probably arrived in the bacterium via a plasmid and then became inserted into the bacterial chromosome. We can be near-certain about this because the traces of this genetic surgery are still visible in the chromosome... (122-123)

Most Vibrio strains do not carry the gene cluster for the cholera toxin... If it had been left alone, the Thames would never have brewed up the deadly combination of brackish water and sewage that gave rise to London's cholera epidemics of the 19th century. Such fatal events require manipulation and simplification of the environment by humans... (128)

Google "0139 bengal" (100+ hits)

Google "el tor" cholera (4000+ hits)

Cholera Clusters in Bangladesh

Cholera in the Mediterranean: outbreak in Albania (1995)

Imported Cholera Associated with a Newly Described Toxigenic Vibrio cholerae O139 Strain -- California, 1993 (from a search of CDC resources on cholera, nearly 2000 hits)

Reemergence of Epidemic Vibrio cholerae O139, Bangladesh (Shah M. Faruque et al. 2003)

Endemic and epidemic dynamics of cholera: the role of the aquatic reservoir Cláudia Torres Codeço BioMedCentral Infect Dis. 2001; 1 (1): 1

Global Climate and Infectious Disease: The Cholera Paradigm Rita R. Colwell Science Volume 274, Number 5295, Issue of 20 Dec 1996, pp. 2025-2031. --see also From Cholera to Complexity to Society: A Journey to New Dimensions (script for Dr. Rita Colwell, Director National Science Foundation, for her Keynote speech to DIMACS International Conference on Computational and Mathematical Epidemiology, June 29, 2002 Rutgers University

Cholera from eMedicine.com (register for full article)

from WHO's EMERGING FOODBORNE DISEASES Fact Sheet

Vibrio cholerae was introduced into waters off the coast of southern United States when a cargo ship discharged contaminated ballast water in 1991. It is likely that a similar mechanism led to the introduction of cholera for the first time this century into South America in 1991.

Cholera Epidemiology and Molecular Pathogenesis of Vibrio cholerae Prepared by Ellen Wiewel, Class of 2001 BIO 344, Emerging Infectious Diseases Dr. Christine White-Ziegler Spring 2001

In January 1991, a ship most likely from China emptied its sewage collected along the journey into Peruvian coastal waters. This is the commonly cited source of the V. cholerae O1 El Tor serotype Inaba bacteria in the region. However, the day after cholera struck the port of Chancay, Peru, another outbreak hit a port city 400 miles to the north...

Unique Genes Found in 7th Pandemic Cholera Strain

Researchers have identified 22 specific genes in a particularly nasty strain of cholera bacteria that has evicted classic varieties from Asia and established the deadly diarrheal disease in Africa and Latin America. The genes may give the bacteria an edge as a human pathogen or environmental organism or both.

The cholera genome: an advance for science or for medicine? The Scientist August 2000

Disease and Water Supply: The Case of Cholera in 19th Century Iran (Amir Afkhami)