c
[1] is a severe bacterial infection caused by the bacteria Vibrio cholerae6 which

primarily affects the small intestine. The main symptoms include profuse watery diarrhea
and vomiting. Transmission is primarily by the acquisition of the pathogen through
contaminated drinking water or infected food. The severity of the diarrhea and associated
vomiting can lead to rapid dehydration and electrolyte loss6 which can lead to death.
Cholera is a major cause of death in the world.

The study of cholera has been used as an example of early epidemiology. Study of the V.
cholerae bacterium has also shed light on many of the mechanisms used by bacteria to
infect and survive in their hosts.

c

[hide]

`„ 1 Signs and symptoms

`„ x Cause
`„  Pathophysiology
„ .1 Susceptibility
„ .x Transmission
ë„ .x.1 Potential human contribution to transmissibility
`„  Diagnosis
„ .1 Enrichment media
„ .x Plating media
`„ G Prevention
`„ ^ Treatment
`„ u Epidemiology
„ u.1 Pandemic genetic diversity
`„ Œ History
„ Œ.1 Origin and spread
„ Œ.x False historical report
„ Œ. Cholera morbus
„ Œ. Other historical information
„ Œ.G Research
„ Œ.^ Notable cases
`„  Notes
`„ 10 See also
`„ 11 References
`„ 1x Further reading
`„ 1 External links

?
  


The primary symptoms of cholera are profuse diarrhea6 severe dehydration and
abdominal pain. Cholera may also cause vomiting. These symptoms start suddenly6
usually one to five days after infection6 and are the result of a toxin produced by the
vibrio cholerae bacterium that compels profuse amounts of fluid from the blood supply
into the small and large intestines. [x] An untreated cholera patient may produce several
gallons of diarrhoeal fluid a day.

?
 c

TEM image of Vibrio cholerae

Most of the V. cholerae bacteria in the contaminated water consumed by the host do not
survive the highly acidic conditions of the human stomach.[] The few bacteria that do
survive conserve their energy and stored nutrients during the passage through the
stomach by shutting down much protein production. When the surviving bacteria exit the
stomach and reach the small intestine6 they need to propel themselves through the thick
mucus that lines the small intestine to get to the intestinal wall where they can thrive. V.
cholerae bacteria start up production of the hollow cylindrical protein flagellin to make
flagella6 the curly whip-like tails that they rotate to propel themselves through the mucus
of the small intestine.

Once the cholera bacteria reach the intestinal wall6 they do not need the flagella
propellers to move any longer. The bacteria stop producing the protein flagellin6 thus
again conserving energy and nutrients by changing the mix of proteins which they
manufacture in response to the changed chemical surroundings. On reaching the intestinal
wall6 V. cholerae start producing the toxic proteins that give the infected person a watery
diarrhea. This carries the multiplying new generations of V. cholerae bacteria out into the
drinking water of the next host if proper sanitation measures are not in place.

The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein
subunits: a single copy of the A subunit (part A)6 and five copies of the B subunit (part
B)6 connected by a disulfide bond. The five B subunits form a five-membered ring that
binds to GM1 gangliosides on the surface of the intestinal epithelium cells. The A1
portion of the A subunit is an enzyme that ADP-ribosylates G proteins6 while the Ax
chain fits into the central pore of the B subunit ring. Upon binding6 the complex is taken
into the cell via receptor-mediated endocytosis. Once inside the cell6 the disulfide bond is
reduced and the A1 subunit is freed to bind with a human partner protein called ADP-
ribosylation factor ^ (Arf^).[] Binding exposes its active site6 allowing it to permanently
ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive
cAMP production6 which in turn leads to secretion of HxO6 Na+6 K+6 Clí6 and HCOí into
the lumen of the small intestine and rapid dehydration. The gene encoding the cholera
toxin is introduced into V. cholerae by horizontal gene transfer. Virulent strains of V.
cholerae carry a variant of lysogenic bacteriophage called CTXf or CTXij.

Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into
cells. The toxic part (red) is activated inside the cell (PDB code: 1xtc).

Microbiologists have studied the genetic mechanisms by which the V. cholerae bacteria
turn off the production of some proteins and turn on the production of other proteins as
they respond to the series of chemical environments they encounter6 passing through the
stomach6 through the mucous layer of the small intestine6 and on to the intestinal wall.[G]
Of particular interest have been the genetic mechanisms by which cholera bacteria turn
on the protein production of the toxins that interact with host cell mechanisms to pump
chloride ions into the small intestine6 creating an ionic pressure which prevents sodium
ions from entering the cell. The chloride and sodium ions create a salt-water environment
in the small intestines6 which through osmosis can pull up to six liters of water per day
through the intestinal cells6 creating the massive amounts of diarrhea. The host can
become rapidly dehydrated if an appropriate mixture of dilute salt water and sugar is not
taken to replace the blood's water and salts lost in the diarrhea.

By inserting separate6 successive sections of V. cholerae DNA into the DNA of other
bacteria such as E. coli that would not naturally produce the protein toxins6 researchers
have investigated the mechanisms by which V. cholerae responds to the changing
chemical environments of the stomach6 mucous layers6 and intestinal wall. Researchers
have discovered that there is a complex cascade of regulatory proteins that control
expression of V. cholerae virulence determinants. In responding to the chemical
environment at the intestinal wall6 the V. cholerae bacteria produce the TcpP/TcpH
proteins6 which6 together with the ToxR/ToxS proteins6 activate the expression of the
ToxT regulatory protein. ToxT then directly activates expression of virulence genes that
produce the toxins that cause diarrhea in the infected person and that permit the bacteria
to colonize the intestine.[G] Current research aims at discovering "the signal that makes
the cholera bacteria stop swimming and start to colonize (that is6 adhere to the cells of)
the small intestine."[G]

?
 
 


?
 

Recent epidemiologic research suggests that an individual's susceptibility to cholera (and

other diarrheal infections) is affected by their blood type: those with type O blood are the
most susceptible6[^][u] while those with type AB are the most resistant. Between these two
extremes are the A and B blood types6 with type A being more resistant than type B.[citation
needed]

About one million V. cholerae bacteria must typically be ingested to cause cholera in
normally healthy adults6 although increased susceptibility may be observed in those with
a weakened immune system6 individuals with decreased gastric acidity (as from the use
of antacids)6 or those who are malnourished.

It has also been hypothesized that the cystic fibrosis genetic mutation has been
maintained in humans due to a selective advantage: heterozygous carriers of the mutation
(who are thus not affected by cystic fibrosis) are more resistant to V. cholerae
infections.[Œ] In this model6 the genetic deficiency in the cystic fibrosis transmembrane
conductance regulator channel proteins interferes with bacteria binding to the
gastrointestinal epithelium6 thus reducing the effects of an infection.

?
 

Drawing of Death bringing the cholera6 in Õe Petit Journal

People infected with cholera suffer acute diarrhea. This highly liquid diarrhea6
colloquially referred to as "rice-water stool6" is loaded with bacteria that can infect water
used by other people.[] Cholera is transmitted through ingestion of water contaminated
with the cholera bacterium6 usually from feces or other effluent. The source of the
contamination is typically other cholera patients when their untreated diarrhea discharge
is allowed to get into waterways or into groundwater or drinking water supplies. Any
infected water and any foods washed in the water6 as well as shellfish living in the
affected waterway6 can cause an infection. Cholera is rarely spread directly from person
to person. V. cholerae harbors naturally in the zooplankton of fresh6 brackish6 and salt
water6 attached primarily to their chitinous exoskeleton.[10] Both toxic and non-toxic
strains exist. Non-toxic strains can acquire toxicity through a lysogenic bacteriophage.[11]
Coastal cholera outbreaks typically follow zooplankton blooms6 thus making cholera a
zoonotic disease.

?
 
  

 


Cholera bacteria grown in vitro encounter difficulty subsequently growing in humans

without additional stomach acid buffering. In a x00x study at Tufts University School of
Medicine6 it was found that stomach acidity is a principal agent that advances epidemic
spread.[1x] In their findings6 the researchers found that human colonization creates a
hyperinfectious bacterial state that is maintained after dissemination and that may
contribute to epidemic spread of the disease. When these hyperinfectious bacteria
underwent transcription profiles6 they were found to possess a unique physiological and
behavioral state6 characterized by high expression levels of genes required for nutrient
acquisition and motility6 and low expression levels of genes required for bacterial
chemotaxis. Thus6 the spread of cholera can be expedited by host physiology.
?
 

In epidemic situations6 a clinical diagnosis is made by taking a history of symptoms from
the patient and by a brief examination only. Treatment is usually started without or before
confirmation by laboratory analysis of specimens.

Stool and swab samples collected in the acute stage of the disease6 before antibiotics have
been administered6 are the most useful specimens for laboratory diagnosis. If an epidemic
of cholera is suspected6 the most common causative agent is Vibrio cholerae O1. If V.
cholerae serogroup O1 is not isolated6 the laboratory should test for V. cholerae O1.
However6 if neither of these organisms is isolated6 it is necessary to send stool specimens
to a reference laboratory. Infection with V. cholerae O1 should be reported and
handled in the same manner as that caused by V. cholerae O1. The associated diarrheal
illness should be referred to as cholera and must be reported.[1]

A number of special media have been employed for the cultivation for cholera vibrios.
They are classified as follows:

?
   


1.„ Dlkaline peptone water at pH Œ.^

x.„ [onsur's taurocholate tellurite peptone water at pH .x

?
  


1.„ Dlkaline bile salt agar (BSD : The colonies are very similar to those on nutrient
agar.
x.„ [onsur's gelatin Tauro cholate trypticase tellurite agar (GTTD medium: Cholera
vibrios produce small translucent colonies with a greyish black centre.
.„ TCBS medium: This the mostly widely used medium. This medium contains
thiosulphate6 citrate6 bile salts and sucrose. Cholera vibrios produce flat x  mm
in diameter6 yellow nucleated colonies.

Direct microscopy of stool is not recommended as it is unreliable. Microscopy is

preferred only after enrichment6 as this process reveals the characteristic motility of
Vibrios and its inhibition by appropriate antiserum. Diagnosis can be confirmed as well
as serotyping done by agglutination with specific sera.

?
 

Although cholera may be life-threatening6 prevention of the disease is normally
straightforward if proper sanitation practices are followed. In the first world6 due to
nearly universal advanced water treatment and sanitation practices6 cholera is no longer a
major health threat. The last major outbreak of cholera in the United States occurred in
110-111.[1][1G] Travelers should be aware of how the disease is transmitted and what
can be done to prevent it. Effective sanitation practices6 if instituted and adhered to in
time6 are usually sufficient to stop an epidemic. There are several points along the cholera
transmission path at which its spread may be (and should be) halted:

Cholera hospital in Dhaka6 showing typical cholera beds.

`„ Sterilization: Proper disposal and treatment of infected fecal waste water

produced by cholera victims and all contaminated materials (e.g. clothing6
bedding6 etc.) is essential. All materials that come in contact with cholera patients
should be sterilized by washing in hot water using chlorine bleach if possible.
Hands that touch cholera patients or their clothing6 bedding6 etc.6 should be
thoroughly cleaned and disinfected with chlorinated water or other effective anti-
microbial agents.
`„ Sewage: anti-bacterial treatment of general sewage by chlorine6 ozone6 ultra-
violet light or other effective treatment before it enters the waterways or
underground water supplies helps prevent undiagnosed patients from
inadvertently spreading the disease.
`„ Sources: Warnings about possible cholera contamination should be posted around
contaminated water sources with directions on how to decontaminate the water
(boiling6 chlorination etc.) for possible use.
`„ Water purification: All water used for drinking6 washing6 or cooking should be
sterilized by either boiling6 chlorination6 ozone water treatment6 ultra-violet light
sterilization6 or anti-microbal filtration in any area where cholera may be present.
Chlorination and boiling are often the least expensive and most effective means of
halting transmission. Cloth filters6 though very basic6 have significantly reduced
the occurrence of cholera when used in poor villages in Bangladesh that rely on
untreated surface water. Better anti-microbial filters like those present in
advanced individual water treatment hiking kits are most effective. Public health
education and adherence to appropriate sanitation practices are of primary
importance to help prevent and control transmission of cholera and other diseases.
A vaccine for cholera is available in some countries6 but prophylactic usage is not
currently recommended for routine use by the Centers for Disease Control and Prevention
(CDC).[1^] During recent years6 substantial progress has been made in developing new
oral vaccines against cholera. Two oral cholera vaccines6 which have been evaluated with
volunteers from industrialized countries and in regions with endemic cholera6 are
commercially available in several countries: a killed whole-cell V. cholerae O1 in
combination with purified recombinant B subunit of cholera toxin and a live-attenuated
live oral cholera vaccine6 containing the genetically manipulated V. cholerae O1 strain
CVD 10-HgR. The appearance of V. cholerae O1 has influenced efforts in order to
develop an effective and practical cholera vaccine since none of the currently available
vaccines is effective against this strain.[1] The newer vaccine (brand name: Dukoral)6 an
orally administered inactivated whole cell vaccine6 appears to provide somewhat better
immunity and have fewer adverse effects than the previously available vaccine.[1^] This
safe and effective vaccine is available for use by individuals and health personnel. Work
is under way to investigate the role of mass vaccination.[1u]

Sensitive surveillance and prompt reporting allow for containing cholera epidemics
rapidly. Cholera exists as a seasonal disease in many endemic countries6 occurring
annually mostly during rainy seasons. Surveillance systems can provide early alerts to
outbreaks6 therefore leading to coordinated response and assist in preparation of
preparedness plans. Efficient surveillance systems can also improve the risk assessment
for potential cholera outbreaks. Understanding the seasonality and location of outbreaks
provide guidance for improving cholera control activities for the most vulnerable. This
will also aid in the developing indicators for appropriate use of oral cholera vaccine.[1Œ]

?
 

Cholera patient being treated by medical staff in 1x.

In most cases cholera can be successfully treated with oral rehydration therapy (ORT).
ORT is highly effective6 safe6 and simple to administer: prompt replacement of water and
electrolytes is the principal treatment for cholera6 as dehydration and electrolyte depletion
occur rapidly. In situations where commercially produced ORT sachets are too expensive
or difficult to obtain6 alternative homemade solutions using various formulas of water6
sugar6 table salt6 baking soda6 and fruit offer less expensive methods of electrolyte
repletion. In severe cholera cases with significant dehydration6 the administration of
intravenous rehydration solutions may be necessary.
Antibiotics shorten the course of the disease and reduce the severity of the symptoms;
however6 oral rehydration therapy remains the principal treatment. Tetracycline is
typically used as the primary antibiotic6 although some strains of V. cholerae have shown
resistance. Other antibiotics that have been proven effective against V. cholerae include
cotrimoxazole6 erythromycin6 doxycycline6 chloramphenicol6 and furazolidone.[1]
Fluoroquinolones such as norfloxacin also may be used6 but resistance has been
reported.[x0]

Rapid diagnostic assay methods are available for the identification of multi-drug resistant
V. cholerae.[x1] New generation antimicrobials have been discovered which are effective
against V. cholerae in in vitro studies.[xx]

The success of treatment is significantly affected by the speed and method of treatment.
If cholera patients are treated quickly and properly6 the mortality rate is less than 1%;
however6 with untreated cholera6 the mortality rate rises to G0 ^0%.[x][x]

?
 




By 1x February x006 the number of cases of infection by cholera in sub-Saharan Africa

had reached 1xŒ6GŒ and the number of fatalities6 60G.

`„ In x0006 some 106000 cholera cases were officially notified to WHO. Africa
accounted for Œu% of these cases.[xG]

`„ Úuly - December x00u - A lack of clean drinking water in Iraq has led to an
outbreak of cholera.[x^] As of x December x00u6 the UN has reported xx deaths
and 6G^ laboratory-confirmed cases.[xu]

`„ August x00u - The cholera epidemic started in Orissa6 India. The outbreak has
affected Rayagada6 Koraput and Kalahandi districts where more than x6000
people have been admitted to hospitals.[xŒ]
 `„ August - October x00Œ - As of x October x00Œ6 a total of ^ laboratory-
confirmed cholera cases6 including eight deaths6 had been verified in Iraq.[x]

`„ March - April x00Œ - x60 people from x0 provinces throughout Vietnam have
been hospitalized with acute diarrhea. Of those hospitalized6 uu patients tested
positive for cholera.[0]

`„ November x00Œ - Doctors Without Borders reported an outbreak in a refugee

camp in the Democratic Republic of the Congo's eastern provincial capital of
Goma. Some G cases were reportedly treated between November u through th.

`„ August x00Œ - April x00: In the x
 

6 which is

still continuing6 an estimated ^6G1 people in the country have been infected
with cholera and6 by 1^ April x006 6x01 deaths had been reported.[1] According
to the World Health Organization6 during the week of xx xΠMarch x006 the
"Crude Case Fatality Ratio (CFR)" had dropped from .x% to .u%.[1] The daily
updates for the period x March x00 to u April x006 list 1uΠcases and ^
fatalities6 giving a weekly CFR of .^^% (see table above);[x] however6 those for
the period Œ April to 1^ April list 1uG new cases and ^x deaths (and a resulting
CFR of .G%).[x] The CFR had remained above .u% for most of Úanuary and
early February x00.[]

`„ Úanuary x00 - The Mpumalanga province of South Africa has confirmed over
Œ1 new cases of Cholera6 bringing the total number of cases treated since
November x00Πto xxu^. 1 people have died in the province since the
outbreak.[]

?
 
 


Amplified fragment length polymorphism (AFLP) fingerprinting of the pandemic isolates

of Vibrio cholerae has revealed variation in the genetic structure. Two clusters have been
identified: Cluster I and Cluster II. For the most part Cluster I consists of strains from the
1^0s and 1u0s6 while Cluster II largely contains strains from the 1Œ0s and 10s6
based on the change in the clone structure. This grouping of strains is best seen in the
strains from the African Continent.[G]

?
 

Hand bill from the New York City Board of Health6 1Œx. The outdated public health
advice demonstrates the lack of understanding of the disease and its actual causative
factors.

?
  


Cholera likely has its origins in and is endemic to the Indian subcontinent. The disease
spread by trade routes (land and sea) to Russia6 then to Western Europe6 and from Europe
to North America. Cholera is now no longer considered a pressing health threat in Europe
and North America due to filtering and chlorination of water supplies6 but still heavily
affects populations in developing countries.

`„ 1Œ1^-1Œx^ - Ñ 
 

: Previously restricted6 the pandemic began
in Bengal6 and then spread across India by 1Œx0. 106000 British troops and
countless Indians died during this pandemic.[^] The cholera outbreak extended as
far as China6 Indonesia (where more than 1006000 people succumbed on the
island of Úava alone) and the Caspian Sea before receding. Deaths in India
between 1Œ1u and 1Œ^0 are estimated to have exceeded 1G million persons.
Another x million died between 1Œ^G and 11u. [u]

`„ 1Œx-1ŒG1 - 


 
 reached Russia (see Cholera Riots)6
Hungary (about 1006000 deaths) and Germany in 1Œ16 London (more than
GG6000 people died in the United Kingdom)[Œ] and Paris in 1Œx. In London6 the
disease claimed ^6G^ victims and came to be known as "King Cholera"; in Paris6
x06000 succumbed (out of a population of ^G06000) with about 1006000 deaths in
all of France.[] The epidemic reached Quebec6 Ontario and New York in the
same year and the Pacific coast of North America by 1Œ.[0] The 1Œ1 cholera
epidemic killed 1G06000 people in Egypt.[1] In 1Œ^6 cholera struck Mecca6
killing over 1G6000 people.[x] A two-year outbreak began in England and Wales
in 1ŒŒ and claimed Gx6000 lives.[] Cholera was found in Dundee in 1Œx. One
influential UK pamphlet explaining how to nurse cholera patients and prevent the
disease was £ints on the Cholera morbus (1Œx) by the home economics writer
Esther Copley.

`„ 1Œ - Second major outbreak in Paris. In London6 it was the worst outbreak in
the city's history6 claiming 161u lives6 over twice as many as the 1Œx outbreak.
Cholera hit Ireland in 1Πand killed many of the Irish Famine survivors already
weakened by starvation and fever.[] In 1Œ cholera claimed G60Œ lives in the
port city of Liverpool6 England6 and 16Œ in Hull6 England.[] An outbreak in
North America took the life of former U.S. President Úames K. Polk. Cholera6
believed spread from ship(s) from England6 spread throughout the Mississippi
river system killing over 6G00 in St. Louis[] and over 6000 in New Orleans[]
as well as thousands in New York.[] Mexico was similarly attacked.[x] In 1Œ
cholera was spread along the California6 Mormon and Oregon Trails as ^6000 to
1x6000[G] are believed to have died on their way to the California Gold Rush6
 Utah and Oregon in the cholera years of 1Œ-1ŒGG.[] It is believed that over
1G06000 Americans died during the two pandemics between 1Œx and 1Œ.[^][u]
`„ 1ŒGx-1Œ^0 -  

 
 mainly affected Russia6 with over a
million deaths. In 1ŒGx6 cholera spread east to Indonesia and later invaded China
and Úapan in 1ŒG. The Philippines were infected in 1ŒGŒ and Korea in 1ŒG. In
1ŒG6 an outbreak in Bengal once again led to the transmission of the disease to
Iran6 Iraq6 Arabia and Russia.[x] There were at least seven major outbreaks of
cholera in Úapan between 1ŒGŒ and 10x. The Ansei outbreak of 1ŒGŒ-^06 for
example6 is believed to have killed between 1006000 and x006000 people in Tokyo
alone.[Œ]
`„ 1ŒG - Outbreak of cholera in Chicago took the lives of G.G% of the population
(about 6G00 people).[][] In 1ŒG-6 London's epidemic claimed 106uŒ lives.
The Soho outbreak in London ended after removal of the handle of the Broad
Street pump by a committee instigated to action by Ú
 
.[G0] This proved
that contaminated water (although it didn't identify the contaminant) was the main
agent spreading cholera. It would take almost G0 years for this message to be
believed and acted upon. Building and maintaining a safe water system was and is
not cheap²but is absolutely essential.

`„ 1Œ^-1ŒuG - Ñ
 
 

 spread mostly in Europe and Africa. At
least 06000 of the 06000 Mecca pilgrims fell victim to the disease. Cholera
claimed 06000 lives in Russia in 1Œ^^.[G1] The epidemic of cholera that spread
with the Austro-Prussian War (1Œ^^) is estimated to have claimed 1^G6000 lives
in the Austrian Empire.[Gx] Hungary and Belgium both lost 06000 people and in
the Netherlands x06000 perished. In 1Œ^u6 Italy lost 116000 lives.[G]

1Œx cholera outbreak in Hamburg6 hospital ward

1Œx cholera outbreak in Hamburg6 disinfection team

`„ 1Œ^^ - 1Œu - Outbreaks in North America. It killed some G06000 Americans.[^]

In London6 a localized epidemic in the East End claimed G6G^ lives just as
London was completing its major sewage and water treatment systems²the East
End was not quite complete. William Farr6 using the work of Úohn Snow et al. as
to contaminated drinking water being the likely source of the disease6 was able to
relatively quickly identify the East London Water Company as the source of the
contaminated water. Quick action prevented further deaths.[] Also a minor
outbreak at Ystalyfera in South Wales. Caused by the local water works using
contaminated canal water6 it was mainly its workers and their families who
suffered6 11 died. In the same year more than x16000 people died in Amsterdam6
The Netherlands. In the 1Œu0s6 cholera spread in the US as epidemic from New
Orleans along the Mississippi River and related ports of tributaries6 with
thousands dying.

`„ 1ŒŒ1-1Œ^ - Ñ 
 

 ; According to Dr A. Ú. Wall6 the 1ŒŒ-
1ŒŒu epidemic cost xG06000 lives in Europe and at least G06000 in Americas.
Cholera claimed x^u6Œ0 lives in Russia (1Œx);[G] 1x06000 in Spain;[GG] 06000 in
Úapan and over ^06000 in Persia.[G] In Egypt cholera claimed more that GŒ6000
lives. The 1Œx outbreak in Hamburg killed Œ6^00 people. Although generally
held responsible for the virulence of the epidemic6 the city government went
largely unchanged. This was the last serious European cholera outbreak.

`„ 1Œ-1x -   
 

 had little effect in Europe because of
advances in public health6 but major Russian cities (more than G006000 people
dying of cholera during the first quarter of the x0th century)[G^] and the Ottoman
Empire were particularly hard hit by cholera deaths. The 10x-10 cholera
epidemic claimed x006000 lives in the Philippines.[Gu] xu epidemics were recorded
during pilgrimages to Mecca from the 1th century to 106 and more than x06000
pilgrims died of cholera during the 10u 0Πhajj.[G^] The sixth pandemic killed
more than Œ006000 in India. The last outbreak in the United States was in 110-
111 when the steamship [oltke brought infected people to New York City.
Vigilant health authorities isolated the infected on Swinburne Island. Eleven
people died6 including a health care worker on Swinburne Island.[1][1G][GŒ]

`„ 1^1-1u0s -  
 

 began in Indonesia6 called El Tor after
the strain6 and reached Bangladesh in 1^6 India in 1^6 and the USSR in 1^^.
From North Africa it spread into Italy by 1u. In the late 1u0s6 there were small
outbreaks in Úapan and in the South Pacific. There were also many reports of a
cholera outbreak near Baku in 1ux6 but information about it was suppressed in
the USSR.

`„ Úanuary 11 to September 1 - Outbreak in South America6 apparently

initiated when a ship discharged ballast water. Beginning in Peru there were 1.0
million identified cases and almost 106000 deaths. The causative agent was an O16
 El Tor strain6 with small differences from the seventh pandemic strain. In 1x a
new strain appeared in Asia6 a non-O16 nonagglutinable vibrio (NAG) named
O1 Bengal. It was first identified in Tamil Nadu6 India and for a while
displaced El Tor in southern Asia before decreasing in prevalence from 1G to
around 10% of all cases. It is considered to be an intermediate between El Tor and
the classic strain and occurs in a new serogroup. There is evidence of the
emergence of wide-spectrum resistance to drugs such as trimethoprim6
sulfamethoxazole and streptomycin.

?
 Ñ 
 


Main article: Chicago 1ŒŒG cholera epidemic myth

A persistent myth states that 06000 people died in Chicago of cholera and typhoid fever
in 1ŒŒG6 but this story has no factual basis.[G] In 1ŒŒG6 there was a torrential rainstorm
that flushed the Chicago River and its attendant pollutants into Lake Michigan far enough
that the city's water supply was contaminated. However6 because cholera was not present
in the city6 there were no cholera-related deaths6 though the incident caused the city to
become more serious about its sewage treatment.

?
 c
 


The term cholera morbus was used in the 1th and early x0th centuries to describe both
non-epidemic cholera and other gastrointestinal diseases (sometimes epidemic) that
resembled cholera. The term is not in current use6 but is found in many older
references.[^0] The other diseases are now known collectively as gastroenteritis.

?
   
 



In the past6 people traveling in ships would hang a yellow quarantine flag if one or more
of the crew members suffered from cholera. Boats with a yellow flag hung would not be
allowed to disembark at any harbor for an extended period6 typically 0 to 0 days.[^1]. In
modern international maritime signal flags the quarantine flag is yellow and black.

?
 !

The Russian-born bacteriologist Waldemar Haffkine developed the first cholera vaccine
around 100. The bacterium had been originally isolated thirty years earlier (1ŒGG) by
Italian anatomist Filippo Pacini6 but its exact nature and his results were not widely
known around the world.

One of the major contributions to fighting cholera was made by the physician and pioneer
medical scientist Úohn Snow (1Œ1 1ŒGŒ)6 who found a link between cholera and
contaminated drinking water in 1ŒG.[] Dr Snow proposed a microbial origin for
epidemic cholera in 1Œ. In his major "state of the art" review of 1ŒGG6 he proposed a
substantially complete and correct model for the aetiology of the disease. In two
pioneering epidemiological field-studies6 he was able to demonstrate that human sewage
contamination was the most probable disease vector in two major epidemics in London in
1ŒG.[^x] His model was not immediately accepted6 but it was seen to be the more
plausible as medical microbiology developed over the next thirty years or so.

Cities in developed nations made massive investment in clean water supply and well-
separated sewage treatment infractures was made between the mid-1ŒG0s and the 100s.
This eliminated the threat of cholera epidemics from the major developed cities in the
world. Robert Koch6 0 years later6 identified V. cholerae with a microscope as the
bacillus causing the disease in 1ŒŒG.

Cholera has been a laboratory for the study of evolution of virulence. The province of
Bengal in British India was partitioned into West Bengal and East Pakistan in 1u. Prior
to partition6 both regions had cholera pathogens with similar characteristics. After 1u6
India made more progress on public health than East Pakistan (now Bangladesh). As a
consequence6[clarification needed] the strains of the pathogen that succeeded in India had a
greater incentive in the longevity of the host. They have become less virulent than the
strains prevailing in Bangladesh. These uninhibitedly draw upon the resources of the host
population6 thus rapidly killing many victims.

More recently6 in x00x6 Alam et al. studied stool samples from patients at the
International Centre for Diarrhoeal Disease (ICDDR) in Dhaka6 Bangladesh. From the
various experiments they conducted6 the researchers found a correlation between the
passage of V. cholerae through the human digestive system and an increased infectivity
state. Furthermore6 the researchers found that the bacterium creates a hyper-infected state
where genes that control biosynthesis of amino acids6 iron uptake systems6 and formation
of periplasmic nitrate reductase complexes were induced just before defecation. These
induced characteristics allow the cholera vibrios to survive in the "rice water" stools6 an
environment of limited oxygen and iron6 of patients with a cholera infection.[1x]

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The pathos in the last movement of Tchaikovsky's (c. 1Œ0-1Œ) last symphony made
people think that Tchaikovsky had a premonition of death. One observer noted that a
week after the premiere of his Sixth Symphony6 "Tchaikovsky was dead--^ November
1Œ. The cause of this indisposition and stomach ache was suspected to be his
intentionally infecting himself with cholera by drinking contaminated water. The day
before6 while having lunch with Modest (his brother and biographer)6 he is said to have
poured tap water from a pitcher into his glass and drunk a few swallows. Since the water
was not boiled and cholera was once again rampaging St. Petersburg6 such a connection
was quite plausible ...."[^]

Other famous people believed to have died of cholera include:

`„ Elliott Frost6 son of American poet Robert Frost[^]

„