Dont Drink the Water

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Dont Drink the Water

• Cholera

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Case Study

• Vibrio Illnesses After Hurricane Katrina ---
  Multiple States, August--September 2005 MMWR
  September 23, 2005
• List the key information you learned and any
  questions you have.

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Cholera 1800s
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First Cholera Pandemic

• Why does an epidemic end?

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Second Cholera Pandemic
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Cholera New York 1830s

• What is the message of this political cartoonist?

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John Snow and the Pump Handle

• London cholera epidemic 1850s

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John Snow

• John Snow is credited by many with developing the
  modern field of epidemiology

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London in the 1850s

• Germ theory of disease not widely accepted
• People lived in very crowded conditions with
  water and privies in yard (NY 1864 900 people in
  2 buildings 1 pump a block away, privy in yard)

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Water Supply London 1850s
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Cholera Victorian England
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John Snows Observations

• People with cholera developed immediate digestive
  problems cramps, vomiting, diarrhea
• Face, feet, hands shriveled and turned blue died
  in less than a day
• Probably spread by vomiting and diarrhea

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Cholera Epidemiology

• Comparison of pump location with cholera deaths,
  first 3 days of epidemic in 1854

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Cholera Epidemiology

• Of 83 people, only 10 lived closer to a different
  pump than Broad Street
• Of these 10, 5 preferred taste of Broad Street
  water and 3 were children who went to nearby
  school

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Cholera Epidemiology

• Snow convinced neighborhood council to let him
  remove handle from water pump on Broad Street -
  new cases declined dramatically
• Many on council not convinced by his evidence

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Snow Index Case
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Snow Index Case

• Index case is first person to become ill
• 40 Broad Street husband and child became ill
• Wife soaked diapers in pail and emptied pail into
  cistern next to pump

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The Great Experiment

• Retrospective study
• Two water companies supplied central London
• Customers mixed in same neighborhood

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The Great Experiment

• Lambeth Company water intake upstream of London
  sewage outfall into Thames
• Southwark Vauxhall Company water intake
  downstream of sewage outfall

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The Great Experiment

• Snow went door to door asking which water company
  served home and compared locations with cholera
  data

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The Great Experiment
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Discovery of Vibrio cholerae

• Filippo Pacini was a physician in Italy
• Chair of General and Topographic Anatomy at the
  University of Florence
• Described V. cholerae in epidemic in Florence in
  1854

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Discovery of Vibrio cholerae

• Until 1965, Koch credited with the discovery of
  V. cholerae
• Earned Nobel Prize in Physiology in 1905 for TB
  work
• Koch traveled to India in 1884 and succeeded in
  culturing V. cholerae
• Showed it was found in people with cholera and in
  rice water stools but not in healthy people

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Cholera at the Gates
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Cholera 1912
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Seventh Cholera Pandemic
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Cholera in the 1990s

• Epidemic in Peru beginning 1991
• From 1991-1994
• Cases 1,041,422
• Deaths 9,642 (0.9)
• Originated at coast, spread inland

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1992 Bangladesh

• In a 12 week period
• 220,000 cases
• gt8,000 deaths
• Mortality
• Untreated 60
• Treated lt 1

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World Cholera 1999
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Vibrio cholerae

• Lives in riverine and estuarine environments -
  fresh and salt water
• Facultative pathogen for humans
• Spreads quickly from human to human
• 206 serotypes

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Cholera the Disease

• Entry oral
• Colonization small intestine
• Symptoms nausea, diarrhea, muscle cramps, shock
• Severe loss of fluids and salt can result in
  death in just a few hours

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Cholera The Disease

• Severe dehydration is usual cause of death
• Treatment by oral or i.v. rehydration

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Cholera Transmission

• Ingestion of contaminated food or water
• Contact with feces or vomit from infected person
• Organism survives in environment and some foods
• Killed by heat and acidity

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Cholera Prevention
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Vibrio cholerae Identification

• Lab culture
• Nonculturable isolates
• PCR

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Vibrio cholerae

• V. cholerae is a curved rod with a polar
  flagellum
• Gram negative
• Motile

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Vibrio cholerae

• Vibrio cholerae attach to villi of small
  intestine using TCP pili protein to colonize

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Survival in Intestine

• Bile salts are bacteriocidal
• Bile salts stimulate V. cholerae to form biofilms
• Organisms in biofilm are more resistant to bile
  salts

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Cholera Toxin

• Produced by Vibrio cholerae in intestine
• Binds to ganglioside GM1 receptors
• Enzymatic subunit (A) enters cells
• Increases cellular cAMP --gt over- activity of
  sodium pump

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Sodium Pump (Na/K ATPase)
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Cholera Toxin Action

• Rapid efflux of sodium is followed by movement of
  water from the body into the lumen of the large
  intestine
• Loss of water and electrolytes results in
  acidosis (low blood pH) and hypovolumeic shock
  (low blood volume)

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Why Has Cholera Re-emerged?

• Deteriorating sanitary facilities as larger
  population moves into shanty towns
• Trujullo, Peru fear of cancer from chlorination
  so water untreated
• Use of wastewater on crops
• Africa civil wars and drought caused migrations
  into camps

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Why Has Cholera Re-emerged?

• Simultaneous appearance along whole coast of
  Peru
• Traveled in ship ballast?
• Traveled in plankton from Asia?
• Always present in local zooplankton (copepods)
  but dormant until triggered by ???

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Copepod Carrying Vibrio cholerae
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Cholera Virulence

• Vibrio cholerae O1
• Classical and El Tor
• Vibrio cholerae O139
• Nontoxogenic Vibrio cholerae
• Associated with gastroenteritis, septicemia,
  extraintestinal infections

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Cholera Virulence

• Evidence that toxin genes can be spread by
  filamentous phage
• DNA donated to bacteria expressing TCP pili
  (intestine)

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Cholera Virulence

• CTXf is lysogenic in V. cholerae
• Can be induced to propagate by sunlight may
  help spread toxin gene to non-pathogens in
  coastal areas
• Can be spread horizontally and vertically

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Survival in Environment

• A chitin binding protein allows for adherence to
  zooplankton and also to GlcNAc on intestinal
  epithelial cells
• Biofilm formation protects V. cholerae from
  grazing protozoa

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Survival in Environment

• Cholera can become Viable but Non-Culturable
  (VBNC)
• Low temperature, salinity
• Remain viable in environment for years but not
  detected
• Epidemics begin in coastal areas, local summer

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Survival in Environment

• Easier to isolate non-O1 strains from environment
• Genetic evidence that toxigenic strains arise
  independently from non-O1 strains

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Cholera in the 1990s

• Cholera O139 emerged in Asia and South America
• Different O (coat) antigen, 99 genetic identity
• O antigen is how human immune system recognizes
  and protects against V. cholerae
• More people susceptible

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Cholera and El Niño
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Cholera and El Niño

• Periodic warming of water near coast of Central
  and South America
• Large plankton blooms, especially in coastal
  waters with nutrients from sewage runoff

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Cholera in Bangladesh
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Cholera and El Niño

• Cholera in Bangladesh also seen to fluctuate with
  El Niño, but with 11 month lag
• Rita Colwell and multinational group studying
  link between climate and cholera
• Satellite and surface data used

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Cholera from Space
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Cholera and Sea Surface Temperature
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Cholera Antibiotic Resistance

• Cholera is becoming resistant to several
  antibiotics

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Cholera Vaccine

• Two vaccines currently available
• Not approved for use in US or advised for
  travelers on CDC web site
• Vaccine against O1 Vibrio not effective against
  O139 Vibrio

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Cholera Prevention

• Drink only boiling hot beverages, boiled or
  chlorinated water, or canned or bottled
  carbonated beverages
• Eat only food cooked and kept hot and fruits that
  can be peeled (scrub outsides first)

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Key Concepts

• Discuss the kinds of experiments that John Snow
  did to trace the source of the cholera outbreak
  in London.
• Why does cholera periodically reappear as
  pandemics?
• Discuss the relationship of Vibrio cholerae,
  biofilms, zooplankton, sea surface temperature,
  and bacteriophages in the ecology of cholera.