Cholera

(Last Updated 2 January 2015)

Clinical features

  • diarrhea
  • vomiting (early)
  • dehydration
  • death

Diarrhea

  • early on, fecal and malodorous
  • later “rice water stool”
  • painless
  • non-straining
  • sometimes a little cramping (like an enema)
  • massive

Dehydration

  • massive diarrhea — can be more than 1/5 your entire body weight in a single day!
  • symptoms
    • sunken eyes and cheeks
    • slow “pinch response”
    • rapid and weak or missing pulse
  • can be diagnosed on sight!

Death caused by dehydration

  • can occur in 12 hours or less
  • can be treated by rehydration

Therapy

  • Intravenous solutions to rehydrate after dehydration sets in
  • Oral Rehydration to maintain fluid (and electrolyte) balance
  • Immunity follows and is both effective and long-lasting

Rehydration to replace

  • water (4 gallons a day is not a lot)
  • salts (mostly sodium chloride [salt] and potassium bicarbonate)
  • glucose (energy for transport and survival)
  • rice water stool isotonic with plasma, so replace quart for quart

Cholera cot

  • plastic cot with a hole
  • calibrated bucket
  • replace with “gatorade”
    • orally if strong enough
    • nasogastric tube if not

Antibiotic therapy

  • reduces recovery time by half
  • 2-3 days of diarrhea rather than 4-6 days
  • untreated, a very few will become “carriers” for a few months

Infection

  • Causative agent Vibrio cholerae
  • Grows in humans, but also in environment
    • salt water best
    • “viable but non-culturable”
    • association with chitin (shellfish)
  • fecal-oral transmission
  • contaminated water supply most common source

Incubation

  • Normally requires high dose (about a billion cells) for infection
  • Antacids reduce that by ten-thousand-fold!
  • (Data from infecting prisoners)

Pathology

  • onset of symptoms usually 12-72 hours after ingestion
  • depends on dose
  • Vibrio cholerae don’t invade cells, just attach to intestine
  • Secrete a toxin

Cholera toxin has two parts

  • an enzyme that damages the salt/water balance
  • a hormone-like part that fools the cell into taking it up
  • Cholera toxin inactivates the regulatory part of adenylate cyclase
    • causes Chloride to be excreted into intestine (crypt cells)
    • blocks uptake of sodium chloride (and water) from intestine (villus cells)
    • water follows salt

Effects of water flowing into intestine

  • Small intestine recycles about 9 quarts per day
  • Large intestine recycles another quart or so
  • Cholera overwhelms that
    • Water loss is in small intestine
  • Death from dehydration is rapid (shock and general collapse)

Epidemiology of Cholera

  • Begins in 1817 “Asiatic Cholera”
  • “Seven” pandemics since then
  • We’ll look at three epidemics
  • Definition of “epidemic” and “pandemic”

John Snow

On the Mode of Communication of Cholera

This is really the beginning of modern epidemiology (see assigned reading for discussion)

  • by John Snow, M.D.
  • Second edition, much enlarged
  • 1855 (preface dated 11 December 1854)
  • Reprinted in 1936
  • Analysis After the Fact!

Influence of the Water Supply on the Epidemic of 1832, 1849, and 1854 in London

  • Early Outbreaks
  • Southwark and Vauxhall Water Co. dirty
  • Lambeth Water Co. dirty
  • Cholera about the same for both
  • Chelsea Water Works, clean
    • much less cholera

Outbreak of Aug 1853-Jan 1854

  • Lambeth found new source of water
  • upstream of London’s sewage outlet
  • Some districts purely Southwark and Vauxhall, some purely Lambeth
  • Some districts had BOTH sets of pipes on the same street!

Death rates from Cholera (by district)

  • Outbreak of 1854
  • Probably from the Baltic Fleet
  • Look at districts supplied by BOTH on house by house basis

Differences in the water

  • S&V water had 37.9 grains of salt per gallon
  • Lambeth water had 0.95 grains of salt per gallon
    • easy to tell apart
    • Vibrio cholerae requires some salt for survival
  • Lambeth, clean; S&V, dirty

Death rates from Cholera (by district)

Water Co. Deaths/10,000 houses
Southwark and Vauxhall 315
Lambeth 37

Outbreak at the Broad Street Pump

  • London 1854
  • “Worst outbreak ever”
  • over 500 fatal cases within 250 yards of the pump
  • Led him to analyze the waterworks data from the earlier outbreak

The Outbreak

  • a few cases in late August
  • Probably originally came in from the Black Sea Fleet
  • Really began the night of Aug. 31/Sep. 1

Actual Cause of the Outbreak

  • Learned by the clergyman (Henry Whitehead) after the fact
  • Infant (baby Lewis) developed diarrhear on Aug 28 (dies Sept. 2)
  • Mother (Sarah Lewis) soaked diapers in pails
  • Emptied pails into a cesspool 3 feet from the pump

The first week (ending Sept 2) 83 cases

  • all but ten were nearer the Broad St. Pump than any other
  • 5 families said they preferred the water from the Broad St. Pump
  • 3 were children who went to school near the pump
  • 2 occurred before the real outbreak

The majority lived near the pump

  • 61 known to drink from the pump
  • 6 no info (whole family died)
  • 6 did NOT drink from the pump directly
    • may have drunk indirectly
    • water in drinks (liquor) or sodas

Pump handle removed on Sept 8

  • Board of Guardians of St. James’ parish on the 7th
  • ended the outbreak (as did the departure of 3/4 of the residents!)
  • Pump water was probably already cleared of cholera by then anyhow
  • But the pump handle makes a more dramatic story

Added twist

  • Baby Lewis dies on Sept. 2
    • ending contamination of the well
  • Thomas Lewis (father) fell ill on Sept 8
    • same day as pump handle removed
  • Removing pump handle did not end the outbreak, but it did prevent a second wave
  • No other apartment in the house had access to the old cesspool

Lessons from the Broad Street Pump

  • Almost everyone who died drank from the pump
  • No question: cholera is transmitted in the water. Period.

Hamburg 1892

  • Hanseatic State
  • Oligarchic rule (Senate)
  • No civil service
  • Capitalism (Trade) rules all

Filtration of Water

  • known to be effective since John Snow
  • costs money, so delayed
  • Altona (downstream and next to Hamburg) had filtration

The Hamburg-America Line

  • transporting immigrants to America
  • especially from central and eastern Europe
  • A trainload of immigrants from Ukraine
  • Known cholera outbreak
  • Hamburg accepted them anyhow
  • Cholera broke out in the warehouse where they were kept
  • Shipped them to America

Cholera ships

  • shipowners feared closing the port of Hamburg
  • Medical officer forced American vice-consul to give clean bill of health to ships
  • Several ships forced to sail back to Hamburg
  • Many deaths

Hamburg vs. Altona (effects of filtration)

City Population Cholera cases Cases/1000
Hamburg 580,000 19,891 34
Altona 143,000 572 3.9

Anti-contagionism

  • Petenkofer and conservatism of physicians
  • could not culture bacteria or use microscope
  • Koch was Prussia
  • Anti-contagionism was more “intuitive” and cheaper!
  • Slow action on an epidemic cost thousands of lives.

Miasmatic Theory of Cholera

  • Von Pettenkofer’s “experiment
    • Drank a vial of pure V. cholerae (no ill effects)
    • (Student [Rudolph Emmerich] did same, got cholera!)
  • Three factors required
    • Specific infectious element (new idea!)
    • Porous soil with decaying matter in it
    • Toxic substance produced by these two

Importance of Snow’s work

  • Miasmatists used his spot map to support their own (less specific) theories
  • General sanitation vs. specific cause
  • Not really recognized until much later
  • Now he is “myth” and parish committee is forgotten, especially Henry Whitehead
  • Myth?