1. Cholera

2. Vibrio Cholerae Bacteria that cause the disease. Discovery
Pacini- 1854
Koch- 1883
Vibrio Cholerae was first isolated as the cause of cholera by Italian anatomist Filippo Pacini in 1854, but his work ignored.
Robert Koch, unaware of Filippo Pacini’s work publicized the same knowledge almost 30 years later in 1883
Because of his greater prominence, the discovery gained wide recognition.
Koch worked with a French research team in Alexandria, Egypt. studying cholera. Koch identified the vibrio bacterium that caused cholera, though he never managed to prove it in experiments.. Koch was unaware of Pacini's work and made an independent discovery, and his greater preeminence allowed the discovery to be widely spread for the benefit of others.

3. Host Humans Stomach Intestines
Human stomach acid kills the majority of the bacteria, but if you ingest enough some will inevitably make it to your intestines.
This is the main place of residence in your body. I’ll expand upon that a lot more in 2 or 3 slides.
Marine life can also serve as a vector for the bacteria.
Thus the disease is associated with shellfish (oysters in particular) and zooplankton.
Vibrio Cholerae harbors naturally in the zooplankton of fresh, brackish, and salt water, thus zooplankton are a reservoir of the disease. The vibrio cholerae attach to the exoskeletons of the zooplankton and this allows them to survive a lot longer in an aquatic environment outside of the human body.
This symbiotic relationship leads to cholera outbreaks following zooplankton blooms, for example in the rainy season in many south east Asian and African countries.

4. Host Vector Humans Marine Life Shellfish Zooplankton Stomach
Intestines
Vector
Marine Life
Shellfish
Oysters
Zooplankton
Human stomach acid kills the majority of the bacteria, but if you ingest enough some will inevitably make it to your intestines.
This is the main place of residence in your body.
Marine life can also serve as a vector for the bacteria.
Thus the disease is associated with shellfish (oysters in particular) and zooplankton.
Vibrio Cholerae harbors naturally in the zooplankton of fresh, brackish, and salt water, thus zooplankton are a reservoir of the disease. The vibrio cholerae attach to the exoskeletons of the zooplankton and this allows them to survive a lot longer in an aquatic environment outside of the human body.
This symbiotic relationship leads to cholera outbreaks following zooplankton blooms, for example in the rainy season in many south east Asian and African countries.

5. Vibrio cholerae has a strong connection to water
Not only harbored in marine life, can survive in the water without a host for a long enough time to be ingested by its next host. (I couldn’t find exactly how long)
Thus extremely connected with water, which is unfortunate because obviously water is our most crucial natural resource.
Children in Harare, Zimbabwe., collect available water for their home. Amid water-supply breakdowns, a cholera epidemic swept Zimbabwe late in 2008

6. It lives in our small intestines
Pass through stomach
Activated in small intestine
The bacteria lives in intestine
Once in intestines environmental triggers cause the bacteria to start production of flagellin protein to make a flagella
Propel themselves through the mucus that lines the lumen of the small intestine.
Reach the intestinal wall, don’t need flagella
New environmental triggers here cause them to conserve energy by halting flagellin production
Start producing cholera toxin proteins.

7. It lives in our small intestines
Pass through stomach
Activated in small intestine
Flagella production
Mucus layer
The bacteria lives in intestine like I said before.
Once in intestines environmental triggers cause the bacteria to start production of flagellin protein to make a flagella
Propel themselves through the mucus that lines the lumen of the small intestine.
Reach the intestinal wall, don’t need flagella
New environmental triggers here cause them to conserve energy by halting flagellin production
Start producing cholera toxin proteins.

8. It lives in our small intestines
Pass through stomach
Activated in small intestine
Flagella production
Mucus layer
Epithelial cell surface
Produce: Cholera Toxin
The bacteria lives in intestine like I said before.
Once in intestines environmental triggers cause the bacteria to start production of flagellin protein to make a flagella
Propel themselves through the mucus that lines the lumen of the small intestine.
Reach the intestinal wall, don’t need flagella
New environmental triggers here cause them to conserve energy by halting flagellin production
Start producing cholera toxin proteins.

9. Normal Intestine Function
Sodium: Na+
20-30g
Before talking about cholera toxin lets do a quick review of the intestines.
Fluid/mucus is pumped into the intestinal lumen during digestion. This fluid is make up of a host of enzymes and ions (all kinds of stuff, just look at all those glands) Sodium is the component of the secretions most pertinent to our discussion. A healthy individual will secrete grams of sodium per day.
Normally, nearly all of this is reabsorbed by the intestines via SGLT1 proteins on the surface of your intestinal epithelial cells. They help absorb sodium via co-transport with glucose. Thus glucose is required to re-absorb your sodium, therefore glucose is crucial in oral rehydration therapy.

10. Normal Intestine Function
Sodium: Na+
20-30g
SGLT1 Proteins
Na+
Glucose
Before talking about cholera toxin lets do a quick review of the intestines.
Fluid/mucus is pumped into the intestinal lumen during digestion. This fluid is make up of a host of enzymes and ions (all kinds of stuff, just look at all those glands) Sodium is the component of the secretions most pertinent to our discussion. A healthy individual will secrete grams of sodium per day.
Normally, nearly all of this is reabsorbed by the intestines via SGLT1 proteins on the surface of your intestinal epithelial cells. They help absorb sodium via co-transport with glucose. Thus glucose is required to re-absorb your sodium, therefore glucose is crucial in oral rehydration therapy.

11. Cholera Toxin Pathway:
Section A enters
Stimulation Pathway
Two parts to the cholera toxin protein. The red “toxic” section up top (part A) and the blue ”delivery” section at the bottom (part B)…how generic.
①The cholera toxin B section attaches to a ganglioside (membrane protein involved in sell signal transduction)
②Subunit A is endocytosed into epithelial cell and permanently rybosylates a heterotrimeric G protein.
③G protein stimulates adenylate cyclase.
④Adenylate cyclase (with ATP) catalyzes the constitutive production of cAMP
⑤cAMP stimulates protein kinase.
⑥Protein kinase stimulates secretion Cl- into lumen.
⑦Flow of negatively charged Cl- leaving cell attracts positively charged Na+ to leave cell into lumen too. (Ionic balance, homeostasis etc…)
⑧Osmosis is inevitable with such a highly concentrated salt environment in the lumen, water in cell rushes out.
You can lose 6 liters of water per day because your Na/glucose uptake can’t keep up.
Once inside the cell, toxin permanently ribosylates the Gs alpha subunit of the heterotrimeric G protein resulting in constitutive cAMP production
Germann, William J., Cindy L. Stanfield. Principles of Human Physiology. 2nd ed. San Francisco: Pearson, 2005

12. Cholera Toxin Pathway:
Section A enters
Stimulation Pathway
Cl- flowing out
Na+ follows it
H20 follows them
Two parts to the cholera toxin protein. The red “toxic” section up top (part A) and the blue ”delivery” section at the bottom (part B)…how generic.
①The cholera toxin B section attaches to a ganglioside (membrane protein involved in sell signal transduction)
②Subunit A is endocytosed into epithelial cell and permanently rybosylates a heterotrimeric G protein.
③G protein stimulates adenylate cyclase.
④Adenylate cyclase (with ATP) catalyzes the constitutive production of cAMP
⑤cAMP stimulates protein kinase.
⑥Protein kinase stimulates secretion Cl- into lumen.
⑦Flow of negatively charged Cl- leaving cell attracts positively charged Na+ to leave cell into lumen too. (Ionic balance, homeostasis etc…)
⑧Osmosis is inevitable with such a highly concentrated salt environment in the lumen, water in cell rushes out.
You can lose 6 liters of water per day because your Na/glucose uptake can’t keep up.
Once inside the cell, toxin permanently ribosylates the Gs alpha subunit of the heterotrimeric G protein resulting in constitutive cAMP production
Germann, William J., Cindy L. Stanfield. Principles of Human Physiology. 2nd ed. San Francisco: Pearson, 2005

13. Cholera Toxin Pathway:
Section A enters
Stimulation Pathway
Cl- flowing out
Na+ follows
H20 follows them
Na+ /glucose uptake can’t keep up.
Two parts to the cholera toxin protein. The red “toxic” section up top (part A) and the blue ”delivery” section at the bottom (part B)…how generic.
①The cholera toxin B section attaches to a ganglioside (membrane protein involved in sell signal transduction)
②Subunit A is endocytosed into epithelial cell and permanently rybosylates a heterotrimeric G protein.
③G protein stimulates adenylate cyclase.
④Adenylate cyclase (with ATP) catalyzes the constitutive production of cAMP
⑤cAMP stimulates protein kinase.
⑥Protein kinase stimulates secretion Cl- into lumen.
⑦Flow of negatively charged Cl- leaving cell attracts positively charged Na+ to leave cell into lumen too. (Ionic balance, homeostasis etc…)
⑧Osmosis is inevitable with such a highly concentrated salt environment in the lumen, water in cell rushes out.
You can lose 6 liters of water per day because your Na/glucose uptake can’t keep up.
Once inside the cell, toxin permanently ribosylates the Gs alpha subunit of the heterotrimeric G protein resulting in constitutive cAMP production
Germann, William J., Cindy L. Stanfield. Principles of Human Physiology. 2nd ed. San Francisco: Pearson, 2005

14. Effects on health Extremely watery diarrhea: “rice-water” stool
Dehydration (have to replenish)
thirst- kids will just drink more contaminated water
Tears
You literally can’t produce them because your lacrimal glands don’t have water available. These kids will be dying of thirst…and crying…without tears. dehumanizing.
If untreated, volume depletion can rapidly lead to hypovolemic shock (massive loss of blood fluid volume. Not enough blood serum) Death follows shortly after. (this whole process can be as short as several hours)
(Tachycardia, you can’t bath your cells in oxygen rich blood and interstitial fluid, body trying to get oxygen to your cells, pass out with no oxygen in your brain)

15. Effects on health Extremely watery diarrhea: “rice-water” stool
Vomiting
Dehydration
Extreme thirst **
Low urine output
Lack of tears

16. Effects on health Extremely watery diarrhea: “rice-water” stool
Vomiting
Dehydration
Extreme thirst **
Low urine output
Lack of tears
Hypovolemic shock
Death

17. Life cycle of Vibrio Cholerae
Mode of transmission
Fecal to oral
(Human)
Host
Diarrheal Response
Feces contaminate water source
Water source not filtered/treated
Collected as drinking water
So bringing all of that together.
fecal to oral transmission- pretty obvious by now. The massive amounts of diarrhea, hard to contain.
You can see the inevitable cycle that develops.

18. Life cycle of Vibrio Cholerae
Mode of transmission
Fecal to oral
Diarrhea
Is this the body’s evolved defense mechanism?
Or cholera’s evolved infection method?
(Human)
Host
Diarrheal Response
Feces contaminate water source
Water source not filtered/treated
Collected as drinking water
So bringing all of that together.
So fecal to oral transmission- pretty obvious by now. The copious amounts of diarrhea, hard to contain.
You can see the inevitable cycle that develops.
Interesting question:
You have a receptor (ganglioside) which the toxin can bind and enter thus causing the diarrhea:
1) Theory one: it is a defensive mechanism. Supported because it is self limiting. These bacteria are not naturally in your body and the diarrhea pushes ALL of the bacteria out eventually… if you survive the dehydration you’re clear.
2) On the flip side, cholera’s insurance mechanism that It will be released into drinking water of next host.

19. As usual… 3rd world predominantly Drinking water Lack knowledge
No filtering
No processing
No purifying
Lack knowledge
Children
Little to no
water Infrastructure
In 2005, 14 West African countries accounted for 58% of all cholera cases reported world- wide
A Rwandan refugee holding a bag of rehydration fluids for a victim of cholera during a major outbreak of the disease in Zaire, 1994.
Cholera hospital with several empty beds, made up with plastic sheets and a hole for drainage

20. Incidence reports probably barely scratch the surface
WHO estimates that the officially reported cases represent around 5-10% of actual cases worldwide
Actual number cases much higher because of poor surveillance systems and frequent under-reporting, often motivated by fear of trade sanctions and lost tourism. (like Haiti and AIDS- you can imagine the impact)

21. Treatment Oral Rehydration therapy (ORT): Oral rehydration salts H2O
Intravenous rehydration
OR salts (the sugar and ions- mix with clean water! educate, they may think this purifies their water)
IV bypasses the problem of vomiting back up your salts, it’s fast.
Where good treatment is readily accessible, the case fatality rate is less than 1%.
In untreated cases with bad conditions the case fatality rate may reach 30-50%.
So treatment is literally that simple. Get them hydrated, replace their ions

22. Prevention is crucial Public health is the main way (right now)
Water infrastructure
Clean drinking water
Sanitation
Hygiene
Education
Vaccine
Cholera kind of epitomizes the situation of the developing world. It’s not really medical brilliance that’s preventing it. It’s public health, it’s infrastructure.
No effective vaccine in US. There are 2 (one used only in India is decently effective), but side effects are bad and it doesn’t last long.
Same problem as TB, it affects the poor, thus the rich don’t have incentive to fund research.
But water born diseases (like cholera) are the number 2 killer of children world wide.

23. UNICEF picture of the year for 2008 taken by a 21-year-old Belgian photographer named Alice Smeets
A slum just outside Port-au-Prince (before the earthquake)
Think cholera could live here? Tropical environment, no water infrastructure, little sanitation

24. References www.wikipedia.org
Cholera, Vibrio Cholerae, Cholera Toxin, Zooplankton, Small Intestine, SGLT1 Protein, Enterotoxin, ORT,
Cholera Toxin Pathway:
Germann, William J., Cindy L. Stanfield. Principles of Human Physiology. 2nd ed. San Francisco: Pearson, 2005
Effects on Heatlh
As Usual:
Weekly epidemiological report- 4 AUGUST 2006, 81st YEAR
Incidence Reports
Treatment
WHO/CDS/CSR/ISR/ WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases-