1. Case Study #3 - Cholerae

Front 1

What is virbrio cholerae an exmaple of?

Back 1

It is an example of a pathogen that uses an enterotoxin to damage the host

Front 2

Describe the properties of virbrio cholerae

Back 2

1) Motile, Gram-negative curved rod with a single polar flagellum
2) Survive in both frsh and brackish water
3) Only affects humans; no insect vector or animal reservoir host

Front 3

How is virbrio cholerae serotyped (determination of antigen on the basis of antibodies that recognize them)

Back 3

They are serotyped based on their LPS O antigen

Front 4

What are the major virulence factors of virbrio cholerae

Back 4

1) Cholera toxin
2) Tcp pili
3) Flagellum for motility

Front 5

How is virbrio cholerae spread?

Back 5

-Disease is spread by fecal contamination of water and food and is linked to poor sanitation
-Disease usually occurs in epidemics
-All people are believed to suseptible to infection but individuals with damaged or undeveloped immunity, reduced gastric acidity or malnutrition may suffer more severe forms of the illness

Front 6

What are the symptoms of the disease caused by virbrio cholerae

Back 6

1) Caused by enterotoxin produced by bacterium which is manifested as massive diarrhoea
2) Waterfly diarrhoea is speckled with flakes of mucus and epithelial cells and contains enormous numbers of vibrios

Front 7

What can the massive diaharrhea cause/

Back 7

1) Severe fluid and electrolyte loss results in dehydration, anuria (loss of urinartion) acidosis and shock
2) Can lead to muscle crmaping, nausea, vomitting, and fever
3) Loss of potassium ions may result in cardiac complications and circulatory failure

Front 8

How do we diagnose virbrio cholerae infections?

Back 8

1) GI symptoms and presence of a rice water stool
2) Confirmed only by isolation of the causative organism from stools of diarrheic patients

Front 9

Describe the toxin of virbrio cholerae

Back 9

-Toxin is called cholera toxin (CT)
-Naturally occuring strains that do not cause the full-blown form of the idsease cause milder form of diarrhoea due to presence of other toxins

Front 10

How does the CT cause diarrhea

Back 10

-It is a multimeric protein complex composed of five identical binding subunits and an A (enzymatic) subunit
-Once one of the B subunits has bound to a glycolipid receptor in the cytoplasmic membrane of the intestinal epithelial cells, the A subunit is cleaved.
-A1 portion of the A subunit enters into the cytosol of the intestinal epithelial cell
-A1 activates host cell's adenylate cyclase enzyme which converts ATP into clyic AMP
-cAMP stimulates the active secretion of large amounts chlorine ions from the cell into the lumen of the intestine
-Sodium, postassium and bicarbonate ions follow due to osmosis and the electrical gradients caused by the loss of chlorine ions
-Lost water and electrolytes in mucosal cells are replaced from the blood
-Thus the toxin-damaged cells become pumps for water and electrolytes causing diarrhea, loss of electrolytes and dehydration

Front 11

How does virbrio cholerae invade the host defences?

Back 11

-It is ingested orally and is spread by the fecal-oral route
-Humans become infected with virbrio cholerae by ingestion of food and water that has been contaiminated with sewage (bacteria in feces of an infected person enter the drinking water supply in situations where sanitation procedures are inadequate)

Front 12

How can the body prevent virbrio cholerae?

Back 12

-Gastric acidity plays an important role in preventing cholera infection as these organisms are sensitive to acid pH
-Acid sensitivity of virbrio cholerae means that most cells die and a large dose is required to produce disease

Front 13

What is the infectious dose needed to cause virbrio cholerae?

Back 13

>10^6 vibrios
-But patients with gastric abnormalities are susceptible to low infectious doses
-Consumption of food or antacid may provide protection for the bacterium during passage through the stomach

Front 14

What are the criteras needed to survive in the small intestine/

Back 14

-Able to withstand gastric secretions and low pH of the stomach

Front 15

What is virbrio cholerae reistant to?

Back 15

-Bile salts and it can adhere to and penetrate the mucous layer of the small intestine
-They withstand propulsive gut motility by their own swimming ability and chemotaxis directed against the gut mucosa

Front 16

What role does Tcp pili play in the coloinzation of virbrio cholerae in the small intestine?

Back 16

1) Tcp pili (for toxin coregulated pili) that seem to cause the bacteria to aggregate
-Vibrios that lack the TCP pili are not pathogenic to humans
-

Front 17

What role does the products of acf genes (accesorry coloinzation factor) (products = outer membrane proteins) play in the colonization of virbrio cholerae in the small intestine?

Back 17

Mediates tighter binding to host cells

Front 18

How do we treat cholera?

Back 18

-Rapid replacement of fluids and electrolytes through oral rehydration
-Water alone does not work
-We have to give patient large amounts of solution of water containing prescribed amounts of salts and glucose (similiar to Gatorade)
-Salts are needed for proper osmolarity and glucose stimulates the uptake of water and salts by mucosal cells
-Intravenous rehydration therapy is required for patients who are in profound shock or cannot drink

Front 19

In addition to rehydration therapy, what else might be helpful in treating cholera patients?

Back 19

Antimicrobial therapy but it is not essetnial
-This is because bacteria are lost in the waterly stool
-Antimicrobial agents reduce the duration of illness by reducing production of the CT, the volume of stool and duration of sheding of bivrios in the feces

Front 20

Do patients who have been infected by V. cholerae naturally develop antibodies against cholera?

Back 20

Yes, patients develop antibodies against several cholera antigens including antibodies that will neutralize the enterotoxin
-Recurrent infections of cholera are rare and this is probably due to local immune defense mediated by antibodies secreted onto the surfaces of intestinal mucosa

Front 21

Is there a vaccine against cholera?

Back 21

Yes
-Oral, live attenuated cholera vaccine is partially effective against cholera (only against serogroup O1)
-Approved for adults and children over 2 ages

Front 22

How do we control cholera outbreaks?

Back 22

-Sanitary measures
-Adequate sewage and water treatments

Front 23

How do people prevent cholera while travelling?

Back 23

-Drink water that has been boiled or treated with cholrine or iodine, tea and and coffee made with boiled water and carbonated, bottle beverages without ice
-Eating only foods that have been thoroughly cooked and are still hot, or fruit that has been peeled
-Avoid undercooked or raw fish or shellfish
-Eat vegetables that are cooked, no salads
-Not eating foods beverages or ice cream from street vendors