Cholera; Campylobacter; Helicobacter Flashcards
Explain the historical importance of cholera.
John Snow - father of epidemiology
Mapped out cases of cholera -> removed handle from Broad St. pump
Explain the pathophysiology of diarrhea in cholera, including virulence factors involved. (6 steps)
Painless, odorless, copious secretory diarrhea (“rice water stool”) -> rapid dehydration -> hypovolemic shock -> death
- Inactivated by gastric acid, but some survive (rice helps)
- Enters small bowel, binds to epithelium
- (VF) Toxin Coregulated Pilus -> microcolony formation in intestinal crypts
- > **Organism remains in intestine and DOES NOT invade - (VF) Cholera toxin: expressed & secreted
- B subunit of CT binds ganglioside GM1 -> endocytosis
- —–(VF) Neuraminidase makes more GM1, increasing binding sites - A subunit is the TOXIN: ADP ribosylation of G protein on AC -> cAMP production -> PKA activation -> increased secretion of electrolytes and water, decreased NaCl absorption
Explain the morphology of cholera bacteria, including serogroups.
Vibrio cholerae = Gm- enteropathogen
- –Comma-shaped
- –Polar flagellum
- Over 250 serogroups (only O1 causes epidemic cholera)
- –Classical biotype: the type until 1961
- –El Tor biotype: the type now, acquired toxin gene from classical (makes way more toxin)
Explain how cholera is diagnosed.
Can be isolated on TCBS agar - makes yellow colonies
–Both selective (Vibrio enterics) and differential (cholera = yellow)
Describe the basic epidemiology of cholera, including the recent epidemic in Haiti. What is the infectious dose?
Water-borne disease caused by Vibrio cholerae
- –Spreads by contaminated water, shellfish/seafood
- –Refugee camps, poverty, inadequate sanitation
- –Endemic to south-central/southeast Asiaa
HAITI - as of March 2014, 1/16 people have gotten cholera, 8,500 deaths
ID= source dependent (100-10^9), rice highly infectious
Explain the treatment of cholera. Is there a highly effective vaccine?
Treatment = oral rehydration therapy, IV fluids
-Abx (doxycycline, azithromycin) can reduce duration
Vaccine = NONE that are highly effect, but do have some
- -Parenteral:
- —Toxoid vaccine: inefffective
- —Killed whole cells: ineffective
- -Oral (mucosal):
- —Killed whole cells + CT-B - 50% efficacy
- —New killed, whole cell - 70% efficacy
- —Live attenuated (toxin genes deleted) - unproven in field
Describe the basic epidemiology of Campylobacter jejuni. Recognize its high incidence.
Worldwide zoonosis: in cattle, swine, goats, dogs, cats, rodents, fowl (does NOT sicken animals)
—In 70% of all chickens in grocery stores, even more in farmers markets
RARE human to human transmission
Typically sporadic cases
MOST COMMON cause of diarrhea in the world
Describe the pathogenesis of Campylobacter jejuni (5 steps).
- Organisms ingested in contaminated food/water
- If they survive gastric barrier, arrive in bowel.
- Enters cell at epithelial surface (invasive)
- Exocytoses through basal side
- —-These movements -> inflammation - (Rare) Enters bloodstream -> bacteremia
Explain the prevention and treatment of Campylobacter jejuni.
Prevention: pasteurization of milk, fully cooking meats
Treatment: oral rehydration therapy, Abx (erythromycin, cipro) for some
Describe the bacterial structure of Campylobacter jejuni.
Looks like Vibrio (curved rod)
Microaerophilic Gm- rod
Explain how Campylobacter jejuni infections are diagnosed.
Gm stain stool specimen
Enrich with filters (very small)
Hippurate positive (very diagnostic)
Explain the growth conditions used to identify Campylobacter in the clinical laboratory.
Culture at 42C in microaerophilic conditions
Discuss the link between the microorganism Helicobacter pylori and chronic disease. List virulence factors. (3)
Spiral-shaped, Gm- bacterium that lives in stomach/duodenum
–Secretes UREASE, which generates base
Adhesins: bind to membrane-associated lipids/carbs; aid in adherence to epithelial cells
—BabA binds Lewis b Ag on surface of stomach epithelial cells
CagA: injected into stomach epithelial cells; disrupts cytoskeleton, adherence to adjacent cells, signalling, and cell polarity
VacA: further damages epithelial cell lining
Explain the pathogenesis underlying gastritis, peptic ulcers, and mucosal lymphomas with Helicobacter pylori infection. (5 steps)
- Immune system reacts to H. pylori -> deploys lymphocytes
- Lymphocytes cannot penetrate mucus lining -> ineffective against H. pylori
- Lymphocytes die -> release of superoxide radicals -> destruction of stomach cells
- Gastritis, possible peptic ulcer develops
- Chronic gastritis -> intestinal metaplasia -> gastric cancer (MALT lymphoma)
Describe the transmission, infectious dose, and enormous global load of Helicobacter.
Orally transmitted
ID not determined in humans, but > 10^4 in primates
Affects 50% of world population
–Highest in developed countries
