Diarrhea is a major cause of pediatric mortality and one of humankind’s most serious infections.
in the US viral diarrhea dominates over parasite or bacterial diarrhea (the opposite is true in the developing world)
Host Defenses:
Age: the extremes of age (elderly and infants) are more susceptible to diarrhea
Personal hygiene: Please remember to wash your hands
Gastric acidity: the low pH kills some pathogens, patients on acid depressing treatment have
Ý susceptibility
Intestinal motility: movement through the intestine is important in the excretion of pathogens
Normal enteric flora: competes with the pathogens for both nutrients and space
Immunity: IgA in intestinal mucous, previous infections with Vibrio Cholera confer long-lasting protection
Intestinal receptors: Pepto-Bismol works by coating and covering pathogen attachment sites
Bacterial "Virulence" Factors
Toxin production: entero-toxins alter intestinal and H2O transport mechanisms / cyto-toxin of Clostridia difficile (a Gram pos rod) causes Pseudomembrane colitis in Antibiotic Associated Diarrhea.
Adherence and Invasion: the ability to disrupt absorptive cells involves 6 steps; a) ingestion, b) colonization and proliferation in the intestine, c) mucosal invasion, d) intramucosal multiplication, e) stimulation of intestinal secretion, f) dissemination from the intestine.
two types: Inflammatory (with PMN’s in stool) and non-inflammatory (due to malabsorption, no PMN’s)
inflammatory diarrhea (invasive)
– Salmonella, Shigella, Yersina, Invasive E. coli
ß
volume/bloody stools/ PMN’s
non-inflammatory diarrhea (non-invasive) –
Vibrio cholera, Staph. Aureus, Yersina, Invasive E. coli, parasites Giardia
Ý
volume/ watery stools/ no blood
Cholera
slightly curved Gram negative rod with flagella that grows best on alkaline media; non-spore forming, motile, facultative anaerobe
Bacteria adhere but do not invade the intestinal mucosa.
Secrete an enterotoxin "Choleragen" that much like Diphtheria toxin, uses a B subunit to adhere and an A subunit to activate cAMP leading to the hypersecretion of H2O and Cl- while inhibiting Na+ absorption.
Found only in the GI tract of primates. Human to human transmission is
Ý in crowed areas institutional outbreaks are common (i.e., refugee camps) – water-borne outbreaks occur
4 types: Sh. dysenteriae, Sh. flexneri, Sh. boydii, Sh. sonnei. (Sh. flexneri and Sh. sonnei =99% of US infection)
Shigella
infect and replicate in the intestinal epithelia, pass laterally from cell to cell, entering the lamina propria, but rarely penetrate the muscularis mucosa and enter the blood stream.
Causes "Classic Dysentery" – tenesmus, small bloody stools, abdominal pain, and fever
Shigatoxin- cytoplasmic toxin, same mechanism and effect as EHEC. (effects rRNA to block protein synthesis)
Typhoid fever is a major cause of Morbidity and Mortality worldwide. S. typhi only infects humans.
Other Salmonella species are in animal hosts. Found often in chicken, cookie dough, Brewer’s yeast, spaghetti sauce
Infection occurs through ingestion of excreta contaminated food, milk, or water
4 separate but not always distinct syndromes associated with Salmonella and humans:
(1) Acute Enteritis- follows ingestion of contaminated food, 24-48 hrs later
Þ diarrhea, cramps, nausea. Usually resolves spontaneously within 7 days. Treatment: support (e.g. fluids and control of vomiting)
(2) Enteric Fever (Typhoid Fever)- the unique feature of this illness is invasion and multiplication within the intestinal lymphoid tissue, with secondary dissemination of organisms from this tissue reservoir. Two week incubation period
Þ fever with headache, slow pulse, rash on chest Þ diarrhea
(3) Bacteremia – septicemia; acute gastroenteritis is associated with transient or persistent bacteremia. Tends to colonize sites of pre-existing structural abnormality (cardiovascular lesions, etc)
(4) Asymptomatic Carrier State- chronic infection of the gallbladder and intrahepatic biliary passages is chiefly responsible for the 3% chronic intestinal carrier state that follows Typhoid Fever.
E. coli
Diarrhea causing E. coli are classified by their virulence properties. All share plasmid-mediated adherence. Toxins that are phage or plasmid-mediated play an important role in infection and disease.
ETEC
enterotoxigenic – "Traveler’s diarrhea", caused by LT (heat labile toxin) an AB toxin that ADP-ribosylates a regulatory protein Þ Ý [cAMP]Þ secretion of H2O and electrolytes into bowel lumen. An additional smaller, heat stable toxin, ST, activates membrane bound guanylate cylcase Þ Ý [cGMP] Þ Ý secretion
EPEC
enteropathogenic – bundle forming pilus (BFP) is responsible for attachment, "pedestals" are formed. >20% of infant diarrhea in developing nations.
EIEC
enteroinvasive – similar to Shigella infection but less aggressive. Infection limited to children £ 5 years
EHEC
enterohemorrahagic – a Shiga-like toxin acts on rRNA to block protein synthesis. Systemic circulation of toxin causes Hemolytic Uremic Syndrome HUS (renal failureÞ death). Bloody diarrhea with intense abdominal pain. 8-10% go onto HUS (1o children £ 5 years old). Cows are the source, hamburger consumption Ý risk.
Campylobacter
curved or spiral, motile, oxidase positive, Gram negative rods. Invasive. Normal flora in farm animals
Campylobacter fetus
produces a characteristic colitis, associated with bloody diarrhea, severe abdominal pain, and very little vomiting. It is a self-limiting disorder. A common cause of abortion in sheep and cattle, as well as a rare cause of sepsis in humans. 30-40% of patients with Guillian-Barre syndrome had a Camplyobacter infection preceding their G-B syndrome.
C. jejuni
- acute enteritis in man; extraintestinal spread Þ endocarditis, meningitis, organ abscess
Yersinia
3 species of Gram negative coccobaccilli that are pathological for humans.
Yersinia pestis
– bubonic plague, Y. pseudotuberculosis – a TB-like illness in rats, and
Y. enterocolitica
– a newly appreciated cause of enterocolitis and systemic illness in humans.
Yersinia
Virulence factors include: ST-like enterotoxin, Invasin (an attachment protein), AIL (a complement resistance factor), and YOPS (Yersinia outer membrane proteins that neutralize phagocytes)
An invasive organism, producing bloody diarrhea, fever, and acute abdominal pain.
Antibiotic Associated Diarrhea
– a.k.a. Pseudomembrane colitis
occurs when antibiotics wipe out the normal flora
Seen in the elderly and in burn victims
Can be up to six weeks after antibiotic treatment with broad spectrum antibiotics
Clostridium difficle
- a Gram positive, spore-forming rod, takes over the intestine and produces a toxin.
Food Poisoning Syndromes
Typically it’s bacteria that live in food and produce a toxin that make a person sick
S. aureus
and B. cereus are the most common food poisonings (both have a rapid onset)
Salmonella and Shigella
have a longer time to onset because they need to attach, invade, etc