a day at the fair dr. howard, dr. fine, dr. howard

A Day at the Fair

Dr. Howard, Dr. Fine, Dr. Howard

Calling: Dr. Howard, Dr. Fine, Dr. Howard

1st SLIDES ... DISCUSS THE ANATOMICAL DIAGNOSIS

- SUMMARIZE YOUR PATIENTS INITIAL PRESENTATION IN THE E.R.

- DISCUSS YOUR PATIENT’S SYNDROME(S) ACTUALLY FOUND IN YOUR PATIENT

– ITS(THEIR) TYPICAL SIGNS SYNDROMES vs. THOSE OBSERVED IN YOUR

PATIENT

(BASE YOUR DISCUSSION ON YOUR "ENLIGHTENED" ANATOMICAL

DIAGNOSIS i.e. ON EVERYTHING THAT YOU DISCOVERED

THROUGHOUT THE CASE LEVELS, RATHER THAN ONLY ON YOUR

INITIAL, PERHAPS NAIVE, DIAGNOSIS FROM LEVEL 1)

Patient Background(Anatomical & Epidemiological Diagnosis)

• Mr. H. M. Burgas– 75 year-old man– History of acute abdominal discomfort for 3 days– Copious bloody diarrhea for last day

– Been to a country fair four days ago– Their son-in-law, who had accompanied them, is also

exhibiting the same symptoms as Mr. B – Mrs. B is fine

Examination in the ER

– Temperature 39.1o C (normal: 37o C)

– Pulse 110/min (normal: 60-100/min )

– BP 80/40 mm Hg (normal: 90-150/50-90 )

– Respirations 22/min (normal: 9-18/min)

– Mr. Burgas continued to display symptoms such as lethargy, pale skin, very low urine output, vomiting, and continual bloody diarrhea

2. DISCUSS THE DIFFERENTIAL DIAGNOSIS

- BRIEFLY DISCUSS THE PATHOGENS TYPICALLY ASSOCIATED WITH YOUR

PATIENT’S SYNDROME(S) THAT SHOULD HAVE BEEN INITIALLY CONSIDERED

- BRIEFLY DISCUSS WHY MANY OF THOSE PATHOGENS WERE “RULED-OUT”

(BASE YOUR DISCUSSION ON YOUR "ENLIGHTENED" DIFFERENTIAL

DIAGNOSIS i.e. ON EVERYTHING THAT YOU DISCOVERED

THROUGHOUT THE CASE LEVELS, RATHER THAN ONLY ON YOUR

INITIAL, PERHAPS NAIVE, DIAGNOSIS FROM LEVEL 1)

The Syndrome• Bacterial Gastroenteritis

- Can range from mild to severe, and usually manifests with symptoms of vomiting, *diarrhea, and *abdominal discomfort

- If symptoms occur within 1–6 hours after eating the food, it suggests that it is caused by a bacterial toxin or a chemical rather than live bacteria

- A long incubation period tends to cause sufferers to attribute their symptoms to "stomach flu"

The Syndrome• Bacterial Gastroenteritis

- During the incubation period, microbes pass through the stomach into the intestine, attach to the cells lining the intestinal walls, and begin to multiply there

- Some types of microbes stay in the intestine, some produce a toxin that is absorbed into the bloodstream, and some can directly invade the deeper body tissues

- Bacterial gastroenteritis can be caused by a range of bacteria

The Most Likely Suspects(Differential Diagnosis)

• Bacterial Gastroenteritis

- The symptoms produced depend on the type of microbe

- The most common causes of bloody diarrhea:

– Campylobacter jejuni– Shigella sp.– Salmonella sp.– Escherichia coli

3. DISCUSS THE ETIOLOGICAL DIAGNOSIS

- SUMMARIZE THE STEPS THAT WERE FOLLOWED (e.g. MICROSCOPY/STAINS,

GROWTH ON MEDIUM, BIOCHEMICAL TESTS, SEROLOGY, MOLECULAR BIOLOGY,

etc.)

- EXPLAIN HOW THE RESULTS LED TO THE ULTIMATE IDENTIFICATION OF THE

CAUSATIVE AGENT

(BASE YOUR DISCUSSION ON EVERYTHING THAT YOU DISCOVERED

THROUGHOUT THE CASE LEVELS)

Specimens & The Lab(Etiological Diagnosis)

• Blood Sample– Blood– CHOC– MAC– ANA-LIVER

• STOOL– MAC-containing sorbitol

instead of lactose

– BLOOD– PEA– HE– SS– XLD– CAMPY

.

Complete Blood Count (CBC)Acute Inflammation - Suggestive of Bacterial Disease

Normal Range Patient

Red Blood Cells (RBCs) 4.1-6.2 x 106/ mm3

Normal

Platelets 150-400 x 103/mm3

Normal

White Blood Cell (WBCs) 4,000-10,000/mm3

15,500/mm3

"Leukocytes" Percentage of Total WBC

Granulocytes – “PMNs”

- Neutrophils 47 - 77% 85%

- Segmented Neutrophils 60 - 70% 58%

- Banded Neutrophils 0 - 5% 27%

- Basophils 0 - 2% 1% - Eosinophils 0 - 7% 1%

Monocytes 2 - 10% 10%

Lymphocytes 16 - 43% 3%

Complete Blood CountPatient Value Normal Range

WBC 15,800/mm3 HIGH 4,000-10,000/mm3

Granulocytes (PMNs)

Neutrophil 84% HIGH 47 - 77%

- Segmented 58% LOW 60 - 70%

- Banded 26% HIGH 0 - 5%

Basophils 2% 0 - 2%

Eosinophils 1% 0 - 7%

Lymphocytes 11% LOW 16 - 43%

Monocytes 2% 2 - 10%

- Leukocytosis - Elevated total WBC count … Causes: infectious diseases (including viral, bacterial, fungal, or parasitic infection), tissue damage, acute inflammatory disorders, severe physical or emotional stress, metabolic disorders, medications, … - Neutriphilia (neutrophil leukocytosis) - A strong indication of many inflammatory processes: acute bacterial infection, acute viral infections, … - Leukemoid Reaction -Severe neutrophilia with “left shift” (increase in both the total number of mature neutrophils and the less mature bands or stabs to respond to the infection)

Cause of the DiseaseE. coli 0157:H7

– The patient’s stool tested positive for verotoxin (shega-like toxin) produced by E. coli 0157:H7, as did his son-in-law’s stool

– After discussing these finding with the patient, it was determined that they had shared a medium-rare hamburger at the town fair

Diagnostic Tests ForE. coli 0157:H7

• Cannot ferment sorbitol: - Stool culture on sorbitol-MacConkey agar (or cefeximine potassium tellurite sorbitol-MacConkey) - Not a routine test and must be specifically requested

• Diagnosis is slow using culture methods, more rapid diagnosis is possible using PCR or ELISA for Shega-like toxin

Hospital Course …– His urine became dark and “smoky” and he voided

only twice in the last 24 hours – Mr. Burgas developed “hemolytic-uremic syndrome”

(HUS) … discussed below

– He was treated with antibiotics, peritoneal dialysis, and by blood and platelet transfusions

– His urine output gradually increased from 100 to 1000-2000 mL/day by the seventh day of hospitalization, so peritoneal dialysis was discontinued

– He was discharged 17 days after admission

4. DISCUSS THE EPIDEMIOLOGICAL DIAGNOSIS

- DEFINE EACH TERM, THEN DISCUSS THAT ASPECT OF THE ECOLOGY OF THE

MICROBE THAT IS THE CAUSE OF DISEASE IN YOUR PATIENT

E. coli 0157:H7• First recognized as a pathogen as a result of an

outbreak of unusual gastrointestinal illness in a fast food chain (1982)

Epidemiological Diagnosis• Reservoir (Animal Carriers): Found on cattle farms

and can live in the intestines of healthy cattle:

- Shiga toxin requires highly specific receptors on the cells' surface in order to attach and enter the cell … discussed below

- Species such as cattle, swine, and deer which do not carry these receptors may harbor toxigenic bacteria without any ill effect, shedding them in their feces from where they may be spread to humans

Epidemiological Diagnosis• Transmission:

- Meat can become contaminated during slaughter, and organisms can be thoroughly mixed into beef when it is ground into hamburger

- A major source of infection is undercooked ground beef ("hamburger disease" - association with home-made hamburgers)

Epidemiological Diagnosis• Transmission - Other sources:

- Unpasteurized milk and juice (Bacteria present on the cow's udders or on equipment may get into raw milk)- Raw sprouts, lettuce, etc.- Salami- Contact with infected live animals- Waterborne transmission through swimming in contaminated lakes, pools, or drinking inadequately treated water- Easily transmitted from person to person - difficult to control in child day-care centers

Pathogenesis & Virulence• Entry: “Oral-Fecal Route”• Attachment: Adheres to mucous surfaces of gut via

fimbriae (found in serotypes O157 and O111)• Avoidance of Host Defenses: Initial infection

restricted to gut (not exposed to circulating antibodies and immune cells)

• Damage: Shiga-like toxins … discussed on next slides• Exit: In feces

Shiga-Like Toxins• The toxin has two subunits

- B subunit is a pentamer that binds to specific glycolipids on the host cell, specifically globotriaosylceramide (Gb3)- Gb3 is present in greater amounts in renal epithelial tissues - the renal toxicity of Shiga toxin

• Inhibition of protein synthesis: - After entering a cell, the A subunit is internalized and cleaved into two parts - A1 component is an N-glycosidase - cleaving several bases from the RNA of the ribosome - halting protein synthesis

Shiga-Like Toxins• Shiga-like toxins are functionally identical to

toxins produced by virulent Shigella sp.

• Strains of E. coli that express shiga-like toxins gained this ability due to infection with a prophage (a bacterial virus) containing the Shigella’s gene for the toxin

Clinical Features of E. coli 0157:H7 Disease

• Often severe, acute bloody diarrhea (non-bloody diarrhea also possible)

• Abdominal cramps• Usually little or no fever• Illness resolves in 5 to 10 days• Can be asymptomatic• Majority of infections resolve completely• About 2%–7% of infections lead to haemolytic-

uremic syndrome …

Hemolytic-Uremic Syndrome (HUS)

• Particularly in children under 5 years of age, elderly, and immunocompromised

• Due to effects of Shiga-like toxin on renal endothelial cells and red blood cells

• Results in renal failure: - Red blood cells are destroyed - Local intervascular coagulation with platelet aggregation - Cell swelling - Reduction in glomerular filtration

HUS – Patient Prognosis• 3–5% of those with HUS die, causing about 61 deaths

annually in the USA

• Long-term consequences of HUS: - 33% have abnormal kidney function many years later, few require long-term dialysis - HUS is the principal cause of acute kidney failure in children in the US - 8% of this group develop other lifelong complications (high blood pressure, seizures, blindness, paralysis) - If surgery is required to remove part of the bowel, may be procedure-related side-effects

Treatment of HUS

• Hemofiltration

• Kidney dialysis

• Platelet infusions

• Transfusion of packed erythrocytes

Treatment of E. coli 0157:H7 Disease

- Most people recover without antibiotics or other specific treatment in 5–10 days -No evidence that antibiotics improve the course of disease

- Treatment with some antibiotics may precipitate kidney complications

- Antidiarrheal agents, such as imodium, should also be avoided

Prevention• Cooking all ground beef and hamburgers thoroughly,

to at least 72 °C (160 °F)

• When preparing meat, it should be kept separate from other food items and all surfaces and utensils

• Proper hand washing after handling raw meat, using the lavatory, or changing a diaper

Prevention• Avoid unpasteurized milk, juice, and cider

• Fruits and vegetables should be washed thoroughly, especially those that will not be cooked

• Children under 5 years of age, immune-compromised persons, and the elderly should avoid eating alfalfa sprouts

• Contaminated water should be boiled at a rolling boil for at least one

Prevention• Preventive measures that either reduce the number of

cattle that carry E.coli O157:H7 or reduce the contamination of meat during slaughter and grinding

• In January 2007 Canadian bio-pharmaceutical company Bioniche announced it had developed a bovine vaccine capable of reducing O157:H7 in cattle by over 99%

What’s New with E. coli 0157:H7

• One does not know if they have a product tainted with E. coli 0157:H7 just by sight or smell

• A test is being designed to give and instant reading of E. coli 0157:H7 contamination

The End

Copyright © The McGraw-Hill Companies. Permission required for reproduction or display.

35

Traveler’s Diarrhea and Escherichia coli infections

• traveler’s diarrhea– caused by certain viruses, bacteria, or protozoa

normally absent from traveler’s environment– E. coli is one of major causative agents

• six categories or strains are recognized


36Figure 38.25


37

Other diarrheagenic strains

• enterotoxigenic E. coli (ETEC)– produces one or both enterotoxins responsible

for diarrhea; distinguished by their heat stability

• enteroinvasive E. coli (EIEC)– multiplies within intestinal epithelial cells– may produce a cytotoxin and an enterotoxin

• enteropathogenic E. coli (EPEC)– causes effacing lesions

• caused by destruction of brush border microvilli on intestinal epithelial cells


38

More diarrheagenic strains

• enterohemorrhagic E. coli (EHEC)– produces effacing lesions, leading to hemorrhagic

colitis– releases shiga-like toxins

• implicated in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura

– e.g., E. coli 0157:H7


39

More strains

• enteroaggregative E. coli (EAggEC)– forms clumps adhering to epithelial cells– toxins have not been identified

• diffusely adhering E. coli (DAEC)– adheres in a uniform pattern to epithelial cells– particular problem in immunologically naïve or

malnourished children


40

Traveler’s disease…• diagnosis

– past travel history and symptoms, isolation and identification of causative agents using DNA probes, tests for virulence factors, and PCR

• treatment, prevention, and control– symptomatic/supportive therapy and antibiotic

therapy– avoiding contaminated food and water

E. coli Serogroups

• Four main serogroups

– 026.H11- Enteropathogenic E. coli (EPEC)– 0157.H7- Enterohemorragic E. coli (EHEC)– 0148.H28- Enterotoxigenic E. coli (ETEC)– 04.H5- Urinary Tract Infections (UTI's)

Enterohemorragic E. coli (EHEC)

• EHEC as typified by the serotype 0157:H7– Causes hemorrhagic colitis

• CHARACTERIZED BY COPIOUS BLOODY STOOL

• EHEC associates with cells through the afimbrial adhesion intimin and type 1 pili

• The defining characteristic of EHEC is the production of phage-encoded Stx

EHEC

• The Stx produced by the EHEC strains

• Responsible for the GI effects (pain, discomfort)

• After absorption-once in circulation appears to be responsible for most kidney damage during HUS

EHEC

• Strain also express hemolysin = intense inflammatory response

• EHEC also expresses a specialized iron transport system- it allows them to utilize the iron bound to heme ( derived from eukaryotic cells lysed by hemolysin)

Complete Blood CountPatient Value Normal Range

WBC 15,800/mm3 HIGH 4,000-10,000/mm3

Granulocytes (PMNs)

Neutrophil 84% HIGH 47 - 77%

- Segmented 58% LOW 60 - 70%

- Banded 26% HIGH 0 - 5%

Basophils 2% 0 - 2%

Eosinophils 1% 0 - 7%

Lymphocytes 11% LOW 16 - 43%

Monocytes 2% 2 - 10%

- Leukocytosis - Elevated total WBC count … Causes: infectious diseases (including viral, bacterial, fungal, or parasitic infection), tissue damage, acute inflammatory disorders, severe physical or emotional stress, metabolic disorders, medications, … - Neutriphilia (neutrophil leukocytosis) - A strong indication of many inflammatory processes: acute bacterial infection, acute viral infections, … - Leukemoid Reaction -Severe neutrophilia with “left shift” (increase in both the total number of mature neutrophils and the less mature bands or stabs to respond to the infection)

What’s new with E. coli 0157:H7

• The test uses thin layer film to act as the binding area fro the bacterial toxins

• When it binds to the film it triggers a color change


• The film of composed of a long diacetylene lipid

• This molecule is similar to the building blocks for cell membrane


• The red color change indicates a a presence of the toxin

• These sensors are so inexpensive they can be placed on all high risk good products

a day at the fair dr. howard, dr. fine, dr. howard

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