Transcript A Day at the Fair - Framingham State University

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
Red Blood Cells (RBCs)
Platelets
White Blood Cell (WBCs)
"Leukocytes"
Patient
4.1-6.2 x 106/
Normal
mm3
150-400 x
Normal
103/mm3
4,00015,500/mm3
10,000/mm3
Percentage of Total WBC
Granulocytes – “PMNs”
- Neutrophils
47 - 77%
85%
60 - 70%
58%
0 - 5%
27%
- Basophils
0 - 2%
1%
- Eosinophils
0 - 7%
1%
Monocytes
2 - 10%
10%
Lymphocytes
16 - 43%
3%
- Segmented Neutrophils
- Banded Neutrophils
Complete Blood Count
Patient Value
Normal Range
15,800/mm3 HIGH
4,000-10,000/mm3
84%
HIGH
47 - 77%
- Segmented
58%
LOW
60 - 70%
- Banded
26%
HIGH
0 - 5%
WBC
Granulocytes (PMNs)
Neutrophil
Basophils
2%
0 - 2%
Eosinophils
1%
0 - 7%
Lymphocytes
11%
Monocytes
2%
LOW
16 - 43%
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 Disease
E. 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 mediumrare hamburger at the town fair
Diagnostic Tests For
E. coli 0157:H7
• Cannot ferment sorbitol:
- Stool culture on sorbitol-MacConkey agar (or
cefeximine potassium tellurite sorbitolMacConkey)
- 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 haemolyticuremic 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
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
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35
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Figure
36
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
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37
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
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38
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
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39
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
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required for reproduction or
40
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 Count
Patient Value
Normal Range
15,800/mm3 HIGH
4,000-10,000/mm3
84%
HIGH
47 - 77%
- Segmented
58%
LOW
60 - 70%
- Banded
26%
HIGH
0 - 5%
WBC
Granulocytes (PMNs)
Neutrophil
Basophils
2%
0 - 2%
Eosinophils
1%
0 - 7%
Lymphocytes
11%
Monocytes
2%
LOW
16 - 43%
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
What’s new with E. coli 0157:H7
• The film of composed
of a long diacetylene
lipid
• This molecule is
similar to the building
blocks for cell
membrane
What’s new with E. coli 0157:H7
• 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