34 - Bacterial Infections of the GI Tract II Flashcards
There are several different diagnostic methods to test for a gram negative bacteria. What are they?
- MacConkey agar
- Indole test
- Hydrogen sulfite (H2S)
What type of test is the MacConkey agar?
It is a lactose fermentation test
- Positive: colonies of RED will form
- Negative: colonies of WHITE will form
What would give a positive test result on the MacConkey agar test?
E coli
What would give a negative test on the MacConkey agar test?
Salmonella
Shigella
What type of test is the indole test?
A test for indole production
- Positive: RED color change
- Negative: NO color change (white)
What would give a positive test result on the indole test?
E. Coli
Vibrio spp.
What would give a negative test result on the indole test?
Salmonella
What type of test is the hydrogen sulfite (H2S) production test?
A test which can use a variety of medias and can test for gram negative bacteria
What will you see in a positive test result?
A black precipitate
What does the indole test differentiate between?
- Salmonella = black precipitate (produces H2S)
- Shingella = no precipitate (does NOT produce H2S)
What are the different types of E coli pathogens that we will talk about?
ETEC: Enterotoxigenic
EPEC: Enteropathogenic
EHEC: Enterohemorrhagic
EIEC: Enteroinvasive
What part of the intestines do these pathogens affect?
The small intestine
What are the characteristics of EPEC?
Enteropathogenic E. Coli
- Non-inflammatory
- Gram negative
- Facultative anaerobe
- Moderately invasive
What disease does EPEC cause?
Enteropathogenic E. Coli
- Watery diarrhea
- Symptoms are caused by tissue destruction of the microvilli
What is very important to remember about the epidemiology of EPEC?
It is a PEDIATRIC disease
Think P in EPEC is for Peds
Describe the pattern of infection in pediatric patients
- Important pathogen in infants (infantile diarrhea) in developing countries
- Accounts for 5-10% of pediatric diarrhea in developing countries
Describe the pathogenesis of EPEC
Adhesins
- BfpA (bundle forming pilus)
- Type III secretion system, Tir
- Tight binding
Does EPEC use toxins?
No, watery diarrhea occurs without toxins in this case
What is a quick way to summarize the actions of EPEC?
“Attaching and effacing”
It is really good at attaching to the small intestine wall and taking out the microvilli there
How do you diagnose EPEC?
Culture
- RED on MacConkey agar test for lactose fermentation
- Indole positive, RED
PCR
How do you treat EPEC?
Supportive therapy
What are the characteristics of ETEC?
Enterotoxigenic E. coli
- Gram negative
- Facultative anaerobe
- Non-invasive
What disease does ETEC typically cause?
Traveler’s diarrhea
- It is associated with travel to developing countries and consumption of contaminated water or ice
- Watery diarrhea
T in ETEC is for Traveler’s
What is the epidemiology of ETEC?
- It is the leading cause of bacterial diarrhea in children living in developing countries
- 200 million cases of diarrhea and 380,000 deaths per year worldwide, mostly in children in developing countries
What is the pathogenesis of ETEC?
- Fimbriae (pili)
- Toxins
Describe the fimbriae of ETEC
- Adherence to epithelial cells via fimbriae
- The active portion activates adenylate cyclase
- It then converts ATP to cAMP
What toxins are secreted from ETEC?
- LT (heat liable toxin)
- ST (heat stable toxin)
- Plasmid encoded toxins
What type of toxin is the LT (heat liable) toxin?
- An AB toxin
- Increases cAMP*
What type of toxin is the ST (heat stable) toxin?
- A non-AB toxin
- Does NOT enter the cell
- Increases cGMP*
What other characteristics do we know about the pathogenesis of ETEC?
- Non-invasive
- Non-inflammatory
- Does NOT kill cells, just makes them release a lot of water leading to diarrhea
How do you diagnose ETEC?
- Clinical history
- DNA probes to detect LT and ST encoding genes in clinical samples and cultures
Is it common to do a DNA probe to detect ETEC?
- Research labs and reference labs do this
- It is not common in the clinical setting, but it is becoming more common
What is the treatment for ETEC?
Supportive therapy
How do we name all the different types of salmonella?
There are over 2500 serotypes
Salmonella enterica serovar ______
There is one typhi type and three non typhi types of salmonella that we will focus on. What are the names?
Salmonella enterica serovar Typhi
- “S. Typhi”
Non-typhoidal salmonella
- S. Cholerasius
- S. Enteritidis
- S. Typhimurium
What is important to know about S. Typhi?
It is an inflammatory bacteria of the small intestine
What are the characteristics of S. Typhi?
- Gram negative
- Facultative anaerobe
- Motile rods, flagellated with H antigen
- Acid tolerant
- Intracellular pathogen
- Highly adapted to humans
What is the epidemiology of S. Typhi?
- Humans are the ONLY reservoir
- There are only 400-500 cases per year in the US
- 21 million cases per year
- 200,000 deaths worldwide
What is the mode of transmission?
- Fecal-oral route
- Contaminated food or water from an infected person
What is the infectious dose of bacteria for S. Typhi?
10^5 to 10^6 bacteria
You have to have a fairly high amount of bacteria in your system in order for it to cause disease
What is the incubation period for S. Typhi?
Approximately 13 days
What are the progression of symptoms in S. Typhi?
General
- Fever with headache
- Rising fever over 3 days
Sustained bacteremia (untreated)
- Typhoid fever (prolonged (4 weeks)
- GI symptoms
What GI symptoms will you see with S. Typhi?
- Chronic colonization of the gall bladder
- Gall bladder can then be a source as well
- Re-infection of the intestines due to gall bladder colonization
Why is S. Typhi dangerous in terms of the fecal-oral route of transmission?
S. Typhi is shed in the stool, even when the person is asymptomatic (Typhoid Mary)
What is the pathogenesis of S. Typhi?
S. Typhi adheres to M-cells and enterocytes
What are M cells?
- Immune cells of the GI tract - macrophages
- Also associated with Peyer’s patches in the ileum
How does S. Typhi get inside the M cells?
S. Typhi has a Type III Secretion System (T3SS) which mediates the uptake of S. Typhi into M cells
What will you see during T3SS mediated uptake of S. Typhi into M cells?
- You will see membrane ruffling where the membrane “ruffles” around the bacteria
- Once the S. Typhi is inside the M cell, it is able to escape from the vacuole
Why do we call T3SS a bacterial molecular syringe?
Because it directly injects proteins into the host cell
How does S. Typhi travel throughout the body?
- Phagocytosis or T3SS mediated uptake into macrophages
- Macrophages move to lymph nodes and drain there
- S. Typhi excapes from macrophages
- Bacteremia
What does bacteremia consist of with S. Typhi?
- Fever from septicemia
- Septicemia from LPS (endotoxin)
How do you diagnose S. Typhi?
Culture of stool and blood samples on selective media
How do you treat S. Typhi?
Antibiotic therapy based on susceptibility profile
- Fluoroquinolones
- Trimethoprim-sulfamethoxazole
- Broad spectrum cephlosporin
How do you prevent S. Typhi
- Avoid sources of infection (bottled water only, no ice, thoroughly cooked food, avoid raw fruits/vegetables)
- Vaccination for travelers to endemic areas
What is the S. Typhi vacination?
- Ty21A capsule by mouth, 4 doses
- VICPS injection, 1 dose
There are also non-typhoidal types of salmonella. What are they again?
- S. Cholerasuis
- S. Enteritidis
- S. Typhimurium
What are the characteristics of the non-typhoidal types of salmonella?
- Gram negative
- Facultative anaerobe
- Motile rods flagellated with H antigen
- Acid tolerant
- Intracellular pathogens
The characteristics of typhoidal and non-typhoidal salmonella are the same… What is the difference between the two?
Non-typhoidal types of salmonella are not as adapted for humans
Is non-typhoidal salmonella restricted to humans?
NO
- There are numerous animal resivours
- Animals can be a source of infection
- Contaminated poultry, eggs, dairy
Is non-typhoidal salmonella commonly transferred human-to-human?
No, rarely
What is the infectious dose of bacteria for non-typhoidal salmonella?
Quite a bit… 10^6-10^8
How many cases of non-typhoidal salmonella do we see each year in the US?
- 50,000 cases per year in the US
- It is a disease of industrialized countries
- There is a higher incidence in young children and the elderly
Are both typhoidal and non-typhoidal types of salmonella inflammatory or just one of them?
Both types
When will you see symtpoms begin after ingestion?
6-48 hours
What symptoms will you see?
Nausea, vomiting, abdominal cramps, watery diarrhea
How long will symptoms last?
Persistent diarrhea for 3-4 days
- With or without blood in stool
Spontaneous resolution within 7 days
What percent of cases will present with a fever?
50%
This is problematic for diagnosis… Not always the same symptoms
What does it mean that there is a large symptomatic range for nontyphoidal salmonella?
It can present as anything from a loose stool to severe dysentery-like diarrhea
The more severe cases are generally rare
What is the pathogenesis of nontyphoidal salmonella?
- Initial stages of infection are very similar to S. Typhi pathogenesis
- After entry into the macrophage, there are two different scenarios: rapid killing or macrophage carriage
Describe the scenario of rapid killing
Massive inflammatory response that…
- Confines the infection
- Causes active fluid secretion (diarrhea)
Describe the scenario of carriage in macrophage
This occurs in immunocompromised individuals
- There is a systemic dissemination or bacteremia of the non-typhoidal salmonella
- You will see focal infections such as arthritis, osteomyelitis and endocarditis
How do you diagnose nontyphoidal salmonella?
Serology or culture from blood and stool
Describe the serology test for nontyphoidal salmonella
The serology aims to detect anti-vi antigen antibodies
Describe the culture test for nontyphoidal salmonella
You can use selective (differential) media for testing
- It will be non-lactose fermenting, so WHITE on the MacConkey’s test
- It will produce H2S, so it will be BLACK on the hydrogen sulfite test
How do you treat nontyphoidal salmonella?
It depends on whether or not it has become a systemic infection
How do you treat salmonella gastroenteritis that is NOT systemic?
Supportive therapy
- Electrolyte replacement
- Antibiotics are NOT recommended
Why are antibiotics not recommended for a nonsystemic infection of nontyphoidal salmonella?
Because the antibiotics will actually enhance the carrier state… They can grow better when you wipe out the natural flora with a broad spectrum antibiotic
How do you treat a systemic infection from nontyphoidal salmonella?
Antibiotic therapy depending upon its resistance profile
Is there a vaccine available for nontyphoidal salmonella?
No
What is campylobacter jejuni?
Another inflammatory bacteria that can infect the small intestine
What are the characteristics of campylobacter jejuni?
- Gram negative
- Rod or curved “sea-gull” shaped
Is campylobacter jejuni exclusive to humans?
No - there are many animal reservoirs such as turkey and pets
Is campylobacter jejuni invasive?
Yes - it is invasive in the jejunum, ileum and colon
What disease does campylobacter jejuni cause?
- Ulceration and acute enteritis
- Watery diarrhea
- Sepsis eventually
Is campylobacter jejuni common?
Yes it is the most common cause of bacterial diarrhea
What is the incubation period for campylobacter jejuni?
2-11 days
What does sequelae mean?
A condition that is the consequence of a previous disease or injury
What sequelae can result from campylobacter jejuni?
Guillain-Barre syndrome
What is Guillain-Barre syndrome (GBS)?
Now called “heterogeneous syndrome”
- It is an acute immune-mediated polyneuropathy
What does GBS cause?
It causes progressive, symmetric muscle weakness accompanied by absent or depressed deep tendon reflexes
Are all cases of GBS similar?
No, symptoms vary
- Anywhere from difficulty walking to nearly complete paralysis of extremities, facial muscles, respiratory muscles and bulbar muscles
What percent of GBS is attributed to a campylobacter infection?
30-40%
What is the pathogenesis of campylobacter jejuni?
Not much is known, but we think it is similar to salmonella
How do you diagnose campylobacter jejuni?
Culture
- This is routinely done
- Use a selective media in a microaerophilic environment
What is the treatment for campylobacter jejuni?
- Supportive therapy mostly
- Antibiotic therapy only in invasive disease and dependent upon the susceptibility profile
If you do use antibiotics for campylobacter jejuni, what do you use?
Macrolides
