Gram Negative Pyogens (Neisseria, H. Influenzae, Bordatella) Flashcards
What are the four fastidious gram negative pyogens?
1) Neisseria gonorrheae
2) Neisseria meningitidis
3) Haemophilus influenzae
4) Bordetella pertussis
What are the two pathogenic species of Neisseria?
1) N. gonorrhoeae
2) N. meningitides
Gram negative organisms cause disease primarily through their production of _____ and the resulting host _____
Gram negative organisms cause disease primarily through their production of ENDOTOXINS and the resulting host IMMUNE RESPONSE
Species of Neisseria are differentiated by their ability to _______
Use specific sugars for energy
What sugars and pH indicator are placed into a broth to help differentiate N. gonorrheae and N. meningitidis in the lab?
Sugars: Glucose, maltose, sucrose, and lactose
pH indicator: Phenol red
What sugars do N. gonorrheae and N. meningitidis ferment (use for energy)?
N. gonorrheae: ONLY glucose
N. meningitidis: Glucose AND maltose
What are the two main structural differences between N. gonorrheae and N. meningitidis?
Encapsulation and amount of pili
N. gonorrheae: NO capsule, A LOT of pili
N. meningitidis: Thick CAPSULE, some pili (not as many as gonorrheae)
How does Neisseria appear upon gram staining?
Gram negative
Non-motile
Diplococci
Usually in pairs
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T/F: Neisseria is capable of surviving for long periods in the external environment
FALSE
This is why it must be transmitted by close or intimate contact. It dries out in the environment
Neisseria attach to _____ of mucosal surfaces via their pili and outer membrane surface proteins
Non-ciliated columnar epithelium
T/F Both pathogenic species of Neisseria are phagocytosed as a part of their life cycle inside the host
FALSE
N. gonorrheae: Actively phagocytosed by PMNs → Remains localized → Generates pus
N. meningitidis: EVADES phagocytosis (capsule) → Enters blood stream → Sepsis
What is the lab test that differentiates Neisseria for other organisms? How does it work?
Oxidase Test
1) Oxidase reagent placed on filter paper
2) Bacteria rubbed on top
3) Oxidase positive → Purple-blue (Neisseria!)
4) Oxidase negative → no color change
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What species of Neisseria is responsible for the STI gonorrhea?
N. gonorrheae
Duh
What virulence factor of N. gonorrheae mediates attachment to other cells (sticking to a spermatozoa and moving up the female reproductive tract, e.g.)?
Pilin and Opa protein
N. gonorrheae has 3 proteins that strip _____ from transferrin, lactoferrin, and hemoglobin that is used for survival of the organism
Iron
What virulence factor of N. gonorrheae is an endotoxin with high activity that generates the pus characteristic of infection?
LipoOLIGOsaccharide
What virulence factor of N. gonorrheae is found on mucosal surfaces and protects the organism?
IgA1 Protease
What virulence factor of N. gonorrheae lends it its resistance to penicillin or other Beta-lactams?
Beta-lactamase
Neisseria gonorrheae forms micro-colonies by attaching their pilito the microvilli of epithelial cells. After formation of the micro-colony, they exhibit _____, where the pili actively extend, grab another cell, and retract, moving the micro-colony across the cell surface.
Twitching motility
T/F Women have a higher incidence of acquiring N. gonorrheae infectioTns from sexual contact
TRUE
The vagina and cervix have an 80% chance of infection after exposure, while the male urethra has only a 20% risk of infection after exposure
The majority of N. gonorrheae cases occur in 15-29 year olds, and is associated with _____ and _____
Sexual activity
Lack of condom use
What are the non-genital sites of N. gonorrheae infection?
Oropharynx, rectum, conjunctiva
T/F N. gonorrheae in non-genital and genital sites of juveniles/childres is a sign of sexual abuse.
TRUE
When infected with N. gonorrheae, males present with _____ 2 to 3 days after the sexual encounter with _____ and _____
Acute urethritis w/ severe dysuria and purulent dischagre
T/F: Most females infected with N. gonorrheae present with a cervicitis and/or urethritis.
FALSE
Most females infected with N. gonorrheae are asymptomatic
Females presenting with symptoms typically do have cervicitis and/or urethritis though
Why is there no effective vaccine against N. gonorrheae?
N. gonorrheae undergoes antigenic drift, changing their pili and outer membrane proteins (Opa) to avoid immune eradication
Neonates who acquire gonorrhea from infected mothers often present with _____. Tx?
Neonatal ophthalmia
Tx: Abx eye drops
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A very small percentage of N. gonorrheae infections lead to bacteremia. What are the two characteristic features of the disseminated infection?
1) Painful hemorrhagic lesions on the hands
2) Septic arthritis (usually knees - can culture from pus of infected joints)
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How can N. gonorrheae cause an ectopic pregnancy (a life threatening condition)?
Untreated → ascends female GU → to fallopian tubes → Inflammation damages tubal cilia → Egg isn’t pushed along normally → Egg trapped and fertilized ectopically
What are the symptoms of Gonorrhea?
2-7 Days after exposure:
Burning/itching during urination w/ thick yellowish discharge from penis or vagina
Polyuria/Increased frequency
Swelling/redness of urethral opening
Vulvar itching/burning/pain
Etc
What is the special agar used to culture N. gonorrheae? What components of the agar select against other organisms?
Thayer-Martin VCN Agar (Chocolate agar)
- Vancomycin selects against G(+) organisms
- Colistin selects against G(-) organisms
- Nystatin selects against fungi
After other organisms are selected against, oxidase reagent is added to see if N. gonorrheae is there
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What test that is not a culture looks for the presence of both N. gonorrheae and Chlamydia DNA? It has largely replaced VCN/Chocolate agar
Nucleic acid amplification test (NAAT)
What is the treatment of N. gonorrheae infxn? What organism is treated at the same time?
IM Ceftriaxone + Oral azithromycin or oral doxycycline
Azithromycin treats Chlamydia also
What is the morphologic feature of N. meningitidis that distinguishes it from N. gonorrheae?
Presence of polysaccharide capsule.
Virtually indistinguishable on media/Gram staining
What serogroup of N. meningitidis causes the majority of meningococcal disease? What forms the basis of meningococcal serogrouping in addition to group specific immunity?
Group D
Polysaccharide capsule tested for serogrouping and is the basis for group specific immunity
What is the exception to the rule that meningococcal capsule serogroups confer specific immunity? Why?
Group B
Its sialic acid polymer is recognized as “self”, resulting in little immunity to Group B meningococci and little autoimmune damage
There is an inverse correlation between _____ and meningococcal disease
Humoral immunity
High incidence in kids < 2 y/o: Immature immune systems
Decreases in incidence as they acquire antibodies thru vaccination
Small increase in incidence at about 20 y/o: Need booster/in close proximity to those without vaccination
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T/F: N. meningitidis only causes disease in a specific age group
FALSE
N. meningitidis causes can seriously infect humans of all ages
How is N. meningitidis transmitted?
Respiratory droplets or direct contact with nasopharyngeal secretions
After colonizing the _____, N. meningitidis invades the _____. If the patient does not have protective antibodies (not vaccinated), the organism may then get into the _____ and disseminate
1) Colonization of nasopharynx
2) Invasion of epithelial lining
3) No vaccination/Abs: Gets into the bloodstreat and disseminates to tissues (Meninges)
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N. meningitidis can shed its outer membrane, releasing blebs/vesicles that are rich in _____. What are the consequences of this?
Rich in LOS (endotoxin)
If released throughout the body, the endotoxins generate a huge cytokine response that cause a lot of problems (micro-clots, shock, e.g.)
Meningococcemia presents as ______ that develop within 1-2 days
Flu-like symptoms (fatigue, vomiting, cold hands/feet, chills, severe myalgia, joint pain, pain in chest/abdomen, rapid breathing, diarrhea)
What is the characteristic physical findings in late stage disseminated meningococcemia?
- DARK PURPLE RASH that may be seen all over the body (vs. GC’s rash appearing only on the hands)
- Appears as a trasient macular/papular rash on upper chest and face
- Purpura from EARLY DIC COAGULATION due to septicemia forming grey-black areas on infarction
- Progression leads rapid enlargement of lesions → ISCHEMIC NECROSIS AND GANGRENE
- Ischemia can be focal or within entire extremity (amputate)
- Progression leads rapid enlargement of lesions → ISCHEMIC NECROSIS AND GANGRENE
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Bilateral infection by N. meningitidis and necrosis of adrenal glands causing a lethal adrenal insufficiency (5-15% of pts with meningococcemia) is known as _____
Waterhouse-Friedrichsen Syndrome
_____ is a medical emergency characterized by the sudden onset of fever, headdace, stiff neck, nausea, vomiting, photophobia, altered mental status due to N. meningitidis infection. How is diagnosis accomplished?
Meningitis
Diagnosed by lumbar puncture of purulent CSF for gram staining
Which polyvalent meningitis vaccine is very effective in young adults, is non-conjugated, and is a freeze dried mixture?
MENOMUNE - MPSV4
Which polyvalent meningitis vaccine is administered to patients who can’t make antibodies to N. meningitidis capsule, and is composed of 4 serogroups conjugated to diphtheria toxoid?
MENACTRA - MCV4
Exposure prophylaxis of meningococcal meningitis is administered within 24 hours of close contact w/ infected individuals and includes _____ + _____ +/- _____
Oral rifampin and ciprofloxacin + parenteral ceftriaxone +/- booster shot
The presence/absence of a _____ determines the spectrum of disease caused by H. influenzae
Capsule
What diseases are caused by encapsulated/non-encapsulated H. influenzae?
- Encapsulated: Meningitis, epiglottitis, cellulitis, conjunctivitis (aegyptius)
- Non-encapsulated: Otitis media, bronchitis/bronchopneumonia
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How is H. influenzae transmitted?
Respiratory/droplet inhalation
How is infection by H. influenzae prevented?
- PRP conjugate vaccine
- Rifampicin prophylaxis
What two factors are required to grow H. influenzae in the lab? What agar has these factors?
- Hemin (Factor X) + NADH (Factor Y)
- Chocolate agar contains RBC that, when lysed, release both of these factors.
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What is the major pathogenic serotype of H. influenzae? What diseases can it cause?
- Encapsulated HiB
-
Meningitis - Requires dissemination into bloodstream
- Sx similar to those of other meningitides but with fewer petechial lesions
- Cellulitis - local invasion of skin
- Epiglottitis - obstructs air flow, may need cricothyrotomy
-
Meningitis - Requires dissemination into bloodstream
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Post infectious sequelae of HiB occur in 1/10 infected infants. What are some of them?
- Blindness
- Deafness
- Obstructive hydrocephalus
- Mental retardation
- Poor reading/language skills
What drug is used as to prevent HiB infection in immune & non-immune household members?
Rifampicin
What H. influenzae biotype causes conjunctivitis?
Aegyptius
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If trapped in specific locations, nonencapsulated H. influenzae causes local disease such as _____ and _____
- Otitis media
- Bronchopneumonia/Bronchitis
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What is the major virulence factor of H. influenzae?
Capsule
What virulence factor of H. influenzae functions in attachment?
Outer membrane proteins/Pili
What virulence factor of H. influenzae is an endotoxin that causes ciliary stasis in respiratory epithelium and endotoxin shock?
Lipo-oligosaccharide
What virulence factor of H. influenzae protects the organism at mucosal sites?
IgA-ase
The PRP vaccine most effective against HiB is a Type B capsular antigen containing what three components?
- Pentose sugars
- Ribose
- Ribitol phosphate
What gram negative pyogenic organism causes whooping cough?
Bordatella pertussis
What vaccine is administered to provide immunity against Whooping Cough (B. pertussis)
DTaP
aP = acellular pertussis
Attachment of B. pertussis to cilia of respiratory epithelium is mediated by _____, _____, and _____
- Pili
- Filamentous hemagluttinin
- Pertactin
After attachment of B. pertussis to respiratory epithelium cilia, what two chemicals are made that injure the ciliated epithelium? Additional injury is from the peptidoglycan fragments of what toxin?
- Pertussis toxin
- Adenylate cyclase
- Additional injury: Tracheal cytotoxin (TCT)
After damage from the toxins and adenylate cyclase of B. pertussis, the mucosa is _____ and pertussis toxin _____
- Mucosa is denuded without protective cilia
- Pertussis toxin enters the bloodstream to act systemically
The first stage of B. pertussis infection is characterized by _____ and _____.
- Attachment to respiratory epithelium
- Cold like symptoms (slight cough, runny nose, low grade fever)
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In the first stage of B. pertussis infection, the organism is slightly _____, and is responsive to _____
- Slightly infectious
- Responsive to abx (azithromycin)
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What stage of B. pertussis infection is highly infectious, with the bacteria being expelled to the environment via a productive cough that produces thick mucus?
Second (Catarrhal/Commuicable) stage
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The death of epithelial cells in the second/catarrhal stage of B. pertussis infection increases risk of _____
Secondary infection
What stage of B. pertussis infection produces the characteristic “whooping” cough?
Third / Paroxysmal Stage
T/F The second stage of B. pertussis infection is susceptible to abx (azithromycin)
TRUE
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What are the caracteristic features of the third stage of B. pertussis infection?
- Whooping cough
- Leukocytosis
- Hypoglycemia
- Unresponsive to abx
- Danger to infant posed by inability to clear secretions and maintain nutrition
What stage of B. pertussis infection is characterized by a diminished cough, a hypoglycemic state, and a lymphocyte count that returns to normal?
Fourth/Convalescent stage
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What are the consequences of the Fourth/Convalescent stage of B. pertussis infection?
- Secondary bronchopneumonia
- Acute encephalopathy
- Convulsions/Brain damage
- Generation of protective immunity