L3 MHD: Niesseria/Hemophillus/Bordetella Flashcards
Neisseria, Haemophilus and Bordetella are all gram ____________
Gram Negative
Neisseria – Key Characteristics
- Gram Negative ____________ (shape)
- Oxidase +/-?
- Differentiated by their _____________ reactions
- Gonorrhae oxidizes __________
- Mening oxidizes _________ & __________ - Increased susceptibility if ____________ deficiency
Two key virulence factors (VFs) of N. Meningitidis: _________ & _________
Two key VFs of N. Gonorrhoeae: _________ & ____________
- Gram Negative Diplococci
- Oxidase +
- Differentiated by their oxidation reactions
- Gonorrhae oxidizes glucose
- Mening oxidizes glucose & maltose - Increased susceptibility if complement C5-C8 deficiency (genetic deficiency)
Two key VFs of N. Meningitidis: LPS & Capsule
Two key VFs of N. Gonorrhoeae: Pili & OMPs (gonorrhea- OMPs- think “ow my penis”)
both have capsules & LPS, it’s just more important for N. meningitidis’s virulence
Neisseria meningitidis - Key Virulence Factors
- Pili- ____________
- A post-translational modification of pili helps meningitis do what? - Polysaccharide Capsule
- How many serogroups?
- Which ones are relevant to humans (5 groups)?
- Which one is not immunogenic?
Polysaccharide capsule is an especially important virulence factor for
a. ____________ invasion & __________
b. __________ penetration
- LPS
Helps cause cell _________ and systemic __________ which produces _______-like symptoms
- Pili- attachement (usually to nasopharynx cavity)
- Post translational modification of type 4 pilus helps with dispersement of virus - Polysaccharide Capsule
- 13 Serogroups
- A,B,C,Y,W-135 are important to humans
- Group B is non-immunogenic (does not produce an immune response)
Polysaccharide capsule:
- Bloodstream invasion and survival- prevents phagocytosis
- CNS penetration- important cause of meningitis- has tendency to cross BBB
- LPS
Helps cause cell damage and systemic inflammation- septic like symptoms
Pathogenesis of N. Meningitidis
- Enters thru _________
- Attaches to ciliated or non-ciliated cells of the _____________
- Multiples and alters ___________
- Transcytosis to _________ space
- Enters ____________ to cause __________ infection
Enters through nasal cavity
Attaches to cells of the respiratory tract
Multiplies and alters pilus which allows for dispersement (to environment to infect other people and to the submucosal space)
Transcytosis to submucosal space
Enters bloodstream to cause disseminated infection
Epidemiology of Meningococcal Disease
Developed world:
- Who is most at risk for the disease?
- Cases are most likely…?
- Men who have sex with men or a college campus outbreak is an example of an outbreak in ________ populations- what group of meningitis usually causes this?
Developing World:
-Usually outbreaks of Group _____ or ________
Disease is spread by ______________ _____________ & there is a 1,000 fold increase in attack rates in _________ contacts
Developed world:
- Children under 5 or teens/young adults are most at risk
- Most cases are sporadic and isolated
- MSM & College campuses may have a closed population outbreak- Group B Meningitidis causes this
- Rarely community outbreak of group A
Developing World:
-Usually community outbreaks caused by Group A or W-135
(Examples of this are the meningitis belt in Sub-Sahara Africa that affects infants or people on a pilgrimage to the Mecca)
Transmitted by Respiratory droplets; household contacts are 1000 times more likely to get the disease
Clinical Manifestations of Neisseria meningitidis Infection
Respiratory _________ followed by overt disease or transient carrier state
Symptoms of Meningococcemia: 1. 2. 3. 4. Key skin symptom is \_\_\_\_\_\_\_\_\_\_\_\_
Meningitis Symptoms: 1. 2. 3. 4. Key skin symptom is \_\_\_\_\_\_\_\_\_\_\_\_\_
Another clinical manifestation is urethritis, which is typically seen in which patient population?
Respiratory colonization (usually in nasopharynx)
Symptoms of Meningococcemia:
- Shock
- Hemorrhage
- Adrenal Hemorrhage- unable to respond to inflammatory stimulus (WATER-HOUSE Friedrickson)
- Purpura (serious symptom- patients who present with this usually do not survive)
Meningitis Symptoms:
- Headache
- Change in mental status
- Neurological symptoms
- Petecheae–>Purpura
Urethritis is typically seen in MSM
Laboratory Diagnosis: Neisseria meningitidis
Cultures can be taken from:
1.
2.
3.
Cultures are…
- Oxidase +/-?
- Able to oxidize what sugars?
- What media do they grow best on?
- Their growth is enhanced by what?
Gram stain- CSF
Cultures can be taken from:
- CSF
- Blood (toxic granulation- seen when magnitude of bacteremia is tremendous- specimen may look like a basophil under the microscope- it is really an immature neutrophil that has phagocytosed a bacteria particle)
- Skin (usually not likely to recover it from skin)
Cultures are…
- Oxidase +
- Oxidize glucose and maltose
- Nonselective growth on blood or chocolate agar
- Growth is enhanced by CO2
What is the best way to treat Neisseria Meningitidis?
What other drugs can be used?
What antibiotics are given as a prophylactic measure to household contacts?
Penicillin – resistance is uncommon
- Ceftriaxone- DRUG OF CHOICE because it penetrates the BBB better than penicillin G
- Can use penicillin G if sensitive
- Other cephalosporins can be used
Treat Household contacts with:
- Rifampin
- Ciprofloxacin
- Ceftriaxone (1 dose)
N. Meningitidis Vaccination
Vaccine – polysaccharide containing Groups \_\_\_\_, \_\_\_\_, \_\_\_\_, and \_\_\_\_\_\_\_ conjugated to diphtheria toxoid Vaccine Recommended For: 1.\_\_\_\_\_\_\_\_\_\_\_ 2.\_\_\_\_\_\_\_\_\_\_\_ 3.\_\_\_\_\_\_\_\_\_\_\_ 4. \_\_\_\_\_\_\_\_\_\_\_ 5.\_\_\_\_\_\_\_\_\_\_\_ 6.\_\_\_\_\_\_\_\_\_\_\_ 7.\_\_\_\_\_\_\_\_\_\_\_
New Serogroup ____ Vaccine
-Recombinant protein vaccine that is recommended to who?
-Vaccine contains Groups A, C, Y, W-135
Vaccine Given to/Recommended for:
- All Adolescents age 11-12
- College Freshmen living in dorms
- Microbiologists who are routinely exposed
- Populations in which an outbreak occurs (MSM)
- Military recruits
- Persons with increased susceptibility (asplenia, terminal complement deficiency)
- Travelers in hyperendemic regions (sub-sahara, saudi arabia)
New Serogroup B vaccines (MenB-FHbp, MenB-4C)
- Recommended for very high risk only
- i.e. patients who have had splenectomies
The two main disease states Meningoccus causes are what?
- Severe sepsis
- meningitis
Polysaccharide capsule and LPS are most important in causing these disease states
Key Characteristics of Neisseria gonorrhoeae
- What are the two main adhesins?
- What two factors contribute to antigenic diversity?
- What is the most common way gonorrhoeae is spread? Is it symptomatic or asymptomatic?
- What areas of the body are most commonly infected in men? Women?
- Where is the disease most commonly disseminated to?
- What is the most common lab test(s) for diagnosis?
- What is the most effective treatment for gonorrohaea? How is it administered?
- Adhesins: pili, Opa
- Antigenic diversity: pili(recombination ability), Opa(on-off switch)
- Intimate sexual contact, asymptomatic reservoir
- Urethra (men), cervix (women), other exposed sites (throat or anus); there’s local spread to prostate, epididiymis, fallopian tube
- Joints & skin
- Gram stain (90+% from male urethra), culture, PCR
- Ceftriaxone- injected; no oral therapy
What are 4 virulent factors of Neisseria gonorrhoeae that are found on the outer membrane? What do they do? 1. 2. 3. 4.
- Pili – stacked units of repeating protein (MW 19 kD)
- PorB– Porin
Pores (channels) that facilitate epithelial cell invasion - Opa – adherence proteins confer opaque appearance to colony
-Opaque: localized disease
-Transparent: disseminated disease - Rmp proteins – stimulate blocking antibodies
Antigenic Variation in Pili and Opa in Neisseria gonorrhoeae
Pili: use DNA ________ involving transfer of variable sequences form ______ to _______
Opa:
How many different Opa genes in genome?
How is the gene turned on?
Pili
-DNA recombination involving transfer of variable sequences from unexpressed (silent) loci, pilS, to expression locus, pilE
Opa – Up to 11 different Opa genes in genome
- Switch on an off Opa genes by varying length of 5 nucleotide (CTCTT)n repeats in the leader sequence encoding the Opa gene
- Alteration in number or repeats turns on or off expression
Epidemiology of Gonorrhea
Transmission occurs by what type of contact?
What age group is most at risk?
What percent of women are asymptomatic? What percentage of men?
What is the likelihood a man who has sex with an infected woman will get the disease? A woman who has sex with an infected man?
- Transmission across mucosal surfaces by direct contact
- High rate among adolescents and young adults
Asymptomatic: 50% women, 5+% men
Risk
Men 20% per contact with infected woman
Women 50% per contact with infected man
Pathogenesis of Gonorrhea- Invasion & Damage
- Adherence
What structures do pili attach to? Opa? - Epithelial cell invasion involves what outer membrane protein?
- LOS & Peptidoglycan fragments promote what response in the host?
- What deeper male/female structures does the disease spread to?
- Attachment:
- Pili - urethral, vaginal, fallopian tube, sperm, neutrophils
- Opa – cervical, urethral and other gonococcal cells (mediates adherence to various tissues of the genital tract) - Epithelial cell invasion involves Por B, other proteins
- LOS & Peptidoglycan promote inflammatory response and damage
- Deeper male structures affected: epididymus, prostate
- Female structures: paracervical glands, fallopian tubes (carried here by sperm) which may cause pelvic inflammatory disorder
- -Serum resistant strains invade bloodstream and disseminate
