What 2 bacterial CNS infections are most prominent in Children (1mo - 15y)
Neisseria meningitidis (25-40%) Haemophilus influenzae (40-60%)
Structure of Neisseria meningitidis
Gram negative diplococci - Lipooligosaccharide (LOS instead of LPS)
Polysaccharide capsule
Possesses pili
Porins A and B
How does Neisseria Meningitidis take up iron?
Host transferrin
N. Meningitidis pathogenisis
- Attach to non ciliated columnar epithelia cells of nasopharynx via pili
- Internalized into phagocytic vacuoles
- Replication occurs and transcytosis to subepithelial spaces
- Polysaccharide capsule is major virulence determinant - blocks phagocytic destruction
- LOS induces vascular damage, inflammation, thrombosis
N. Meningitidis carriage
Asymptomatic and usually transient - highest for school-age children and young adults
When is N. Meningitidis most common?
During the dry, cold months of the year
Meningitis Belt
Major epidemics on an 8-12 year cycle in Sub Saharan Africa
Occurs during the dry season
Most N. Meningitidis epidemic are associated with which serogroup?
Serogroup A
N. Meningitidis
Acute bacterial meningitis:
Infants:
Older Children/Adults:
Acute bacterial meningitis: Abrupt onset of chills, fever, severe headache, meningeal inflammation
Infants: irritability, refusal to take food, seizures, disturbed motor tone, coma
Older Children/Adults: altered mental status, severe headache
Petechiae:
Purpura:
Petechiae: Minute hemorrhagic spots in the skin
Purpura: Hemorrhagic spots
N. Meningitidis - Laboratory Diagnosis
- Gram stain of CSF
- Blood culture
- Oxidase positive, gram negative diplococci
- Biochemical tests
N. Meningitidis treatment - vaccination
- Serogroup tetravalent vaccine specific for A, C, Y and W135
- Tetravalent vaccine - conjugate diptheria toxoid
N. Meningitidis drug treatment
Cefotaxime
Ceftriaxone
Penicillin G
Why is Group B meningitidis hard to treat?
K1 capsular polysaccharide in E. Coli is identical to group B antigen - hard to make selective vaccine
4CMenB
4 components of the serogroup B bacterium
Which Meningitis serogroup is most often associated with infections in infants and children?
Serogroup B
Neisseria gonorrhea - structure
Gram negative diplococci, oxidase positive
Does not posses a polysaccharide capsule
Possesses pili
N. Gonorrhea is a _____ specific pathogen and is sensitive to ____
human; cold
N. Gonorrhea surface antigens: porins
Trimeric major outer membrane proteins that form pores for the passive uptake of nutrients
Expression of PorB - interferes with neutrophil degranulation, facilitates bacterial invasion and resistant to complement
N. Gonorrhea surface antigens: Opa proteins
- Opaque vs. Transparent
- Opaque colonies (Gonococci expressing proteins) are usually localized infections - those from disseminated infections are usually transparent
- Mediate binding to epithelial cells
N. Gonorrhea surface antigens: Receptors for human transferrin
Mediate iron uptake in human hosts
N. Gonorrhea surface antigens: LOS
Lipooligosaccharide - core oligosaccharide without the O antigens side chain
Pathogenesis - Gonocci
- Acquisition by sexual contact with an infected individual
- Attachment to non ciliated epithelial cells; transcytosis to subepithelial spaces
- Replication and release of LOS
- Inflammatory response - damage to urethra or vagina
For which Gonococcal structures do humans make antibodies?
Pillins, Opa proteins, LOS, and bacterial antigens that block the anti-pillin, Opa or LOS antibodies
How are Gonoccal antigens highly variable?
Pili: phase variation (On or off) and antigenic variation (alter epitopes through recombination)
PorB - serological variation - many antigenic types
Why is there no vaccine for Gonococci
No capsule, highly variable surface proteins
Asymptomatic carriage of Gonorrhea is more common in ____
Women
Women have a ____% risk of acquiring infection after single exposure; men have a ____% risk
50%; 20%
Clinical presentation of Gonorrhea: Men
Purulent urethral discharge and dysuria 2-5 days post exposure (95% of infected men will be symptomatic)
Clinical presentation of Gonorrhea: Women
Vaginal discharge, dysuria and abdominal pain - can become pelvic inflammatory disease
Laboratory Diagnosis of Gonorrhea
Gram stain
Culture and biochemical identification
Nucleic acid amplification assays
Treatment of Gonorrhea
1st line therapy: dual therapy with ceftriazone
2nd line therapy: cefixim and either azithromycin or doxycycline
Chlamydia and Chlamydophila
Obligate intracellular parasites once considered viruses
Chlamydia and Chlamydophila: structure
Typical gram-negative envelope with lipopolysaccharide
Do not synthesize peptidoglycan - no cell wall
Chlamydia and Chlamydophila: Life cycle (2 forms)
- Elementary body - infectious form, stable in the environment because of highly cross-linked outer membrane structure
- Reticulate body - Replicative intracellular form, metabolically active, osmotically fragile, not stable to the environment - replicate by binary fission
Inclusion body
Chlamydia replicate within the protective environment of the inclusion body
Chlamydia Pathogenesis
- C. Trachomatis EBs attach to nonciliated columnar cuboidal or transitional epithelial cells
- Replicate within mononuclear phagocytes
- Access through abrasions or lesions - primary lesion occurs at the site
- Inguinal nodes become inflamed and swell
What is the most common bacterial STD in the US?
C. trachomatis (1.3 million cases in 2010 in the US)
Approximately ___% of women and ___% of men have asymptomatic C. Trachomatis infection
80%; 25%
Reiter syndrome
Usually occurs in young Caucasian males - urethritis, conjunctivitis (C. Trachomatis)
C. Trachomatis and Inclusion Conjunctivitis
Progressive disease that can lead to blindness
- Eyelashes turn inward abrading the cornea
- Loss of vision
- Infections occur predominantly in children whose living conditions are crowded
Chlamydia laboratory diagnosis
- Cytology
- Antigen detection
- Nucleic acid amplification
- Culture
Common properties of N. Gonorrhoeae and C. Trachomatis
- Gram negative
- Results in inflammatory symptoms
- Target non ciliated columnar epithelia cells
- Can be asymptomatic
- Should be treated promptly to prevent spread
- No vaccine
- Number 1 (Chlamydia) and Number 2 (N. Gonorrhoeae) bacterial STDs in the US
