Non-enteric GN Bacteria Flashcards
Neisseria meningitidis: Sources
human nasopharynx; part of normal microbiota
Obligate human pathogen
Neisseria meningitidis: types of infection
Nasopharyngeal colonization
Meningitis
• Leading cause of acute bacterial meningitis in teens, young adults
Sepsis
• Sequelae: gangrene, ampuatation
Disseminated intravascular coagulation (DIC) with petechial rash progressing to purpurae
Waterhouse-Friderichsen syndrome: adrenal infarction
Sequelae (of meningitis):
• Cranial nerve damage: deafness (CV VIII), blindness
• Brain damage and cognitive dysfunction: seizures, learning disorders, speech problems
Haemophilus influenzae: sources
o Source: nasopharynx
• Aerosol transmission via respiratory droplets
Haemophilus influenzae: types of infection
- Meningitis
- Sepsis
- Cellulitis
- Mastoiditis
- Epiglottitis
Moraxella catarrhalis: sources
asymptomatic colonization of nasopharynx (especially in children)
Moraxella catarrhalis: types of infection
- Upper respiratory infection
* Otitis media
Bordetella pertussis: source
aerosol transmission (highly contagious)
Bordetella pertussis: types of infection
- Tracheobronchitis
* Whooping cough
Pseudomonas aeruginosa: source
ubiquitous in environment
Pseudomonas aeruginosa: types of infection
usually aerobic sites
Skin, nail, and soft tissue infections
• Ex: folliculitis after pool or hot tub use
Otitis externa
• Complication: malignant otitis externa: disease extends to surrounding tissues and bones
Burn and wound infections
• Loss of protective barrier function
• Tissue damage disturbs vascular supply → diminished host immune response
Ocular infections (ex. From contact lens solution)
• Keratitis (corneal inflammation)
• Ulceration
• “Corneal melt” from hydrolytic enzymes
Bacteremia
• If have hematogenous dissemination → Ecthyma gangrenosum
• Deep ulcerative and necrotic skin lesions
• Usually in neutropenic host
Infective endocarditis
Lung infections
Hospital acquired pneumonia; ventilator associated pneumonia
Mucoid strains colonizing CF patients (leading cause of death)
• Genotypically and phenotypically distinct strains
• Establish a persistent biofilm
• By ages 3-7, nearly all CF patients have Pseudomonas colonized in oropharynx and upper respiratory tract
Contributing factors:
o Thick viscous mucous secretions
o Decreased mucociliary clearance
o Decreased host phagocyte function
o Mutant CFTR may serve as Pseudomonas receptor (attachment effect)
Long term therapies:
o Chest percussion = loosen secretions
o Continuous or intermittent antibiotic prophylaxis
Neisseria meningitidis: Risk factors
High incidence in “meningitis belt” of sub-Saharan Africa; during Muslim pilgrimage (Hajj) to Mecca
B lymphocyte or Ab deficiencies
Anatomic or functional asplenia
• From trauma, sickle cell disease
Deficiency in 1 or more terminal complement components (C5-9) [Also a risk factor for disseminated gonococcal infection]
Communal living conditions
• Promotes aerosol spread
• Nasopharyngeal colonization
• Bloodstream invasion and meningitis
Neisseria meningitidis: pathogenesis
o Invades bloodstream
o Transits to CNS
o Results in sepsis and meningitis
o High morbidity and mortality = death may occur within hours
Neisseria meningitidis: virulence factors
Capsule = anti-phagocytic
• Serogroups expressing different capsular polysaccharides: A, B, C, Y, W-135, etc.
• Specific anticapsular Ab fosters opsonization and phagocytosis of encapsulated microbes
Pili and other adhesions
Cell wall components LPS/ endotoxin and peptidoglycan
• Damage host mucosal cells
• Facilitates bloodstream invasion
• Neisserial LPS has few side chains = “Lipo-oligosaccharide” or LOS
Immune evasion
• Surface proteins (pilin and Opa), capsule, and LOS = antigenic variation
• Variability interferes with host immune response
• IgA protease secretion = degrades IgA
Readily takes up/releases DNA → phenotype switching
Iron acquisition
• Via surface proteins
• Bind host iron-containing proteins (transferrin, lactoferrin)
Prevention of Neisseria meningitidis
Acquired humoral immunity protects from invasive disease (not from colonization)
o Specific Abs against capsule or other surface component → opsonization and phagocytosis or complement-mediated bactericidal activity
• Maternal Abs in neonates from passive acquisition
• Ab derived from vaccine (capsular polysaccharides)
• Ab derived from nasopharyngeal colonization
• By meningococcal
• By related microbiota (ex: N. lactamica) with cross-reactive epitopes
Functional spleen
• Major lymphoid organ
• Lots of B lymphocytes and macrophages
Functional terminal complement components (C5-9)
• Form membrane attack complex (MAC) → complement-mediated lysis
Vaccination with MCV4 quadrivalent serogroup A/C/Y/W-135 capsular polysaccharide protein (diphtheria toxin) conjugate vaccine
• Does not cover serogroup B
Prophylactic antibiotics for close contacts of index cases:
• Rifampicin
• Fluoroquinolone
• Cephalosporin
• Essential features: efficacy against meningococci and good penetration into mucosal secretions
Treatment of Neisseria meningitidis
o Typically broad spectrum treatment with initial presentation
• Cover other potential etiologic agents
o Penicillin or cephalosporin
o Chloramphenicol (in parts of world where low cost and easy storage are important; but has side effects of bone marrow suppression and aplastic anemia)
o Additional treatment:
• IV fluids
• Vasopressors
• Ventilator assistance
• Some cases: glucocorticoid replacement and anticoagulants
Neisseria meningitidis vs. Neisseria gonorrhoeae
Neisseria meningitidis
Host: Humans only
Transmission: Aerosol
Location: Nasopharynx
Virulence: Most determinants; including capsule
Sequelae: Sepsis; meningitis; significant morbidity and mortality
Invasion: Invasion leads to disease (sepsis, meningitis)
Incidence: Rare
Vaccine: Against some
Neisseria gonorrhoeae Host: Humans only Transmission: Sexually Location: UG tract Virulence: Most determinants; NO capsule Sequelae: PID, fallopian tube scarring, infertility, ectopic pregnancy, and cervicitis in females; neonatal ocular infection; urethritis in males Invasion: Seldom invades (can cause rare disseminated gonococcal infection, septic arthritis) Incidence: Common (2nd bacterial STI) Vaccine: none
Encapsulated Haemophilus influenzae variants
Encapsulated = mainly type B H. influenza (Hib)
o Small GN coccobacillus (rod)
Transmission: aerosol via respiratory droplets
Pathogenesis: • Entry from nasopharynx → blood → CNS • Results in sepsis and meningitis • Rapid disease • Considerable mortality and morbidity
Virulence factors:
• Anti-phagocytic polysaccharide capsule
• Serotype b has capsule of polyribosyl ribitol phosphate
History:
• Formerly: main (70%) cause of meningitis in kids < 5 years
• Now: relatively rare (< 5 years
• Humoral immunity deficient (immunoglobulin or complement)
• Anatomic/functional asplenia
Non-typable Haemophilus influenzae variants
Diseases: Nasopharyngeal colonization • Asymptomatic • Very common Vaginal colonization Sinusitis Conjunctivitis • Major cause in older children Otitis media • Along with S. pneumonia = most common causes Bronchitis Pneumonia • 2nd most common cause of CAP in adults (after S. pneumonia) Perinatal and neonatal infections: • Premature birth • Chorioamnionitis • Postpartum sepsis in mother • Pneumonia, sepsis and meningitis in neonate
Identify the infections caused by Moraxella catarrhalis
Upper respiratory tract infections in children
• Sinusitis
• Otitis media
• 3rd most common cause (after pneumococcus and NTHi)
Lower respiratory tract infections
• Bronchitis
• Pneumonia
• In people with underlying lung conditions (viral URI in kids, COPD in adults)
Infections: sepsis, meningitis, other disseminated infections
• In immunocompromised patients
• Ex: CF, neutropenia, SLE, leukemia
Nosocomial infections
• Especially in pulmonary or pediatric ICUs
Characteristics of Bordetella pertussis
GN bacillus
o Slow growing
o Nutritionally fastidious (requires blood agar or synthetic media with growth factors like nicotinamide)
• Obligate human (primate) pathogen
No other environmental reservoir
o Adults = main reservoir for infection
• If unimmunized
• If vaccine immunity has waned since childhood
Bordetella pertussis: virulence factors
Adhesins: Attachment to respiratory ciliated epithelial cells
• Filamentous hemagglutinin (FHA)
• Fimbriae/ pili
• Pertussis toxin
Tracheal cytotoxin (TCT) • Peptidoglycan fragment • Causes ciliostasis and ciliated epithelium damage/death
Pertussis toxin (PTx)
• A/B subunit exotoxin
• ADP ribosylation of a G protein → disrupts cAMP regulation → interferes with cell signaling
Local and systemic effects:
• Acts as an adhesin
• Disordered host phagocyte and lymphocyte function
• Decreased transit of lymphocytes from blood → lymph nodes = lymphocytosis
• Decreased bacterial clearance → Frequent secondary infections
Adenylate cyclase toxin
• Interferes with host signaling
Lethal toxin
Bordetella pertussis: diagnosis
o Culture, PCR, Gram stain (during Catarrhal stage)
Bordetella pertussis: prevention
Vaccination!
Old: Inactivated whole cell vaccine
• Part of DTP/DPT vaccines
• Associated with side effects
Newer vaccine: acellular bacterial component vaccines
• Has multiple purified bacterial components
• Part of DTaP/Tdap vaccines
• Low level of side effects
• Less durable/shorter-lasting immune response
• May be contributing to increased rates of pertussis
Current recommedations:
• DTaP series in infants and young children
• Tdap booster at 11-12 years
• Single pertussis booster in all adults (regardless of prior immunization or infection status)
• Tdap vaccination of women during each pregnancy
Bordetella pertussis: treatment
Antibiotics for patient (macrolide like erythromycin)
• Useful during catarrhal stage
• May also decrease transmission to others
• Start treatment in symptomatic patient only when cough duration < 3 weeks
Respiratory isolation (only during catarrhal stage)
Antibiotic prophylaxis for close contacts if within 3 weeks of exposure
Supportive care once late whooping stage • Maintain respiratory status (oxygen or ventilator) • Nasal suctioning • Hydration • Nutrition • Monitor for secondary infections • Hospitalization if necessary o Report to public health department
