39. Haemophilus, Legionella, Bordetella Flashcards
species of haemophilus?
H.influenzae (most important childhood pathogen)
H.ducreyi (chanchroid - genital ulcerts)
H.parainfluenzae, H.haemolyticus are COMMENSALS and rarely cause disease
haemophilus morphology?
small, non-motile gram negative coccobacilli
encapsulated strains have polysaccharide capsule
- 6 antigenic types (a-f)
- type b (Hib) predominant
many strains unencapsulated (non-typeable - NTHi)
haemophilus growth/metab?
- facultative anaerobes
- require blood factors: hemin (X factor) & NAD (V factor) on chocolate agar
haemophilus disease?
Unencapsulated: respiratory infections
- Otitis media
- sinusitis
- bronchitis & pna
- COPD
Encapsulated (Hib)
- meningitis in kids
- bacteremia (w/fever & no localization)
- cellulitis (face)
- epiglottitis
- arthritis
Age dependent susceptibility to Hib (6 mos to 3 years)
haemophilus virulence factors?
Polysaccharide capsule (antiphagocytic)
- Hib = invasive
- polyribosyl ribitol phosphate (PRP)
- abs to ^ are protective
- C’ deficiency = risk factor
Adherence factors
- Pili (30%)
- non-pilus HMW adhesins in NTHi)
LOS (lipooligosaccharide) (adhere and invade epithelium; modified by addition of terminal sialic acid = molecular mimicry to evade immune response)
Biofilm (promoted by LOS sialylation, possible contributor to CF pathogenesis)
haemophilus influenzae diagnosis
- Culture from sterile site (blood, CSF) on chocolate agar (requires X and V factors)
- latex particle agglutination test (for Hib capsule)
haemophilus influenzae treatment and prevention?
- amoxicillin for non-invasive infections (unencapsulated)
- amoxicillin/ clavulanate for resistant strains - 3rd gen cephalosporin (cefotaxime or ceftriaxone) for invasive Hib (meningitis)
- Immunization w/ polysaccharide-protein conjugates
- New vaccines for nontypeable strains in clinical trial
moraxella?
M. catarrhalis is most important species
gram negative coccobacilli
otitis media, sinusitis and conjunctivitis but rarely systemic
dx if otitis media but r/o H.flu or pneumococcus
treat w/ amoxicillin/clavulanate, cephalosporins
legionella morphology?
L. pneumophila
- long, thin bacilli on lab media
- short coccobacilli in tissues
- gram (-) staining but poor staining w/common dyes
legionella epidemiology?
- present in natural waters, spread by aerosols (not person-to-person)
- intracellular parasites of protozoa (amoebae)
- oubreaks are newsworthy, but minority of cases
- CA and nosocomial cases
- elderly & immunocompomosed at highest risk
- smoking, chronic lung disease, malignancy, and TLR5 polymorphism=RFs
legionella diseases?
- legionnaires Disease
- severe pna
- fever, non-productive cough, chills, headache (multi-organ inv. Poss)
- cerebellar inv,
- mortality 15-20%
- low attack rate, no person-person spread
- Abx therapy required - Pontiac Fever
- flu-like illness (no pna)
- high attack rate, low mortality (
legionella pathogenesis?
Facultative intracellular parasites, multiply in alveolar macrophages
- can bind C’ components (C3b and C3bi) to gain access via C’ receptors on macrophages
- enter by “coiling phagocytosis” into membrane bound phagosome
- inhibit phagosome acidification and phagolysosome fusion, and establish isolated replication vacuole in ER markers (use Dot/Icm type IV secretion system, deplete aa’s and convert to virulent form, to escape from vacuole and cell
legionella virulence factors?
- attachment and entry (C’ binding, type IV pilli)
- vacuole formation (Dot/Icm type IV secretion system exports plasmid and putative virulence factors into host cell, Dot/Icm mutants are mistargeted to endosomal/lysosomal pathway)
- intracellular replication
- Intracellular spread
legionella diagnosis?
- difficult due to poor staining and slow fastidious growth in lab
- gram stain ineffective
- gimenez stain for smears
- dieterle stain for tissue sections
- culture on BCYE medium (buffer charcoal yeast extract - can’t grow on blood agar) - urine antigen test (detects LPS, so only serogroup 1 strains)
- direct fluorescent Ab test from sputum
legionella treatment/prevention?
- B-lactam abx ineffective (produce B-lactamases)
- fluoroquinolone (levofloxacin) or macrolide (azithromycin) for CA-pna
- azithromycin if legionellosis diagnosed
- prevention involves water system treatment
coxiella - morphology, reservoirs, those at risk, pathogenesis, disease, diagnosis, and treatment?
Coxiella burnetti
gram(-) obligate intracellular bacillus most closely related to legionella
animal reservoirs include cattle, sheep, goats - disease seen in farmers, ranchers, veterinarians
env’t stable form w/very low infectious dose by aerosol route
causes Q fever in humans, self-limiting flu-like illness
chronic form includes endocarditis
serological dx (abs to this org’s ags)
treat w/ DOXYCYCLINE
bordetella morphology?
B. pertussis most common (whooping cough)
Small, gram negative coccobacilli
- no polysaccharide capsule
bordetella growth/metabolism?
- aerobes
- don’t utilize sugars
- slow growth in lab (3-4 days to see colonies)
bordetella epidemiology?
highly contagious, spread by aerosols
- maj of cases (of severe disease) in infants
- most deaths in kids
bordetella disease?
Catarrhal stage: cold-like sxs, highly infectious, 2 weeks
Paroxysmal stage: severe cough paroxysms, apnea, may cause hypoxia, striking leukocytosis, several other possible complications (pulm and CNS)
Convalescent stage: cough may persist for several months, bacteria absent
Critical pertussis in infants: lymphocytosis, apnea, can progress to respiratory failure and death
bordetella pathogenesis?
- bacteria in aerosol droplets adhere to ciliated respiratory epithelium
- grow in upper and lower respiratory tract but do not disseminate
- produce several toxins that cause pathogenic effects (pertussis toxin, adenylate cyclase toxin, tracheal cytotoxin)
bordetella virulence?
Pertussis toxin (PTX)
- ADP-ribosylating toxin
- target: G proteins
- inhibits innate immune response
- exacerbates airway inflammation and pathology
- responsible for systemic symptoms (lymphocytosis assoc w/poor outcome in infants)
Tracheal cytotoxin (TCT)
- spontaneously released peptidoglycan fragment
- tetrapeptide-disaccharide
- causes damage and deciliation of epithelial cells in combo w/LPS
bordetella dignosis?
Pertussis:
- culture on Bordet-Gengou or Regan-Lowe agar plates
- PCR
- serology (shows lots of case underreporting)
bordetella treatment and vaccines?
- azithromycin to prevent further spread (no benefit to pt)
- supportive therapy: hydration, nutrition, oxygen (mechanical ventilation, extracorporeal membrane oxygenation in critical infant pertussis)
- anti-tussive medications ineffective
Vaccines
1st generation (1940’s, DTP vaccine, effective, waning immunity by adulthood, reactogenic)
2nd generation
(acellular vaccines, Tdap, much less reactogenic but immunity wanes rapidly [3-5 yrs], pertactin/PRN deficient mutant strains now prevalent = vaccine escape mutants)
