39. Haemophilus, Legionella, Bordetella Flashcards

1
Q

species of haemophilus?

A

H.influenzae (most important childhood pathogen)

H.ducreyi (chanchroid - genital ulcerts)

H.parainfluenzae, H.haemolyticus are COMMENSALS and rarely cause disease

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2
Q

haemophilus morphology?

A

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)

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3
Q

haemophilus growth/metab?

A
  • facultative anaerobes

- require blood factors: hemin (X factor) & NAD (V factor) on chocolate agar

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4
Q

haemophilus disease?

A

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)

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5
Q

haemophilus virulence factors?

A

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)

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6
Q

haemophilus influenzae diagnosis

A
  1. Culture from sterile site (blood, CSF) on chocolate agar (requires X and V factors)
  2. latex particle agglutination test (for Hib capsule)
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7
Q

haemophilus influenzae treatment and prevention?

A
  1. amoxicillin for non-invasive infections (unencapsulated)
    - amoxicillin/ clavulanate for resistant strains
  2. 3rd gen cephalosporin (cefotaxime or ceftriaxone) for invasive Hib (meningitis)
  3. Immunization w/ polysaccharide-protein conjugates
  4. New vaccines for nontypeable strains in clinical trial
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8
Q

moraxella?

A

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

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9
Q

legionella morphology?

A

L. pneumophila

  • long, thin bacilli on lab media
  • short coccobacilli in tissues
  • gram (-) staining but poor staining w/common dyes
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10
Q

legionella epidemiology?

A
  1. present in natural waters, spread by aerosols (not person-to-person)
  2. intracellular parasites of protozoa (amoebae)
  3. oubreaks are newsworthy, but minority of cases
  4. CA and nosocomial cases
  5. elderly & immunocompomosed at highest risk
  6. smoking, chronic lung disease, malignancy, and TLR5 polymorphism=RFs
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11
Q

legionella diseases?

A
  1. 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
  2. Pontiac Fever
    - flu-like illness (no pna)
    - high attack rate, low mortality (
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12
Q

legionella pathogenesis?

A

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
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13
Q

legionella virulence factors?

A
  1. attachment and entry (C’ binding, type IV pilli)
  2. 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)
  3. intracellular replication
  4. Intracellular spread
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14
Q

legionella diagnosis?

A
  1. 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)
  2. urine antigen test (detects LPS, so only serogroup 1 strains)
  3. direct fluorescent Ab test from sputum
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15
Q

legionella treatment/prevention?

A
  1. B-lactam abx ineffective (produce B-lactamases)
  2. fluoroquinolone (levofloxacin) or macrolide (azithromycin) for CA-pna
  3. azithromycin if legionellosis diagnosed
  4. prevention involves water system treatment
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16
Q

coxiella - morphology, reservoirs, those at risk, pathogenesis, disease, diagnosis, and treatment?

A

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

17
Q

bordetella morphology?

A

B. pertussis most common (whooping cough)

Small, gram negative coccobacilli
- no polysaccharide capsule

18
Q

bordetella growth/metabolism?

A
  • aerobes
  • don’t utilize sugars
  • slow growth in lab (3-4 days to see colonies)
19
Q

bordetella epidemiology?

A

highly contagious, spread by aerosols

  • maj of cases (of severe disease) in infants
  • most deaths in kids
20
Q

bordetella disease?

A

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

21
Q

bordetella pathogenesis?

A
  • 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)
22
Q

bordetella virulence?

A

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

23
Q

bordetella dignosis?

A

Pertussis:

  • culture on Bordet-Gengou or Regan-Lowe agar plates
  • PCR
  • serology (shows lots of case underreporting)
24
Q

bordetella treatment and vaccines?

A
  1. azithromycin to prevent further spread (no benefit to pt)
  2. supportive therapy: hydration, nutrition, oxygen (mechanical ventilation, extracorporeal membrane oxygenation in critical infant pertussis)
  3. 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)