Respiratory Infections 7 Flashcards

1
Q

Mycobacterium tuberculosis Biology

A
  • Acid fast Bacilli
  • Grow in long parallel chains “serpentine cords”
  • strict aerobe
  • Catalase& SODPositive
  • Thick lipid rich cell wall
  • Mycolic Acid & Cord Factor
  • Has peptidoglycan but stains poorly with crystal violet
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2
Q

M. Tuberculosis cord factor (trenalose dimycolate) is made up of

A

2 mycolic acids + 1 disaccharide tetrahalose

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3
Q

M. Tuberculosis epidemiology

A

• Endemic Regions esp. SE Asia, Sub-Saharan African

  • Targets all age groups
  • Children more likely to present Primary Active
  • Immunosuppressed (ex. HIV/AIDS) at high-risk of Reactivated

Transmitted by aerosol droplet

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4
Q

How to prevent M. tuberculosis

A

• Prophylactic anti-mycobacterial drugs
• BCG (Bacillus Calmette-Guérin) vaccine
Live Attenuated M. bovis straint

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5
Q

M. tuberculosis Epidemiology: HIV

A

MTB-HIV co-infection has very poor prognosis if person has subsequently developed AIDS immunosuppression

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6
Q

Primary TB vs Reactivated/ post primary TB

A

Primary

- First time infection
- Large droplets with bacteria 
- Gains access to alveolar sacs 
- Bacteria internalized by macrophage 
- If macrophages not activated yet then bacteria wins 
- Need help from cd4

Reactivated

- Bacteria already in lung 
- Bacteria is replicating again
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7
Q

MTB Pathogenesis: primary

A
  1. Initial infection
    - bacteria gets to alveolar sacs; binds c3b on cell wall
    - resident alveolar macrophages engulf MTB
  2. Bacterial colonization
    - intracellular replication
    - Prevent oxidative burst & inhibit phagosome- lysosome fusion (cord factor /mycolic acid)
  3. Host immune response
    - Macrophages secrete IL-12 & TNF-α triggering local inflammation
    • TH1 cells, secrete robust amounts of IFN-γ
    • Activated Macrophages, Th1, PMNs surround infected Macrophages
  4. Control (asymptomatic) or Active Disease
  • Healthy individuals form microscopic granuloma -> Latent
  • Patients with low CD4+ fail to control infection, forming larger granuloma (Ghon focus)
  • Cytokines & PMNs contribute to DTH tissue damage
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8
Q

M. Tuberculosis Pathogenesis: Re-activated

A
  1. Initial Re-activation
    • Live Bacteria remain dormant in granuloma
    • Reduction of CD4+ T cells (AIDS) destabilizes encased granuloma
    • MTB begin replicating
  2. Disease Progression
    Bacteria preferentially migrate to lung apex (high oxygen)
    Macrophages attempt to form granuloma, fail without Th1-> IFN-γ
  3. Contribution of Host Immune response
    • Extensive host- mediate tissue damage results in cavitation and extensive necrosis
    • Damage to vascular barrier can result in dissemination of MTB

Outcome disease
• Infection overwhelms host
• Lung damage can result in hypoxia

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9
Q

Clinical Presentation:

Active Pulmonary Tuberculosis

A

Slow onset-> weeks to months

  • Dyspnea
  • Productive cough
  • Sputum can be scant, clear, or bloody
  • Regions of inflammation range
  • Primary – Mid lung
  • Reactivated–Apex
  • Miliary - Dispersed
  • Fever (variable)
  • Anorexia, weight loss
  • Extreme fatigue
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10
Q

Clinical Presentation:

Extrapulmonary / Disseminated Tuberculosis

A

Slow onset weeks to month

  • Symptoms correspond to affected organ
  • Fever (variable)
  • Generalized fatigue
  • Cancer-like wasting
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11
Q

What’s being shown ?

A

Extrapulmonary Miliary TB of the Spleen

- “millet seed-like” granuloma formation in overwhelming M. tuberculosis infection

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12
Q

M. Tuberculosis Diagnosis: Microscopy

A
  • Ziehl-Neelsen stain (Acid Fast Bacilli - AFB)

* Rhodamine-Auramine Fluorescent stain higher sensitivity

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13
Q

How to diagnose M. Tuberculosis

A
  • Culture: require enriched or special medium l Löwenstein-Jensen medium
  • Antimicrobialsusceptibilitytesting= increasingly important (MDR strains)
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14
Q

Sensitivity testing for MTB can be FALSE negative of sputum if ?

A

Disease is disseminated

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15
Q

Tuberculin Mantoux PPD Test: prior exposure to Mycobacterium tuberculosis will result in what ?

A

Delayed Type IV Hypersensitivity DTH reaction

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16
Q

M. Tuberculosis Diagnosis: Interferon-γ Release Assays IGRA

A

QuantiFERON & ELISpot: more sensitive in vitro immuno-assays to detect MTB-specific memory CD4+ T cells

Can distinguish FALSE (+) if person is vaccinated
and FALSE (-) if person is immunocompromised
17
Q
A

Pulmonary Primary Tuberculosis
• Ghon focus in mid-lung
• Hilar lymphadenopathy + visible granuloma

18
Q
A

Pulmonary Miliary Tuberculosis
• Even distribution of “millet” seeds
• Can be primary (child) or reactivated (cancer, HIV+ adult)

19
Q
A

Latent Tuberculosis
• Calcified Hilar granuloma Ranke
• May have complete clear lung field

20
Q
A

Pulmonary Reactivated Tuberculosis
• Cavitation (red circle)
• Inflammation in lung apex (pink circle)

21
Q

M. Tuberculosis Treatment

A
•M. tuberculosis is inherently resistant to β-lactams due to the thick rigid glyco-lipid cell wall.
Multiple combination therapy
RIPE for 2 months, RI continued for 4+ months
•First-line:
Rifampin – RNA Polymerase 
isoniazid  – Cell wall synthesis 
pyrazinamide – Cell wall synthesis 
ethambul – Cell wall synthesis
22
Q

M. Tuberculosis Treatment: MDR-TB

A

MDR-TB: Resistant to both Isoniazid (INH) and Rifampin

23
Q

M. Tuberculosis Treatment: XDR-TB

A

XDR-TB: MDR + resistant to any fluoroquinolone + 1 of second-line anti-tuberculosis drugs

24
Q

Nocardia asteroides (Nocardiosis)

A

• Acid-Fast Branching Filamentous
• Mycolic acid & cord factor
• Aerobic,Weakly Gram Positive
• Exogenous transmission via inhalation
of dust particles
• Forms insidious opportunistic abscesses or cavitation
• Immunocompromised patients are at highest risk
• Inhalation causes pulmonary infections (Most common)
• Local traumatic infection produces cutaneous,
lymphocutaneous infections
• Disseminated infections ex. CNS infection – brain abscess

25
Q

Clinical Presentation:

Nocardiosis

A
• Pulmonary form is clinically
indistinguishable
from Tuberculosis
• Chest Pain
• Cancer-like wasting
• Sputum may be blood
tinged
26
Q
A

Norcardiosis