Respiratory Infections 7 Flashcards
Mycobacterium tuberculosis Biology
- 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
M. Tuberculosis cord factor (trenalose dimycolate) is made up of
2 mycolic acids + 1 disaccharide tetrahalose
M. Tuberculosis epidemiology
• 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
How to prevent M. tuberculosis
• Prophylactic anti-mycobacterial drugs
• BCG (Bacillus Calmette-Guérin) vaccine
Live Attenuated M. bovis straint
M. tuberculosis Epidemiology: HIV
MTB-HIV co-infection has very poor prognosis if person has subsequently developed AIDS immunosuppression
Primary TB vs Reactivated/ post primary TB
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
MTB Pathogenesis: primary
- Initial infection
- bacteria gets to alveolar sacs; binds c3b on cell wall
- resident alveolar macrophages engulf MTB - Bacterial colonization
- intracellular replication
- Prevent oxidative burst & inhibit phagosome- lysosome fusion (cord factor /mycolic acid) - 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 - 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
M. Tuberculosis Pathogenesis: Re-activated
- Initial Re-activation
• Live Bacteria remain dormant in granuloma
• Reduction of CD4+ T cells (AIDS) destabilizes encased granuloma
• MTB begin replicating - Disease Progression
Bacteria preferentially migrate to lung apex (high oxygen)
Macrophages attempt to form granuloma, fail without Th1-> IFN-γ - 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
Clinical Presentation:
Active Pulmonary Tuberculosis
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
Clinical Presentation:
Extrapulmonary / Disseminated Tuberculosis
Slow onset weeks to month
- Symptoms correspond to affected organ
- Fever (variable)
- Generalized fatigue
- Cancer-like wasting
What’s being shown ?
Extrapulmonary Miliary TB of the Spleen
- “millet seed-like” granuloma formation in overwhelming M. tuberculosis infection
M. Tuberculosis Diagnosis: Microscopy
- Ziehl-Neelsen stain (Acid Fast Bacilli - AFB)
* Rhodamine-Auramine Fluorescent stain higher sensitivity
How to diagnose M. Tuberculosis
- Culture: require enriched or special medium l Löwenstein-Jensen medium
- Antimicrobialsusceptibilitytesting= increasingly important (MDR strains)
Sensitivity testing for MTB can be FALSE negative of sputum if ?
Disease is disseminated
Tuberculin Mantoux PPD Test: prior exposure to Mycobacterium tuberculosis will result in what ?
Delayed Type IV Hypersensitivity DTH reaction