M24 - TB Flashcards
(36 cards)
what is the obligate pathogen of tuberculosis?
Mycobacterium tuberculosis
what percentage of infected develop tuberculosis?
5-10%
How long does primary TB take to develop?
1-2 years
who is tuberculosis associated with?
disseminated disease associated with children
when and why does post-primary TB occur?
later in life and involve re- activation of organism
what is TB linked to?
immune status (e.g HIV)
what is the resistance rate of TB?
1.5-6% - stable
How many bacteria need to be inhaled to cause disease?
3
Describe the steps of pathogenesis of TB.
- Inhalation (3 bacteria)
- Penetrate deep into lung alveoli
- Initial lesion formed after entry into pulmonary epithelium & macrophages
- Phagocytosis, phagolysosome acidification arrested (LAM)
- Persist & replicate
- Induce localised immune response & recruit macrophages
- Destroy cells & infect new cells especially macrophages
- Granulomatous lesion forms
Describe the steps of the persistent infection of TB.
- Myco tb & cell wall fragments taken to lymph nodes
- Prime T cells & in turn stimulate more macrophages
- Immune response localises but leads to more macrophages becoming infected.
- Infected macrophages continue to escape & disseminate organism to lymph nodes, spleen, kidneys etc.
- Innate & adaptive immune response normally controls infection (2-6 weeks)
- Leaves behind infected macrophages & in some individuals tubercle
- Bacteria either lay dormant or lyse cells, escape and infect more macrophages.
Name the 5 stages of how TB has its effect.
- Bacilli inhaled into the alveoli and ingested by macrophages
- Bacilli multiply in macrophages
& cause more macrophage to migrate to the site of infection - After several weeks, many of the macrophages
die releasing Mycobacteria and forming caseous centre surrounded by mass of macrophages & lymphocytes Disease dormant - Mature Tubercle formed
Outer firm layer of fibroblasts
Caseous centre enlarges by liquefaction Forming cavity in which bacilli multiply - Tubercle ruptures Bacilli spill into bronchiole & are disseminated throughout the body.
When is it likely for the reactivation of tuberculosis?
If primary lesions fail to heal by becoming fibrous & calcified can lead to Tubercle that is prone to reactivate
Describe the reactivation of tuberculosis.
• Dormant bacteria survive Tubercle & escape in relatively high numbers
• Organisms shed in sputum & individual is highly infective
• Also spreads in the body and causes new sites of infection
• Reactivation can be linked to immune system
– e.g. Age, stress, malnutrition, alcoholism, immunosuppressive
drugs or diseases.
• Damage to lung & other tissue leads to debilitating cycle of disease that ultimately can lead to death
What are the likely hood of symptoms developing?
• Infection limited to lung
(majority)
• Cellular immunity halts replication within 2 to 6 weeks. Most hosts unaware of infection.
• 10% progress to disease state, 5% in first 2 years
What are the initial symptoms innocuous?
- Malaise
- Weight loss (appetite)
- Cough
- Night fever/sweats
- Productive cough (sputum)
What does sputum stained with blood (hemoptysis)?
indicates tissue
destruction or cavitary disease
Describe the diagnosis of TB.
- +ve skin test using tuberculin (mixture of TB Ags)
- Radiographic evidence of pulmonary disease.
- Laboratory diagnosis of Mycobacteria
Describe the tuberculin skin test.
• Purifiedproteinderivative
– Consists of cultured filtrates of
organism
– Injected intradermally in forearm
– Read 48 to 72 hours later
– Presence and size of swollen hardened area read >10mm
– Detects presence of sensitized T Cells
How long after initial contact can tuberculin skin test get a positive reaction?
6 weeks
Describe the characteristics of mycobacterium.
- Non-motile
- Non-Sporeforming
- Aerobic bacilli
- Complicated cell wall that is rich in lipids and when stained cannot be decolourised with acid solutions
- High GC content
- Fastidious
- Slow Growing (12-24h)
Describe mycobacterium’s waxy cell wall.
• CellWall
– 60% Lipid
– Mycolic Acids
– Complexed with polysaccharides & peptides producing strongly hydrophobic waxy cell wall
– Cord Factor toxic to mammalian cells & inhibits migration of PMN cells
• Lipoarabinomannan
Describe the laboratory diagnosis.
Sputum specimen taken
– Microscopic analysis
• Smears examined for acid fast bacteria
• Or fluorescent antibody detection 50% accurate
• Culturing
• Solid media Lowenstein-Jensen media (4-8 weeks)
– Nucleic Acid Amplification • Amplification of 16S rRNA – Sensitivity 75-100% – Specificity 90-100% • PCR of M.tb genes – As specific as culturing and results within 8 hours.
What is the treatment?
• Long course of antibiotic treatment (6-9 mths) : – Isonazid (primary antibiotic) – Rifampicin – Pyrazinamide (first 2 months) – Ethambutol (first 2 months)
What is the control?
Vaccination:
– Bacille Calmette-Guerin (BCG)
– attenuated M. bovis
• Enhances ability of macrophages to become activated and kill bacteria
• >70% protective against serious forms of the disease
• UK targeted policy (areas > 40 per 100,000)
