16. Mycobacteria Flashcards
Medical conditions that increase the risk that TB infection will progress to TB disease
-HIV
-prolonged corticosteriod therapy
-other immunosuppressive therapy
-diabetes mellitus
high risk progression to TB after undergoing these therapies
Mycobacteria species
- Tuberculosis
- mycobacterium tuberculosis complex: 7 closely related species
- e.g. M. tuberculosis, M. bovis, M. africanum - Non-tuberculosis mycobacteria
- mycobacteria other than tuberculosis (MOTT)
- e.g. M.kansasii, M. xenopi, MAI-M. avium-intracellulare complex, M. chelonae, M. leprae
- more opportunistic
- disease in individual who has underlying heart disease or underlying immunosuppresants
- e.g. HIV, persistant cystic fibrosis
Bacteriology of mycobacteria
- do not grow on conventional agar plates like blood/chocolate
- specimen containing other bacteria require decontamination by NaOH before culture to prevent overgrowth
How long does M. tuberculosis have to be incubated
3-8 weeks
How long does fast growing mycobacterium such as M.chelonae, M, abscussus become positive
1-2 weeks
Characteristics of mycobacterium
- aerobic, non-spore forming, non-motile rods
- includes obligate pathogen (M. leprae), opportunistic pathogen (MOTT) and saprophytes
- cell wall has high lipid content:
a) difficult to stain w commonly used dyes such as gram stain
b) resist decolourisation by acid hence the term ‘acid-fast bacili’ (AFB)
c) resistant to common antibacterial agents
Transmission and pathogenesis of TB
airborne
- expelled when person with infectious TB coughs, sneezes, speaks (respiratory TB)
- transmission occurs from person with infectious TB, NOT latent TB infection
What is primary complex TB
A primary (Ghon) complex is formed, consisting of a granuloma, typically in the middle or lower zones of the lung (primary or Ghon focus) in combination with transient hilar and/or paratracheal lymphadenopathy and some overlying pleural reaction.
Clinical presentation of primary complex TB
- may mimic community-acquired pneumonia but with persistent symptoms (night sweats) and not responsing to antibiotics
1. heal by calcification fibrosis detectable on chest x-ray - reactivation usually at upper lobe as O2 tension is higher and the mycobacterium is aerobic
2. invade bloodstream (Miliary TB) - bloodstream infection
- CNS dissemination
- miliary spread may involve liver, spleen, lymph nodes, adreanl, bones and fallopian tube
3. Glands compress bronchus and pneumonia - pleural effusion
Pathogenesis of M.TB
- TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages.
- Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis. During this process, the bacterium is enveloped by the macrophage and stored temporarily in a phagosome. The phagosome then combines with a lysosome to create a phagolysosome.
- In the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances.
- M. tuberculosis is able to reproduce inside the macrophage and will eventually kill the immune cell.
Secondary TB
- occurs in previously infected person
- can be reactivation of dormant infection
- slow erosion of tubercle bacilli into bronchus draining the secretion, leaving a cavity that can be seen on chest x-ray
What happens during reactivation of apical focus (2nd TB)
[SECONDARY TB/REACTIVATED TB]
- cavitation
- haemoptysis if erosion occurs into a pulmonary vessek
- disease localised to lung
- bloodstream infection unusal
- no lymph node involvement
Diagnostic test for TB
- Clinical suspicion
- specific symptoms - haemoptysis
- systemic symptoms - weight loss, night sweats over weeks
- no response to antibiotics
- pyrexia of unknown origin - TB screening
- skin test - Mantoux, Heaf
- interferon-gamma release assay (IGRA) - Microbiology
- Radiology
- chest x-ray - apical cavitation
- CT, MRI - Histology
- caseating granulomata in tissues and postive ZN
What is Mantoux/Heaf
intradermal injection of purified protein derivative of tuberculin
- delayed type cell mediated hypersensitivity (usually develops 3-9 weeks after infection)
- useful where BCG vaccination not used
- positive: recent or previous TB/previously vaccinated
- negative: excludes diagnosis, unless very early infection. disseminated disease or immunosuppresed
What is interferon gamma release assay (IGRA)
whole blood assay that detects release of interferon gamma by sensitised cells incubated with M. tuberculosis peptides or proteins
-not affected by BCG vaaccine but does not distinguish active from latent TB