16. Mycobacteria Flashcards

1
Q

Medical conditions that increase the risk that TB infection will progress to TB disease

A

-HIV
-prolonged corticosteriod therapy
-other immunosuppressive therapy
-diabetes mellitus
high risk progression to TB after undergoing these therapies

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2
Q

Mycobacteria species

A
  1. Tuberculosis
    - mycobacterium tuberculosis complex: 7 closely related species
    - e.g. M. tuberculosis, M. bovis, M. africanum
  2. 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
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3
Q

Bacteriology of mycobacteria

A
  • do not grow on conventional agar plates like blood/chocolate
  • specimen containing other bacteria require decontamination by NaOH before culture to prevent overgrowth
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4
Q

How long does M. tuberculosis have to be incubated

A

3-8 weeks

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5
Q

How long does fast growing mycobacterium such as M.chelonae, M, abscussus become positive

A

1-2 weeks

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6
Q

Characteristics of mycobacterium

A
  • 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
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7
Q

Transmission and pathogenesis of TB

A

airborne

  • expelled when person with infectious TB coughs, sneezes, speaks (respiratory TB)
  • transmission occurs from person with infectious TB, NOT latent TB infection
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8
Q

What is primary complex TB

A

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.

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9
Q

Clinical presentation of primary complex TB

A
  • 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
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10
Q

Pathogenesis of M.TB

A
  • 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.
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11
Q

Secondary TB

A
  • 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
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12
Q

What happens during reactivation of apical focus (2nd TB)

[SECONDARY TB/REACTIVATED TB]

A
  • cavitation
  • haemoptysis if erosion occurs into a pulmonary vessek
  • disease localised to lung
  • bloodstream infection unusal
  • no lymph node involvement
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13
Q

Diagnostic test for TB

A
  1. Clinical suspicion
    - specific symptoms - haemoptysis
    - systemic symptoms - weight loss, night sweats over weeks
    - no response to antibiotics
    - pyrexia of unknown origin
  2. TB screening
    - skin test - Mantoux, Heaf
    - interferon-gamma release assay (IGRA)
  3. Microbiology
  4. Radiology
    - chest x-ray - apical cavitation
    - CT, MRI
  5. Histology
    - caseating granulomata in tissues and postive ZN
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14
Q

What is Mantoux/Heaf

A

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
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15
Q

What is interferon gamma release assay (IGRA)

A

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

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16
Q

Microbiology in diagnosing TB

A
  1. Specimen
    - sputa
    - early morning urine
    - CSF
    - pus
    - tissue
  2. Microscopy
    - ZN stain or auramine - see fluroscent bacteria
    - if ZN positive, presumptive diagnosis and menas lots of bacilli present
  3. Culture and sensitvity
    - automated liquid culture with radiometric detection of 14CO2 or Lowenstein-Jensen (LJ) slopes
  4. PCR
    - confirm identity/resistance genes diagnosis of negative microscopy
17
Q

Treatment of TB

A
  1. Combination therapy
  2. Months of antibiotics
  3. Different agents to conventional antibiotics
  4. Drugs that penetrate intracellularly
18
Q

First line drugs

A
  • Isoniazid
  • Rifampicin
  • Ethambutol
  • Pyrizinamide
19
Q

Second line drugs

A
  • Streptomycin
  • Amikacin
  • Kanamycin
  • P-aminosalicyclic acid
  • Capreomycin
  • Ethonamide
  • Moxifloxacin
20
Q

Potential toxicity with agents

A
  • isoniazid and hepatitis/peripheral neuropathy
  • rifampicin and hepatitis/discolours bodily fluids
  • ethambutol and optic neuritis
21
Q

Drug resistance for TB

A
  1. primary resistance
    - in patient initally infected with resistant organism
  2. secondary resistance (acquired)
    - develops during TB therapy
22
Q

Patients who are at increased risk of drug resistance

A
  1. history of treatment with TB drugs
  2. contact of drug-resistant TB
  3. foreign-born persons from high prevalance drug resistant areas
  4. received inadequate treatment regimens for >2 weeks
  5. non-compliance
23
Q

What is multi-drug resistant TB (MDR-TB)

A

resistance to isoniazid and rifampicin and maybe other drugs

24
Q

What does Bacilli-Calmette-Guerin (BCG) vaccine consist of

A

live attenuated strain of M. bovis

  • produce a delayed type hypersensitivity reaction similar to that of natural infection
  • contraindicated in immunosuppressed patients and those who are skin test positive
  • 100% protection against meningitis and miliary TB
  • 70% protection against TB
25
Q

What are non-tuberculous mycobacteria

A
  • less pathogenic, often in environment
  • not considered infectious
  • some resemble TB in presentation (M. kansasii)
  • respiratory infection often seen in patient with underlying respiratory illness such as cystic fibrosis
26
Q

M. Avium-intravellulare complex

A
  • environmental source (water/soil)
  • present as primary infection, typically in AIDS patient especially in terminal stages
  • occasionally damaged lungs (e.g. CF patients)
  • large number of organisms disseminated in blood, marrow, GIT
  • not infectious
  • difficult to treat
27
Q

How is M. marinum presented

A

small, raised, erythematous lesion

28
Q

What is leprosy

A

M. leprae

  • in vitro culture not possible
  • do not stain as strongly as M.TB
  • found in macrophages
  • Schwann cell the primary target leading to anaesthesia and paralysis with granulomata
  • skin lesions with or without pigmentation, disability, nasal destruction and eye lesions
29
Q

Diagnosis of M.leprae

A
  • tissue smears for acid-fast bacilli

- histopathology

30
Q

Treatment of leprosy

A

-Dapsone
-rifampicin
-clofazimine
for > 6-12 months
-surgery to correct deformities