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Microbiology year 3 > Mycobacteria Tuberculosis > Flashcards

Mycobacteria Tuberculosis Flashcards

1
Q

Tuberculosis and mycobacteria: Introduction:

Tuberculosis is caused by what bacteria?

A
  • TB is caused by Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacteria. africanum, Mycobacteria microti, Mycobacteria. canetii.
  • Mycobacteria tuberculosis accounts for 98% of infections in the UK.
  • Mycobacteria other than tuberculosis (atypical/MOTT) or non-tuberculosis mycobacteria (NTM) can also cause infections (respiratory/non-respiratory).
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2
Q

Mycobacteria species and clinical diseases:
- 5 species of interest.

  • Reservoir?
  • Virulence in humans?
  • Clinical disease?
A
  • Mycobacteria tuberculosis:
  • Reservoir in humans
  • High virulence in humans
  • Clinical disease: TB
  • M. bovis:
  • Reservoir: animals
  • High virulence in humans
  • Bovine TB
  • M. leprae:
  • Reservoir: Humans
  • High virulence in humans
  • Clinical disease: leprosy.
  • M. abcessus:
  • Reservoir: Environment water systems.
  • Low virulence in humans
  • Only infects people with underlying conditions (CF)
    or bronchiectasis.
  • M. avium-intracellularae
  • Reservoir: Environment birds
  • Low virulence in humans
  • Causes TB-like lung infections or disseminated
    infections in AIDS patients.
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3
Q

Characteristics of Mycobacteria species:

  • Phylum?
  • Acid fast?
  • Most abundant virulence factor?
  • Trehalose dimycolate (TDM) cord factor causes what?
  • Generation time?
A
  • Mycobacteria are actinobacteria and are
    filamentous.
  • Acid fast organism: cell envelop contains 60% long chain branched hydrocarbons (waxes) (means difficult to stain).
  • Mycolic acid is the most abundant- virulence factor.
  • Trehalose dimycolate (TDM) cord factor:
    • Reduces permability to many
      molecules: confers resistance to
      chemicals, stains and antibiotics.
    • Confers to resistance to drying:
      increased survival in environment.
  • Slow growing: generation time 15 -22
    hours.
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4
Q

Pathogenesis of M. tuberculosis:

5 stages?

A
  1. Inhalation of infectious particles. Droplet nuclei (5mm approx. 3 bacilli)
  2. (7-21 day incubation) M. tuberculosis multiples within macrophages. (TDM cord factor prevents the phagosome fusing with the lysosome) (intracellular). Macrophages secrete IL-12 and present MTB antigen on surface, eventually bursting releasing MTB.
  3. IL-12 stimulates CD4/CD8 T cells to infiltrate: recognizes MTB antigen: become activated (sensitized): CD4 T cells release inflammatory factors INF-y resulting in a tubercle formation (primary lesion).
  4. MTB continues to multiple within inactivated or poorly activated macrophages and tubercle expands.
  5. Primary lesion heals (ghon focus) type of granuloma (dormant lesion, contains MTB: may re-activate). In disseminated infection the a cluster of granulomas are formed ghon complex which can be detected on x-ray.

N.B: it is the cell mediated response in healthy individuals that heals the primary lesion.

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5
Q

Primary tuberculosis: (primary exposure): Outcomes:

  • Ghon focus?

Immunocompetent individuals?

Immunocompromised individuals?

A
  • Ghon focus is a calcified nodule within the subpleural of the lung. (inflamed, infected, lymph node).

Immunocompetent individuals:

  • Cell mediated immunity (CMI) prevents the spread of MTB, minimal/no symptoms in 90%.
  • MTB remains latent (latent TB)
  • Reactivation may occur.

Immunocompromised individuals:

  • Primary lesion worsens (pneumonia develops)
  • systemic dissemination (lymph nodes, meninges, upper parts of the lungs).
  • Symptoms result from host cell mediated immunity response: chronic inflammation. (MTB has no endotoxins or exotoxins.
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6
Q 
Secondary TB (reactivation of TB): 
- Endogenous reactivation is?
- What can cause endogenous reactivation? 
Caseous lesions?
A
  • Endogenous reactivation of initial infection: commonly within 2 years but may occur any time after.
  • Associated with any impairment in the cell mediated immune response. (immunosuppression) & local disturbances to the dormant tubercle.
  • The granuloma undergoes caseous necrosis which liquefies and discharge into bronchi.
    - well-aerated environment.~
    - Distribution to other parts of the lung.
    - Contents of caseous lesions are
    coughed up becoming infective
    droplet nuclei.
  • TB pneumonia may result.
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7
Q

Mycobacteria & AIDS:

  • Why is it important and what does it cause?
  • Developing nations aids problem?
A
  • Cell mediated immune response is important in TB infections. In HIV/AIDs the CD4 T helper cells are depleted impairing this response.
  • 2/3 of AIDs patients in sub-Saharan Africa have TB.
    - Pt prone to rapid primary infection and reactivation.
    - Advanced AIDs pt (<50% T cell/uL) are very susceptible to M. avium-intracellularae (environmental)
    - Disseminated M.avium-intracellularae complex (MAC) infections: chronic, fever, wasting, multiple organ involvement and death.
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8
Q

Tuberculosis: Symptoms:
-General stats (%)
- symptoms?
Other possible complications?

A
  • 90% are asymptomatic.
  • 10% develop primary tuberculosis and experience symptoms; re-activation may occur.

Symptoms:

  • LRTI
  • Cough (bloody sputum)
  • Significant weight loss
  • Night sweats
  • Fatigue
  • Fever

Complications: May spread to other parts of the body (miliary TB):

  • Meningitis
  • Septicaemia
  • Kidney infection
  • Joint infection; Potts disease.
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9
Q

Diagnosis of TB: Clinical diagnosis:

  • Clinical indication and rapid test?
  • Laboratory diagnosis?
    • Non-culture?
    • Culture?
A
  • Presenting symptoms.
  • Radiological changes on x-ray, tuberculan skin test (TST): Mantoux test (tradition)- injection of purified protein derivate it is an extract from Mycobacteria sp.(PPD).

Laboratory:

Non-Culture:

  • Interferon gamma release assay (IGRA)
  • Molecular detection in clinical samples (Nuclei acid amplification tests (NAAT) PCR.
  • Microscopy

Culture:
- Gold standard: MGIT (Mycobacteria growth indicator culture.

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10
Q

Mycobacteria sample collection:

  • Primary Sample?
  • Renal TB?
  • Meningitis?
  • Other possible samples?

Safety considerations?

A
  • Early morning sputum x 3
  • Renal TB - Complete early morning urine (EMU x 3)
  • CSF (meningitis)
  • Lymph node biopsy
  • Blood/bone marrow aspirate
  • Whole blood (for IGRA)

Safety considerations: Tuberculosis is a category 3 pathogen!!

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11
Q

Non Culture techniques: Interferon gamma release assay (IGRA):

Theory?
The process?
The vaccination false positives?

Sample used?
What is the difference in genetic antigen from TB and NTM? + the antigens they encode?

Commercial kits?

A
  • Theory: A person’s T-cell that previously were sensitized to TB antigen (i.e Tb infection). Produce a high level of INF-y when re-exposed to the same mycobacteria antigen.

Process:
- Antigen specific T cell + antigen and APC = Antigen specific T -cell to release high amounts of INF-y.

  • Unlike the Mantoux (TST) this assay does not produce false positives against BCG vaccinated people.
  • Samples is blood.
  • Antigen utilized are encoded in region of difference (RD-1) a genomic sequence that is absent from NTM (e.g. BCG vaccine, environmental mycobacteria).

RD1 encodes antigens:

  • early secretory antigenic target 6 (ESAT-6)
  • Culture Filtrate protein (CFP-10)

Commercial kits:

  • QuatiFERON -TB Gold: INF-y secretion measured.
  • T-spot. TB; INF-y secreting T-cells enumerated.
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12
Q

Non-culture techniques: Microscopy:

  • primary stain? difficulties with diagnosis?
  • New stain? Sensitivity?
  • TB read?
A
  • Ziehl-neelson is an acid fast stain primarily used for TB. how ever need a large quantity of bacteria need to be present for detection!!

New stain in use:

  • Fluorescence auramine stain.
  • Rapid diagnosis (within 1 hour)
  • Negative does not rule out TB (low numbers in sample)
  • more effective than the ZN stain.
  • overall microscopy sensitivity = 50%
  • TB read (extra reading)
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13
Q 
TB Culture: (GOLD STANDARD): 
- Sample preparation: 3 steps. 
Culture: 
- Solid culture?
- Broth culture
A

Sample preparation: e.g Sputum (non-sterile)
- Liquefaction of sputum (sputasol; N-acetyl cystine)
- Concentration: (Centrifugation)
- Decontamination: 4% NaOH
N.B: sterile samples do not require decontamination.

Solid culture:

  • Lowenstein-Jenson slopes (LJ)
  • contains: whole eggs, salts, glycerol, potatoes flour, malachite green, penicillin, nalidixic acid.
  • Incubation at 37 degrees for up to 8 weeks.
  • Broth culture: e.g Bactec mycobacteria broth.
  • Semi-automated system Bactec.
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14
Q

Full identification of TB colonies:

  • what is required?
  • biochemical test?
  • molecular testing?
A
  • Colonial appearance macroscopy and microscopy.
  • Ziehl-neelson stain positive.
  • Biochemical tests:
  • Niacin: MTB POS . Atypical mycobacteria NEG.
  • Nitrate reductase: MTB POS. Atypical mycobacteria: NEG.

Molecular testing:

  • Nucleic acid amplification tests: PCR.
  • utilizing species specific DNA probes.
  • or ribosomal rRNA probes which are more sensitive.
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15
Q

Treatment of MTB: Current guidelines:

  • British thoracic society and NICE guidelines?
  • Improving patient compliance? DOT?
  • Combination therapy?
A
  • Current guidelines for treatment of active TB infections is a 6 month course of antibiotics split into 2 phases.
  • initial phase 2 months: Isoniazid, rifampicin, Pyranzinamide and ethambutol .
    • Continuation phase: 4 months: Isoniazid and rifampicin.
  • Patient compliance is key to prevent resistance forming. controlled by directly observed therapy from a trained physician. DOT is used for pts at high risk i.e alcoholic/vagrants.
  • Combination therapy: aids in pt compliance as reduces the pill burden.
    • Rifater: initial phase: isoniazid, rifampicin, Pyranzinamide.
    • Rifinah 300 or rimactazid 300: continuous phase: isoniazid and rifampicin.
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16
Q

Method of action of TB drugs:

  • Isoniazid?
  • Rifampicin?
  • Pyranzinamide?
  • Ethambutol?
A
  • Isoniazid: Inhibits cell wall formation. Isoniazid is converted to isonicotinic acid-NADH complex and binds to Inha this inhibits mycolic acid synthesis.
  • Rifampicin: Binds to RNA polymerase thus blocking mRNA synthesis & subsequent nucleic acid synthesis. (turns body fluid orange).
  • Pyranzinamide: cell acidification, drug is converted to pyrazinoic acid by pyrazinamidase (decreases pH). Inhibits ribosomes.
  • Ethambutol: Inhibits cell wall formation. binds to arabinosyl transferase disrupting formation of cell wall components.
17
Q

MDR-TB, XDR-TB, TDR-TB:

  • MDR-TB
  • XDR-TB
  • TDR-TB
A
  • Multi-drug resistant TB: SHREZ (streptomycin, isonicotinyl hydrazine, rifampicin, ethambutol, Pyranzinamide) with moxifloxacin + cycloserine.
  • Sensitivity testing.
  • Case by case treatment strategy (susceptibility vs toxicity).
  • Extensive drug resistant TB:
  • MDR-TB + a quinolone, + at least one of the second line TB injectables (kanamycin, capreomycin, amikacin).
  • Totally drug resistance TB:
  • Identified in India, Iran and Italy (2009-2012).
  • not recognized by the WHO as an experimental antibiotic could be used!!

Microbiology year 3 (10 decks)

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