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Respiratory > Tuberculosis and mycobacterium > Flashcards

Tuberculosis and mycobacterium Flashcards

1
Q

Importance

A

Highly infectious
Severe morbidity
High mortality
-people of all ages

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2
Q

Who is susceptible

A

Everyone

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3
Q

Epiemiology

A

Around >4000 years
-Egyptian mummies
1/3 world’s population infected with TB (2.3 billion)
2nd only to HIV/AIDS as greatest infectious killer worldwide
Causes 1/4 of all HIV deaths

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4
Q

Epidemiology 2010

A
  1. 8 million contracted disease
    - 1.4 million died
    - 10 million orphans
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5
Q

Mycobacterium tuberculosis size

A

2-4μm by 0.2-0.5μm (half the size of an E.coli)

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6
Q

Mycobacterium tuberculosis

A

Obligate aerobe
-well-aerated upper lobes
Facultative intracellular parasite
-usually macrophages

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7
Q

Mycobacterium tuberculosis generation time

A

Slow: 15-20 hours

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8
Q

M.bovis

A

From cattle

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9
Q

In the UK TB most commonly affects

A

Lungs - pulmonary TB

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10
Q

TB can affect

A

Lungs, lymph nodes, bones, joints and kidneys

Can cause meningitis

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11
Q

How do people catch TB?

A

Most commonly spread in droplets being coughed or sneezed into the air
Frequent or close prolonged contact with infected person necessary

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12
Q

At risk

A

More likely to affect people whose immune systems are already weakened

  • HIV infection
  • steroids, chemotherapy, transplants, elderly
  • unhealthy, over-crowded conditions
  • stay in high-rate country (S.E Asia, sub-Saharan Africa, part E. Europe)
  • those exposed to TB in youth
  • children of parents from high-rate countries
  • prisoners, drug addicts, alcoholics
  • malnourished
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13
Q

Primary TB

A

Droplet nuclei inhaled
Taken up by alveolar macrophages - not activated (lipids)
Droplet nuclei (c. 5μ) reach alveoli where infection begins

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14
Q

Primary TB - granuloma in lung (Ghon focus) + enlarged lymph nodes

A

Primary focus

Walled off

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15
Q

What is secondary (post primary) TB

A

Reactivation of dormant mycobacteria
-impaired immune function
Reinfection in person previoulsy sensitised to mycobacterial antigens

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16
Q

When and where does secondary TB occur

A

Months, years or decades after primary infection

Reactivation most commonly occurs at apex of lungs - highly oxygenated

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17
Q

How does secondary TB work

A

Caseous (cheese-like) centres of tubercles liquefy
Organisms grow very rapidly in this
Large Ag load
-bronchi walls become necrotic and rupture
-cavity formation
-organisms spill into airways and spread to other areas of lung - highly infectious
Primary lesions heal - Ghon complex, Simon foci

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18
Q

Miliary TB

A

Widespread dissemination (spread) of Mycobacterium tuberculosis via hematogenous spread

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19
Q

TB infection

A 
Organism present
Tuberculin skin test positive
Chest X-ray normal
Sputum smears -ve
Sputum culture -ve
No symptoms
Not infectious
Not defined as a case of TB
20
Q

TB lung disease

A 
Organism present
Tuberculin skin test +ve
Lesion on chest X-ray
Sputum smear +ve
Sputum culture +ve
Symptoms
Infectious
Defined as a case of TB
21
Q

How many infected with TB develop active disease?

A

Only 3-4% upon initial infection

-5-10% within one year

22
Q

Most common symptoms

A

Cytokines (TNF, IL-3, GM-CSF) –>

  • persistent cough, +/- sputum
  • anorexia
  • weight loss
  • swollen glands (usually in neck)
  • fever
  • night sweats
  • sense of tiredness and being unwell
  • coughing up blood
23
Q

Standard recommended regimen

A

Isoniazid, rifampicin, pyrazinamide and esthambutol

-for 2 months followed by isoniazid & rifampicin for 4 months

24
Q

Standard recommended regimen to prevent spread of MDR-TB

A

Standardised drug regimens
Directly observed treatment (DOT)
Good supply of high quality drugs
Isolation of infectious pts

25
Q

Vit D

A

Has role in activating macrophages to destroy mycobacteria

Often a vit D deficiency in ethnic populations in UK

26
Q

Prognosis after treatment

A 
Non-infectious after c. 2 weeks
Begin to feel better after 2-4 weeks
Treatment must continue for 6 months +
-must prevent resistance developing
Longer treatment for TB meningitis or if TB is resistant
27
Q

Fatality rates

A

Untreated TB - 40-60%
Treated TB
-as low as 4%
-depending on nutrition; quality and availability of medical care; HIV status

28
Q

Bacille Calmette Guerin (BCG)

A

Protection restricted to childhood TB which is rarely infectious
No impact on HIV-related TB
Does not prevent infection - only disease
Invalidates tuberculin skin test
Therefore - targeted vaccination; effective for about 15y

29
Q

TB and HIV/AIDs

A

HIV/AIDs and TB are overlapping epidemics - “unholy alliance”
-worldwide 30-80% of AIDS pts get TB
HIV > risk o`f aquiring TB - destroys immune system
TB makes HIV worse - > replication rate of HIV
TB treatment slows down HIV and keeps pts alive to get HIV drugs

30
Q

TB in animals

A

Mid 20th C, TB common in cattle and humans infected with M.bovis
-pasteurisation; skin-testing and slaughter
Rapid > in TB in cattle over last 10 years
-spread by badgers?
-threat to humans?

31
Q

Obstacles to TB control

A 
Lack of financial resources
Social instability e.g. Russia
HIV epidemic
Drug resistance
Stigma
32
Q

Lack of financial resource

A

Half of all cases in China, Indonesia, India, Pakistan and Bangladesh

33
Q

HIV epidemic

A

HIV/AIDS doubles TB death rate
30-70% of TB cases in Africa HIV positive
Reinfection in South Africa

34
Q

Diagnosis of TB

A 
Suspicion - TB is great imitator
Chest X-ray - indicates but does not confirm TB
Microscopy?
Tuberculin tests?
T_SPOT?
Sputum culture?
Nucleic acid detection tests?
Sensitivity tests?
35
Q

Tuberculin tests

A

Heaf, Tine, Mantoux

  • ascertains infection rather than disease
  • may be -ve in severe TB or concomitant HIV, malnutrition, steroids
  • may be +ve with BCG or after exposure to environmental mycobacteria
36
Q

T-SPOT TB and QuantiFeron Gold

A

Blood tests to replace tuberculin tests
Detect reactive T cells
Specific for MTB
Not affected by BCG

37
Q

Microscopy

A

Ziehl-Neelsen stain
-needs >10,000 organism/ml at 100x lens
Rhodamine-Auramine more sensitive
1/3 of pulmonary TB (2/3 extra-pulmonary) undiagnosed by microscopy
Very quick - 15-20mins but misses 1/3 of all cases

38
Q

Sputum culture

A 
Homogenise (Sputasol)
Decontaminate (4% NaOH Petroff) - kills all bacteria except mycobacteria
Concentrate (centrifugation)
Middlebrook’s medium
Löwenstein-Jensen medium
4-6 weeks for visible colonies
Liquid media
-Kirchner’s
*ROUGH, TOUGH, BUFF*
39
Q

Automated culture

A

MGIT 960

  • fluorescent reaction quenched by O2
  • growth of mycobacteria lefts quenching and tubes fluoresce
  • 10 days
40
Q

Nucleic acid detected tests

A

RFLP IS6110
Strand displacement – BD ProbeTec
Amplified Mycobacterium tuberculosis Direct Test - Gen-Probe (rRNA)
Enhanced Amplified Mycobacterium tuberculosis Direct Test - Gen-Probe
AMPLICOR Mycobacterium tuberculosis Test – Roche (DNA PCR)
Multiplex PCR assay for 23S rDNA
HAIN
takes around an hour

41
Q

Sensitivity tests

A

Resistance ratio method
Conventional sensitivity tests
Proportion method
Radiometric growth detection

42
Q

Microchips

A

E.g. rifiampicin resistance
Rpo B gene codes for ß-subunit of RNA polymerase
30 point nucleotide substitutions, 7 deletions and 2 insertions

43
Q

Typing

A 
Spoligotyping
Variable Number of Tandem Repeats
Mycobacterial Interspersed Repetitive Units
VNTR-MIRU
e.g. VNTR 84455 MIRU 244428223533
*cluster analysis*
44
Q

Rigor

A

Sudden feeling of cold with shivering accompanied by a rise in temperature, often with copious sweating, especially at the onset or height of a fever

45
Q

Multi-/ Extensive-drug resistance

A

MDR TB - rifamipicin and isoniazid
XDR TB - also fluoroquinolones and aminoglycosides
Risk factors
-previous treatment, current failure, contact with MDR TB, HIV +, London resident, male 25-44%y, travel from endemic country
Mortality
-25% MDR TB, 50% XDR TB

Respiratory (5 decks)

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