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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
Vit D
Has role in activating macrophages to destroy mycobacteria | Often a vit D deficiency in ethnic populations in UK
26
Prognosis after treatment
``` 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
Fatality rates
Untreated TB - 40-60% Treated TB -as low as 4% -depending on nutrition; quality and availability of medical care; HIV status
28
Bacille Calmette Guerin (BCG)
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
TB and HIV/AIDs
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
TB in animals
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
Obstacles to TB control
``` Lack of financial resources Social instability e.g. Russia HIV epidemic Drug resistance Stigma ```
32
Lack of financial resource
Half of all cases in China, Indonesia, India, Pakistan and Bangladesh
33
HIV epidemic
HIV/AIDS doubles TB death rate 30-70% of TB cases in Africa HIV positive Reinfection in South Africa
34
Diagnosis of TB
``` 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
Tuberculin tests
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
T-SPOT TB and QuantiFeron Gold
Blood tests to replace tuberculin tests Detect reactive T cells Specific for MTB Not affected by BCG
37
Microscopy
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
Sputum culture
``` 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
Automated culture
MGIT 960 - fluorescent reaction quenched by O2 - growth of mycobacteria lefts quenching and tubes fluoresce - 10 days
40
Nucleic acid detected tests
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
Sensitivity tests
Resistance ratio method Conventional sensitivity tests Proportion method Radiometric growth detection
42
Microchips
E.g. rifiampicin resistance Rpo B gene codes for ß-subunit of RNA polymerase 30 point nucleotide substitutions, 7 deletions and 2 insertions
43
Typing
``` Spoligotyping Variable Number of Tandem Repeats Mycobacterial Interspersed Repetitive Units VNTR-MIRU e.g. VNTR 84455 MIRU 244428223533 *cluster analysis* ```
44
Rigor
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
Multi-/ Extensive-drug resistance
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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