Mycobacteria and Tuberculosis Flashcards

1
Q

Why is tuberculosis important?

A

It is highly infectious, has a high morbidity and mortality

It can affect people of all ages.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What proportion of the World’s population have been infected with TB?

What % will contract the disease at some point?

A

1/3rd of the population are infected with TB

5-10% will contract the disease at some point

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the link between TB and HIV/AIDS?

A

HIV/AIDS is the biggest infectious killer worldwide, TB is in second place.

TB causes 1/4 of all HIV deaths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What causes tuberculosis?

A

mycobacterium tuberculosis.

It is 2-4 micrometres by 0.2-0.5 micrometres

It is an obligate aerobe - it prefers specific conditions, such as our well-aerated upper lobe

it is a facultative intracellular parasite (so can live in macrophages)

It has a slow generation time (15-20hrs) and v slow growth

M.bovis from cattle

Its wall contains a v high lipid content

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

In the UK, what does TB most commonly affect?

Where else can it cause disease?

A

Most commonly the lungs (pulmonary TB)

Can affect anywhere in the body - e.g. lymph nodes, bones, joints, kidneys and can cause meningitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do people catch TB?

Who is it more likely to affect?

A

Most commonly in droplets (coughing or sneezing)

We need frequent or close prolonged contact with somebody to acquire the organism.

It is more likely to affect people with weakened immune systems (not a true primary pathogen)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the at risk groups for TB?

A
  • HIV infection
  • steroids, chemotherapy, transplants, elderly (all have weakened immune systems)
  • unhealthy, overcrowded conditions
  • those exposed to TB in youth
  • children of parents from high-rate countries (S.E.Asia, sub-Saharan Africa)
  • prisoners, drug addicts, alcoholics
  • malnourished
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do you get infected by primary TB?

Where do the droplet nuclei travel to to begin the infection?

What forms in this area?

What makes up the primary complex?

A

Droplet nuclei are inhaled (they’re so small that they dont drop due to gravity)

They’re taken up by alveolar macrophages - not activated (lipids). Because of the lipids, the macrophages aren’t activated, so the TB can live in them.

Droplet nuclei reach the alveoli where the infection begins (most commonly in the base of lungs)

Body’s immune system then reacts to form a granuloma in the lung, called a ghon focus.

Even though it is walled off, it is still alive and dormant.

Englarged lymph nodes and ghon focus form the primary complex. This may result in flu-like symptoms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What happens to cause secondary TB? (Post-primary TB)

When and where does this happen in relation to primary TB?

A

Reactivation of dormant mycobacteria = impaired immune function

Reinfection in a person previously sensitised to mycobacterial antigens.

Occurs months/years/decades after primary infection. Reactivation most commonly occurs at the apex of lungs (highly oxygenated area)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What happens during secondary TB?

A

Caseous (cheese-like) centres of tubercles liquefy.

Organisms grow very rapidly.

Large Ag load

  • Bronchi walls become necrotic and rupture (leaving the cavity behind). There is then a massive influx of O2 which the organism likes, allowing it to grow rapidly.
  • cavity formation
  • organism spills into airways and spreads to other areas of lung (it is highly infectious)

Primary lesions heal (Ghon complex and Simon foci) so can be seen on X-ray

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is miliary tuberculosis?

A

Sometimes the immune system can be overwhelmed = organism spills into the bloodstream and spreads throughout the body.

X-ray appearance looks like millet seeds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the difference between TB infection and TB lung disease?

A

INFECTION:

  • organism present
  • tuberculin skin test positive
  • chest X-ray normal
  • sputum smears and culture negative
  • no symptoms and not infectious
  • not defined as a case of TB

DISEASE:

  • organism present
  • tuberculin skin test positive
  • chest x-ray = lesion present
  • sputum smears and culture positive
  • symptoms and infectious
  • defined as a case of TB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What % of those infected develop active disease upon initial infection?

A

3-4%

5-10% within one year

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the most common symptoms of TB? What are they caused by?

A

Mostly caused by cytokine activity (TNF, IL-3, GM-CSF)

  • persistant cough (+/- sputum)
  • anorexia
  • weight loss
  • swollen glands (usually in neck)
  • fever
  • night sweats
  • sense of tiredness and being unwell
  • coughing up blood (if organism breaks into bronchi)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the standard treatment of a patient with TB? (4 drugs)

A

isoniazid, rifampicin, pyrazinamide and ethambutol - for two months followed by isoniazid and rifampicin for 4 months

6 month standard treatment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can we prevent the spread of MDR-TB?

A

Standardised drug regimens

DOT (directly observed treatment)

Good supply of high quality drugs

Isolation of infectious patients

17
Q

How is vitamin D linked with mycobacteria and TB?

A

It has a role in activating macrophages to destroy mycobacteria.

Often a vit D deficiency in ethnic UK populations

18
Q

If a patient is suspected of TB, what will they be tested for?

A

HIV test and vit D levels will be measured.

19
Q

What is the timescale of TB and the treatment timescale?

Which forms of TB require longer treatment?

A

Non-infectious after 2 weeks.

Feel better after 2-4 weeks.

Treatment must continue for 6 months at least. Must prevent resistance from developing.

Longer treatment for non-pulmonary infection, for TB meningitis or if TB is resistant (up to 2yrs)

20
Q

What are the fatality rates for untreated and treated TB?

A

untreated = 40-60%

treated = 5-50% - depends on quality of medical care, HIV status and nutrition.

21
Q

What is the BCG vaccine?

What are its limitations? (4)

How long is it effective for?

A

Bacille Calmette Guerin vaccine.

Protection is restricted to childhood TB which is rarely infectious.

Has no impact on HIV-related TB

Doesn’t prevent infection, only disease

Invalidates tuberculin skin test

Targeted vaccination - effective for about 15yrs.

22
Q

Why are TB and HIV/AIDS called the ‘unholy alliance’?

How do they encourage each other?

How does TB treatment affect HIV?

A

They’re overlapping epidemics - worldwide, 30-80% of AIDS patients get TB

HIV increases the risk of acquiring TB - therefore destroys the immune system

TB makes HIV worse - so increases the replication rate of HIV

TB treatment slows down HIV and keeps the patient alive to get HIV drugs

23
Q

What is MDR TB and XDR TB?

Which drugs are involved in these cases?

A

Multi-drug resistant TB - rifampicin and isoniazid

Extensive-drug resistant TB - also fluoroquinolones and aminoglycosides.

24
Q

What are the mortalities of MDR-TB and XDR-TB?

What are risk facotrs to developing them? (7)

A

Mortality is 25% (MDR-TB) and 50% (XDR-TB)

Risk factors:

Previous treatment, current failure, contact with MDR-TB, HIV+, London resident, male 25-44yrs old, travel from endemic country.

25
Q

How do we diagnose TB? (3)

A

Be suspicious - as TB can imitate any disease or condition.

Chest X-rays are indicative but does not confirm TB.

Tuberculin tests (Heaf, Tine, Mantoux) - ascertains infection, not disease.

T-SPOT TB & QuantiFeron Gold - blood tests to replace tuberculin tests. This detects reactive T cells. It is highly specific for MTB, not BCG.

26
Q

What can give a negative result in tuberculin tests?

What can give a positive result?

A

Negative - severe TB / concomitant HIV / steroids / malnutrition

Positive - BCG (vaccine) / after exposure to environmental mycobacteria

27
Q

What are some of the obstacles to TB control?

A

lack of financial resources

social instability

HIV epidemic (HIV/AIDS doubles the TB death rate)

Drug resistance

Stigma

28
Q

What interventions have been made to combat TB?

A

Chemotherapy

BCG (vaccination)

Pasteurisation

Short course therapy

29
Q

What stains are used for microscopy when investigating TB? (2)

What are the pros (2) and cons (2) to using microscopy?

A

Ziehl-Neelsen stain (the organism will stain red against a green background)

Rhodamine-Auramine (a fluorescent stain which is more sensitive)

PROS: rapid and cheap

CONS: not very specific or sensitive

1/3rd of pulmonary TB and 2/3rds extra-pulmonary TB are undiagnosed by microscopy.

30
Q

How do we create a culture from sputum to investigate TB?

A
  • Homogenise (using sputasol)
  • Decontaminate (4% NaOH Petroff) - to kill all bacteria but leave mycobacteria behind.
  • Concentrate (centrifugation)
  • Deposit on Middlebrook’s medium (Lowenstein-Jensen medium)
  • Breadcrumb-like colonies will grow after 4-6 weeks.
31
Q

How do we do an automated culture? What media is used?

Will the media fluoresce if only mycobacteria is present?

A

Liquid media - Kirchner’s

MGIT 960 - in media has a fluorescent agent. Growth of mycobacteria lifts quenching and tubes fluoresce. This cuts the upto 6 week wait down to 10 days.

MPT64 Ag - laminar strip looking for specific antigen called MPT64.

If media only has mycobacteria present and not other bacteria, then growth of media will use O2 and allow fluorescence.

32
Q

What is the molecular method to detect TB?

A

Nucleic acid detection tests - specific to the DNA of organism

If rifampicin resistance genes are present - likely to me MDR-TB (multi drug resistant)

33
Q

How does it come about that Rifampicin may not work to treat TB?

Think about the genes?

A

Rifampicin acts on the beta subunit of RNA polymerase - if there is a mutation in rpo B (the gene involved in transcription) then rifampicin cant act = Rifampicin resistance

34
Q

What does TYPING give us? When is it useful?

A

Once the organism is identified and isolated, we can follow the epidemic spread of it via typing.

Typing is unique to the organism.

Involves VNTR-MIRU (Variable Number of Tandem Repeats and Mycobacterial Interspersed Repetitive Units)

Different organisms have a different typing sequence.