Tuberculosis and non-tuberculous mycobacterium Flashcards
What is tuberculosis?
A contagious infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB).
What is latent tuberculosis?
When a person is infected with Mycobacterium tuberculosis (MTB), but the bacteria remain in an inactive, dormant state within the body.
How is Mycobacterium tuberculosis transmitted?
It is transmitted by airborne route exclusively, especially to people in close proximity to the affected individual
How does age influence the presentation of tuberculosis?
TB is more severe in younger children.
Infants and young children are more susceptible to developing severe forms of TB, and to have progression of the disease.
Name some key features of the Mycobacterium tuberculosis (4)
- Shape: aerobic, slightly curved non-motile rod
- Grows best in high oxygen tension, but can survive in adverse conditions for a long time in a dormant state
- Very thick waxy outer layer which protects it and gives acid fast property
- Only known host is human
What is the probability of transmission of MTB?
It is the probability of inhaling a viable bacterium, which is proportional to the concentration of the bacterium in air.
What is the probability of MTB transmission in a small room vs a big room?
Small room
* greater concentration
* greater probability of transmission
Big room
* smaller concentration
* smaller probability of transmission
How can MTB be eliminated from the environment?
- MTB can be killed by sunlight or drying
- Ventilation can remove airborne bacteria
What are markers of TB contagiousness?
Cavities on chest X-ray and positive acid-fast smear
What are the two possible results of exposure to MTB?
Either new infection or no infection.
This is determined by innate immunity - mechanism poorly understood
Define primary infection
When exposure results in new infection
How does the initial (innate) immune response respond to TB.
It is largely ineffective
What is our body’s primary defence mechanism for MTB?
Cell-mediated immunity: Special immune cells form a hard shell called granuloma around the MTB to contain the infection.
Following primary infection, cell-mediated immunity (CMI) determines…
Whether the disease develops or the infection becomes dormant.
CMI can be defective in… (4)
- the very young and very old
- patients with HIV infection
- patient with other immuno-compromising conditions
- patients with co-morbidities (diabetes, renal failure)
Development of effective CMI occurs by weeks 4-7 after infection. What happens if CMI is defective?
Primary TB infection is not controlled and symptomatic disease develops within 3-6 months.
What is disseminated TB or TB meningitis?
Severe, life-threatening forms of TB.
Who is most likely to develop more severe forms of TB, including disseminated TB or TB meningitis?
Very young children
If CMI is effective, what happens to TB?
It enters a latent or dormant state, because the TB bacteria are contained within granulomas.
Explain why the latent state of TB is a dynamic state.
The latent state results from homeostasis between MTB constantly trying to “escape” the granulomas and host defences constantly trying to “hold them back”. This is an active immune process.
How long can dormant TB bacteria remain viable?
40 years or more!
What are some clinical test features of latent TB? (4)
- patient is asymptomatic
- interferon gamma release assay is positive
- tuberculin skin test is positive (5mm+)
- chest X-ray is normal
In 5-10% of cases of latent infection, active TB develops at some point. What are some risk factors for this? (6)
- interval since infection
- uncontrolled HIV/AIDS
- age (infants and young children, elderly)
- smoking, alcohol use
- malnourishment (underweight)
- diabetes (renal failure and silicosis)
When is the highest risk for an active infection to develop from latent TB?
Within the first 1-2 years after infection
What is the strongest known risk factor for latent TB to develop into active infection?
Uncontrolled HIV/AIDS
What are some clinical features (symptoms) of TB?
- Cough, sputum
- Fever and night sweats
- Hemoptysis (coughing up blood)
What are some physical exam features of TB?
Chest exam usually normal
Individual may be thin
What is the first step in diagnosing TB?
Chest X-ray: very sensitive (good at ruling out), but not very specific (a lot of false positives because of scarring)
After CXR, how do we diagnose TB? (3 tests)
TB is diagnosed using microbiology testing.
Microscopic exam of sputum smear, stained for acid fast bacilli
* at least 3 samples of sputum
* rapid but not sensitive
Cultures (most specific and most sensitive - gold standard test)
* however, takes a long time
Nucleic acid amplification
* rapid and more sensitive than acid-fast smear
How can latent TB be diagnosed? (2)
Two immune-based tests:
- Tuberculin skin test (PPD)
- Interferon gamma release assays (IGRAs)
However, we know that most people with positive tests will never develop an active disease (only 5-10% will)
Briefly describe the key points of TB treatment (you won’t really be tested on this)
- At least 2 antibiotics at all times to prevent MTB from developing resistance (initially, at least 3-4 drugs)
- Prolonged therapy (usually at least 6 months long)
- 3 important drugs:
- Isoniazid (INH)
- Rifampin (RIF)
- Pyrazinamide (PZA)
Active TB is a reportable disease, i.e….
Active TB must be reported to public health authorities at the time of diagnosis, by Quebec law.
Also, treatment for contagious forms of TB is mandatory, by Quebec law.
How is latent TB treated?
Single drug therapy is adequate (relatively long treatment - 3-4 months)
Do patients with latent TB require treatment?
Not everyone with latent TB requires treatment, and latent TB is not reportable.
What are some adverse effects of TB treatment?
Liver toxicity (can be fatal, and risk increases with age).
Therefore, balance risk vs benefits esp. in individuals with latent TB.
Describe key epidemiology features of TB in Canada (2)
- Overall TB rates in Canada have decreased and “plateaud” in the last 20 years
- Mortality declined rapidly after TB treatment became available
What demographic of the Canadian population is disproportionally affected by TB?
Indigenous peoples, especially the Inuit
Indigenous people account for … of all persons with TB in Canada.
17%
Describe the key trends of TB in Indigenous Peoples in Canada
- High incidence in Inuit populations (100/100,000)
- 100 times higher incidence in Indigenous vs non-Indigenous
- Substantial variation between communities
Historically, in Canada, TB was a major cause of death in…
residential schools.
The overall estimated global incidence rate of TB was 133 new cases per 100,000 - how does this compare to the Canadian rate?
That is over 25 times the Canadian rate!
Before the Covid-19 pandemic, TB was…
the leading cause of death from a single infectious agent
What were the impacts of Covid-19 on diagnosis and treatment of TB
Inadequate care, increased mortality, increased transmission
What is an important challenge in TB treatment?
Antibiotic resistance
“Non-tuberculous mycobacteria” refers to…
all mycobacteria EXCEPT MTB and Mycobacterium leprae.
How many species of non-tuberculous mycobacteria? Do they cause human disease?
150 species - most do not cause human disease
Why do non-tuberculous mycobacteria not automatically require treatment and are not reportable?
They do not directly spread between humans (they are not contagious) and may be present in humans without causing disease (colonizers/bystanders).
What non-tuberculous mycobacterium is most often associated with human disease?
Mycobacterium avium
Which is more common in Canada?
a) Mycobacterium tuberculosis
b) Mycobacterium avium
b) Mycobacterium avium
What is the difference between active and latent TB tests?
Active: microbiologic tests
Latent: immunologic tests
What are some major syndromes seen in pulmonary M. avium complex disease?
- Nodular lung infiltrates associated with bronchiectasis on CXR
- Cavitary lung disease
M. avium disease is often seen in people with…
previously underlying lung disease (eg. CF, bronchiectasis, scarring)
M. avium disease symptoms
cough, sputum, fatigue, weight loss
Disseminated M. avium disease is seen in…
persons with advanced, uncontrolled AIDS or severely immunocompromised persons (eg. post-transplant).
Common symptom of disseminated M. avium is diarrhea
