8.3 Pathophysiology & Diagnosis of Tuberculosis Flashcards
Can TB only infect the lungs?
No. It can also infect:
- Lymph nodes
- Bones
- Joints
- Other organs
What percentage of people have active vs latent TB?
Active: 10%
Latent: 90%
What is the estimated proportion of the global population that has latent TB?
1 in 3
Is TB more common in men or women?
Men
Are richer or poorer countries suffering more from TB?
Poorer
What % of TB cases in Australia come from high burden countries?
90%
Risk factors for TB (other than being from a high burden country)
- Aboriginal heritage
- Elderly
- HIV
- Contacts with TB-infected people
Is drug-resistant TB more common in Australia or higher burden countries?
Higher burden countries
Number/replication status of organisms in TB infection vs TB disease
Infection: low number, dormant
Disease: high number, dividing
Are the TB organisms detectable in TB infection vs TB disease?
Infection: No
Disease: Yes
Diagnosis of TB infection vs TB disease
Infection: Immune response detected
Disease: Detecting MTBC
Are there symptoms in TB infection vs TB disease?
Infection: No
Disease: Yes
Are TB infection vs TB disease infectious?
Infection: No
Disease: Yes
How is TB spread?
By droplet nuclei when a person coughs, speaks, or sings
Give two uncommon examples of how TB can be transmitted
- High risk procedures
- Ingestion of unpasteurised milk
What are the four possibilities following TB exposure?
- Exposure with no infection/infection is cleared
- Latent TB infection (dormant)
- Subclinical (asymptomatic, but with radiological evidence, likely to progress)
- Symptomatic disease
Describe the early stages of TB infection (up to granuloma formation)
- TB inhaled
- ALveolar macrophages try to phagocytose all
- If unsuccessful, the mycobacterium will travel to the parenchyma, causing local inflammation and recruitment of T and B cells from lymph nodes
- Combination of cells engulf infected alveolar macrophages, forming a granuloma
Does TB remain localised to the lungs?
- No
- During early infection, the non-specific immune responses cannot prevent dissemination to other areas of the body (e.g. hilar nodes)
True or false: TB can survive in granuloma’s for several decades
True
What determines whether TB resolves into a dormant state or progresses to active disease?
Balance between host immune response and ‘virulence’ of TB organism
Does TB release toxins into the host?
No.
True or false: TB bacilli cannot replicate once inside a granuloma
- False
- They can; in fact, the granuloma may eventually fail to control the infection, allowing it to progress
What is the characteristic lesion of TB?
Granuloma
What is the function of the granuloma in TB infection? What is the downside of this?
- Function: Walls off and controls the infection
- Downside: provides an environment in which the TB bacillus can persist
What happens to the macrophages in a TB granuloma? What transformation can they undergo?
They can transform into epitheliod cells, sometimes forming multi-nucleated giant cells
What can cause central necrosis in tuberculosis granulomas?
Release of inflammatory cytokines
Is granuloma unique to TB
No
Is the virulence of TB the specific driver of overall virulence?
No, it seems that a majority of the tissue damage comes from the host immune response
Describe how changes in the host immune response can cause virulence in TB
- Reduced/delay response to pro-inflammatory cytokines
- Excess inflammatory responses
How does changing the bacterial burden of TB effect its ability to be transmitted?
Higher bacterial load, more efficient transmission
Are all strains of TB equally transmissible throughout all populations
- No
- For example, the Beijing strain is less transmitted throughout Australia
Describe primary TB infection
- Sufficient immune response to kill most bacteria
- However, some survive, causing latent TB infection
Can latent TB be “cured”? How?
- Yes
- With preventative TB therapy (iosoniazid inhibtis cell wall formation)
What is broncho-pneumonia?
Acute inflammation of the bronchi and alveoli in surrounding areas of the lung
What is primary progressive TB? What are the characteristics of a patient who is most at risk of this?
- Immune response fails to control the spread of TB
- Primary pulmonary focus may invade bronchi or blood vessel, possibly disseminating to other organs
- More common in patients who are immunosuppressed
Primary progressive TB can disseminate into other organs outside the lungs. Give two examples of conditions that can arise as a result of this
- Meningitis
- Renal disease
How soon after primary infection does active TB usually come about?
2-5 years
Why does TB more often affect the upper lobes of the lungs?
- This is a more oxygen rich environment
- TB flourishes in oxygen rich environments
Other than the lungs, what organs can tuberculosis infect?
- Brain
- Spine
- Kidneys
Broadly, describe the pathogenicity of tuberculosis
- Infects tissue, forms granuloma
- If escapes granuloma, spreads throughout lungs (and possibly other organs)
- Leads to imbalance of inflammatory response, causing tissue destruction and scarring
Under what circumstances would you consider that a patient may have TB?
- Cough > 2-3 weeks (+- fever, night sweats, weight loss)
- Persistent resp infection unresponsive to antibiotics
- TB exposure risk factors
Which people are high risk of TB?
- People who have come in contact with others who have active TB
- Spending time in high burden countries
Which groups of people are at a high risk of developing active TB if already infected?
- Children younger than 5 years old
- People who have already had TB (especially in the last 2 years)
- People with HIV/immunosuppressed (e.g. organ transplant)
What is the most common form of TB?
- Postprimary
- Reactivation after latent infection
Pulmonary symptoms of TB
- Cough (2-3 weeks or longer)
- Haemoptysis
- Chest pain
- Dyspnoea
Systemic symptoms of TB
- Fever
- Night sweats
- Weight loss
In what percentage of pulmonary TB cases does extra-pulmonary TB occur?
~15%
List some common sites of extra-pulmonary TB
- Pleura
- Cervical lymph nodes
- Kidneys
- Bones
- Meninges (uncommon, but still check just in case)
List one symptom of TB of the kidney
- Blood in the urine
List one symptom of TB of the meninges
- Headache/confusion
List one symptom of TB of the spine
- Persistent back pain
List one symptom of TB of the larynx
- Hoarseness
List one symptom of TB of the peritoneum
- Abdominal discomfort, bloating
General inspection signs of tuberculosis
- Pallor
- Clubbing
- Wasted appearance
Can CXR be used to definitively diagnose TB? Why, or why not?
- No, it cannot
- Other conditions can cause similar appearances
List some x ray findings typical of TB
- Lung cavitation in the posterior apical regions of the upper lobes
- However, pre-HIV, 30% of findings were atypical
What is the most common form of extrapulmonary TB?
Lymph node TB
What are the main forms of lab testing used in TB diagnosis?
- Smear microscopy for acid fast bacilli
- Culture & Drug susceptibility test
Can acid fast bacilli smearing differentiate between all AFBs and tuberculosis?
No
How long does it take to get a detectable culture in Tb culturing for a -ve vs +ve case?
+ve: average 14 days
-ve: average 21 days
How many good sputum specimens are needed for lab testing?
2-3
Do tissue specimens or body fluids produce higher yield in terms of lab diagnosis?
Tissue specimens
Does extrapulmonary TB involve a high or low number of TB bacilli? What is this called?
- Low number of bacilli
- This is called paucibacillary
Can Tuberculin skin testing and interferon gamma release assay differentiate between latent and active TB? What are the implications of this?
- No
- +ve does not guarantee active TB
- -ve does not exclude active TB
How can undiagnosed TB cause haemoptysis?
Erosion of blood vessels overlying a lung cavity
List some complications of TB
- Haemoptysis
- Lung fibrosis
- Pneumothorax
- bronchiectasis
- Aspergillus (fungal ball)
Are mycobacteria aerobic or anaeobic?
Aerobic (think: this is why they congregate near the apices of the lungs, where oxygen is rich)
Do mycobacterial cell walls have high or low lipid content?
Low
What does it mean that tuberculosis is acid-fast?
It can resist decolorisation in the presence of acid.
A patient is smear positive for TB. Are they necessarily infectious? Are all these mycobacteria necessarily TB?
- Yes
- No; not necessarily TB
Is acid-fast microscopy sensitive? How does this impact specimen size?
- No, it is not sensitive
- Therefore, a relatively large sample is needed
Describe Gene Xpert testing for TB
- Process sputum and place into cartridge, and put cartridge into machine
- Machine does PCR, tests if it’s TB, and tests resistance to rifampicin
Which is cheaper: gene xpert or acid-fast smear microscopy?
Acid-fast spear microscopy
Does TB grow slower in solid or liquid media?
Solid
Why would you use solid media TB culturing over liquid media? After all, it’s slower.
Because it may pick up on rare TB strains
Describe immunochromatographic testing for tuberculosis
- Place sputum sample on pad
- Runs along test, binding to antigens if present
- tests for the presence of a secretory protein of M. Tuberculosis
- Two lines: present. One line: not.
Which cultures are tested for drug susceptibility
- All new culture positive cases
- Those that are still culture-positive at 3 months
How does tuberculosis drug resistance testing work?
- Incubate sample with drug
- If grows: resistant. If not: not.
Should you do a bronchoscopy before sending sputum samples?
No. This is higher risk; try and do sputum samples first.
How do you test for latent TB infection?
Tuberculin skin test