TB - Worldwide Control, Testing Flashcards
What is a primary tuberculous infection?
This is the initial infection with Mycobacterium tuberculosis (MTB).
Primary tuberculous infections almost always occur through the ______
respiratory tract
True or False: In immunocompetent individuals, most primary infections do not develop into active disease. Instead, such individuals continue to harbor the organisms, resulting in a state of latent tuberculous infection.
True
What is latent tuberculous infection?
This is when an individual is infected with MTB but has no active disease
True or False: Most active disease of TB are due to reactivation of LTBI
True
____ people in the world are infected with TB
2 billion
TB is a global threat and is the number _ or _ killer by an infectious agent
1 or 2
What kind of patients progress to primary (active) TB when exposed?
HIV, infants, elderly, immunocompromised
What are the stages of MTB?
- Ingestion by resident alveolar macrophages
- Symbiotic stage - MTB multiplies and macrophages accumulate.
- Migration of T-cells to the site of infection
4a. Latent tuberculosis infection
* 4b. Decline in immunity leads to reactivation of TB*
When TB is ingested by resident macrophages, it’s possible that the macrophage engulfs and kills the MTB. However, if the MTB cannot be killed that way, the macrophage either goes through apoptotic or necrotic cell death. Does MTB get killed in apoptotic or necrotic cell death?
After a macrophage engulfs MTB, if it undergoes apoptotic death, it will kill itself as well as the MTB. If it goes through necrotic death, the MTB survives and is released to be taken up by other macrophages
What happens in the symbiotic stage of MTB?
Blood monocytes migrate into the lungs where the differentiate into macrophages and continue to ingest MTB but is not able to destroy it. MTB multiplies within inactivated macrophages and form the early primary tubercle (nodule)
What happens when T-cells migrate to the site of TB infection?
T-cells begin to activate macrophages to kill or prevent the spread of MTB. Granulomas form and MTB is unable to multiply within the solid caseous material. This contains the infection.
Note that in AIDS patients, CD4+ lymphopenia results in granuloma breakdown, resulting in the inability to control the primary infection or in reactivation of latent infection.
What happens in latent tuberculosis infections at the cellular level?
The solid caseous center of the granuloma remains intact. Any bugs that escape the caseous edge are ingested by highly activated macrophages. LTBI is established if the caseation remains solid and does not liquify.
What happens to LTBI in the event of a decline in immunity?
Reactivation of TB.
If there is immunosuppression (Aids, cancer, anti-TNFalpha, aging, malnutrition, etc), there is a loss of integrity of the granuloma and liquifaction of the caseous material (caseous necrosis). This provides a favorable medium for multiplication of MTB which leads to cavity formation and rupture and spread to other parts of the lung and to other individuals
True or False: Latent TB can look completely normal on CXR
True
What are ghon and rhanke complexes?
Ghon complex = calcified lung nodule at site of initial TB infection
Ranke complex = ghon complex plus calcified regional hilar and/or mediastinal lymph nodes
Compare and contrast LTBI and active TB in the following ways:
- How much MTB is present
- Tuberculin skin test
- CXR
- Sputum and cultures
- Symptoms
- Infectious or not
In LTBI,
- There is only a little MTB
- Tuberculin skin test is positive
- Normal CXR (may have ghon complex)
- Sputum smears and cultures are negative
- No symptoms
- Not infectious
In active TB,
- There is MTB present in large numbers
- Tuberculin skin test is positive
- Abnormal CXR with pneumonia with or without cavitary lesions
- Sputum smears and cultures are positive
- Symptomatic with cough, fever, night sweats, and weight loss
- Often infectious before treatment
How do we make a diagnosis for LTBI?
Tuberculin skin test.
PPD (a culture filtrate of MTB with over 200 different mycobacteria antigens) is injected intradermally creating a wheal 6-10 mm in diameter.
After 48-72 hours, the diameter of the induration is measured (not the erythema).
What is M. bovis-BCG?
This is a vaccine given in most parts of the world that shares the same antigen as many of the PPD antigens used for the tuberculin skin test and by many tuberculous mycobacteria. Patients who were vaccinated by this in other parts of the world will give a false positive result on the tuberculin skin test.
A positive tuberculin skin test is an example of a ______ reaction.
type IV delayed-type hypersensitivity
What is considered a positive test on TST?
The size of the induration as well as patient risk factors need to be considered.
What are the advantages of TST?
It is very familiar to healthcare workers, it’s inexpensive, and it can be performed in the field an in resource-poor countries. Studies have shown that treatment of LTBI diagnosed by TST is very effective in preventing reactivation of TB (~90%)
What are the disadvantages of TST?
Two visits are required, 2-5 days apart. Measuring the size of the induration is more subjective than you would think. Thus, self-reading is not done.
False-positivity can occur in patients who have received the BCG vaccine because there is cross-reactivity to PPD as late as 15 years after vaccination.
False-positivity can also occur in individuals infected with environmental mycobacteria (in soil and stuff)
False-negativity can occur in individuals who are T cell depleted (e.g. AIDS, organ transplants, patients on chemo, etc). These patients that are immunocompromised don’t have the ability to react to the skin test.
What are 2 tests that are starting to be used instead of TST?
INF-gamma release assays:
- Quantiferon (incubate whole blood over night with antigens specific for MTB)
- T-spot. TB (add patient’s blood to a plate with anti-IFNgamma antibodies. (likely to be more accurate than quantiferon in immunocompromised patients because you’re counting individual cells)
In each of these, if a patient has TB, their adaptive immune system will launch an augmented response with greater levels of IFN-gamma released compared to patients who have never had TB.
