5/1 Intro to TB & Mycobacteria Flashcards
What are the reporting requirements for TB?
State by state, but usually mandated reporting of active TB; often mandated reporting of suspected TB.
Most of TB in the US is from people belonging to what category?
What % of the global population is infected with TB?
what % of the US population is infected with TB?
TB in US: generally in those who were foreign-born.
global population: 33%
US population: 1%
Terminology: how do we refer to groups of clinically relevant mycobacteria?
Mycobacteria divided into “complexes”
Ie, within the M tuberculosis complex are: M tuberculosis, M africanum, M bovis (x2??!), and M cannetti
There is also an M avium complex. (and many others)
Usefully diagnostically
How is TB transmitted?
Bacteria are aerosolized in 1micron “droplet nuclei”. Each contains a small amount of bacilli.
They can linger in the air for up to 8 h after a TB person has left the room.
Very efficient!!
Once TB finds its way into someone’s alveoli, what are the 4 possible outcomes?
- Eliminated by immune system
- Causes immediate disease (Primary TB)
- Survives dormant as Latent TB Infection (LTBI) (possible granulomas on imaging)
- Later, LTBI can convert to active TB (Reactivation TB)
What are the most common clinical manifestations of TB?
what about extrapulmonary TB?
- cough, fever, weight loss, hemoptysis
- Extrapulm s/s depend on the site that is involved.
What ist the lifetime risk of progressing from LTBI to active TB?
what if you are HIV+?
Lifetime risk = 10%
If HIV+, 10% annual risk of LTBI -> TB
When we are talking about “high risk groups” what do we want to be sure we are clear about?
are we talking about people at high risk for TB infection
or high risk for progression to active TB?
(they are different groups_
What people ar at high risk for TB infection?
- close contacts of infectious people
- people who are foreign-born
- low income, homeless
- occupational settings
- racial/ethnic minorities
- infants, children, adolescents
- IVDU
People at high risk for TB disease?
- HIV+
- with medical conditions known to increase risk for TB
- infected with M tuberculosis within past 2 yrs (higher risk for conversion LTBI to active)
- infants/kiddos < 4 yo
- IVDU
LTBI:
- what are the bacilli doing?
- TST and IGRA results?
- CXR?
- Sputum/cultures?
- symptoms?
- is person infectious?
bacilli are inactive, contained
- TST and IGRA results: positive
- CXR: usually normal (may see slight abnormality)
- Sputum/cultures: negative
- symptoms NO
- is person infectious NO
TB disease (lungs):
- what are the bacilli doing?
- TST and IGRA results?
- CXR?
- Sputum/cultures?
- symptoms?
- is person infectious?
- what are the bacilli doing: active, multiplying in body
- TST and IGRA results: usually positive
- CXR: abnormal
- Sputum/cultures: positive
- symptoms: couth, fever, wt loss
- is person infectious: Often infectious before treatment
describe the TST?
Tuberculin Skin Test
inject Partially Purified Derivative (PPD) intradermally, measure induration at 48-72 hours.
(do not measure redness! close your eyes if you have to)
describe the IGRA?
Inerferon Gamma Release Assays
Remove patient’s immune cells, conduct in vivo exposure to measure interferon release
Problems with both TST and IGRA?
Problems specific to TST?
Both: not ideal to test for disease by measuring patient’s immune reaction.
TST: cutoffs for positive interpretation depend on health status of patient.
Can cross-react with other mycobacteria (ie M bovis: BCG)
What is the booster phenomenon?
In what patients is it seen?
Booster phenomenon:
ONLY seen in patients who have LTBI!
Pt who has LTBI has a TST (negative). Several weeks later, if the same patient has another TST, it may be positive because the initial TST has ‘boosted’ the immune response.
Can be assumed that the second test was a Booster Phenomenon rather than a new exposure.
What is two-step testing?
Done in patients who will be tested periodically
-If pt has initial negative TST, can be given a second test a few weeks later. Interpretation: if second test = negative, pt was never infected. If second test = positive, assume boosted reaction.
If negative at both tests above, a positive TST later is a recent infection.
If positive at second test above, don’t ever TST that person again.
Why do we never TST someone who has previously had a positive TST result?
Pt can have necrosis, allergy, anaphylaxis, urticaria.
Overall, patients that we DON’T TST test?
Patients that we DO TST test?
Overall, patients that we DON’T TST test?
- anyne with prior positive TST
- anyone who has had live virus <6w ago
Patients that we DO TST test?
- patients about to receive immunosuppression
- Pts who have had BCG, if it has been long enough
What is the timeframe for TST testing in someone who has had the BCG vaccine?
- If had BCG in early infancy, can generally rely on TST result 10+ years later
- If had BCG as an older child (2+), harder to rely on TST result (20% will be positive after 10 yrs due to vaccine). She says to test people anyhow.
Advantages of IGRA?
2 issues with IGRA?
IGRA: operationally preferable.
- single patient visit
- does not rely on health care worker’s measurement of induration (less likely to be incorrectly read)
- does not cross react with BCG
- Does not cause booster phenomenon
Issues:
- have to process blood samples pretty quickly
- not much data on use in certain populations
What groups of people shoudl we test for TB?
Not everyone
People who are at high risk for infection
People who are at high risk for developing TB once infected.
Treatment regimens for LTBI?
(2 most preferable regimens)
- INH, daily for 9 months.
- INH-RPT, twice weekly for 3 months (relatively new)
(INH = isoniazid, RPT = cousin to rifampin)
Before treating LTBI, what must you do?
why?
Rule out active TB!
because treatment for LTBI is monotherapy, which may leave a patient with active TB with a resistant bug.
Approaches to active TB diagnosis?
- History
- PE (pulm findings)
- febrile, wt loss
Imaging: CXR, CT
Sputum culture (aka bacteriologic examination)
4 tests we can do on the expectorant sample from a possible TB patient?
- Acid fast bacilli smears (AFB)
- Nucleic acid amplification (NAA)
- Specimen culture (takes up to 6w)
- Drug susceptibility testing
What do we conclude if the AFB is positive but the NAA is negative for a possible TB specimen?
NAA is negative -> not-TB
AFB positive -> bacilli present
So neg NAA + pos AFB –> bacilli but not TB
“nonTB mycobacterium infection”
Treatment for TB Disease? (not LTBI)
how long, what drugs?
(2 phases: initial and continuation. 6m total)
Initial:
4 drugs, 2 months. Drugs = RIPE (rifampin, isoniazid, pyrazinamide, ethambutol)
_Continuation: _
2 drugs, 4 months
RIPE drugs: which are cidal, which are static?
what side effects do we worry about?
Cidal: (RIP!) rifampin, isoniazid, pyrazinamide
Static: ethambutol
RIP drugs cause hepatitis. concern for treating alcoholics, Hep C patients
define primary resistance
the version of TB the patient inhaled was already resistant
define secondary resistance
secondary resistance is someone’s fault…..
resistance developed during treatment
- pt given insufficient drugs, imappropriate drugs
- pt didn’t take regimen as prescribed
what do we mean by multi-drug resistant TB? (MDR TB)
MDR TB: Resistant to at least Rifampin and Isoniazid (most effective first-line drugs)
commit this to memory
what do we mean by extensively-drug resistant TB? (XDR TB)
Resistant to rifampin & isoniazid
PLUS resistant to any fluoroquinolone
AND at least 1 of the 3 injectable second-line drugs (e.g., amikacin, kanamycin, or capreomycin)
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Non-tuberculous mycobacteria: do they respond to the same treatment as TB?
Of course not. that would be way too easy.
what is the most commonly given childhood immuniz in the world? what does it derive from?
BCG
derived from M bovis from culture medium
what does Mycobacterium avium cause?
disseminated disease in AIDS patients, smoldering lung disease w chronic cougn in immunocompetents
what can Mycobacterium marinum cause?
skin infections in people exposed to fish and aquatic environments.
Once TB is inhaled into the lungs, what are the various things that can happen? (+ freq of each)
- 95% of the time, nothing happens. Immune system walls it off, no disease. For the rest of that patient’s life, 5% may go on to have reactivation to active TB
- 5% of the time, turns directly into disease that looks like community-acquired pneumonia
(Lahey’s YouTube)
for a pt with LTBI, what may cause their TB to reactivate?
immune compromise
-cancer/chemo, HIV, malnutrition
(Lahey’s YouTube)
with LTBI, where is the TB bacillus/what are the cells around it?
the TB has been swallowed by macrophages (sometimes the macs die, sometimes they stay alive for decades)
the macs are surrounded by a wall of lymphocytes that assist with TB control.
This will keep it from reactivating 95% of the time….
LTBI: treatment?
9 months of Isoniazid only. not replicating quickly; take a long time to kill it
(Lahey’s YouTube)
If a pt is HIV+ (or otherwise immunocomp, or has a close TB contact), what size induration will indicate a positive TST?
>=5mm
If a pt has some risk factors for TB (occupational, foreign-born from country with lots of TB, prisoners, homeless), what size induration will indicate a positive TST?
>=10mm
In a healthy person with very low risk for TB, what size induration will indicate a positive TST?
>=15mm
(from Jen’s small group)
Does this patient likely have active TB?
5m old male, received MMR 2d ago, born in Botswana. TST negative.
Probably not
could possibly be false neg based on Botswana.
(from Jen’s small group)
Does this patient likely have active TB?
32yo male with history of IVDU. Current hemoptysis and fever; recent travel to Mexico.
TST is positive, a CXR from 2y ago shows fibrosis and calcifications in R middle lobe.
Yes.
(from Jen’s small group)
Does this patient likely have active TB?
25yo asymptomatic female, international student from Zimbabwe. Had BCG as child. TST is positive.
haha this is supposed to be Tamu
May be a false positive due to her childhood BCG; may be reactivatd TB. Get an IGRA to determine.
(from Jen’s small group)
Does this patient likely have active TB?
25yo asymptomatic female, international student from Zimbabwe. NO BCG as child. TST is positive. History of close contact with TB as child (mom had active)
TST was negative 2 wks ago; is positive today
TST today is probably a false positive for active disease, but indicates LTBI and Booster Phenomenon.
Treat for LTBI
(from Jen’s small group)
Does this patient likely have active TB?
40yo male gardiner w fever, wasting, fatigue. CD4 count <50
AFB is positive, NAA is negative, TST is negative
Pt has a mycobacterium based on AFB – but NAA indicates that it is not TB.
it is MAC.
(from Jen’s small group)
Does this patient likely have active TB?
24yo, grumpy becuaase she had to show up at Dick’s House at 7:30am for PPD testing. Fatigued, has lost a lot of weight over the last 2 years. TST is negative.
Does not have TB.
