Tuberculosis Flashcards
Why was there a TB resurgence in the 1980s/1990s?
- Inadequate funding in control programs (decreased federal funds)
- HIV epidemic
- Increased immigration from endemic areas
- TB in homeless and correctional facilities
- Increase and spread in multidrug-resistant TB (MDR-TB)
What causes TB?
Caused by mycobacterium tuberculosis
What does TB affect in the human body?
Can cause disease of any organ system, but most commonly the lungs
What is the difference between TB disease and TB infection?
Infection = Latent TB (LTBI) occurs after exposure to TB and it is controlled by the immune system. The patient is asymptomatic. Within 2-8 weeks of infection, immune system produces barrier shell around bacilli
Disease = Active Disease/Active TB happens when the immune system is no longer able to keep the bacteria under control. Risk of progression to TB disease is highest first 2 years after infection
5-10% of individuals with LTBI will progress to active TB at some point in their lives (may be soon or many years after infection) (higher chance in pts with DM, immunocompromising meds, etc.)
90-95% never progress
How is TB transmitted?
Spread from person to person through air via droplets that contain VERY small particles
The droplets can remain suspended in air for several hours
Expelled when an infectious person coughs, speaks, sings, etc. and it is transmitted when another person inhales the droplet
What increases the probability that TB will be transmitted?
- Infectiousness of the TB patient (is it pulmonary? Acid fast bacilli in sputum? etc.)
- Environment (more in poorly ventilated/enclosed areas)
- Frequency and duration of exposure (prolonged exposure to TB pt?)
- Immune status of exposed individual
What are the types of drug resistance in TB?
Mono-Resistant: resistant to a single first-line drug
Poly-Resistant: resistant to more than 1 drug but not to
Rifampin and Isoniazid
MDR-TB: Resistance to at least Rifampin and Isoniazid
XDR-TB (Extensive): MDR + resistant to fluoroquinolones and at least 1 of 3 injectable drugs
TDR (Total): resistant to all first and second-line TB drugs
What are characteristics of Latent TB Infection? (Pulmonary)
No symptoms
Patient doesn’t feel sick
CANNOT spread TB bacteria to others
Usually has a skin/blood test indicating TB infection
Has normal CXR and negative sputum smear
Needs treatment for latent TB infection to prevent TB disease
What are characteristics of Active TB Disease? (Pulmonary)
Symptoms may include: Bad cough that lasts 3+ weeks Pain in chest Coughing up blood/sputum Weakness/fatigue Weight loss or no appetite Chills/fever Sweating at night
Pt feels sick
May spread TB bacteria to others
Usually a skin/blood test indicates TB infection
May have an abnormal CXR or positive sputum smear/culture
Needs treatment to treat TB disease
What are conditions that increase the probability of progressing to active TB disease?
Immunosuppressive therapy Infection with HIV (7-10% greater risk PER YEAR) Smokers or those abusing drugs/alcohol Children DM (3x greater risk) Contacts (family members) Cancer Low body weight Silicosis High risk settings (congregate) Health care workers Gastric bypass
What are the different body sites that TB can affect?
Brain Eyes Larynx Lymph nodes Pleura Bones and joints, bone marrow (e.g., Pott's disease) Kidney Lung Pericardium Spine Adrenal glands GI/GU systems Skin (lupus vulgaris)
What are examples of extrapulmonary TB?
- Larynx = probably MOST infectious TB; others on this list, not so much
- Lymph nodes
- Pleura
- Brain
- Kidneys
- Bones and joints
Who develops extrapulmonary TB?
More likely in:
- HIV-infected or other immunosuppressed patients
- Young children
What’s the deal with disseminated TB?
It is RARE and is when TB is carried to all parts of the body through the bloodstream
What impact does race/ethnicity have on TB?
85% of cases in racial/ethnic minorities!! Over 2/3 in foreign-born people. In US, 60-70% of cases are foreign born.
Highest risk in Native Hawaiians or other Pacific Islanders with case rate of 16.9%
Asians have next highest risk, and a case rate of 17.8%
Blacks have 5.1% case rate
American Indians have 5% case rate
Hispanics/Latinos have 5% case rate
Multiple race have 2.8% case rate
Non-Hispanic Whites have 0.6% case rate
Who should undergo targeted testing for TB?
- Contacts of people with known/suspected TB disease
- People who have come to the US within the past 5 years from highly endemic areas
- People who visit areas with high prevalence of TB
- People who live or work in high-risk congregate settings
- People with chronic medical conditions (e.g., immunosuppression)
How is LTBI diagnosed?
Mantoux tuberculin skin test (TST):
- made from proteins derived from (5 units) inactive tubercle bacilli, recognized by immune system
- most pts who have infection will have a reaction at injection site
Interferon-Gamma Release Assay (IGRA) Blood tests:
- Quantiferon-TB Gold In-Tube: tube must be run within 8-24 hours otherwise hard to interpret
- T-SPOT
In active TB, these tests can be negative 2/2 immunosuppression (or maybe you have HIV); so diagnosis is more based on clinical picture
How do you read the Mantoux Tuberculin Skin Test?
Read the forearm within 48-72 hours
Reaction = area of induration around the injection site that is measured in millimeters (NOT indicated by erythema)
Positive:
Induration >5 mm = close contact w/ TB pt; suspected of having TB; immunosuppressed
Induration >10 mm = kids; concomitant medical conditions that predispose; healthcare workers (increased risk of exposure)
Induration >15 mm = anyone
What might lead to a false-positive TST?
- Infection with nontuberculous mycobacteria
- BCG vaccination as a kid (but this wanes over time, so if you’re an adult and you test positive, it probably is positive)
- Incorrect measuring or interpretation of TST reaction
What might lead to a false-negative TST?
- Anergy (lack of reaction by body’s defense)
- Recent TB infection (w/in past 8-10 weeks)…because it can take up to 8 weeks for body’s immune system to recover
- Very young age (<6 mos)
- Recent live-virus vaccination (e.g., measles)
- Incorrect measuring or interpretation of TST reaction
How to interpret a positive IGRA result?
M. tuberculosis infection is likely
How to interpret an indeterminate IGRA result?
The test didn’t provide useful info
Repeat an IGRA or TST
How to interpret a negative IGRA result?
Infection is unlikely, but cannot be excluded, especially if:
- Patient has s/sx of TB
- Patient has high risk for developing TB disease once infected with M. tuberculosis
How to interpret a borderline T-Spot result?
No useful info
Repeat IGRA or TST
How do you decide between IGRA or TST?
IGRAs for: pts who may not return for the TST reading or for pts who received the BCG vaccine
TST for children <5 yrs
Routine testing with TST and IGRA NOT recommended
What are the advantages of IGRA?
- Single patient visit (doesn’t have to come back for reading)
- Results can be available within 24 hrs
- Does not cause booster phenomenon (possible with repeat TSTs)
- BCG vaccination does not affect the results
What are the limitations of IGRA?
- Samples must be processed within 8-30 hours
- Limited data for children <5, people recently infected, or immunocompromised
- Tests are expensive
What is the booster phenomenon with TST?
As years pass, a person’s ability to react to tuberculin lessens
The booster phenomenon occurs mostly in previously infected, older adults
When they are skin tested years after infection, they have a negative reaction (2/2 lessened ability to react to tuberculin), but that “jogs the memory” of the immune system
When they are skin tested again (up to 1 year later), they will have a positive reaction due to the TB infection that occurred a long time ago
What is the two-step TST test?
Used in pts who will be re-tested periodically
If the TST is negative, re-test 1-3 weeks later
If the second test is negative, the person probably does NOT have TB infection and this should be repeated at regular intervals (a positive reaction will probably be due to a recent TB infection)
If the second test is positive, the reaction is considered a boosted reaction (due to TB infection that occurred a long time ago) and re-testing is not necessary
What are the components of a medical evaluation of a patient with suspected TB?
- Medical history
- Physical exam
- Test for TB infection
- CXR
- Bacteriological examination
What are components of the medical history for patient with suspected TB?
Symptoms of TB disease (present for weeks/months?)
- Fever, chills, night sweats
- Weight loss, appetite loss
- Fatigue, malaise, cough (3 or more weeks, +blood)
Exposure to person with infectious TB or have risks for exposure?
Risk factors for developing TB?
Had LTBI or TB disease before? When? Treatment?
Note: anyone who has received a quinolone recently will be misleading because that will suppress sx and delays recognition of TB disease (also pre-disposes to MDR-TB)
What does PPD stand for?
Purified Protein Derivative
What might you see on a CXR?
- Pleural effusions
- Scarring
- Hilar adenopathy
Can a CXR confirm TB?
NO IT CANNOT
Only a bacteriologic culture can
CXR may appear normal
What is involved in a bacteriologic examination?
1) Specimen collection (sputum, urine)
2) Examination of acid-fast bacilli (AFB) smears
3) Direct identification of specimen (NAAT)
4) Culturing and identification
5) Drug susceptibility
Pulmonary: sputum (cough), inducing sputum, bronchoscopy, gastric washing
How is sputum specimen collected?
- Cough into sterile container (may require saline mist to elicit deep cough, but not ideal because waters down sample)
- At least 3 samples are required at 8 to 24 hour intervals and at least one early morning specimen (when highest bacillary load)
- May require gastric washing
If extrapulmonary TB: collect specimen from body site (lower test sensitivity for extrapulmonary)
How do you examine AFB smears?
- AFB are mycobacteria that remained after acid solution
- Less sensitive outside of pulmonary sputum
- Classified by number of AFB on smear: 4+, 3+, 2+, 1+
- Negative DOES NOT rule out TB
What’s the deal with Nucleic Acid Amplification Tests (NAAT)?
These tests amplify DNA and RNA segments and can help guide decisions about therapy and isolation
If NAAT and AFB are positive, pt is presumed to have TB
If NAAT is negative, AFB is positive, pt is presumed to have non-tuberculous mycobacteria infection
What’s the deal with Xpert MTB/RIF Assay?
- NAAT that detects Mycobacterium tuberculosis and resistance to Rifampin
- Available within 2 hours
- If rifampin resistance, drug resistance is performed
What is the importance of culturing?
Confirms diagnosis!
- All specimens should be cultured
- Detects growth: solid in 3-6 weeks and liquid in 4-14 days (if the culture starts to grow immediately, TB is not likely)
- NAA probes: 2-4 hours
A negative culture does NOT rule out TB
What culturing should be performed during/after TB treatment?
Drug susceptibility testing: performed on initial cultures and may be repeated if patient is not getting better or if they have a positive culture after 3 months of treatment
Specimens should be cultured monthly until 2 consecutive cultures are negative
Culture conversion is an objective measure of response to treatment
What is the medical evaluation of a patient with LTBI?
- Excluded possibility of TB disease
- Assess for comorbidities
- Assess for HIV
- Assess for alcohol use
- Pregnancy?
- Review med interactions
- Construct f/u plan
Treatment of LTBI with Isoniazid (INH)
Isoniazid (INH) 300 mg QD for 9 months,
(may also give for 6 months, but not as effective if <6 mos and always give for 9 mos in children and HIV+)
(Plus pyridoxine 50 mg daily?)
Treatment of LTBI with INH and Rifapentine (RPT)
Combo of INH 900 mg + RPT 900 mg once a week for 12 weeks under DOT (directly observed therapy) (3 months)
Okay as a treatment option for: >12 years old Recently exposed to infectious TB TST/IGRA conversion CXR of previous TB disease Otherwise healthy HIV+ with no ART interactions
NOT okay as tx for: Children <2 yrs Certain ART regimens Drug resistance (to INH or RIF) Pregnant or expecting to be
Treatment of LTBI with Rifampin (RIF)
Rifampin 600 mg daily for 4 months
Important to consider drug interactions
What are special circumstances in which you may consider treatment of LTBI?
Contacts = people exposed to infectious TB
Negative test result, but one of the following:
-Less than 8-10 weeks since exposure
-Children <5 yrs
-HIV+
-Immunosuppression
To prevent life-threatening forms of TB
What are alternative treatment regimens for LTBI?
When treating MDR-TB, regimens may be 6-12 months
How do you treat LTBI in pregnancy?
May delay until after delivery
Vitamin B6 and INH not shown to harm fetus
For breastfeeding, can take INH and B6
What are adverse reactions to INH treatment?
Hepatitis (N/V, abd pain) and in about 10-20% there will be mild, abnormal LFTs during tx, but will return to normal (usually)
Risk factors: older age, alcoholism
Peripheral neuropathy (B6 helps prevent this)
More likely SE if Rifampin is combined with INH
STOP tx if signs of liver failure (N/V, fever, jaundice, abd pain, brown urine)
What are adverse reactions to Rifampin treatment?
- Rash
- Orange discoloration of urine, saliva, and tears (normal)
- Hypersensitivity
What are adverse reactions/SE to RPT treatment?
Flu-like sx
What are the patient monitoring recommendations?
- Monthly evaluations
- Ask about nausea, abd pain, rash
- LFTs, considered abnormal if:
- 3x higher than upper limit with sx
- 5x higher than upper limit without sx
- Document results, treatment, duration
What are the phases of TB disease?
Intensive = first 8 weeks of tx with 4 drugs, most bacilli are killed during this phase
Continuation = after the first 8 weeks, bacilli that remain are treated with at least 2 drugs
Relapse = occurs if tx is not continued for long enough, surviving bacilli may cause TB disease at a later time
What is the treatment for active TB disease?
Intensive phase: isoniazid, rifampin, pyrazinamide (PZA), ethambutol (EMB)
Never use a single agent or change a single agent
Other agents sometimes used: quinolones, aminoglycosides, linezolid, cycloserine, ethionamide, bedaquiline
Should be treated by the Department of Health in most cases and all cases reported to PDPH
What is the duration of treatment for TB disease?
Pulmonary: 6 months
TB of meninges or CNS: 9-12 months
TB of bone and joint: 6-9 months
Extend treatment for patients who are slow to respond
What is the monitoring plan for active TB treatment?
- Collaboration with local health department
- Description of treatment regimen
- Monitor with DOT: adherence, adverse reactions, treatment response
- Blood and vision tests
