TB - clin med Flashcards
Where does TB occur
- primarily in teh lungs
- also in other organ systems: lymphatics, bones, meninges, intestines, uterus/ovaries, etc.
TB Sx
- productive, prolonged cough >3 weeks
- chest pain
- hemoptysis
- low grade fever
- night sweats
- weight loss
- excessive fatigue
what causes lung damage in TB
The body’s immune response to the bacteria, “spilling enzymes that eat teh lung tissue”, not the bacteria itself
Mycobacteria
- how many species
- how often pathogenic
- how stain in lab
- cell wall & significance
- how common in environment
- 150 species
- most non-pathogenic
- acid-fast stain
- waxy cell wall means resistant to dehydration, harder to kill
- very common in environment and normal flora
what is most common org to cause TB
mycobacterium tuberculosis
M. tuberculosis
- what O2 conditions
- fast/slow growing
- cell wall
- how big
- obligate aerobe, requires high O2
- very slow growing, 20 hour generation time
- durable cell was, major factor in virulence
- 2-4 microns in length
How many M. tuberculosis orgs required to show up as smear positive
10,000 orgs/ mL
What is the M. tuberculosis complex?
the types of mycobacteria that can cause TB. In OK only two ever seen:
- M. tuberculosis (95%)
- M. bovis (5%)
What is a very common sputum test for TB
AFB - acid fast bacillus
When AFB is positive, what are the two main types of bacterial causes
- M. tuberculosis complex bacteria
2. non-tuberculous mycobacteria
evolutionary hx of M. tuberculosis and M. bovis
ancient orgs that probably first appeared in the soil millions of years ago, gradually adapted to animal hosts
Who was the first scientist to ID TB
Robert Koch
- 4 postulates demonstrating TB to be an infectious disease to Berlin Physiological Society in 1882
- nobel prize for his work
- proved contagious, not inherited
What is the basic infectious particle of TB
droplet nuclei
- aerosolized, dry rapidly and float
- can float into alveoli
How does a person get TB
- adequate exposure to viable orgs
- prolonged contact in poorly ventilated space
- not easy to acquire
- cannot be transmitted outdoors
Once infected, what percentage of people progress to TB disease
10% over a lifetime
Once “get” TB, what happens with the bacteria
- multiplication of bacilli in alveolar macrophages
- some spread to bloodstream
What does the immune system do to bacilli when first contract the disease
usually prevents the disease by surrounding the bacilli with cells and creating granulomas resulting in latent TB infection (LTBI)
TB infection vs. disease
- what in common
- mycobacteria causing TB present
- positive skin test
TB infection vs. disease
- differences
- Infection has normal CXR, lesions in disease
- Sputum smear/culture negative in infection, positive in disease
- no symptoms and not infectious in infection, yes to both in disease
- not defined as a case of TB in infection, is defined as case of TB in disease
Range of response to TB infection/disease
- rapid killing of bacilli by alveolar macrophages = no infection
- rapid progression of initial infection to death (usually <1 yo or immunocompromised)
- and everything in between
- can proceed with stops and starts
What affects the probability that someone who is exposed to TB will get TB
- concentration of infectious droplet nuclei in the air
- duration of exposure to a person with infectious TB disease
How to tell M. tuberculosis from M. bovis
- cannot clinically, radiographically, or pathologically
- can differentiate via biochemical methods
what is one major problem with M. bovis TB
universally resistant to one of the first line drugs (didn’t specific which one…)
Transmission of M. bovis TB
- contact through cuts, abrasions, etc.
- airborne (human to human, human to cattle, cattle to human)
- foodborne - onsumption of unpasteurized dairy products
Who is at high risk for exposure to/infection with TB
- close contact with someone known or suspected to have TB
- foreign-born person from area where TB is common
- residents/employees of high-risk congregate settings (jail, prison, homeless shelter, etc.)
- health care workers who serve high-risk clients
- medically underserved, low-income
- high-risk racial or ethnic minority populations
- children exposed to adults in high-risk categories
- use illicit drugs
Two CDC classifications of TB applicable to PAs
- Class 2 - infection
2. Class 3 - active TB
Treatment of latent TB
- Isoniazid for 9 or 6 months
- Rifampin with or without Isoniazid for 4 months
- Isoniazid and rifapentine for 3 months (1 X week)
Treatment of inactive TB
- Isoniazid for 9 months
- Rifampin with or without Isoniazid for 4 months
- Rifampin and Pyrazinamide for 2 months
What situations is TB disease more likely to develop
- infected contact of active case
- documented TB skin test converters
- have medical risk factors for disease reactivation
HIV/TB co-infection
- Risk is up to 37% in first year co-infected (vs. 10% with normal immune system)
- risk of developing T disease 7 to 10% each year
TB skin testing
- old test that is often used incorrectly
- report in millimeters of induration, disregard erythema
- negative PPD does NOT rule out TB (15-20% active TB has negative PPD)
- Anergy, a false negative reaction, can occur
Two blood TB tests
- QuantiFERON-TB gold
2. T-spot.TB or ELISPOT
Tx of TB prior to drugs
- bed rest
- sanitarium
- collapse therapy/thoracoplasty
First line TB drugs
- isoniazid
- rifampin
- Rifapentine
- Rifabutin
- Ethambutal
- Pyrazinamide
Second line TB drugs
LOTS
- other abx
- linezolid was singled out in class
*in general less effective, more side effects
What is history of using multiple drug therapy to treat TB
- 1940s tried using streptomycin alone but 40% developed resistance within 60 days
- tried two drug therapy = fewer drug resistant bacteria
- decided standard of therapy is multidrug
List the four drugs used in active TB tx
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
When would extend treatment of active TB to 9 months (HIV negative person)
- cavitation initially
- positive culture after 2 months of therapy
what is MDR-TB
multidrug resistant TB
- INH and Rifampin
what is Pre-XDR TB
pre-extensively drug resistant TB
- INH, rifampin resistance plus resistant to flouroquinolone OR injectable
what is XDR-TB
Extensively drug resistant TB
- INH, rifampin, fluoroquinolone and at least one injectable resistance
what is TDR-TB
Total drug resistant TB
How long treat susceptible TB
6-9 months with 4 drugs for first 2 months
How long treat MDR TB
- first 8 months with 5 drugs (on injectable)
- 20 months with 4 drugs
- if prior treatment for MDR then 24+ months on 4 drugs
How long treat Pre-XDR and XDR TB
24-36 months
Who must go through mandatory TB screening?
immigrants and refugees
- majority of air passengers are not these…
- people with TB most often IDed after air travel
how many cases have occurred due to exposure to someone on an airplane
None - evidence of transmission in one case but no disease
How long must you be in contact with someone with TB to acquire infection?
> 8 hours exposure in close contact situations
What is the vaccine many non-US people get for TB
Bacille Calmette-Guerin
(BCG) Vaccine
What does BCG vaccine protect against? What does it not protect from
- preventing severe TB in children
- does not prevent TB later in life
What might cause a false-positive skin test reaction?
- non tuberculosis mycobacteria (usually =< 10 mm induration)
- BCG vaccination possible but not guaranteed (20%). Disregard BCG vaccination when applying and reading skin tests
- Reader error - don’t read erythema, just induration
What test will be NOT be positive for TB due to BCG vaccine
Blood tests (IGRA or interferon gamma release assay)
What is TB-PCR
- Detects presence of MTB DNA directly from respiratory specimens
- Not approved from non-respiratory specimens
- high positive and negative predictive values with AFB smear positive
- cheaper, not labor intensive
- automatically performed on undiagnosed 1st time AFB positive clinical smears
What is a surrogate marker for MDR-TB
Rifampin
90% will also be INH resistant
What does molecular detection of drug resistant MDDR look for
- to confirm rifampin resistance and not just a silent mutation in the DNA sequence
- Looks for mutations in DNA for INH, ethambutol, PZA, fluroquinolones, etc.
Is TB a disease we should be concerned about?
- Yes! but not funded well by local and federal governments
- deadliest dz in human history
- kills more people in three days than died during entire ebola epidemic
What is a very unusual way to test for TB that has been recently developed
African giant pouch rats
- 100 sputum in 20 minutes with near 100% accuracy
(just think of the pictures Kathleen haha)
Legal TB Control
- what is required by law for TB cases
- compliance/isolation order
- Directly observed therapy (DOT)
- Noncompliance can result in court-ordered DOT
- noncompliance with DOT can lead to jail or confinement of pt until therapy is complete
What are contraindications to PPD test
- previous ulcer necrotic reaction
- true anaphylactic reaction to PPD in past
What reaction can look like a positive PPD but is not
Arthus reaction - rapid type III rxn, redness and edema for 12-24 hours after injection. NOT a positive test
What is a secondary location to place PPD for those with atrophic skin or who might scratch teh site
between shoulder blades
What is two-step testing and why is it necessary
- some people with latent TB might have a negative skin test years after infection due to waning response
- The first test might stimulate the ability to react (boost)
- a positive reaction with subsequent testing can be interpreted as a new infection rather than true old latent infection
What is the name for two-step testing
boosting or anamnesis
anamnesis -forgetting to forget
What is a main concern about dx TB today
- failure to consider TB in the differential
- lack of consistent and simple plan to address TB
- “ER” mentality
- lack of provider awareness of the necessity for early and extensive involvement of the health department
TB misconceptions
- TB doesn’t occur in young, healthy Americans
- Believing patients are adherent with meds
- sputum for gram stain and culture helps diagnose/exclude TB
- Health Dept doesn’t need to be involved
- TB best txed by pulmonologist
what is TB often confused with in the ER
Pneumonia - right upper lobe infiltrate…
- always include TB in ddx of upper-lobe pulmonary infiltrate of unknown etiology
What is important in early TB evaluation
- collect sputum early!
- consider TB-PCR test on sputum
- call the health department (they will go to the patient!)
