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Latent TB
classic model, Dx, Tx
- "classic" model:
 - -90% remain well
- -10% reactivate (aka Post-Primary TB)
- Dx: delayed type hypersensitivity reaction
- 1. TST (TB Skin Test) - many false positives
- 2. Interferon Gamma Release Assay - eliminates false positives (99.7% negative predictive value)
- -positive for M tuberculosis, M africanum, M bovis, M kansasii, M marinum, and M szulgai
- -aka QFT, T spot (backup), QFT GIT (automated)
- -works by determining IFN-γ levels
- Tx: of latent TB infection (LTBI)
- -Not everyone who has LTBI requires treatment: look at other factors such as epidemiological factors (healthcare workers, alcoholics,...)
- -reactivation can be prevented (~60% reduced) when treated with INH (isoniazid)
- Tx options:
- -INH 300mg/day for 6-9 mos
- -Rifampin 600mg/day for 4 mos
- -INH 900mg +Rifapentine 900mg Qweek x 12 weeks (must be given under direct observation)
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Latent TB
current model
- LTBI isn't really 'latent' - waxes and wanes
-
- Distinguishing factors:
- 1. Host (innate/acquired immune response
- -Vulnerability to infection
- -Infection/disease status
- 2. Microbe
- -Strain
- -Metabolic activity
- 3. Environment
- -likelihood of exposure/re-exposure
- -other mycobacteria
- -other infections
- Tx: not everyone requires treatment
- -look to epidemiology, recent infections, co-morbidities to determine who should get LTBI treatment
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Active Tuberculosis
Epidemiology and clinical suspicio
- Epidemiology:
- -US-born rates are declining
- -Foreign-born rates have stayed flat
- -In San Diego: Mexico, Viet Nam, Philippines make up >80% of cases
- -In US: Mexico, philippines, Viet Nam make up >40% of cases
- M bovis:
- -5-10% of TB in San Diego County
- -transmission through unpasturized dairy
-
TB
Clinical suspicion
- Clinical suspicion of TB
- 1. Risk factor analysis
- -Demographics: country of birth
- -Social history: homeless, prison, alcoholic
- -TB history: exposures, history of BCG, LTBI
- 2. Clinical presentation
- -Cough > three weeks
- -minimal symptoms with highly abnl CXR (out of proportion to sx)
- -other sx tend to be minimal: fever, chills, night sweats, anorexia, weight loss, hemoptysis, chest pain, dyspnea
- -PE: rales, wheezes, adenopathy, splenomegaly, pleural changes
- 3. Comorbidity
- -Conditions: HIV (with low CD4 count), DM, Malignancy, chronic renal failure, immunosuppressive disease
- -Immunosuppressive medications: steroids, Anti-TNF preparations, etc.
- 4. Radiology
- (next slide)
- 5. Microbiology
- (next slide)
- -recommendation is to collect multiple sputum on the first day (Q8hrs), and one on each of the following two days
- Clinical suspicion:
- -Low suspicion --> 4% probability
- -Intermediate-->28% probability
- -High--> 85% probability
-
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TB microbiology
- Microscopy:
- -6,000-10,000 organisms per ml to see 3 AFB on slide
- -Repeat 3 times
- -Sensitivity: 55%
- -Specificity: 5-50%
- Culture:
- -100 organisms per ml to get 1 colony
- -Sensitivity: 80%
- -Specificity: 1-2% false-positives
- Nucleic Acid Amplification:
- -get answer in ~1day!
- -sensitivity ~ that of culture
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TB - drug resistance
- Large problem around the world (former Soviet Union); not a big problem in the US
- -10-12% are isoniazid resistant
- -1-2% are MDR TB
- Risk factors:
- -Prior tx for TB
- -Foreign born in high incidence country
- -Close contact with pt who had drug resistant TB
- -Host factors: HIV/immunosuppressed, homeless
- Dx of drug resistant TB:
- -Clinical suspicion (bedside epidemiology)
- -Lab:
- 1. Growth based test - standard drug susceptibility testing
- -can take up to 1 week
- 2. Genetic Based - results in 1day!
- -Xpert: rtPCR that tests for Rifampin resistnace
- -Hain Test: line probe assay that tests for MDR TB, second line drugs
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TB
Standard pulmonary treatment
"4 for 2, and 2 for 4"
- Induction phase: QD 2 months, start as direct observed therapy (DOT)
- -Rifampin
- -Isoniazid
- -PZA
- -Ethambutol
- Consolidation phase: QD to BIW for 4 months
- -Isonizid
- -Rifampin or Rifapentine
- In HIV patients:
- -initiation of ART as soon as possible (earlier the better); as soon as patient is tolerating all TB meds
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Extrapulmonary TB
treatment
- -RIPE therapy for 6 months
- -9-12 months for menengitis
- -Corticosteroids added for pericarditis (Prednisone), meningitis (Dexamethisone)
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Reasons for persistently positive cultures
- Poor compliance with medications
- Extensive cavitations and extensive fibrosis
- co-morbidity (HIV, malnutrition, DM, immonocompromising diseases or meds)
- Biological variation
- -Drug resistant TB
- -Poor drug absorption
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Non Tuberculous Mycobacterium
aka NTM
aka Mycobacteria other than tuberculosis (MOTT)
aka Atypical mycobacteria
- More common NTMs: relative frequencies
- -M avium intracellular complex (MAC) 61%
- -M kansasii 10%
- -M fortuitum/cheloni/abcessus complex 19%
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(rapidly growing mycrobacterium [RGM]) - frequency of disease when NTM is isolated:
- -MAC: 45%
- -Kansasii: 75%!!
- -fortuitum/cheloni: 18%
- ...few people who are colonized get disease
- Less common:
- -M gordonae
- -M malmoense
- -M simiae
- -M szulgai
- -M smegmatis
- -M xenopi
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MAC
pathogenesis, disease spectrum, co-morbid conditions
- -Ubiquitous, especially in the southeast US
- -Pathogenesis: oral or inhaled (in water)
- spectrum of disease:
- -adenitis
- -acute pneumonia
- -chronic pulmonary changes
- Co-morbid conditions:
- -CF
- -T cell deficiencies
- -Cytokine web dysfunction
- -Anatomic disruption
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Pulmonary MAC
sx, main types
- Sx:
- -fatigue, afternoon naps
- -weight loss (with good intake)
- -fever & chills, night sweats
- -cough/sputum production
- -hemoptysis
- -chest pain
- -SOB/DOE
- Main types of pulmonary MAC
- 1. Fibro cavity: "classic infection" cause it looks like TB
- -not the most common
- -nodular areas of increased opacity; upper lobes
- -calcified pulmonary nodules with hilar nodes
- 2. Lady Windemere syndrome:
- -old ladies who suppress cough
- -lingual/middle lobe bronchiectasis
- -multiple 1-3 mm diameter centrilobular nodules
- -"tree in bud" appearance on CT
- -adeonpathy
- 3. One or more masses: usually in young women
- -+/- adenopathy
- 4. Pectus excavatum:
- -squeezes the heart, mitral valve prolapse
- 5. Hot tub lung:
- -Sx: dyspnea, cough, hypoxia, fever
- -Hot tub users; immunocompetent
- -CxR shows diffuse infiltrative lung disease, no bronchiectasis
- -Bx: exuberant nonnecrotizing, frequent bronchilocentric, granulomatous inflammation
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NTM
Treatment
- Considerations:
- -Evaluate sx, microbiology, radiographs
- -Comorbidities: past lung injury, smoking, CF, GERD
- -Determine goal of tx
- Tx:
- 1. Clarithromycin (or azithromycin)
- +
- 2. Rifabutin (or rifampin)
- +
- 3. Ethambutol
-also consider Moxifloxacin or Amikacin
- **Duration and frequency of treatments depend on extent of diseases:
- -Pts should be treated till they are culture negative for >12 months
- Surgical treatment:
- -Indications: localized disease, adequate lung function, poor response to medical therapy or resistant
- -High incidence of complications
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M. Kansasii
- Tx:
- -INH
- -Rifampin
- -Ethambutol
-must be culture negative for 12 mos
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