Tuberculosis

Pathophysiology (General)

1. m. tuberculosis in droplet nuclei airborne spread from sick contact

2. host inhales bacteria→bronchial tree→alveoli
   -unexposed
   -immunocompetent

3. macrophages swallow bacteria→can’t kill off due to lipids in cell wall

4. m. tuberculosis continues to multiply+phagocytize by macrophages

5. infected macrophages degrade mycobacteria→present antigens to t-lymphocytes→cell-mediated immune response→macrophages increase lytic enzyme concentrations+eliminate mycobacteria

6. macrophages+lymphocytes release interferon→stimulates macrophage production

7. 
   

eliminated
or
x 3-6 weeks→ghon focus:
granulomatous lesion
prevents active TB
-tubercle bacilli
-macrophages
-immune cells

8. hypersensitivity rxn→tissue necrosis

9. central portion of ghon focus→soft/caseous (cheese-like) necrosis

10. tubercle bacilli drain to tracheobronchial lymph nodes

11. form caseous granulomas→ghon focus+lymphadenopathy (ghon’s complex)

12. resolves x weeks-months→fibrous scarring+calcifications (ranke’s complex)

13. calcifications→become dormant lesions

Etiology (General)

mycobacterium tuberculosis
-rod shaped
-aerobic (oxygen-rich areas→lungs)
-don’t form spores
-waxy outer capsule→resistant

dormant→old/necrotic/calcified lesions→reinitiates growth

acid fast bacilli
-acid fast stain→red dye

Primary Tuberculosis

PP: inhaled bacilli escape macrophage phagocytosis+microbacterial activity→infxn

RF: unexposed+unsensitized pts

CM: asx
found on CXR

DX:
CXR
-lesions (ghon’s complex)
-air space consolidation
-cavitation (10%)
-adenopathy (peds/HIV)
-miliary pattern
-pleural effusions

bronchial washing culture
NAAT-TB

Latent Tuberculosis

PP: granulomas form around inhaled bacilli→wall off infxn→contained/dormant (not eradicated)
can’t transmit infxn

CM: asx

DX: bronchial washing culture
NAAT-TB

Reactivated Tuberculosis

PP: reactivation of previously healed granuloma→bacilli escape granuloma

RF: immunocompromised
years-decades post-infxn
DM
HIV
steroids
chemo

CM: low-grade fever
weight loss
night sweats
productive cough→blood-tinged sputum
anorexia
dyspnea
orthopnea
angina
chronically ill-appearing/malnourished
crackles

DX:
CXR→TB lesions: ghon’s focus
bronchial washing culture
NAAT-TB

Risk Factors (General)

recent TB infxn

immunocompromised

3rd-world countries

jail

mx tx facilities

homeless shelters

HIV-19

malnutrition

alcohol

mx

tobacco

DM

organ transplant hx

severe kidney dx

chronic steroid/immunosuppressive agent use

Bacterial Culture

gold standard→required for definitive dx

3 consecutive morning sputum specimens/aspirations→bronchial washings

6-8 weeks

Nucleic Acid Amplification Testing (NAAT-TB)

detects+identifies resistance markers (NAAT-R)

negative predictive value: smear-negative pts→low

not confirmation→culture needed

48 hrs

Tuberculin Skin Test (TST) (AKA PPD/Mantoux+CXR)

m/c for initial dx

measures delayed hypersensitivity to T Bacillus

not specific (active vs latent infection)

TST→positive→CXR
-positive→t bacillus hypersensitivity rxn
-doesn’t mean that pt has active TB

previously positive/BCG vaccine/contraindication→quantiferon-TB gold/T-SPOT

false positives+negative skin rxns can occur
-HIV coinfection
-m bovis BCG vaccination

process

1. 0.1mL PPD injected intradermally

2. 48-72 hrs post injection→examination

3. local reaction
   -redness/induration
   -no rxn

4. measure size of induration (not redness)

5. no RFs: over 15mm+→positive result

once positive→positive for life (no retest needed)

2-Step PPD

for false negative reaction with latent TB
-2nd PPD in a year→boosted immune system→more likely to trigger positive reaction

process

1. visit 1→PPD 1 given

2. visit 2→48-72 hrs→PPD 1 read

3. visit 3→PPD 2 given x 1-3 weeks post first test

4. visit 4→48-72 hrs→PPD 2 read

positive interpretations

• 5+ mm and
  -HIV infxn
  -recent TB contact
  -CXR findings
  -organ transplant
  -immunocompromised

• 10+ mm induration and
  -high-prevalence country within 5 years
  -injection mx/needle sharing
  -prison/long term care shelter/etc.
  -mycobacterium
  -u4 y/o
  -recent TB contact

• 15+ mm and
  -no TB RFs

Interferon-Gamma Release Assay/QuantiFERON-TB Gold/T-SPOT

additional blood test

detects latent+active TB

24 hr duration

measures interferon-gamma in response to m tuberculosis antigens
-doesn’t detect m bovis BCG→doesn’t work with BCG vaccine pts
-can’t distinguish latent/active dx

more effective to detect latent TB infection (higher specificity+positive predictive value)

CXR (General)

normal findings→doesn’t exclude TB

abnormal findings→don’t distinguish primary disease from reactivation of latent TB

findings

• m/c→upper lobe/cavitary dx

• elderly→lower lobe infiltrates

• hematologic/lymphatic spread→miliary pattern

• HIV/immunocompromised→
  -lower lung zones
  -diffuse/miliary infiltrates+hilar/mediastinal lymph node involvement
  -pleural effusions

Risk Factors (Countries+Races)

one of the world’s most deadly+prevalent dxs

leading cause of death due to a single infectious agent in the world

WHO→9 million cases annually worldwide

2026→2 billion infxd

Countries (m/c to l/c)→foreign-born people more likely to get dx

1. india

2. indonesia

3. china

4. phillippines

5. pakistan

6. nigeria

7. DRC

8. bangladesh

US→one of the lowest TB rates in the world

races (m/c to l/c)

1. hispanic/latino

2. asian

3. black

4. white

5. other

CXR: Typical vs Atypical Pattern Distribution

typical pattern→active TB

• apical/posterior segments of upper lobes

• superior segments of lower lobes

• isolated anterior segment involved that’s unusual for mycoplasma TB
  -ex: m avium complex

atypical pattern→primary TB

• any lobe involved
  -slight lower lobe predominance

• air-space consolidation

• cavitation→rare (u10%)

• adenopathy→common
  -right side
  -peds
  -HIV

• miliary pattern

• pleural effusions

Active TB Patterns of Dx

air-space consolidation

cavitation

cavitary nodule

endobronchial spread

miliary

bronchostenosis

tuberculoma

pleural effusions
-m/c→empyema (in active dx)

Miliary TB

PP: TB infxn goes into bloodstream→TB erodes through a blood vessel→spreads to other parts of body→millet seeds
-can involve almost any organ

CXR→millet seeds

Extrapulmonary TB

PP/E: hematogenous dissemination→TB in organ systems other than lungs
m/c→lymphatic system
-can involve any organ
-immunocompromised pts

CM: immunocompromised→disseminated infxn+CNS sxs

DX: requires high index of suspicion
sputum culture+NAAT testing

Pulmonary TB Tx

previously unknown pulmonary TB

RIPE daily x 2 months→RI x 4 months

• Rifampin (RIF)

• Isoniazid (INH)

• Pyrazinamide (PZA)

• Ethambutol (EMB)

isoniazid sensitive→remove ethambutol

tx should extend at least x 3 months beyond negative sputum cultures

total tx duration→x 6-9 months
-preferred→x 6 months

DOT used→give mx intermittently

mx-susceptible pulmonary TB

RIMP x 2 months→RIM x 2 months

• Rifampin (RIF)

• Isoniazid (INH)

• Moxifloxacin (MOX)

• pyrazinamide (PZA)

Latent TB Tx

I: over 18 y/o+latent TB infxn

HIV

• isoniazid+rifapentine

• significant CIs→isoniazid

liver dx

• rifampin

• isoniazid→hepatitoxicity

no dx+pregnant

• defer tx to x 3 months postpartum

• exception→high-risk for dx progression

• no isoniazid/rifapentine

no dx+not pregnant (normal pt)

• rifampin daily x 4 months

• isoniazid+rifapentine weekly x 3 months

• isoniazid daily x 6/9 months

Mx-Resistant TB Tx

careful supervision+tx

isoniazid-resistant→RELP

• rifampin

• ethambutol

• levofloxacin

• pyrazinamide

rifampin/multi-mx-resistant TB→BPaLM regimen x 6 months

• bedaquiline

• pretomanid

• linezolid

• moxifloxacin

non-isoniazid-resistant TB+tx-resistance

• expert consultation

• requires individualized daily DOT plan

HIV Pts TB Tx

RIPE

• rifampin

• isoniazid

• pyrazinamide

• ethambutol

rifampentine+moxifloxacin

additional considerations

• longer tx duration

• CIs with HIV mxs:
  -protease inhibitors (PI)
  -non-nucleoside reverse transcriptase inhibitors (NNRTIs)

HIV-positive pts+on INH→pyroxidine daily→reduces CNS+PNS mx AEs

Extrapulmonary TB Tx

previously unknown

RIPE daily x 2 months→RI x 4 months

• Rifampin (RIF)

• Isoniazid (INH)

• Pyrazinamide (PZA)

• Ethambutol (EMB)

isoniazid sensitive→remove ethambutol

tx should extend at least x 3 months beyond negative sputum cultures

total tx duration→x 6-9 months
-preferred→x 6 months

DOT used→give mx intermittently

mx-susceptible

RIMP x 2 months→RIM x 2 months

• Rifampin (RIF)

• Isoniazid (INH)

• Moxifloxacin (MOX)

• pyrazinamide (PZA)

miliary/meningeal/bone+joint dx presence→duration: x 9-12 months

pericarditis+neurologic sxs prophx→corticosteroids

Pregnant/Lactating TB Tx

RIE x 2 months→RI x 7 months

• rifampin (RIF)

• isoniazid (INH)

• ethambutol (EMB)

no pyrazinamide→teratogenic

breastfeeding→not CI

peripheral neuropathy prophx→pyroxidine

Tx Dx

routine monitoring during tx→not recommended
-exception→abnormal baseline results

sputum smears+cultures monthly until negative results

tx completion→do CXR→baseline for any future films

CBC

• platelets

CMP (do before tx)

• serum bilirubin

• hepatic enzymes

• renal fxn

before ethambutol

• visual acuity

• red-green color vision

before pyrazinamide

• uric acid levels

Tx Reporting

all suspected+confirmed cases→report to local+state public health authorities

• public health departments do contact tracing→limit spread of potential infectious TB within community

• ensure a plan for monitoring adherence to tx

Tx Compliance

can be improved by

• providing detailed pt education

• providing case manager to each pt
  -oversees all aspects of pt’s care

CDC recommendation (for increasing tx compliance)

• mx-resistant TB/intermittent TB tx→directly obseved therapy (DOT)

• healthcare worker needs to physically obsever pt take mx for dx at home/clinic/hospital

Hospitalization Requirements

usually not necessary

active TB→required to be in a negative pressure room until negative sputum culture
-must be negative on 3 consecutive smears taken on separate days

considerations

• pts not capable of self-care

• pts likely to expose others

Prognosis

almost all properly txd+immunocompetent pts can be cured

relapse rates→less than 5%

m/c of tx fail→mx noncompliance

Screening Prevention (General)

pulmonary/laryngeal TB sick contacts

foreign-born pts

exceptions:
-australia
-canada

marginally housed/homeless

prolonged (1+ month)/frequent travel (2+ times/yr) to TB-endemic countries

employees

• hospitals

• dialysis units

• correctional facilities

• homeless shelters

• nursing homes

• single-room occupancy hotels

• substance abuse tx centers

CDC: annual screening→occupation risk/ongoning exposure

Pts With RFs Screening Prevention

pts with RFs

• HIV

• DM (prioritize: foreign-born+homeless)

• prolonged corticosteroid/immunosuppressive mx tx
  -TNF-antagonists
  -post-transplant immunosuppressive mxs
  -chemotherapy
  -etc.

• radiographic evidence of previous TB

• current+former tobacco smokers (prioritize: foreign born+homeless)

• head+neck cancer

• hematologic malignancy
  -leukemia
  -hodgkin’s lymphoma

• end-stage renal dx

• organ transplant candidates/recipients

• intestinal bypass/gastrectomy

• chronic malabsorption syndromes

• low body wt
  -10% or under→ideal

• silicosis

BCG Vaccine

bacille calmette-guerin

developed from an attenuated strain of m bovis

duration of protection→not clearly known

I: prophx in high-prevalence TB countries
-childhood TB
-meningitis
-miliary dx

not recommended in US→lower risk of infxn

interferes with TST reactivity→false positive test→use QuantiFERON/T-SPOT instead

CDC
TST rxns in BCG-vaccinated pts→interpreted as same for non-BCG-vaccinated pts
-referral to ID