STEPTRACKERMICROBIOLOGY + PATHOLOGY + PHARMACOLOGY | MYCOBACTERIA | HIGH-YIELD REVIEW

Mycobacterium tuberculosis

An acid-fast, obligate aerobe that hides in macrophages — know primary vs secondary disease, how to test, and where else it goes.

FOCUS ON
Virulence: cord factor (serpentine growth, inhibits neutrophils, activates macrophages → granulomas, TNF-α), sulfatides (block phagolysosome fusion). Immunity = Th1: IL-12 → IFN-γ → macrophage activation → caseating granuloma. Primary: Ghon complex (lower/mid-lobe + hilar node) → usually latent. Secondary/reactivation: apical cavitation (high O₂). Tests: PPD/IGRA = exposure, not active disease; sputum AFB smear/culture/NAAT for active. TNF-α inhibitors → reactivation.
TOPIC
WHAT HAPPENS
FINDINGS
CLUE
Primary TB
Inhaled droplets → alveolar macrophages → Th1 response
Ghon focus (subpleural, lower upper/upper lower lobe) + hilar node = Ghon complex; calcifies → Ranke complex
Mostly asymptomatic; children may have hilar adenopathy
Latent TB
Contained in granulomas
+ PPD or IGRA, normal chest X-ray, no symptoms
Treat to prevent reactivation (rifampin 4 mo, isoniazid 6–9 mo, or INH + rifapentine)
Secondary (reactivation) TB
Waning immunity (HIV, age, steroids, TNF-α inhibitors, diabetes, silicosis)
Apical fibrocaseous cavities, fever, night sweats, weight loss, hemoptysis
Most transmissible form
Progressive primary / miliary
Poor immunity (infants, AIDS) → hematogenous spread
Millet-seed nodules in lungs, liver, spleen, marrow, meninges
Can follow primary or reactivation
TB meningitis
Basilar meninges
Subacute headache, CN palsies, hydrocephalus; CSF: lymphocytes, very high protein, low glucose
Add dexamethasone
Pott disease
Vertebral osteomyelitis (thoracic)
Back pain, gibbus deformity, psoas abscess
—
Other extrapulmonary
Hematogenous seeding
Scrofula (cervical lymphadenitis), adrenal insufficiency, sterile pyuria, pericarditis, peritonitis, ileocecal disease, erythema nodosum
"Sterile pyuria" → TB of kidney
PPD (Mantoux)
Type IV hypersensitivity to tuberculin, read at 48–72 h
Induration ≥ 5 mm (HIV, contacts, steroids), ≥ 10 mm (high risk, healthcare), ≥ 15 mm (no risk)
False ⁺: BCG, NTM · false −: anergy (HIV, sarcoid, steroids, malnutrition)
IGRA (QuantiFERON)
T cells release IFN-γ to TB-specific antigens (ESAT-6, CFP-10)
One blood draw
Not affected by BCG
Active TB diagnosis
Sputum × 3: AFB smear, culture (gold standard, weeks), NAAT
Chest X-ray, CT
Airborne isolation (N95, negative pressure)
Treatment
RIPE: rifampin, isoniazid, pyrazinamide, ethambutol × 2 mo → RI × 4 mo
Directly observed therapy
Pyridoxine with isoniazid (see 11.05)
BCG vaccine
Live attenuated M bovis
Prevents severe childhood TB (miliary, meningitis)
Not in routine US use · contraindicated in immunocompromised

Mechanism — building a granuloma

Macrophage engulfs TBSulfatides block killing
→
IL-12→ Th1 differentiation
→
IFN-γActivates macrophages
→
Epithelioid cells + Langhans giant cellsTNF-α holds granuloma
→
Caseous necrosis

Block TNF-α (infliximab, adalimumab) and granulomas fall apart → screen for latent TB first.

Primary vs secondary TB

FEATURE
PRIMARY
SECONDARY
Who
First exposure
Reactivation (or reinfection)
Location
Lower upper / upper lower lobe + hilar node
Apex (highest O₂)
Lesion
Ghon complex
Fibrocaseous cavity
Symptoms
Usually none
Fever, night sweats, weight loss, hemoptysis
Infectious
Rarely
Yes

How it's tested

COMMON CONFUSIONA positive PPD or IGRA means infection (latent or active) — not necessarily active disease. Chest imaging and sputum decide.
THE TRAPA patient about to start a TNF-α inhibitor needs latent TB screening and treatment first.
YOUR APPROACHExposure test → imaging → sputum for active → RIPE vs latent regimen → watch drug toxicities.

If you see… think…

Lower-lobe subpleural nodule + hilar node calcification → Ghon complex (primary TB)
Apical cavity, night sweats, hemoptysis → reactivation TB
Rheumatoid arthritis patient on infliximab with cough and fever → TB reactivation
Millet-seed nodules everywhere → miliary TB
Basilar meningitis with CN palsies, high protein, low glucose → TB meningitis
Thoracic vertebral collapse with gibbus → Pott disease
Sterile pyuria → renal TB
Positive PPD in BCG-vaccinated immigrant → confirm with IGRA
Virulence factor causing serpentine cords → cord factor
Cytokine essential for containing TB → IFN-γ (and TNF-α)