9- TUBERCULOSIS

• Tuberculosis infection

  1. Inhalation of aerosol droplets containing M. tuberculosis

  2. Deposition in the lungs

  3. One of four possible outcomes
• Possible outcomes of tuberculosis infection

  • Immediate clearance of the organism (no infection)
  • Primary disease: immediate onset of active disease
  • Latent infection: infected by Tb but infection is contained by the immune system & the patient develops cell-medicated immunity
  • Reactivation disease: onset of active disease many years following a period of latent infection
• Primary tuberculosis


  Initial infection with Mycobacterium tuberculosis
• Primary tuberculosis

  • Mostly asymptomatic; may present as erythema nodosum, pleural effusion, or collapse (if compressed by enlarged LNs)
  • Upper region of lungs
  • Ghon focus: granulomatous lesions: central areas of caseation surrounded by epithelioid & giant Langerhans cells. subpleural lesion
  • Ghon complex: Ghon focus + caseous lesions in mediastinal & cervical LNs
  • The majority heal and calcifyàLatent infection. May reactivate in the future.
• Reactivation tuberculosis

  • Only 5-10% of people with primary Tb get active disease in their life
  • Reactivation if immunosuppressed
• Causes of reactivation tuberculosis

  • HIV co-infection
  • Chemotherapy, steroids, cytotoxins
  • DM, ESKD, lymphoma
  • Malnutrition, aging
• Active tuberculosis

  • Fever, night sweats, weight loss
  • Cough: dry>> purulent (mucoid purulent or blood stained) >> hemoptysis
  • Apical areas
• Extrapulmonary tuberculosis sites

  • LNs
  • GI: ILEOCECAL REGION (like Crohn's)
  • Any organ (LNs, pleura, GI, GU, spine, kidneys, meninges)
  • LNs: firm nontender enlargement, centrally necrotic, overlying skin may be indurated or have sinus tract formation
  • Tuberculous meningitis
  • Choroidal tubercles (yellow/ white raised lesions) in eyes
  • Hepatosplenomegaly (in later stages)
• Miliary tuberculosis


  • Hematogenous dissemination; characterized by the presence of small, firm 1-2mm white nodules
  • Mostly in lungs, LNs, bones, CNS (detect with MRI), liver/spleen
• Chest X-ray

  • Upper lobe patchy/nodular infiltrates with cavitation
  • Healed primary Tb: Ghon complex (calcified primary focus w/LN)
  • Ranke complex= Ghon complex calcified & fibrosis
• Sputum testing

  1. Serial sputum samples, at least 3 occasions, ideally early morning

  2. Sputum smear for acid-fast bacilli (Ziehl-Neelsen stain)

  3. Definitive Dx is by sputum culture (takes 3 weeks, must be done for antibiotic sensitivity) and PCR (more rapid, nucleic acid amplification test)
• Extrapulmonary tuberculosis

  • Needs high index of suspicion + organism in [LN biopsy, bone biopsy, urine testing, or aspiration of pericardial fluid]
  • If military: must look for CNS Tb: umbar puncture & CSF exam (high risk of meningitis) (2-3g protein lymphocytosis)
• Tuberculosis treatment - Intensive phase

  Isoniazid, Rifampin, Pyrazinamide, Ethambutol administered for 2 months
• Tuberculosis treatment - Continuation phase

  1. Isoniazid and rifampin administered for 4 months

  2. May be extended up to 7 months if: Patients with both cavitary pulmonary TB on initial CXR and positive sputum culture after the 2-month intensive-phase treatment, Intensive phase did not include 2 months of pyrazinamide, Some patients with HIV co-infection
• Continuation phase is shortened to 2 months for HIV-uninfected patients with negative sputum cultures and symptomatic and/or radiographic improvement in the absence of an alternative diagnosis
• Daily therapy

  Preferred over intermittent therapy during both phases (esp. intensive phase)
• Dexamethasone

  • Added as adjunct in treatment initiation in CNS and pericardial disease (decreases risk of constrictive pericarditis & neurological complications)
• Baseline liver function


  • Must be established before treatment due to risk of hepatotoxicity
• Asymptomatic aminotransferase elevations resolve spontaneously over days to weeks in most patients
• Drug-induced hepatitis

  1. Stop all hepatotoxic drugs if bilirubin ≥3 mg/dL or transaminases >3-5 times the upper limit of normal

  2. Once LFTs return to baseline (or fall to less than twice normal), hepatotoxic drugs can be restarted one at a time with careful monitoring between resumption of each agent
• Treatment failure

  Positive cultures after 4 months of therapy
• Relapse


  Recurrent tuberculosis at any time after completion of treatment with apparent cure
• Isoniazid

  • MOA: inhibits cell wall synthesis
  • Side effects: allergic reactions, rash, peripheral neuropathy: polyneuropathy & paresthesia (give pyridoxine Vit B6)
• Rifampicin

  • MOA: inhibits DNA-dependent RNA synthesis by inhibiting RNA polymerase
  • Side effects: stain body secretions pink (urine, tears, sweat), thrombocytopenia
  • Induces liver enzymes (drugs cleared by liver enzymes won't be as effective. ex: OCPs, antidepressants, anticoagulants, antiepileptics)
• Pyrazinamide

  • MOA: prodrug; converted to pyrazinaid acid, accelerate effect of isoniazid & rifampicin. May inhibit fatty acid synthetase 1 of mycobacterium tuberculosis
  • Side effects: hyperuricemia, gout, rash, arthralgia
  • Contraindicated in pregnancy
• Ethambutol

  • MOA: inhibits cell wall synthesis
  • Side effects: optic neuritis, visual acuity, color blindness
  • Must decrease the dose in renal failure
• Latent TB

  Detected in asymptomatic patients using the purified protein derivative (PPD) skin test or interferon gamma release assay (IGRA) blood test
• PPD test

  Considered positive based on the size of the INDURATION, not the erythema
• Induration larger than 5 millimeters is considered +ve in


  • HIV-positive patients
  • Glucocorticoid users
  • Close contacts of those with active TB
  • Abnormal calcifications on chest x-ray
  • Organ transplant recipients
• Induration larger than 10 millimeters is considered +ve in


  • Recent immigrants/individuals from high-incidence settings
  • Prisoners
  • Healthcare workers
  • Close contacts of someone with TB
  • Hematologic malignancy, alcoholics, diabetes mellitus
• Induration larger than 15 millimeters is considered +ve in


  • Those with no risk factors
• If the patient has never had a PPD skin test before

  A second test is indicated within 1 to 2 weeks if the first test is negative because it may be falsely negative
• Everyone with a reactive IGRA or PPD test should have a chest x-ray to exclude active disease before starting latent Tb treatment
• Latent TB treatment

  Isoniazid continued for 9 months
• Previous BCG has no effect on these recommendations