Mycobacterium Tuberculosis - Microbiology

Snapshot
- A 33-year-old man presents to his primary care physician for a cough and generalized malaise. His symptoms are associated with 2 episodes of mild hemoptysis and night sweats. He denies any sick contacts or recent travels; however, he states he was released from prison 4 months ago. Physical examination is unremarkable. A chest radiograph is obtained, which demonstrates pulmonary infiltrates and cavitations in the upper lobe.

Introduction
- Classification
  - acid-fast, rod-shaped, obligate aerobic, intracellular bacteria
- Epidemiology
  - risk factors
    
    traveling to endemic areas (e.g., Angola and the Central African Republic)
    
    close contact (e.g., prisons, nursing homes, homeless shelters, and hospitals)
    
    immunocompromised (e.g., HIV, immunosuppressive medications, and diabetes)
- Transmission
  - airborne spread of droplet nuclei from patients with infectious tuberculosis (TB)
- Microbiology
  - acid-fast on Ziehl-Neelsen staining
  - immune system itself causes damage
    
    TB contains no endotoxins or exotoxins
  - cord factor
    
    inhibits leukocyte migration
    
    causes characteristic serpentine growth pattern
    
    induces TNF-α release
  - tuberculin
    
    triggers cell-mediated immunity → caseation and granulomas
    
    triggers delayed hypersensitivity reaction
    
    a surface protein
  - sulfatides
    
    prevent phagosome-lysosome fusion
- Pathogenesis
  - the infected person coughs up small droplets containing the bacteria that reaches the terminal alveoli of the uninfected person
    
    alveolar macrophages are recruited, which eventually become infected, transporting the microbe to deeper tissues
    
    more alveolar macrophages are recruited, leading to granuloma formation
    
    granulomas are formed to "wall off" TB, where it lies dormant
  - secondary TB occurs when the patient's immune system is weakened (e.g., newly acquired HIV infection, being on immunosuppressant medications, malignancy, and poor nutrition)
    
    macrophages' ability to maintain their barrier decreases, facilitating possible dissemination
    
    TB infection typically manifests in the apical/posterior segments of the lung due to its increased oxygen tension

Presentation
- TB can lead to pulmonary and extrapulmonary manifestations
  - lymph nodes (tuberculous lymphadenitis)
  - pleura
  - genitourinary
  - skeleton (can lead to Pott disease with spinal involvement)
  - meninges
  - gastrointestinal system
  - pericardium (tuberculous pericarditis)
- Symptoms
  - typically asymptomatic in primary TB
  - cough
  - hemoptysis
  - fever
  - night sweats
  - malaise
- Physical exam
  - weight loss
  - lymphadenopathy
  - dullness to percussion or decreased/absent breath sounds if there is a pleural effusion
  - back pain in spinal TB (Pott disease)

Imaging
- Chest radiograph
  - indication
    
    initial imaging study in the evaluation of TB
  - findings
    
    middle or lower lung infiltrate (suggestive of primary infection)
    
    upper lobe infiltrate (suggestive of latent TB reactivation)
    
    apices have higher oxygen tension and reduced perfusion/lymph clearance compared to the base
    
    cavitary lesions
    
    Ghon complex (lobar or perihilar lymph node involvement)

Studies
- Sputum acid-fast testing
  - demonstrates acid-fast bacilli
- Real-time nucleic acid amplification
  - rapidly confirms TB and is considered the first-line diagnostic study
- Tuberculin skin test (TST)
  - most widely used to screen for latent TB infection
  - a delayed-type hypersensitivity reaction against purified protein derivative (PPD) is induced
    
    the size of the induration is assessed after 48-72 hours
    
    note, patients who received the Bacille Calmette-Guerin (BCG) vaccination will have false positive results
    
    a false negative result can be seen in immunocompromised patients
  - interpretation (positive results)
    
    ≥ 15 mm in patients with no risk factors
    
    ≥ 10 mm in patients with risk factors (e.g., healthcare worker, traveling to endemic areas, and being in prison)
    
    ≥ 5 mm in immunocompromised patients (e.g., HIV, on immunosuppressants, and organ transplant recipients)
    
    positive tests require a chest radiograph
- Interferon-γ release assay
  - measures interferon levels released by the patient's immune system in response to TB antigens
    
    the results are not affected by previous BCG vaccination

Differential
- Lung cancer
  - differentiating factor
    
    patients will not have positive TB studies

Treatment
- Medical
  - rifampin, isoniazid, pyrazinamide, and ethambutol therapy
    
    indication
    
    first-line treatment for active pulmonary TB infection for 4 months
    
    after 4 months, treatment involves isoniazid and rifampin
    
    comments
    
    isoniazid can cause peripheral neuropathy as well as sideroblastic anemia due to vitamin B6 deficiency, thus warranting pyridoxine in hopes to prevent this development from occurring
    
    can also cause hepatitis
    
    ethambutol can cause optic neuropathy
    
    mutations in RNA polymerase lead to rifampin resistance
  - isoniazid monotherapy
    
    indication
    
    prophylactic treatment for latent primary TB after active TB has been excluded

Complications
- Pott disease
- Miliary or disseminated TB
- Meningitis
- Pericarditis
- Lymphadenitis
- Adrenal insufficiency

Action	Numeric Key	Letter Key	Function Key
Show Bullets		S	Enter (frontside only)
20%	1	N
40%	2	H
60%	3	F	Enter (backside only)
80%	4	E
100%	5	M
Toss	0	T