Summary
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis, which typically affects the lungs. It is a common infectious cause of morbidity and mortality worldwide. Primary infection, transmitted via airborne aerosol droplet nuclei, is often initially asymptomatic. M. tuberculosis infection is typically dormant (latent TB infection; LTBI) because of intact innate and cellular immune responses. If the immune system is compromised, however, reactivation of the infection may occur. Patients with active disease characteristically present with fever, weight loss, night sweats, and a productive cough (with or without hemoptysis) that does not respond to conventional antibiotic therapy. The infection may spread hematologically to any organ, causing extrapulmonary TB. However, disseminated disease is rare, occurring in severely immunocompromised individuals. Patients with suspected LTBI should be tested using the tuberculin skin test (TST) or interferon-γ release assay (IGRA) and then treated accordingly. Treatment of LTBI reduces the risk of active infection in up to 90% of cases and, therefore, plays a crucial role in the prevention of active TB. If active TB infection is suspected, imaging should be obtained as well as microscopy, cultures, and/or polymerase chain reaction (PCR) to identify M. tuberculosis. The treatment of tuberculosis is prolonged due to the slow growth of M. tuberculosis, its concealment in macrophages, and the inability of drugs to easily penetrate its cell wall. Standard empirical treatment includes combination therapy with rifampin, isoniazid, ethambutol, and pyrazinamide for two months, followed by rifampin and isoniazid for an additional four months. The incidence of multidrug-resistant TB is steadily increasing.
Overview
Types of tuberculosis | |||
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Primary tuberculosis (primary infection) | Reactivation tuberculosis (secondary infection) [1] | ||
Latent tuberculosis infection (LTBI) [2] | Active primary tuberculosis [3] | ||
Definition |
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Features |
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Diagnostics |
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Treatment |
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Drug-resistant tuberculosis [5]
- Definition: a form of TB that is resistant to one or more antitubercular agents
- Types
- Rifampin-resistant tuberculosis (RR-TB): resistance to rifampin with or without resistance to other antitubercular drugs
- Monoresistant TB: resistance to one of the first-line antitubercular drugs
- Multidrug-resistant tuberculosis (MDR-TB): resistance to both isoniazid and rifampin
- Extensively drug-resistant tuberculosis (XDR-TB): resistance to any single fluoroquinolone and at least one of the second-line injectable drugs (e.g., amikacin, kanamycin, or capreomycin) in addition to MDR-TB
- Causes
- Incorrect drug combination therapy
- Inadequate duration or dosage of drug therapy
- Poor treatment adherence
- Poor quality of drugs
- Close contact with an individual with drug-resistant TB
Epidemiology
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United States [6]
- The incidence of TB infection in the US has been slowly declining.
- The incidence rate for 2018 was 2.8 cases per 100,000 population.
- Two-thirds of new TB cases reported in the US in 2019 were in individuals born outside the US.
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Worldwide [7]
- A leading cause of death from a single infectious agent
- The overall incidence and prevalence have been declining.
- The incidence rate for 2018 was 132 cases per 100,000 population.
- One-fourth of the world's population has latent TB.
- The sex ratio varies across countries and communities and largely depends on social and cultural factors. [8]
- Countries with the highest incidence of TB: India, Indonesia, China, the Philippines, Bangladesh, Nigeria, Pakistan, and South Africa
- The incidence of multidrug-resistant TB is steadily rising.
Epidemiological data refers to the US, unless otherwise specified.
Etiology
Mycobacteria
Species
Mycobacterium species that cause tuberculosis are collectively known as the Mycobacterium tuberculosis complex, which includes:
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Mycobacterium tuberculosis
- Mode of transmission: spread via aerosol droplet nuclei
- Reservoir: predominantly humans
- Disease: all forms of tuberculosis
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Mycobacterium bovis
- Mode of transmission: predominantly via ingestion of contaminated cow's milk
- Reservoir: predominantly cattle
- Disease: gastrointestinal tuberculosis in humans
- Mycobacterium africanum: common cause of tuberculosis in West, Central, and East Africa [1]
Features of Mycobacterium tuberculosis
- Type: facultative intracellular rod-shaped bacteria
- Gram stain: does not stain well [9][10]
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Special stains
- Ziehl-Neelsen stain: acid-fast bacilli appear pink [11]
- Auramine-rhodamine stain [12]
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Culture mediums for growth
- Löwenstein Jensen medium
- Middlebrook medium
- Rapid automated broth culture
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Mechanism of resistance
- Remains viable in airborne droplet nuclei and soil [13]
- Able to survive in acidic conditions [14]
- Virulence factors: See “Pathophysiology” below.
Risk factors for tuberculosis
Risk factors for TB exposure [15]
- Working in the health care industry
- Migration from countries with a high TB incidence (≥ 100 cases per 100,000 population) [16]
- Frequent travel to countries with a high TB burden
- Close contact with a patient with active TB infection
- Crowded living conditions (e.g., prisons)
- Homelessness
Risk factors for reactivation of latent TB [17]
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Immunosuppressed state
- HIV infection (TB is the most common cause of death in patients with HIV globally) [18][19]
- Transplant with immunosuppressant use [20]
- Chronic kidney disease [21]
- Diabetes mellitus [22]
- Corticosteroid therapy [23][24]
- TNF-α inhibitor therapy (e.g., infliximab) [25]
- Advanced age [26]
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Lifestyle factors
- Smoking [27]
- Heavy alcohol consumption [28]
- Intravenous drug misuse
- Malnutrition [29]
- Preexisting lung disease
M. tuberculosis remains dormant within the host and may be reactivated once the immune system becomes compromised (e.g., by high doses of glucocorticoids or chemotherapeutic agents, HIV infection).
Classification
Tuberculosis case definitions and management [31][32] | ||||
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Class | Classification | Description | Notifiable | Treatment |
0 | No TB exposure, not infected |
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1 | TB exposure, no evidence of infection |
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2 | Latent TB infection, no disease |
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3 | Clinically active TB |
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4 | TB, not clinically active |
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5 | TB is suspected (diagnosis pending) |
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Pathophysiology
Primary tuberculosis [1][33][34]
Innate immune response
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Exposure to M. tuberculosis
- Individuals with M. tuberculosis infection disperse droplet nuclei that contain bacilli via sneezing or coughing.
- Inhaled droplet nuclei reach the terminal alveoli and are taken up by the alveolar macrophages.
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Entry into macrophages
- Mycobacterial cell wall contains pathogen-associated molecular patterns (PAMPs) such as lipoarabinomannan and lipomannan.
- Alveolar macrophages recognize M. tuberculosis PAMPs via toll-like receptors (TLRs)
- Activation of TLRs leads to the production of proinflammatory cytokines (e.g., IL-1, IL-12, TNF-α) and phagocytosis of mycobacteria.
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Replication within macrophages
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Typically, phagocytosed organisms reside within a phagosome to undergo intracellular killing via the following steps:
- Phagosome maturation: acidification using a proton pump system [35]
- Fusion of phagosome and lysosome: mediated by increased intracellular calcium levels [36]
- Killing of bacteria by reactive oxygen species (ROS), reactive nitrogen intermediates (RNI), and lysosomal enzymes
- M. tuberculosis survives within macrophages because of the inhibition of both phagosome maturation and phagolysosome fusion
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Virulence factors involved include: [10]
- Cord factor (trehalose-6,6'-dimycolate): a surface glycolipid that causes serpentine cord-like growth, inhibits neutrophil migration, and induces TNF-α release to stimulate activated macrophages to form granulomas [37][38]
- Sulfatides: surface glycolipids that inhibit phagolysosome fusion [39]
- Lipoarabinomannan: a lipoglycan that induces TNF-α release from macrophages and scavenges ROS
- Catalase-peroxidase: an enzyme that catalyzes the destruction of ROS and H2O2
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Typically, phagocytosed organisms reside within a phagosome to undergo intracellular killing via the following steps:
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Macrophage lysis and release of bacteria
- Following replication in the alveolar macrophages, the released bacteria attack uninfected macrophages to spread infection.
- Dendritic cells migrate to the site of infection and process mycobacterial antigens.
- Some bacteria enter the bloodstream, causing bacteremia and seeding multiple organs.
Cellular immune response
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Th1 cell activation
- Dendritic cells present mycobacterial antigens complexed with MHC 2 to naive T cells
- Activated CD4+ T cells migrate to the focus of infection (type IV HSR).
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Macrophage activation and bacterial killing
- Activated CD4+ T cells release IFN-γ
- IFN-γ acts on macrophages to enable bacterial killing via the following mechanisms:
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Granulomatous inflammation and tissue destruction
- IFN-γ-activated macrophages secrete TNF-α.
- TNF-α promotes the aggregation of macrophages and T cells to form granulomas, affecting the lungs and regional lymph nodes
- Destruction of M. tuberculosis-infected macrophages causes central caseous necrosis and tissue damage.
- Granuloma limits the spread of infection.
- Ghon focus: a granuloma typically located in the middle/lower lung lobes.
- Ghon complex: formed by the Ghon focus, regional lymph node, and the linking lymphatic vessels
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Disease progression
- Sufficient immune response
- Most of the bacteria are killed.
- Some bacteria may persist, causing LTBI.
- The granulomas in the Ghon complex undergo fibrosis and calcification to form the Ranke complex.
-
Deficient immune response (e.g., HIV, malnutrition)
- Failure of granulomas to limit infection
- Progressive primary TB causing progressive lung disease, bacteremia, and miliary TB
- Sufficient immune response
Secondary tuberculosis [34]
- Latent TB: Dynamic equilibrium is maintained between the host immune response and M. tuberculosis.
- Reactivation of disease: due to weakening of immune response (e.g., resulting from HIV, TNF-α inhibitor therapy)
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Disease progression
- Caseating granulomas with central necrosis and Langhans giant cells are characteristic features.
- Usually affects the upper lobes of the lungs because of higher oxygen tension
- Can also affect other organs (due to seeding of organs in primary tuberculosis)
- Prior sensitization to mycobacterial antigens results in a stronger inflammatory response, causing extensive tissue destruction, cavitation, and scarring.
Subtypes and variants
Pulmonary tuberculosis
Clinical features
Patients with primary TB are typically asymptomatic. Symptomatic patients present with the following features: [40]
- Systemic
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Pulmonary
- Cough with purulent sputum that is occasionally blood-streaked (hemoptysis)
- Shortness of breath
- Pleuritic chest pain [41]
Clinical examination findings
Findings are nonspecific.
- General
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Chest examination
- Percussion
- Dullness over areas of consolidation
- Hyperresonance over areas of cavitation
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Auscultation
- Amphoric breath sounds over areas of cavitation
- Rhonchi
- Crackles
- Diminished breath sounds over areas of consolidation (or pleural effusion)
- Percussion
Depending on the degree of immunosuppression, TB in HIV-positive individuals may progress atypically or more rapidly.
Always consider TB as a differential diagnosis in a young individual with hemoptysis.
Complications [42]
- Rasmussen aneurysm: inflammatory pseudoaneurysm of a branch of the pulmonary artery lying adjacent to a tuberculous cavity and manifesting with hemoptysis
- Hemoptysis: due to erosion of blood vessels overlying a lung cavity, Rasmussen aneurysm, or aspergilloma
- Lung cavitation
- Lung fibrosis
- Aspergilloma
- Pneumothorax
- Bronchiectasis
- Fibrosing mediastinitis
Extrapulmonary tuberculosis
TB lymphadenitis [43]
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Pathophysiology
- Hematogenous dissemination following primary TB
- Local extension of infection from the affected organ
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Sites of lymph node involvement
- Cervical
- Inguinal
- Axillary
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Clinical features
- Constitutional symptoms
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Lymphadenopathy: Findings vary depending on the stage of lymphadenitis. [44]
- Lymphadenitis: firm, mobile, and discrete lymph nodes
- Periadenitis: rubbery and fixed lymph nodes
- Cold abscess: soft and fluctuant lymph nodes
- Draining sinus tract
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Diagnostics
- Ultrasound or CT: matted lymph nodes with a necrotic center
- FNAC: acid-fast staining, PCR, and culture
- Lymph node biopsy: histopathology
- Treatment: See “Treatment” below.
Tuberculous hilar lymphadenopathy [1][45]
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Pathophysiology
- Lymphatic spread of M. tuberculosis from the lung during primary TB infection
- Bronchus compression
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Clinical features
- Commonly seen in children
- Wheezing
- Mostly asymptomatic
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Diagnostics: chest x-ray or CT
- Unilateral or bilateral enlarged hilar lymph nodes
- Lung atelectasis
- Hyperinflation
- Treatment: See “Treatment” below.
Tuberculous pleurisy [46]
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Pathophysiology
- Direct spread of infection from the lungs
- Hematogenous spread
- Delayed hypersensitivity reaction in the pleural space due to mycobacterial antigen
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Clinical features
- Constitutional symptoms
- Nonproductive cough
- Intensive (pleuritic) chest pain
- Dyspnea
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Diagnostics
- Imaging
- Chest x-ray: unilateral pleural effusion
- Chest ultrasound or CT: loculated effusion with septations; pleural thickening
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Thoracentesis: pleural fluid analysis [47]
- Exudative type (Light criteria)
- pH: < 7.4
- Glucose: < 60 mg/dL
- ↑ Adenosine deaminase
- Rich in lymphocytes
- Microbiology: acid-fast staining, PCR, and culture
- Sputum smear examination: acid-fast staining
- Imaging
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Treatment
- Therapeutic thoracentesis for symptom relief
- See “Treatment” below.
Miliary TB [40]
- Definition: a form of TB with multiorgan involvement that manifests with granulomatous lesions (resembling millets) as a result of lymphohematogenous dissemination of bacilli from a pulmonary or extrapulmonary source
- Epidemiology: ∼ 20% of extrapulmonary TB cases [48]
- Pathophysiology: primary infection or reactivation
- Common sites of involvement: lungs, spleen, liver, lymph nodes, adrenals, meninges, vertebrae (Pott disease), joints and long bones, and choroid
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Clinical features: mostly nonspecific
- Cough and dyspnea
- Constitutional symptoms
- Lymphadenopathy
- Hepatosplenomegaly
- Tuberculosis miliaria cutis disseminata
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Diagnostics: requires a high index of clinical suspicion
- Fundoscopy: choroid tubercles
- Microbiology: sputum, body fluids, and tissue
- Acid-fast staining
- PCR
- Culture
- Blood
- ↑ ESR and CRP
- CBC: anemia, leukopenia
- LFT: elevated transaminases and bilirubin
- Electrolytes: hyponatremia, hypercalcemia
- TST: negative
- Imaging
- Chest x-ray: multiple small nodules (< 2 mm) with an appearance resembling millet seeds [48]
- Ultrasound: pleural effusion, ascites, hepatic or splenic lesions
- CT: lung nodules, enlarged hilar lymph nodes
- Brain MRI: meningeal and/or basal cistern enhancement; hydrocephalus; tuberculoma
- Echocardiography: pericardial effusion
- Treatment: See “Treatment” below.
Tuberculous meningitis
- See “Tuberculous meningitis.”
Pericardial TB [49][50]
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Pathophysiology
- Hematogenous spread from the site of primary infection
- Retrograde lymphatic spread from hilar lymph nodes
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Stages
- Stage 1: fibrinous exudate containing neutrophils and mycobacteria
- Stage 2: serosanguineous effusion with lymphocytes
- Stage 3: absorption of effusion and caseating granulomas
- Stage 4: scarring with calcification
- Types
- Clinical features
- Physical examination findings: See “Clinical features” in “Pericardial effusion and cardiac tamponade” and “Pericarditis.”
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Diagnostics
- ECG: nonspecific ST-T changes
- Imaging
- Chest x-ray: enlarged cardiac silhouette or calcification
- Echocardiography: effusion or diminished wall motility
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Pericardiocentesis
- Analysis: exudative, blood-stained
- Microbiology: acid-fast staining, PCR, and culture
- ↑ Adenosine deaminase
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Treatment
- See “Treatment” below.
- Therapeutic pericardiocentesis
Adrenal TB [51]
- Clinical features: See “Adrenal insufficiency.”
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Diagnostics
- CT/MRI: bilateral enlargement or calcification of adrenal glands
- See “Diagnostics” below.
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Management
- Corticosteroid replacement
- See “Treatment” below.
Rifampin can precipitate an acute adrenal crisis in patients with undetected adrenal insufficiency due to tuberculosis.
Cutaneous TB [40][52]
- Classification: based on pathogenesis, morphology of the lesion, and histopathological features
Types of cutaneous TB | |||
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Type | Pathophysiology | Clinical features | Histopathology features |
Exogenous source of TB | |||
Primary inoculation TB (tuberculous chancre) |
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Postprimary inoculation TB (tuberculosis verrucosa cutis) |
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Endogenous source of TB | |||
Scrofuloderma |
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Autoinoculation |
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Hematogenous source of TB | |||
Lupus vulgaris |
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Tuberculosis miliaris cutis disseminata |
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Tuberculous gumma (metastatic tuberculous abscess) |
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Tuberculid | |||
Variable forms |
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- Diagnostics: skin biopsy for histopathology, acid-fast staining, and culture
- Treatment: See “Treatment” below.
Gastrointestinal TB [53][54]
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Pathophysiology
- Ingestion of infected milk or sputum
- Hematogenous spread resulting from primary pulmonary TB
- Contiguous spread via affected lymph nodes
- Sites of involvement: See “Types of gastrointestinal TB” below.
Types of gastrointestinal TB | |||
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Site of involvement | Clinical features | Diagnostics | Differential diagnosis |
Peritoneum |
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Esophagus |
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Stomach |
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Jejunum and ileocecal region |
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Colorectal |
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Treatment
- Surgical: for intestinal obstruction, perforation, fistula, abscess
- Medical: See “Treatment” below.
Genitourinary TB [40][55]
Renal and urologic TB
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Pathophysiology
- Hematogenous spread of infection to the kidneys as a result of primary pulmonary TB that is reactivated in immunosuppressed states
- Ureters and bladder are infected when bacteria are excreted in urine.
- Common sites of involvement
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Clinical features
- Constitutional symptoms
- Flank pain
- Hematuria
- Storage symptoms
- Increased frequency of voiding
- Nocturia
- Urgency
- Hypertension
- Recurrent UTIs unresponsive to antibiotic therapy
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Diagnostics
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Urine examination
- Analysis: hematuria, sterile pyuria, proteinuria
- Microbiology: acid-fast staining, PCR, and culture
- Imaging: CT or IV urography
- Renal scarring
- Hydroureteronephrosis
- Calcification involving the entire urinary tract
- Multiple ureteral strictures
- Bladder wall thickening and fibrosis
- Cystoscopy
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Urine examination
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Treatment
- Medical: See “Treatment” below.
- Ureteral stenting for strictures
- Surgery
- Total or partial nephrectomy
- Bladder augmentation
Male genital tract TB
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Pathophysiology
- Hematogenous spread of infection to the epididymis and prostate
- Extension of infection from the epididymis to the testis, vas deferens, seminal vesicles, and ejaculatory ducts
- Common sites of involvement
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Clinical features
- Scrotal mass (can be painful or painless)
- Scrotal sinus tract with watery discharge
- Infertility
- Increased urinary frequency, nocturia, and hematospermia
- Recurrent prostatitis or epididymitis unresponsive to antibiotic therapy
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Diagnostics
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Urine examination
- Analysis: hematuria, sterile pyuria
- Microbiology: acid-fast staining, PCR, and culture
- Scrotal ultrasound
- Calcification
- Hydrocele
- Diffuse or nodular enlargement of the epididymis
- Transrectal ultrasound: calcification in prostate and seminal vesicles
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Urine examination
- Treatment: See “Treatment” below.
Female genital tract TB [56]
- Pathophysiology: hematogenous spread of infection as a result of primary pulmonary TB that is reactivated in immunosuppressed states
- Common sites of involvement
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Clinical features
- Constitutional symptoms
- Menstrual irregularities
- Abdominal pain
- Infertility
- Adnexal mass on pelvic examination
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Diagnostics
- Menstrual fluid or endometrial curettage sample: acid-fast staining, PCR, and culture
- Imaging
- Ultrasound/CT: tuboovarian abscess
- Hysterosalpingography: occluded fallopian tubes, hydrosalpinx, calcification
- Hysteroscopy: adhesions and obliterated uterine cavity
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Treatment
- Medical: See “Treatment” below.
- Surgery: drainage of tuboovarian abscess
Pott disease [40]
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Pathophysiology
- Hematogenous dissemination of infection to vertebral bodies following primary TB
- Infection from vertebral bodies spreads to the intervertebral disk, causing destruction and collapse of the disk
- Common sites of involvement: thoracic and lumbar vertebrae
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Clinical features
- Constitutional symptoms
- Back pain
- Spinal tenderness
- Kyphosis
- Gibbus deformity
- Neurological deficit (e.g., paraplegia)
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Diagnostics
- Imaging: x-ray, CT, or MRI of the spine
- Involvement of multiple vertebrae
- Osteoporosis of vertebral endplate
- Disk space narrowing
- Lytic lesions in the anterior vertebral body
- Collapse of the vertebral body
- Enlarged psoas muscle shadow (psoas abscess)
- Spinal cord compression (seen on MRI)
- See “Diagnostics” below.
- Imaging: x-ray, CT, or MRI of the spine
- Treatment
Diagnostics
Active TB [40][57]
Individuals with a history and physical examination findings that suggest TB must undergo bacteriological and/or radiological testing to confirm active TB infection.
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Samples used for bacteriological confirmation
- Three early morning sputum samples
- Induced sputum
- Gastric lavage
- Bronchoalveolar lavage
Diagnosis of active TB | |||
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Test | Characteristics | Advantages | Disadvantages |
Bacteriological confirmation | |||
Acid-fast bacilli smear microscopy |
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PCR |
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Culture |
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Radiological confirmation | |||
Chest x-ray [58] |
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Indications for drug susceptibility testing [57]
- Previous history of treated tuberculosis
- Patient has had contact with individuals with MDR-TB
- HIV infection
- Patients born or living (for at least one year) in countries with high TB burden (≥ 20 cases per 100,000 population) or high prevalence of primary MDR-TB (≥ 2%) [57]
- Testing in HIV infection: Urine lipoarabinomannan assay can be used in patients with a CD4 count < 100 cells/mm3. [59]
Latent TB [57][60]
- Testing objective: to identify individuals who will benefit from treatment
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Indications
- High risk of TB exposure
- Close contact with individuals who have TB
- Individuals born in or who frequently travel to countries with a high TB burden (> 20 cases per 100,000 population) [57]
- Individuals living or working in high-risk settings (e.g., homeless shelters, prisons)
- Health care workers who come into contact with individuals who have TB
- High risk of TB reactivation
- HIV infection
- Children < 5 years of age
- Recent TB infection (within 2 years of treatment)
- Intravenous drug users
- Diabetes mellitus
- CKD
- Individuals taking immunosuppressant drugs
- Silicosis
- Individuals with cancer of the head and neck
- Individuals with gastrectomy or jejunoileal bypass
- High risk of TB exposure
- Tests: See “Diagnosis of latent TB.”
Diagnosis of latent TB | ||
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Tuberculin skin test (purified protein derivative test, Mantoux test) | Interferon-γ release assay (IGRA) | |
Mechanism |
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Procedure | ||
Interpretation |
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Benefits |
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Limitations |
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Approach
- Selection of test: based on cost, availability, and history of BCG vaccination
-
Positive IGRA or TST
- Consider a confirmatory test (TST or IGRA) to rule out false positives.
- Evaluate for active TB with chest x-ray.
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Negative IGRA or TST
- Consider a second test (TST or IGRA) to increase sensitivity.
- Two-step TST: baseline test for individuals who are tested periodically (except when IGRA is the baseline test) [60]
- Health care workers with a prior negative TST or IGRA must be retested immediately and again after 8–10 weeks of last known TB exposure. [61]
A healthy individual without any risk factors for TB infection who has an induration smaller than 15 mm is considered negative for TB.
Pathology
Gross pathology [33]
- Multiple granulomas coalesce as grayish-white areas with necrotic centers that have a cheese-like appearance.
- Calcification and fibrosis are visible in healed lesions.
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Ghon complex
- Lung parenchyma: gray-white areas of consolidation
- Hilar lymph nodes: caseous necrosis
Histopathology [33]
Caseating tuberculous granulomas are pathognomonic of reactivation (secondary) tuberculosis.
- Center: area of necrosis
- Periphery: epithelioid histiocytes and Langhans giant cells
Although caseating tuberculous granulomas are a sign of a functioning immune system in TB infection, they do not necessarily indicate TB infection because other mycobacteria (including tuberculoid leprosy) and tertiary syphilis manifest similarly.
Histopathology of other types of tuberculosis
- Acinar nodular tuberculosis: merging of multiple epithelioid granulomas into macroscopically visible areas of necrosis
- Miliary tuberculosis: single, small, and nodular foci without central necrosis
- Urogenital tuberculosis [62]
Differential diagnoses
- Pulmonary TB
- Extrapulmonary TB
The differential diagnoses listed here are not exhaustive.
Treatment
Active TB [63]
General measures
- Case notification: mandatory reporting to local health department [32]
- Infection control: airborne precautions [64]
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Therapy monitoring
- Clinical
- Medication history
- Assessment of symptoms, side effects, and medication adherence
- Weight: checked monthly
- Vision assessment: for visual acuity and color discrimination
- Microbiology
- Laboratory tests: obtained before starting treatment
- Clinical
First-line drugs [40][65]
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Phases of treatment
- Intensive phase: 2 months of rifampin PLUS isoniazid, pyrazinamide, and ethambutol
- Continuation phase: 4 months of rifampin PLUS isoniazid
-
Treatment regime
- Daily dosing is preferred.
- Three times weekly dosing: an alternative if the patient has no HIV infection and is at low risk for a TB relapse
-
Treatment administration
- Self-administered
- Directly observed therapy: health care personnel observe the patient swallowing medication
- Mechanisms of resistance: See “Antimycobacterial drugs.”
First-line drugs for tuberculosis | ||
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Duration of treatment | Common side effects | |
Rifampin |
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Isoniazid |
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Pyrazinamide |
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Ethambutol |
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"RIPE": Rifampin, Isoniazid, Pyrazinamide, and EthambutolRifampin and isoniazid alter the efficacy of drugs metabolized by cytochrome P450 (especially protease inhibitors, NNRTIs, OCPs, warfarin, sulfonylureas).
Second-line drugs
These drugs are typically indicated in drug-resistant TB.
Latent TB infection [68]
- Case notification: mandatory reporting to local health department [32]
- Indication: positive IGRA or TST
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Pretreatment evaluation
- No clinical or radiological evidence of TB
- Comorbid conditions and medication history
-
Therapy monitoring
- Assessment of symptoms, side effects, and medication adherence
- LFTs in patients at high risk of developing liver failure
Prevention
Bacillus Calmette-Guérin vaccine (BCG) [69]
- Composition: live attenuated strain of M. bovis
- Administration: 0.3 mL of reconstituted vaccine using a multiple puncture device over the deltoid region
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Indications
- Countries with a high TB burden: all newborns at birth [70]
- Countries with a low TB burden [70]
- Children with a negative TST and who have come into contact with adults with untreated/inadequately treated TB or drug-resistant TB (if the child cannot take long-term medication for infection)
- Health care workers continually exposed to individuals with drug-resistant TB
- Other uses: intravesical chemotherapy in superficial bladder cancer
- Benefits: protects against tuberculous meningitis and miliary TB in children [71]
-
Adverse effects
- Localized lymphadenitis and abscess
- Disseminated TB disease
-
Contraindications
- Immunocompromised individuals
- Pregnancy
Postexposure management [72]
-
Risk assessment
- Individuals with the following characteristics are highly contagious:
- Pulmonary or laryngeal TB
- Positive sputum smear microscopy
- Cavitary lesions on chest x-ray
- Untreated or inadequately treated TB
- Type of exposure: frequency and duration
- People with the following characteristics and who have had contact with individuals with TB have a high risk of developing severe disease:
- Age < 5 years
- Immune status: HIV infection, corticosteroid use
- Comorbid conditions
- Individuals with the following characteristics are highly contagious:
- Clinical assessment
-
Baseline test: All individuals should be offered HIV testing if HIV status is unknown.
- Symptomatic: sputum smear microscopy and chest x-ray
- Asymptomatic
- Treatment
- Follow up test: TST or IGRA repeated 8–10 weeks following exposure
Disinfectants active against M. tuberculosis [73]
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