What are the diagnostic tests and treatment options for tuberculosis (TB)?

Diagnostic Tests and Treatment Options for Tuberculosis (TB)

The diagnosis of tuberculosis requires a combination of PPD skin testing or interferon-gamma release assay (IGRA), chest radiography, and bacteriologic studies (sputum microscopy, culture, and nucleic acid amplification tests), while the standard treatment for drug-susceptible TB consists of a 2-month intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) followed by a 4-month continuation phase with isoniazid and rifampin. 1

Diagnostic Tests for TB

Initial Evaluation

• A diagnosis of TB should be considered for any patient with persistent cough (≥3 weeks) or other symptoms compatible with TB (bloody sputum, night sweats, weight loss, anorexia, or fever) 1
• The index of suspicion should be higher in areas or among groups where TB prevalence is high 1

Diagnostic Testing Algorithm

1. Skin Testing and Blood Tests

   • PPD skin test (Mantoux method): 0.1 mL of PPD (5 TU) injected intradermally, read by trained personnel at 48-72 hours 1
   • Interferon-gamma release assay (IGRA) is preferred if patient has history of BCG vaccination 1
   • Note: Testing for latent TB infection (TST or IGRA) cannot be used to exclude active TB disease 1

2. Chest Radiography

   • Essential for all patients with suspected pulmonary TB 1
   • Using chest X-ray prior to culture or molecular testing increases diagnostic yield and reduces the number needed to screen from 7.6 to 5.0 2

3. Bacteriologic Confirmation

   • Sputum specimens for acid-fast bacilli (AFB) microscopy and culture 1
   • Two sputum specimens are generally adequate for diagnosis; the third specimen adds little additional value (sensitivity increases from 71% with two specimens to only 72% with three) 3
   • First morning specimens have 12% greater sensitivity than spot specimens 1
   • Concentrated specimens have 18% higher sensitivity than non-concentrated specimens 1
   • Fluorescence microscopy is 10% more sensitive than conventional microscopy 1

4. Molecular Testing

   • Nucleic acid amplification tests (NAATs) provide rapid confirmation of M. tuberculosis complex 1
   • Rapid turnaround time (1-2 days) compared to culture (up to 6-8 weeks) 1
   • Should be performed on initial positive cultures 1

5. Drug Susceptibility Testing

   • Essential for proper clinical management 1
   • Should be performed on a positive initial culture for isoniazid, rifampin, and ethambutol 1
   • Second-line drug susceptibility testing should be done only in reference laboratories for specific cases (prior therapy, contacts of drug-resistant TB patients, etc.) 1

Treatment Options for TB

Treatment of Active TB Disease

Standard First-Line Regimen

• Intensive Phase (2 months): Isoniazid, rifampin, pyrazinamide, and ethambutol daily 1, 4
• Continuation Phase (4 months): Isoniazid and rifampin daily 1, 4
• Therapy should be extended to 9 months if 2-month culture remains positive 1

Special Considerations

• HIV Co-infection: May require longer treatment and more careful monitoring due to potential malabsorption issues 5
• Extrapulmonary TB: Basic principles are the same as for pulmonary TB, but military TB, bone/joint TB, and tuberculous meningitis in children should receive 12-month therapy 5
• Pregnancy: Streptomycin and pyrazinamide are not recommended; initial regimen should consist of isoniazid and rifampin with ethambutol if primary isoniazid resistance is possible 5

Treatment of Multidrug-Resistant TB (MDR-TB)

• MDR-TB (resistance to at least isoniazid and rifampin) requires individualized treatment based on susceptibility studies 6
• Consultation with a TB expert is recommended 7
• Treatment should be conducted in specialized centers 8

Treatment of Latent TB Infection (LTBI)

• Preferred regimens include:
  • Isoniazid + rifapentine for 3 months
  • Rifampin alone for 4 months 7

Monitoring During Treatment

• Monthly clinical evaluations to identify adverse effects and assess adherence 1
• Monthly sputum specimens for microscopy and culture until two consecutive specimens are negative 1
• Baseline and follow-up liver function tests for patients with risk factors for hepatotoxicity 1
• Monthly visual acuity and color discrimination testing for patients on ethambutol 1

Important Considerations and Pitfalls

Infectiousness Assessment

• Patients should be considered infectious if they:
  • Are coughing
  • Are undergoing cough-inducing procedures
  • Have positive AFB sputum smears
  • Are not on chemotherapy or just started therapy
  • Have poor clinical or bacteriologic response to therapy 1

Common Pitfalls to Avoid

• Inadequate specimen collection: Sputum induction or bronchoscopy may be necessary for patients unable to produce sputum 1
• Premature discontinuation of isolation: TB patients should remain in isolation until three consecutive negative sputum smears are obtained and clinical improvement is demonstrated 1
• Failure to test for HIV: All TB patients should have HIV counseling and testing 1
• Inadequate drug susceptibility testing: Essential for proper management, especially in areas with high drug resistance rates 4
• Poor adherence monitoring: Directly Observed Therapy (DOT) is recommended for all patients to ensure compliance 5

Drug Interactions and Side Effects

• Rifampin induces multiple drug metabolizing enzymes and can decrease the effectiveness of many medications including oral contraceptives 4
• Monitor for hepatotoxicity, especially when combining rifampin with isoniazid 4
• Consider pyridoxine (vitamin B6) supplementation for malnourished patients and those predisposed to neuropathy (alcoholics, diabetics) 5

By following these diagnostic and treatment guidelines, clinicians can effectively identify and manage tuberculosis, reducing morbidity, mortality, and disease transmission.