Please provide a concise algorithm for evaluating and treating latent tuberculosis infection, including risk assessment, symptom screening, chest radiography, TST/IGRA testing, contraindication checks, and recommended treatment regimens.

Algorithm for Latent Tuberculosis Infection Management

Step 1: Identify High-Risk Candidates for LTBI Testing

Systematic testing and treatment MUST be performed in the following groups 1:

• HIV-infected persons (5-10% annual reactivation risk) 1, 2
• Adult and child contacts of pulmonary TB cases 1
• Patients initiating anti-TNF or other biologic therapy 1
• Patients receiving dialysis for chronic renal failure 1
• Patients preparing for organ or hematological transplantation 1
• Patients with silicosis 1

Consider testing in these groups 1:

• Prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons, illicit drug users 1

Do NOT routinely test 1:

• People with diabetes alone, harmful alcohol use alone, tobacco smokers alone, or underweight persons alone (unless they meet criteria above) 1

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Step 2: Screen for Active TB Symptoms BEFORE Testing

Ask about ALL of the following TB symptoms 1:

• Cough (especially >2-3 weeks), hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, fatigue 1

If ANY symptoms are present: Investigate for active TB disease before proceeding with LTBI testing 1

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Step 3: Perform Chest Radiography

Obtain posterior-anterior chest X-ray in all candidates 3:

• Children <5 years require both PA and lateral views 3
• Pregnant individuals require chest X-ray with appropriate shielding, even in first trimester 3

If chest X-ray shows ANY abnormality 1:

• Investigate further for active TB and other conditions 1
• If findings suggest prior healed TB, obtain three consecutive sputum samples for AFB smear and culture 3

If chest X-ray is normal AND no symptoms: Proceed to LTBI testing 3

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Step 4: Perform LTBI Testing

Choose testing method based on BCG vaccination status 4:

For BCG-Vaccinated Individuals:

• Use IGRA (QuantiFERON-TB Gold or T-SPOT) - strongly preferred due to superior specificity and no cross-reactivity with BCG 1, 4

For Non-BCG-Vaccinated Individuals:

• Either TST or IGRA is acceptable 1
• TST positive = induration ≥5 mm 1, 4

Special Testing Considerations:

• Children <5 years: TST is preferred over IGRA 4
• Patients on immunosuppressants: TST may be false negative if on corticosteroids >1 month or thiopurines/methotrexate >3 months 4
• Consider booster TST 1-2 weeks after initial negative test in patients on immunomodulators 4

If test is NEGATIVE: No LTBI treatment needed (unless close contact of infectious TB case - see below) 1

If test is POSITIVE: Proceed to Step 5 1

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Step 5: Rule Out Active TB Disease (MANDATORY Before Treatment)

This step is CRITICAL to prevent drug resistance 1, 4, 3:

1. Detailed history and physical examination 1, 4
2. Chest radiography (already done in Step 3) 1, 4
3. If chest X-ray abnormal OR respiratory symptoms present: Obtain three consecutive sputum samples for AFB smear and culture 3
4. HIV-infected patients with respiratory symptoms: Obtain sputum even if chest X-ray is normal 3

Only proceed to treatment if active TB is definitively excluded 1, 4, 3

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Step 6: Assess for Treatment Contraindications

Check baseline liver function tests (AST/ALT, bilirubin) ONLY in these groups 1, 3:

• HIV-infected patients 1, 3
• Pregnant women and women ≤3 months postpartum 1, 3
• History of chronic liver disease (hepatitis B/C, alcoholic hepatitis, cirrhosis) 1, 3
• Regular alcohol users 1, 3
• Clinical suspicion of liver disorder 1, 3

Baseline testing is NOT routinely indicated for all patients or based on age alone 1, 3

Relative contraindications to treatment 1:

• Active hepatitis 1
• End-stage liver disease 1

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Step 7: Select Treatment Regimen

Preferred regimens in order of recommendation 1, 4:

First-Line Regimen:

• 3 months of once-weekly isoniazid (15 mg/kg, max 900 mg) + rifapentine (weight-based dosing) - highest completion rates, excellent tolerability 4

Alternative Preferred Regimens:

• 4 months of daily rifampin (10 mg/kg, max 600 mg) - strong evidence for HIV-negative patients 1, 4
• 3 months of daily isoniazid (5 mg/kg, max 300 mg) + rifampin (10 mg/kg, max 600 mg) - conditional recommendation for HIV-positive patients 4
• 9 months of daily isoniazid (5 mg/kg, max 300 mg) - historically standard therapy 1, 4
• 6 months of daily isoniazid - conditional recommendation with moderate evidence 1, 4

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Step 8: Special Population Modifications

HIV-Infected Patients:

• If using isoniazid, give 9 months (NOT 6 months) 1, 4
• Check antiretroviral drug interactions before prescribing rifamycins 4
• Consider rifabutin substitution if rifampin interactions problematic 1, 4

Pregnant Women (HIV-Negative):

• Isoniazid daily or twice weekly for 9 or 6 months 1, 4
• High-risk women (HIV-infected or recently infected): Do NOT delay treatment even in first trimester 1, 4
• Lower-risk women: Some experts recommend waiting until after delivery 1, 4
• Add pyridoxine supplementation 3

Children and Adolescents:

• Isoniazid daily (10-15 mg/kg, max 300 mg) or twice weekly for 9 months 1, 4

Contacts of Isoniazid-Resistant TB:

• Rifampin + pyrazinamide daily for 2 months, OR 1, 4
• Rifampin alone for 4 months if pyrazinamide intolerance 1, 4

Contacts of Multidrug-Resistant TB:

• Pyrazinamide + ethambutol OR pyrazinamide + fluoroquinolone (levofloxacin/ofloxacin) for 6-12 months 1, 4
• Immunocompetent contacts: 6 months minimum 1, 4
• Immunocompromised contacts: 12 months 1, 4

Close Contacts of Infectious TB:

• Treat regardless of TST/IGRA results, age, or prior treatment 1

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Step 9: Clinical Monitoring During Treatment

For Isoniazid Alone or Rifampin Alone:

• Monthly clinical evaluations 1, 3
• Assess for fever, malaise, vomiting, jaundice, unexplained deterioration 3

For Rifampin + Pyrazinamide:

• Evaluations at weeks 2,4, and 8 1, 3

Laboratory Monitoring:

• Routine monitoring ONLY for patients with abnormal baseline tests or high-risk groups 1, 3
• Withhold isoniazid if: AST/ALT >3× upper limit of normal WITH symptoms, OR >5× upper limit of normal WITHOUT symptoms 3

Patient Education:

• Instruct ALL patients to STOP medication immediately and seek urgent evaluation if they develop: fever, malaise, vomiting, jaundice, or unexplained deterioration 1, 3

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Critical Pitfalls to Avoid

• NEVER start LTBI treatment without definitively excluding active TB - treating unrecognized active TB with single-drug therapy causes drug resistance 4, 3
• NEVER assume normal chest X-ray excludes TB in immunocompromised patients - maintain high clinical suspicion and obtain sputum if symptoms present 4, 3
• NEVER perform baseline liver function tests routinely on all patients - only test high-risk groups 1, 3
• NEVER ignore antiretroviral drug interactions - rifamycins have significant interactions with protease inhibitors and NNRTIs 4
• NEVER use intermittent dosing without directly observed therapy - twice or thrice weekly regimens MUST be directly observed 1
• NEVER delay treatment in high-risk pregnant women - benefits outweigh risks even in first trimester 1, 4