What is the recommended diagnostic workup and treatment for tuberculosis in at-risk populations?

Tuberculosis Presentation and Diagnostic Workup in At-Risk Populations

In at-risk populations, tuberculosis should be suspected when any one of the following symptoms is present: cough, hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, or fatigue, and screening should combine symptom assessment with chest radiography to achieve the highest sensitivity for ruling out active TB before proceeding with latent TB testing. 1

Priority At-Risk Populations Requiring Systematic Testing

The WHO strongly recommends systematic testing and treatment for the following high-priority groups 1:

• People living with HIV (risk of progression 35-162 cases per 1000 person-years; TST positive if ≥5mm induration) 2, 1
• Adult and child contacts of pulmonary TB cases (especially children <4 years; TST positive if ≥5mm) 1, 2
• Patients initiating anti-TNF therapy (requires pre-treatment screening algorithm) 1, 2
• Patients receiving dialysis 1
• Patients preparing for organ or hematological transplantation 1
• Patients with silicosis 1
• Immunosuppressed patients (including those on ≥15mg/day prednisone for ≥1 month; TST positive if ≥5mm) 1
• Persons with fibrotic changes on chest radiograph consistent with prior TB (TST positive if ≥5mm) 1

Secondary At-Risk Groups for Conditional Testing

The WHO conditionally recommends systematic testing for 1:

• Prisoners and residents of congregate settings (TST positive if ≥10mm) 1, 2
• Healthcare workers (TST positive if ≥10mm) 1, 2
• Immigrants from high TB burden countries within the last 5 years (TST positive if ≥10mm) 1, 2
• Homeless persons 1, 2
• Illicit drug users (injection drug users; TST positive if ≥10mm) 1, 2

Additional High-Risk Medical Conditions

Testing should be considered (TST positive if ≥10mm) for 1, 2:

• Diabetes mellitus (2-4 times increased risk) 2, 1
• Chronic renal failure and glomerular diseases (highest risk with SIR 23.36) 2, 1
• Hematologic disorders (leukemias, lymphomas) 1
• Head/neck and lung carcinomas 1
• Gastrectomy or jejunoileal bypass 1
• Weight loss >10% of ideal body weight 1
• Untreated hepatitis C (adjusted HR 2.9 for active TB) 2
• Rheumatoid arthritis (SIR 10.9 vs general population) 2

Diagnostic Algorithm for Active TB

Step 1: Symptom Screening

Before any LTBI testing, all individuals must be screened for TB symptoms 1:

The presence of any one of these symptoms warrants further evaluation 1:

• Cough (especially >2-3 weeks duration) 3, 4
• Hemoptysis 1
• Fever 1
• Night sweats 1
• Weight loss 1
• Chest pain 1
• Shortness of breath 1
• Fatigue 1

Step 2: Chest Radiography

Chest radiography must be performed before LTBI treatment to rule out active TB disease 1. This is a strong recommendation even in asymptomatic individuals being evaluated for LTBI 1. The combination of symptom screening plus chest radiography offers the highest sensitivity and negative predictive value to rule out active TB 1.

Step 3: Microbiological Confirmation (if Active TB Suspected)

When active TB is suspected based on symptoms or radiographic findings 3, 4:

• Collect at least 3 serial sputum samples for acid-fast bacilli (AFB) smear and culture 4
• Liquid medium cultures are indicated in all cases (gold standard) 4, 5
• Nucleic acid amplification tests (NAAT) are adjunctive in moderate-to-high TB suspicion 4, 5
• Drug susceptibility testing should be performed on all initial isolates 4

Testing for Latent TB Infection

Test Selection

Either TST or IGRA can be used in high-income countries with TB incidence <100 per 100,000 1. However:

• IGRA is preferred over TST in BCG-vaccinated individuals to avoid false-positive results 2
• TST should not be replaced by IGRA in low-income countries 1
• Two-step TST is required at baseline if no testing was performed in the preceding year 1

TST Interpretation by Risk Group

The three cutoff levels for TST positivity are 1:

≥5mm induration (highest risk groups):

• HIV-positive persons 1, 2
• Recent TB contacts 1, 2
• Fibrotic changes on chest X-ray 1
• Organ transplant recipients 1
• Immunosuppressed patients 1

≥10mm induration (moderate risk):

• Recent immigrants (<5 years) from high-prevalence countries 1
• Injection drug users 1
• Residents/employees of high-risk congregate settings 1
• Mycobacteriology laboratory personnel 1
• Persons with high-risk clinical conditions (diabetes, chronic renal failure, etc.) 1

≥15mm induration:

• Persons with no risk factors for TB 1

Critical Pitfalls to Avoid

• Do not perform routine testing in low-risk populations without risk factors 1, 2 - this diverts resources and increases false-positive results 1
• Do not test unless prepared to treat - testing should only be conducted when a plan exists to complete treatment in LTBI-positive persons 1
• BCG vaccination does not contraindicate TST but may affect interpretation; use IGRA when available 2
• Do not perform routine anergy testing in HIV-positive or immunosuppressed persons 2
• Immunosuppression may modify clinical and radiological presentation - maintain high index of suspicion even with atypical findings 4
• In pregnant women with positive TST or recent TB contact, perform chest radiography with appropriate shielding as soon as possible, even in first trimester 2

Special Considerations for Healthcare Workers

• Baseline testing required at employment (two-step TST if no testing in prior year) 1
• Annual testing in medium-risk settings 1
• Testing every 3 months if ongoing transmission documented until transmission terminated 1
• Follow-up testing in low-risk settings only after exposure to infectious TB patient 1

Mandatory Reporting

Both suspected and confirmed cases of LTBI and active TB disease must be reported to local or state health departments 3. This is essential for contact tracing and public health surveillance.