What is the recommended treatment for latent tuberculosis (TB) infection in an individual with a positive QuantiFERON (Interferon-Gamma Release Assay) test and a negative chest X-ray, indicating previous exposure?

Management of Latent TB Infection with Positive QuantiFERON and Negative Chest X-Ray

For a patient with a positive QuantiFERON test and negative chest X-ray indicating latent TB infection, treatment with isoniazid for 9 months (or alternatively 6 months) is recommended, with the decision to treat based on the patient's risk category and clinical judgment regarding their likelihood of progression to active disease. 1

Risk Stratification and Treatment Decision

The decision to initiate LTBI treatment depends critically on your patient's risk profile:

High-Priority Groups (Treatment Strongly Recommended)

Treatment should be offered to patients with any of the following risk factors 1:

• HIV/AIDS infection
• Recent close contact with active pulmonary TB (within 2 years)
• Immunosuppressive therapy (organ transplant recipients, anti-TNF biologics, high-dose corticosteroids)
• Chronic renal failure requiring dialysis
• Silicosis
• Chest radiograph showing fibronodular shadows suggesting old untreated TB (though your patient has negative CXR)

Moderate-Priority Groups (Treatment Conditionally Recommended)

Consider treatment based on clinical judgment and additional risk factors 1:

• Recent immigrants from high TB burden countries (within 5 years)
• Healthcare workers
• Prisoners
• Homeless persons
• Injection drug users
• Diabetes mellitus
• Significant underweight (>10% below ideal body weight)
• Chronic corticosteroid use (even lower doses)
• History of gastrectomy
• Current tobacco smoking

Low-Risk Individuals

For persons at low risk for TB (no identified risk factors above), confirmation with tuberculin skin test (TST) is recommended before initiating treatment 1. LTBI therapy is not recommended for low-risk persons who are QuantiFERON-positive but TST-negative 1.

Recommended Treatment Regimens

Once the decision to treat is made and active TB is excluded, choose from these evidence-based regimens 1:

First-Line Options:

• Isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months (preferred regimen) 1, 2
• Isoniazid 5 mg/kg (maximum 300 mg) daily for 6 months (acceptable alternative with substantial protection) 1, 2
• Rifampin 10 mg/kg (maximum 600 mg) daily for 4 months (when isoniazid cannot be used) 1, 3
• Isoniazid plus rifampin daily for 3-4 months 1
• Rifapentine plus isoniazid once weekly for 12 weeks (requires directly observed therapy) 1, 4

The 9-month isoniazid regimen provides maximal benefit, though the 6-month regimen may be preferred in some settings for cost-effectiveness and improved completion rates 1.

Critical Pre-Treatment Steps

Rule Out Active TB Disease

Before initiating LTBI treatment 1:

• Obtain chest radiograph (already done in your case—negative)
• Screen for TB symptoms: cough, hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, fatigue 1
• If any symptoms present or radiographic abnormalities exist, perform sputum examination (3 consecutive samples for AFB smear and culture) to exclude active disease 1
• Never start single-drug LTBI treatment until active TB is definitively excluded 1

Special Populations Requiring Additional Consideration

Pregnant women 1, 2:

• Chest radiograph with abdominal shielding should be performed even in first trimester if TST/IGRA positive
• Avoid pyrazinamide (inadequate teratogenicity data)
• Avoid streptomycin (causes congenital deafness)
• Isoniazid and rifampin are acceptable

HIV-infected patients 1:

• Even with negative chest radiograph, obtain sputum examination if respiratory symptoms present
• May have malabsorption requiring drug level monitoring
• Treatment is strongly indicated given high progression risk

Patients with liver disease or heavy alcohol use 3:

• Regular liver function monitoring required
• Consider rifampin-based regimen if significant hepatic concerns

Monitoring During Treatment

Clinical Monitoring

• Monthly clinical assessment for all patients 2
• Educate patients about hepatitis symptoms: nausea, vomiting, abdominal pain, dark urine, jaundice 3
• Instruct patients to stop medication immediately if hepatitis symptoms develop and contact provider

Laboratory Monitoring

Baseline and periodic liver function tests are indicated for 1, 2:

• Pregnant women
• HIV-positive individuals
• Heavy alcohol users
• History of liver disease
• Age >35 years (increased hepatotoxicity risk)
• Concurrent hepatotoxic medications

Pyridoxine Supplementation

Vitamin B6 (pyridoxine) 10-25 mg daily should be given with isoniazid to prevent peripheral neuropathy in 2:

• Pregnant/breastfeeding women
• HIV infection
• Diabetes
• Alcohol use disorder
• Malnutrition
• Chronic renal failure

Common Pitfalls to Avoid

Do not confirm QuantiFERON results with TST after the fact if the patient is at high risk—the need for treatment when QuantiFERON is positive should be based on clinical judgment and perceived risk, even if subsequent TST is negative 1.

Do not perform TST first then QuantiFERON for confirmation, as PPD injection may affect subsequent QuantiFERON results 1.

Do not ignore treatment completion support—directly observed therapy or enhanced adherence strategies significantly improve completion rates and prevent emergence of drug resistance 2, 4.

Do not forget to coordinate with public health authorities—health departments can provide medication adherence support, public health nurse visits, and assistance with treatment costs 3.