Latent Tuberculosis Infection

Latent tuberculosis infection is a state of persistent immune response to Mycobacterium tuberculosis antigens without evidence of active disease. Lifetime risk of progression to active tuberculosis is about 5 to 10 percent, with highest risk in the first 2 years, in HIV infection and in young children.

• Priority groups: people living with HIV, household contacts of infectious cases (especially children under 5 years), patients starting TNF inhibitors, dialysis, silicosis, transplant, prisoners, healthcare workers, recent converters, people with diabetes or malnutrition.
• Pregnancy, malnutrition, substance use and corticosteroids increase risk.

Asymptomatic with normal chest radiograph.

• Tuberculin skin test induration of 5 mm or more in HIV and immunosuppressed, 10 mm or more in others; or a positive interferon gamma release assay.
• Differential diagnosis: active tuberculosis (cough, fever, weight loss, night sweats), non tuberculous mycobacterial infection, BCG vaccination effect (false positive skin test), sarcoidosis, malignancy, other chronic infections.
• Complications: progression to active pulmonary or extrapulmonary tuberculosis, disseminated disease, transmission, drug induced hepatitis from treatment.

Rule out active disease before treatment.

• Symptom screen (cough, fever, weight loss, night sweats), chest radiograph, sputum Xpert and culture if any abnormality or symptom; urine lipoarabinomannan in advanced HIV.
• Tuberculin skin test (0.1 mL of purified protein derivative intradermally, read at 48 to 72 hours) or interferon gamma release assay; neither is required before treatment of people with HIV and child contacts under 5 years.
• Baseline liver enzymes if liver disease, alcohol use, pregnancy or hepatotoxic drugs; HIV test.

Preventive therapy lowers the risk of active disease by 60 to 90 percent.

• Supportive: counselling on adherence and symptoms, alcohol avoidance, hepatitis screening, directly observed therapy where possible, contact tracing.
• Pharmacological: choose one regimen. 3HP: isoniazid 15 mg/kg (maximum 900 mg) with rifapentine (32 to 49.9 kg 750 mg; 50 kg and over 900 mg) once weekly for 12 weeks. 6H: isoniazid 5 mg/kg daily (maximum 300 mg) for 6 months. 3HR: isoniazid 5 mg/kg (maximum 300 mg) plus rifampicin 10 mg/kg (maximum 600 mg) daily for 3 months. 4R: rifampicin 10 mg/kg (maximum 600 mg) daily for 4 months. Pyridoxine 25 to 50 mg daily with isoniazid. Children: isoniazid 10 mg/kg (7 to 15) with rifampicin 15 mg/kg (10 to 20) daily for 3 months, or isoniazid 10 mg/kg for 6 months. For people on dolutegravir, weekly rifapentine allows dolutegravir 50 mg once daily; daily rifampicin requires dolutegravir 50 mg twice daily. Efavirenz and nevirapine interact with rifamycins, so avoid rifapentine with them.
• Procedures: none.
• Special groups: pregnancy, isoniazid with pyridoxine for 6 months, and avoid rifapentine; HIV, treat regardless of CD4 and tuberculin result; liver disease, avoid isoniazid or monitor liver tests monthly; contacts of drug resistant tuberculosis, a fluoroquinolone based regimen (levofloxacin 750 to 1000 mg daily for 6 months) under specialist guidance; elderly, monitor for hepatotoxicity.
• Red flags: jaundice, dark urine, nausea, abdominal pain, peripheral neuropathy, rash, flu like reaction after rifapentine, symptoms of active tuberculosis.
• Follow-up: monthly visits to assess adherence and adverse effects; liver tests at baseline and when symptomatic or in high risk; symptom screen at every visit.