What is the risk of tuberculosis (TB) reactivation in untreated individuals with latent tuberculosis (TB) infection?

From the Guidelines

The risk of tuberculosis (TB) reactivation in untreated individuals with latent tuberculosis infection (LTBI) is estimated to be 5–15% over their lifetime, with the majority developing TB disease within the first 5 years after initial infection. This risk is not evenly distributed, as certain factors significantly increase the likelihood of progression to active disease, including bacterial, host, and environmental factors 1. Individuals with compromised immune systems face the greatest risk, and the reactivation of TB can be averted by preventive treatment, which has an efficacy ranging from 60% to 90% and can last for up to 19 years 1.

Key Factors Influencing Risk

• Bacterial factors: the strain of Mycobacterium tuberculosis
• Host factors: immune status, age, and presence of underlying medical conditions
• Environmental factors: exposure to TB, socioeconomic status, and access to healthcare The risk of reactivation is higher in certain age groups, with infants and young children under 5 years old and older adults having increased vulnerability. Other risk factors include malnutrition, smoking, and silicosis.

Preventive Treatment

Preventive treatment with medications like isoniazid, rifampin, or the combination of isoniazid and rifapentine is recommended for high-risk individuals with LTBI to reduce their risk of developing active TB disease 1. The potential benefit of treatment needs to be carefully balanced against the risk of drug-related adverse events.

High-Risk Groups

High-risk groups that would benefit most from preventive treatment include those with a high risk of progression to active disease, such as individuals with HIV infection, recent TB infection, diabetes, chronic kidney disease requiring dialysis, organ transplantation, or those on immunosuppressive medications like TNF-alpha inhibitors or high-dose corticosteroids 1.

From the FDA Drug Label

Isoniazid is recommended as preventive therapy for the following groups, regardless of age. Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy. Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly.

The risk of tuberculosis (TB) reactivation in untreated individuals with latent tuberculosis (TB) infection is not directly stated in the provided drug label. However, it can be inferred that the risk is significant enough to warrant preventive therapy in certain groups, such as:

• Persons with HIV infection
• Close contacts of persons with newly diagnosed infectious tuberculosis
• Recent converters, as indicated by a tuberculin skin test
• Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis
• Persons with certain medical conditions that increase the risk of tuberculosis, such as silicosis, diabetes mellitus, and immunosuppressive therapy 2 The label recommends isoniazid preventive therapy for these groups to prevent the reactivation of latent TB infection.

From the Research

Risk of TB Reactivation in Untreated Individuals

The risk of tuberculosis (TB) reactivation in untreated individuals with latent tuberculosis (TB) infection is a significant concern. Several studies have investigated this risk and the factors that contribute to it.

• The risk of TB reactivation is increased in individuals with certain high-risk factors, such as human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts, and kidney dialysis 3.
• The preventive treatment of latent tuberculosis infection (LTBI) is crucial for the elimination and control of tuberculosis (TB) worldwide 3.
• Treatment of LTBI can prevent the progression to TB disease, and several regimens are available, including once-weekly isoniazid plus rifapentine for 3 months, daily rifampin for 4 months, and daily isoniazid for 6-9 months 4.
• The efficacy and completion rates of these regimens have been compared in several studies, and the results suggest that shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens 5.
• Treatment completion rates are higher for shorter regimens, such as 3 months of isoniazid and rifapentine or 4 months of rifampin, compared to 9 months of isoniazid 6.

Factors Contributing to TB Reactivation

Several factors contribute to the risk of TB reactivation in untreated individuals, including:

• HIV infection 3
• Organ transplantation 3
• Silicosis 3
• Tumor necrosis factor-alpha blockers 3
• Close contacts 3
• Kidney dialysis 3
• The presence of these factors can increase the risk of TB reactivation, and preventive treatment of LTBI is essential to prevent the progression to TB disease.

Treatment Options for LTBI

Several treatment options are available for LTBI, including:

• Once-weekly isoniazid plus rifapentine for 3 months 4
• Daily rifampin for 4 months 4
• Daily isoniazid for 6-9 months 4
• The choice of treatment regimen depends on several factors, including the presence of high-risk factors, the patient's age and comorbidities, and the availability of resources.
• The efficacy and completion rates of these regimens have been compared in several studies, and the results suggest that shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens 5.