Latent Tuberculosis Infection (LTBI) occurs when the bacterium Mycobacterium tuberculosis is present in the body but remains inactive. The immune system has contained the bacteria, but not eliminated it. Individuals with LTBI have no symptoms and cannot transmit the infection to others. Treatment is offered to prevent the bacteria from becoming active and causing full-blown tuberculosis disease, thereby reducing the overall number of active TB cases.
Understanding Latent TB and the Need for Treatment
Latent TB infection and active TB disease are two points on a spectrum of infection. With LTBI, the bacteria are dormant, the chest X-ray is normal, and the person feels healthy. Active TB disease means the bacteria are multiplying and causing illness, often resulting in symptoms like weight loss, fever, night sweats, and a prolonged cough. Only a person with active TB disease can spread the infection through the air.
The reason for treating LTBI is the risk of progression, or reactivation, to active TB disease. Without treatment, approximately 5% to 10% of infected individuals will develop active disease at some point, with about half of those cases occurring within the first two years after the initial infection. This risk increases significantly if a person’s immune system becomes compromised. Targeting the dormant bacteria with medication prevents this progression, protecting both the individual and the community.
Treatment is prioritized for those at the highest risk of reactivation, as the benefits of taking medication outweigh the risks of side effects. High-risk groups include:
- People living with Human Immunodeficiency Virus (HIV).
- Recent close contacts of someone with active TB.
- Individuals starting immunosuppressive therapy for conditions like rheumatoid arthritis or organ transplantation.
- Children under the age of five with a positive test result, as they are more likely to progress rapidly to active TB disease.
Treatment decisions are based on a person’s individual risk factors and overall health status.
Overview of Current Treatment Options
Modern guidelines favor shorter treatment courses for LTBI to encourage higher completion rates and reduce the burden on the patient. The preferred regimens are rifamycin-based, which includes the medications rifampin and rifapentine. These shorter courses have demonstrated comparable effectiveness to the older, longer treatments, with lower rates of severe liver toxicity.
One short-course option is the combination of Isoniazid and Rifapentine, known as the 3HP regimen. This involves taking both medications once a week for a total of three months (12 doses). This once-weekly dosing schedule is typically administered under Directly Observed Therapy (DOT), where a healthcare worker watches the patient take the medication to ensure adherence. The major advantage of 3HP is its short duration and high completion rate.
Another regimen is Rifampin monotherapy, taken daily for four months, often referred to as the 4R regimen. This option is effective and can be self-administered, meaning the patient takes the medication at home without supervision. The four-month duration is shorter than the older alternatives, making it a good choice when the once-weekly Isoniazid and Rifapentine regimen is not feasible due to drug interactions or other reasons.
A third short-course option involves taking Isoniazid and Rifampin daily for three months (3HR). While effective, this regimen is sometimes considered a conditional recommendation, often reserved for specific situations. The historical standard, which is now an alternative option, is Isoniazid monotherapy, taken daily for six or nine months (6H or 9H). Although effective, this longer duration is associated with higher rates of liver toxicity and lower completion rates compared to the newer, shorter, rifamycin-based regimens.
Practical Considerations for Treatment Adherence and Safety
Completing the full prescribed course of medication is paramount for the success of LTBI treatment, as stopping early allows the dormant bacteria to survive and reactivate later. Strategies to improve adherence are implemented, such as the use of DOT for intermittent regimens, to provide support and accountability. Patient education about the purpose of the treatment and the importance of taking every dose helps maintain motivation.
Medical monitoring is required to ensure patient safety while on these medications. Baseline laboratory testing for liver function markers like AST and ALT is not required for all patients, but is recommended for those with pre-existing liver disease, heavy alcohol use, or those taking other potentially liver-toxic medications. All patients, regardless of baseline testing, are evaluated at least monthly for adherence and any signs of adverse reactions.
A concern with LTBI treatment is hepatotoxicity, or drug-induced liver injury, particularly with regimens containing Isoniazid. Patients are instructed to immediately stop the medication and contact their provider if they experience symptoms of hepatitis, which include persistent fatigue, weakness, loss of appetite, nausea, vomiting, or yellowing of the skin or eyes (jaundice). Peripheral neuropathy is another side effect associated with Isoniazid, which can be mitigated by supplementing with Pyridoxine (Vitamin B6).
Rifampin and Rifapentine have side effects that require monitoring. These medications can cause a reddish-orange discoloration of body fluids, including urine, sweat, and tears, which patients should be warned about. They also have significant interactions with many other medications, including oral contraceptives and certain HIV drugs, which necessitates a careful review of all concurrent prescriptions before starting LTBI treatment.