Focusing on High-Risk Patients With TB May Help Eliminate the Disease in US

Focusing on patients with latent tuberculosis infection (LTBI) who are at high risk of developing active TB may be key to eliminating the disease in the United States, according to a study by Soumya Chatterjee, MD, and colleagues recently published in PLoS ONE.

Progress toward the goal of eliminating TB in the United States has stalled in recent years, as infection rates, which were declining steadily, have plateaued. A contributing factor likely involves patients who do not complete their full course of treatment, which involves taking a tablet daily for 6 months. However, the rate of completing this therapy is only 50% 60%. Chatterjee and his team theorized that if physicians could identify patients with LTBI at highest risk of active infection, and then focus efforts on helping them complete treatment, the United States could again make progress toward the goal of eradicating TB.

"If we can separate out who is at high, moderate, and low risk of progressing to active status, we can focus on the high-risk group to help ensure that they complete their course of treatment," he said in a statement. While those with LTBI do not have symptoms and usually are not contagious, they are at risk of eventually developing an active form of TB. The CDC recommends that patients with LTBI receive treatment to kill the dormant bacteria to prevent active infection.

The researchers gathered existing data from 125 adult clinic patients seen from 2010 to 2015 who were diagnosed with LTBI and retroactively entered data into a free online risk calculator that uses individual risk factors to generate an overall risk assessment for the likelihood that a patient with LTBI will go on to develop active infection. The test combines tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA) screening results with other clinically pertinent information to estimate the positive predictive value (PPV) of TB infection as well as individual’s annual and cumulative risk of progression to active TB. All the patients were TST and/or IGRA positive. The investigators also assessed provider risk awareness and compared treatment completion rates in subjects at low, intermediate, and high risk of LTBI reactivation.

The study found that among the 125 subjects, 51 (41%), 46 (37%), and 28 (22%) were in low-, intermediate-, and high-risk groups, respectively. The risk calculator was useful in determining the probability of LTBI in TST-positive patients. The overall treatment completion rate was 61% in 114 subjects with complete treatment information, and similar completion rates were seen in all 3 risk groups (low, 60%; intermediate, 63%; high, 57%). Provider assessment of important clinical risk factors was often incomplete. Logistic regression analysis showed no association of assessment of important risk factors with treatment completion.

The study found that physicians are not systematically identifying risk levels for patients with latent TB. "The calculator is a tool to differentiate who is at highest risk for active infection," Chatterjee explained. "It could allow doctors to communicate the importance of completing a treatment regimen to their high-risk patients.”

Provider awareness of a subject being at high risk of progression to active TB could facilitate treatment completion using shorter supervised regimens to ensure treatment completion in that group. Recently, a 3-month directly observed regimen of weekly isoniazid and rifapentine that was approved by the CDC has shown equivalent efficacy. (This regimen is only recommended in selected clinical high-risk groups.)

The researchers note that current standard of care practice did not result in higher treatment completion rates for patients in the high-risk group, and that evaluation of a particular risk factor was not associated with improved treatment completion, but they believe this could be because providers often select treatment regimens based on side-effect profiles of drugs, rather than the patient’s risk of progression to active TB.

“Our main revelation from this study is that we should be doing risk stratification with TB patients," Chatterjee noted.

The major limitations of the calculator are the lack of updated data on country-specific prevalence of TB disease as the global burden of TB continues to decrease, as well as falsely high PPVs that are due to transiently positive IGRA results in subjects from countries with low TB prevalence.

“Nonetheless, our findings suggest that tstin3d.com could be utilized in the US setting for improving providing awareness of risk stratification of patients with LTBI for short-course treatment regimens based on risk," he said.

Reference

Scolarici M, Dekitani K, Chen L, Sokol-Anderson M, Hoft DF, Chatterjee S. A scoring strategy for progression risk and rates of treatment completion in subjects with latent tuberculosis. PLoS ONE. 2018;13(11):e0207582. doi: 10.1371/journal.pone.0207582.