USPSTF recommends latent TB screenings for at-risk adults

The U.S. Preventive Services Task Force is recommending screening for latent tuberculosis infection in populations at increased risk, according to a statement issued in JAMA.

The strategy, which received a B recommendation, is in line with similar guidelines issued by the American Academy of Family Physicians, the CDC, the American Thoracic Society and the Infectious Diseases Society of America.

Joel D. Ernst

“In the United States, tuberculosis remains an important preventable disease, including active tuberculosis infection, which may be infectious, and latent infection (LTBI), which is asymptomatic and not infectious but can later reactivate and progress to active disease,” the members wrote. “The precise prevalence rate of LTBI in the United States is difficult to determine; however, based on 2011-2012 National Health and Nutrition Examination Survey data, estimated prevalence is 4.7% to 5%.”

In its statement, the USPSTF reported adequate evidence that screening tests for LTBI are both accurate and available, that treating LTBI to prevent progression to active disease has a moderate benefit and that there are only small harms in screening and treating LTBI. The agency noted that hepatotoxicity is the primary harm of treatment.

They defined populations at increased risk as individuals who were born in or lived in counties with increased TB prevalence or individuals who previously lived or currently live in congregate settings such as correctional facilities or homeless shelters. The USPSTF recognized that specific areas may have additional populations at high risk and recommended that physicians consult local and state health departments for more information.

The recommendations are an update of previous screening guidelines issued in 1996.

“At that time, the USPSTF recommended screening for tuberculosis infection with the [tuberculin skin test (TST)] in asymptomatic, high-risk persons (A recommendation) and consideration of [bacille Calmette-Guérin (BCG)] vaccination for selected high-risk individuals only (B recommendation),” they wrote. “Given the changes in the epidemiology of the disease, the development of newer screening technologies, and newer methods for developing evidence-based recommendations, the USPSTF decided to update the topic and issue a recommendation using its current methodology and considering all of the available evidence, including studies published prior to 1996.”

In an evidence report published alongside the recommendations, Leila C. Kahwati, MD, MPH, from RTI International, and colleagues reviewed research identified via the Cochrane Library, trial registries, references and experts through May.

They included 72 studies of 51,711 participants that assessed LTBI screening, treatment with pharmacotherapy, TST or interferon-gamma release assays (IGRAs).

Results showed that pooled sensitivity estimates of the TST at 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89; 10-mm: 95% CI 0.71-0.87), while IGRA estimates ranged from 0.77 to 0.9. Specificity estimates of IGRAs and the TST at 10-mm and 15-mm thresholds ranged from 0.95 to 0.99.

In addition, a trial of individuals who were treated with 24 weeks of isoniazid resulted in a risk reduction of active TB at 5 years from 1.4% to 0.5% (RR = 0.35; 95% CI, 0.24-0.52) and an increase in hepatoxicity risk from 0.1% to 0.5% (RR = 4.59; 95% CI, 2.03-10.39) compared with placebo.

Kahwati and colleagues reported that another trial demonstrated 3 months of once-weekly rifapentine and isoniazid was similar to 9 months of isoniazid alone in the prevention of active TB. In a comparison of isoniazid and rifampin, risk difference for hepatoxicity ranged from 3% to 7% (pooled RR = 3.29; 95% CI, 1.72-6.28).

“No studies evaluated the benefits and harms of screening compared with no screening,” Kahwati and colleagues noted. “Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.”

In a related editorial published in JAMA Internal Medicine, Randal Reves, MD, and Charles L. Daley, MD, both from the University of Colorado, wrote that “only through linkage to accessible and affordable treatment” can the U.S. reach its goal of TB elimination.

“Targeted testing for LTBI is a critical but insufficient step in TB prevention,” they wrote. “The potential benefits of increased screening will be attained only by achieving high rates of LTBI treatment acceptance and completion, and this will require engagement of affected communities and enhanced collaboration between primary care clinicians and public health departments.”

Henry M. Blumberg, MD, from Emory University School of Medicine, and Infectious Disease News Editorial Board member Joel D. Ernst, MD, from New York University School of Medicine, discussed the challenge that primary care physicians face in dealing with LTBIs in a separate editorial, also published in JAMA.

They noted that providers will need additional guidance from the CDC as well as state and local health departments in order to implement the USPSTF’s recommendations.

“Given that the highest-risk groups (eg, persons living with HIV, contacts of persons with active TB, persons who will receive tumor necrosis factor-alpha inhibitors) were not part of the USPSTF scope of review, the most frequently encountered high-risk group will include immigrants from countries with high TB burden, which may represent the best target for screening in primary care settings,” they wrote. “Other individuals at increased risk may include homeless persons, illicit drug users, and those who are incarcerated or who work in a correctional facility or other high-risk congregate settings such as homeless shelters.”

Blumberg and Ernst also acknowledged that there will likely be changes to CDC treatment guidelines in the future, which will help in primary care settings, but that physicians need better tools for TB control.

“In the short run, implementation science (operational research) will be needed to help facilitate the best ways of implementing the USPSTF recommendations,” they wrote. “In the long run and to overcome the challenge of LTBI, new tools are needed including new and better diagnostic tests, biomarkers that have a high predictive value for identifying which patients are at risk for progression to active disease, and shorter, more effective and better-tolerated regimens for treatment of LTBI. Such advancements will not be made without substantial investments in TB research by funders, including foundations and, most importantly, the United States and other governments from high- and middle-income countries.” – by Chelsea Frajerman Pardes

Disclosures: Blumberg and Ernst report serving as principal investigators on NIH and other federal grants. The other authors report no relevant financial disclosures.

The U.S. Preventive Services Task Force is recommending screening for latent tuberculosis infection in populations at increased risk, according to a statement issued in JAMA.

The strategy, which received a B recommendation, is in line with similar guidelines issued by the American Academy of Family Physicians, the CDC, the American Thoracic Society and the Infectious Diseases Society of America.

Joel D. Ernst

“In the United States, tuberculosis remains an important preventable disease, including active tuberculosis infection, which may be infectious, and latent infection (LTBI), which is asymptomatic and not infectious but can later reactivate and progress to active disease,” the members wrote. “The precise prevalence rate of LTBI in the United States is difficult to determine; however, based on 2011-2012 National Health and Nutrition Examination Survey data, estimated prevalence is 4.7% to 5%.”

In its statement, the USPSTF reported adequate evidence that screening tests for LTBI are both accurate and available, that treating LTBI to prevent progression to active disease has a moderate benefit and that there are only small harms in screening and treating LTBI. The agency noted that hepatotoxicity is the primary harm of treatment.

They defined populations at increased risk as individuals who were born in or lived in counties with increased TB prevalence or individuals who previously lived or currently live in congregate settings such as correctional facilities or homeless shelters. The USPSTF recognized that specific areas may have additional populations at high risk and recommended that physicians consult local and state health departments for more information.

The recommendations are an update of previous screening guidelines issued in 1996.

“At that time, the USPSTF recommended screening for tuberculosis infection with the [tuberculin skin test (TST)] in asymptomatic, high-risk persons (A recommendation) and consideration of [bacille Calmette-Guérin (BCG)] vaccination for selected high-risk individuals only (B recommendation),” they wrote. “Given the changes in the epidemiology of the disease, the development of newer screening technologies, and newer methods for developing evidence-based recommendations, the USPSTF decided to update the topic and issue a recommendation using its current methodology and considering all of the available evidence, including studies published prior to 1996.”

In an evidence report published alongside the recommendations, Leila C. Kahwati, MD, MPH, from RTI International, and colleagues reviewed research identified via the Cochrane Library, trial registries, references and experts through May.

They included 72 studies of 51,711 participants that assessed LTBI screening, treatment with pharmacotherapy, TST or interferon-gamma release assays (IGRAs).

Results showed that pooled sensitivity estimates of the TST at 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89; 10-mm: 95% CI 0.71-0.87), while IGRA estimates ranged from 0.77 to 0.9. Specificity estimates of IGRAs and the TST at 10-mm and 15-mm thresholds ranged from 0.95 to 0.99.

In addition, a trial of individuals who were treated with 24 weeks of isoniazid resulted in a risk reduction of active TB at 5 years from 1.4% to 0.5% (RR = 0.35; 95% CI, 0.24-0.52) and an increase in hepatoxicity risk from 0.1% to 0.5% (RR = 4.59; 95% CI, 2.03-10.39) compared with placebo.

Kahwati and colleagues reported that another trial demonstrated 3 months of once-weekly rifapentine and isoniazid was similar to 9 months of isoniazid alone in the prevention of active TB. In a comparison of isoniazid and rifampin, risk difference for hepatoxicity ranged from 3% to 7% (pooled RR = 3.29; 95% CI, 1.72-6.28).

“No studies evaluated the benefits and harms of screening compared with no screening,” Kahwati and colleagues noted. “Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.”

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In a related editorial published in JAMA Internal Medicine, Randal Reves, MD, and Charles L. Daley, MD, both from the University of Colorado, wrote that “only through linkage to accessible and affordable treatment” can the U.S. reach its goal of TB elimination.

“Targeted testing for LTBI is a critical but insufficient step in TB prevention,” they wrote. “The potential benefits of increased screening will be attained only by achieving high rates of LTBI treatment acceptance and completion, and this will require engagement of affected communities and enhanced collaboration between primary care clinicians and public health departments.”

Henry M. Blumberg, MD, from Emory University School of Medicine, and Infectious Disease News Editorial Board member Joel D. Ernst, MD, from New York University School of Medicine, discussed the challenge that primary care physicians face in dealing with LTBIs in a separate editorial, also published in JAMA.

They noted that providers will need additional guidance from the CDC as well as state and local health departments in order to implement the USPSTF’s recommendations.

“Given that the highest-risk groups (eg, persons living with HIV, contacts of persons with active TB, persons who will receive tumor necrosis factor-alpha inhibitors) were not part of the USPSTF scope of review, the most frequently encountered high-risk group will include immigrants from countries with high TB burden, which may represent the best target for screening in primary care settings,” they wrote. “Other individuals at increased risk may include homeless persons, illicit drug users, and those who are incarcerated or who work in a correctional facility or other high-risk congregate settings such as homeless shelters.”

Blumberg and Ernst also acknowledged that there will likely be changes to CDC treatment guidelines in the future, which will help in primary care settings, but that physicians need better tools for TB control.

“In the short run, implementation science (operational research) will be needed to help facilitate the best ways of implementing the USPSTF recommendations,” they wrote. “In the long run and to overcome the challenge of LTBI, new tools are needed including new and better diagnostic tests, biomarkers that have a high predictive value for identifying which patients are at risk for progression to active disease, and shorter, more effective and better-tolerated regimens for treatment of LTBI. Such advancements will not be made without substantial investments in TB research by funders, including foundations and, most importantly, the United States and other governments from high- and middle-income countries.” – by Chelsea Frajerman Pardes

Disclosures: Blumberg and Ernst report serving as principal investigators on NIH and other federal grants. The other authors report no relevant financial disclosures.