Asymptomatic adults at higher risk for latent tuberculosis infection (LTBI) should be screened in primary care settings, advises a new recommendation statement from the US Preventive Services Task Force (USPSTF).
Published in the September 6 issue of JAMA, the statement identifies people at increased risk as those born or previously resident in countries with prevalent TB and those exposed in group living settings such as correctional centers, long-term care facilities, and shelters for the homeless. Countries with a high prevalence of the disease include Mexico, Guatemala, Haiti, India, the Philippines, Vietnam, India, and China.
"The Task Force recommends that primary care clinicians screen adults at increased risk for LTBI to help prevent the progression to active TB," said task force member Francisco García, MD, MPH, a professor of public health at the University of Arizona in Tucson, in a JAMA news release. "The best approach to prevention is identifying those populations at high risk for exposure as well as those individuals whose underlying medical disease may make them more susceptible to TB infection."
Although the precise prevalence of LTBI in the United States is difficult to determine, the authors note, the estimated prevalence is between 4.7% and 5.0%, according to the 2011 to 2012 National Health and Nutrition Examination Survey.
About 30% of persons exposed to Mycobacterium tuberculosis will develop LTBI and remain untreated, according to the USPSTF recommendation statement. Of those, 5% to 10% will progress to active or reactivated disease, with progression more likely in individuals with medical and other risk susceptibilities.
Last year, 9563 new cases of active TB were reported in the United States, for an incidence rate of 3.0 cases per 100,000 population, and in 2013, 555 people died of TB; Asians accounted for 33%, followed by Hispanics at 28% and African Americans at 21%.
After a 72-study evidence review, the task force concluded that accurate LTBI screening tests are available, treatment is moderately beneficial for forestalling active disease, and the harms of screening and treatment are small. Current tests include the Mantoux tuberculin skin test and interferon-gamma release assays, both of which are moderately sensitive and highly specific, the statement panel said.
The USPSTF estimated that screening a hypothetical cohort of 100,000 asymptomatic at-risk adults would prevent 52,146 active TB cases and cause 7 to 67 cases of hepatotoxicity, whereas 111 patients would stop treatment because of adverse events. The number needed to treat to prevent a single case of progression would be in the 111 to 314 range, and the range needed to produce a single case of hepatotoxicity would be 279 to 2531.
The task force's Evidence Report and Systematic Review found no studies evaluating the harms of screening vs no screening, and none reporting directly on screening-related harms. However, the authors, led by Leila C. Kahwati, MD, senior research analyst at RTI International–University of North Carolina at Chapel Hill, North Carolina, cited the potential for stigma of screening, diagnosis, and treatment for false-positive results.
In five good- or fair-quality studies involving 36,043 participants assessing isoniazid, rifampin, and rifapentine plus isoniazid, hepatotoxicity was the most frequently occurring harm, especially with isoniazid. Isoniazid was also associated with more gastrointestinal adverse effects and discontinuations.
The USPSTF's final 2016 recommendation follows a draft recommendation posted online in April. It is similar to its 1996 screening recommendation, although it lowered the evidence grade for screening from A (high certainty of substantial benefit) to B (high certainty of moderate benefit). The downgrade reflects recent research, technological advances, and changes in epidemiology and the USPSTF review process.
The statement notes that screening at-risk populations of LTBI has also been recommended by the American Academy of Family Physicians, the American Thoracic Society, the Infectious Diseases Society, and the Centers for Disease Control and Prevention (CDC).
In a related editorial, Henry M. Blumberg, MD, from the Division of Infectious Diseases at Emory University School of Medicine in Atlanta, Georgia, and Joel D. Ernst, MD, from the Division of Infectious Diseases and Immunology at New York University School of Medicine in New York City, said the recommendations "provide a service by focusing discussions on how to expand efforts on targeted testing and treatment of LTBI among adults seen in primary care settings."
However, they foresee challenges in implementation "because of the current inability to precisely define individuals at high risk for progression to active TB."
Because the task force was unable to provide specific guidance on precisely which primary care patients need screening, write Dr Blumberg and Dr Ernst, "[f]urther guidance for clinicians (eg, from the CDC and state and local health departments) is needed to implement these USPSTF recommendations in primary care settings."
They note that the USPSTF evidence review specifically excluded those at highest risk and most likely to benefit from targeted screening, as these populations may be routinely screened in standard care. These include those with HIV, those receiving immunosuppressives, and those in close contact with patients with active TB. "Once these highest-risk groups are removed, which patients are high risk in the primary care setting, and how should clinicians implement the USPSTF recommendations?" they ask.
Dr Blumberg and Dr Ernst also note that the standard estimate of lifetime risk for active TB after LTBI infection is 5% to 10%, and most immunologically healthy individuals do not develop active disease. Complicating the picture are treatment completion rates of less than 50%.
Moreover, as current detection tests are poorly predictive for progression, new biomarkers are called for, the editorial commentators write. These "immunologic signatures" of antigen-specific T-cell responses might help identify infected people who will develop active TB.
The USPSTF, an independent voluntary review panel, is supported by the Agency for Healthcare Research and Quality. The evidence review was cofunded by the Agency for Healthcare Research and Quality and the CDC. The authors have disclosed no relevant financial relationships. The editorial commentators reported support from the National Institutes of Health, but otherwise declared no relevant conflicts of interest.
JAMA. 2016;316:931-933, 962-969. Recommendation statement full text, Editorial full text, Evidence review full text