By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Detection and treatment of latent tuberculous infection remains a key element of tuberculosis control in the United States.

SOURCES: Kahwati LC, Feltner C, Halpern M, et al. Primary care screening and treatment for latent tuberculosis infection in adults: Evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016;316:970-983.

US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement. JAMA 2016;316:962-969.

The prevalence of latent tuberculosis infection (LTBI) in the United States is estimated to be approximately 5% and, if undetected and untreated, approximately 5%-19% of individuals with latent infection will develop active tuberculosis and then likely go on to transmit the infection to others. In the United States, where BCG vaccination is not recommended routinely, the problem is addressed by detection and treatment of individuals with LTBI. The U.S. Preventive Services Task Force (USPTF) has updated their recommendations for LTBI screening, which were last published in 1996.

The USPTF concluded the following:

• The evidence is adequate to indicate that the available screening tests, the Mantoux tuberculin skin test (TST) and interferon-gamma release assays (IGRA), accurately detect LTBI.

Evidence: The TST, with a positive threshold of 10 mm induration, has moderate sensitivity and high specificity for detection of LTBI, with a sensitivity of 79% and specificity of 97% as determined by a pooled analysis of available studies. In similar analyses, the T-SPOT.TB test has a sensitivity of 90% and specificity of 95%, while these results with the QuantiFERON-TB Gold In-Tube test are 80% and 97%, respectively.

• There is adequate evidence to conclude that treatment of patients with LTBI utilizing CDC-recommended regimens decreases the likelihood of progression to active tuberculosis and that the benefit is moderate.

Evidence: The International Union Against Tuberculosis (IUAT) trial, conducted in seven European countries and published in 1982, remains the best evidence for the efficacy of treatment with daily isoniazid, which was administered for 24 weeks. This study, which enrolled patients with a positive TST and fibrotic lesions on chest radiography, found that, compared to placebo, isoniazid administration was associated with a relative risk (RR) of progression to active tuberculosis of 0.35.

• The evidence is adequate to allow the conclusion that the magnitude of potential harm associated with CDC-recommended treatment regimens1 is small, with the primary concern being that of hepatotoxicity.

Evidence: The IUAT trial was found to be the only one that assessed the harm of therapy relative to placebo. The investigators reported the RR of hepatotoxicity was 4.95 at five years for isoniazid recipients relative to those assigned placebo. The number of deaths from hepatotoxicity was numerically, but not statistically, greater in isoniazid recipients (0.14 vs. 0 deaths per patient year). A meta-analysis of three trials found a significantly greater risk of hepatotoxicity with rifampin than with isoniazid administration: RR 3.29.

• The final USPTF assessment “… concludes with moderate certainty that the net benefit of screening for LTBI in persons at increased risk2 for tuberculosis is moderate.”

Evidence: USPTF estimates that screening of 100,000 asymptomatic adults would result in prevention of 52-146 cases of active tuberculosis, while, depending on the treatment regimen, this would result in 7-67 cases of hepatotoxicity and a total of 111 individuals would abort treatment because of adverse events (mostly gastrointestinal). The number needed to treat to prevent one case of progression to active tuberculosis would be, depending on the specific treatment, 111-314, while the number needed to harm by causing drug-related hepatotoxicity would be 279-2,531.

With regard to defining individuals at increased risk for tuberculosis, the USPTF states: “Populations at increased risk for LTBI include persons who were born in, or are former residents of, countries with increased tuberculosis prevalence and persons who live in, or have lived in, high-risk congregate settings (e.g., homeless shelters and correctional facilities). Local demographic patterns may vary across the United States; clinicians can consult their local or state health departments for more information about populations at risk in their community.” This statement does not include, e.g., immunocompromised individuals (in whom the tests for LTBI may prove insensitive) or, preferably, those about to become immunocompromised. A broader picture can be perceived from the CDC recommendation for groups at high priority for anti-LTBI treatment.2 (See Table.)

The publications reviewed here primarily are aimed at primary care physicians whose role in screening has become increasingly important.

REFERENCES

  1. CDC. Treatment regimens for latent TB infection (LTBI). Available at: www.cdc.gov/tb/topic/treatment/ltbi.htm.
  2. CDC. Deciding When to Treat Latent TB Infection. Available at: www.cdc.gov/tb/topic/treatment/decideltbi.htm.

Table. Groups Who Should Be Given High Priority for Latent TB Infection Treatment2

People with a positive IGRA result or a TST reaction of 5 or more millimeters:

  • HIV-infected persons
  • Recent contacts of a TB case
  • Persons with fibrotic changes on chest radiograph consistent with old TB
  • Organ transplant recipients
  • Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of > 15 mg/day of prednisone for one month or longer, taking TNF-α antagonists)

People with a positive IGRA result or a TST reaction of 10 or more millimeters:

  • Recent immigrants (< 5 years) from high-prevalence countries
  • Injection drug users
  • Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other healthcare facilities)
  • Mycobacteriology laboratory personnel
  • Children under 4 years of age, or children and adolescents exposed to adults in high-risk categories

Persons with no known risk factors for TB may be considered for treatment of LTBI if they have either a positive IGRA result or if their reaction to the TST is 15 mm or larger. However, targeted TB testing programs should be conducted only among high-risk groups. All testing activities should be accompanied by a plan for follow-up care for persons with TB infection or disease.