Substantial Risk of TB in Populations With Latent Infection

By Will Boggs MD

April 14, 2020

NEW YORK (Reuters Health) - Individuals with a positive tuberculosis test have a substantial risk of developing tuberculosis, especially if they belong to high-risk groups, researchers in Canada report.

"While many populations are at increased risk for tuberculosis, risk in the general population is very low," Dr. Jonathon R. Campbell of McGill University, in Montreal, told Reuters Health by email. "Testing and treatment should be first focused to those at highest risk. In doing so, people most likely to benefit from treatment will receive it."

The tuberculin skin test (TST) or the interferon-gamma release assay (IGRA) are commonly used to assess for latent tuberculosis infection, but only a few people with a positive test result will progress to active tuberculosis.

Dr. Campbell and colleagues investigated the absolute risk of developing active tuberculosis among different populations of untreated people with a positive TST or IGRA, or both, in a systematic review and meta-analysis of 122 studies.

In studies in HIV uninfected samples from the general population, the incidence of tuberculosis was 0.3 per 1,000 person-years for those with a TST induration of 10 mm or greater, the researchers report in The BMJ.

Among populations exposed to tuberculosis (either close or casual), the incidence of tuberculosis was 8.4 per 1,000 person-years for those with a TST 5 mm or greater and 17.0 per 1,000 person-years for those with a positive IGRA result. These rates are 28 times and 56 times higher, respectively, than the incidence in the general population.

Among people living with HIV, the cumulative incidence of tuberculosis over a mean follow-up of 2.9 years was 7.1% for those with a TST 5 mm or greater and 5.1% for those with a positive IGRA result.

The risk of tuberculosis among populations with other conditions affecting immunity (silicosis, dialysis, transplant recipients and patients receiving immunosuppressant drugs) was more variable but still consistently greater than rates among the general population.

Prisoners, recent immigrants and refugees with positive tests also had high rates of progression to active TB.

"Both the tuberculin skin test and interferon-gamma release assay are useful tests for identifying people at increased risk for tuberculosis," Dr. Campbell said. "There has been a big push away from the tuberculin skin test, but our study shows that it is still a useful test."

"In places where there is access to these diagnostics, I think there needs to be a push to disseminate information on risks and benefits of treatment to healthcare providers as well as more attention to how latent tuberculosis is communicated to patients," he said. "In the majority of cases, a decision to test someone for latent tuberculosis is a decision to treat if they are positive. Equipping providers with information on risks and benefits and effectively communicating this to patients so they can make informed decisions are key steps, in my opinion."

Dr. Luis C. Berrocal-Almanza of Imperial College London, who recently reviewed new approaches to predicting progression to active tuberculosis, told Reuters Health by email, "The results highlight the public-health relevance of proper risk stratification, according to sociodemographic and clinical characteristics along with IGRA or TST test results, to identify individuals in which treatment for latent TB infection may be of great benefit."

"Policy makers, clinicians, and the populations with higher risk must all recognize the value of latent TB-infection testing and treatment," he said. "This should lead to the establishment of evidence-based setting-specific programs. Such programs should be designed involving all relevant stakeholders, and have a strong component of raising awareness and increasing knowledge on latent TB infection and the benefits of treatment among clinicians and at-risk populations."

"There are undoubtedly defined populations with higher risk of developing TB," said Dr. Berrocal-Almanza, who was not involved in the new review. "The wide availability of IGRA and TST must be harnessed for proper risk stratification to guide clinical decision making on testing and treating latent TB infection."

SOURCE: BMJ, online March 10, 2020.