In persons living with someone with active tuberculosis (TB), a new blood test may be able to more accurately predict the development of TB up to 2 years before its onset, according to study results published online in the American Journal of Respiratory and Critical Care Medicine.
Currently, more than 10 million cases of TB are diagnosed annually, and an estimated 1.7 billion people are infected worldwide. Although only about 5%-20% of people who are infected with TB develop the disease, persons who live with someone with active TB are at the highest risk for infection.
Researchers have developed and validated a blood test that measures the expression of four genes to predict more accurately the development of TB in high-risk patients in Sub-Saharan Africa.
“We found that this prediction [up to 2 years before the onset of the disease] is possible through measurements of a combination of a four-gene signature in the blood," said lead author Professor Gerhard Walzl, MMed, PhD, leader of the Stellenbosch University Immunology Research Group, Tygerberg, South Africa.
The RISK4 signature—a combination of four genes that are associated with inflammatory responses—was present in all cohorts of this case-control study. The study was nested within subjects from the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts. Researchers used RNA sequencing, polymerase chain reaction, and the Pair Ratio algorithm in a training/test set approach.
Of 4,466 HIV-negative, healthy subjects from the households of 1,098 index TB cases, researchers included 79 subjects who progressed to TB (progressors) in the 3 to 24 months after exposure, and 328 matched controls (non-progressors) who remained healthy for at least 24 months of follow-up.
The RISK4 signature was derived from samples in a South African and Gambian training set. Researchers found that it predicted progression up to 2 years before the onset of disease in blinded test set samples from South Africa, Gambia, and Ethiopia. The four-transcript signature was also validated in an external cohort of adolescents from South Africa with latent Mycobacterium tuberculosis infection.
Upon their post-hoc meta-analysis, researchers identified the C1QC/TRAV27 gene pair as one that could reliably predict TB progression in household contacts from the African sites, but not in infected adolescents without recent exposure.
Other TB tests are currently available that reliably predict progression to active disease, but these researchers focused on those living in high-risk households. Such a test could mean that fewer people will be unnecessarily treated with preventive therapies.
“Preventative treatment is several weeks long and has potential side effects,” explained Prof. Walzl. “One wants to limit the number of people who have to undergo such treatment to those most likely to be at risk for developing active TB.”
He concluded: “This study is the first step, and now the impact of this test on prevention of TB will have to be tested in multicenter clinical trials. In addition, the validity of the prediction in high-risk individuals in Asia, South America, and other high-priority areas needs to be assessed.”