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TB screening assay may detect latent infection, predict TB disease progression
Screening children with an updated blood-based assay could aid in the detection of latent tuberculosis infection and predict which patients are likely to progress to tuberculosis disease, according to a recent study.
“Young children infected with [Mycobacterium tuberculosis] are at very high risk of progression to tuberculosis disease and, compared with adults, are at increased risk of severe tuberculosis morbidity and mortality,” Jason R. Andrews, MD, and colleagues wrote. “One of the key obstacles to targeted tuberculosis screening and preventive therapy is differentiating only those M. tuberculosis–infected individuals at highest risk of disease from the majority who will remain healthy.”
Although prior studies have noted the sensitivity and specificity of interferon-gamma release assays (IGRAs) for the detection of active tuberculosis in children, there have been studies reporting the predictive value of IGRA conversions or predictive value of quantitative interferon-gamma values for tuberculosis among young children.
To determine whether conversion interferon-gamma values from the QuantiFERON-TB Gold In-Tube (Cellestis; QFT-GIT) assay could forecast subsequent active TB disease, Andrews and colleagues analyzed data from a vaccine efficacy trial of MVA85A, a tuberculosis vaccine, in South Africa.
The researchers enrolled children between the ages 18 and 24 weeks who were QFT and HIV negative. Children were stratified by QFT result (<0.35 IU/mL, 0.35-4.00 IU/mL and >4.00 IU/mL) to determine the risk of progression over the following 6 to 24 months. Researchers included both placebo and MVA85A groups in their analysis because no QFT differences were found.
Generalized additive models were used to evaluate a quantitative connection between the QFT values at the immediate study visit on Day 336 and risk of disease. Disease risk was then compared between QFT strata using a two-sample Poisson test. Although clinicians involved in this study were not masked to QFT values, “strict case definitions were used that excluded QFT results.”
On Day 336, 2,512 young children had QFT tests done. Seven percent were positive, and 7% were positive in both the placebo and MVA85A groups. This study found that children who had conversion at interferon-gamma values between 0.35 and 4.00 IU/mL showed no increased risk for developing active disease (2.5 per 100 person-years); however, children who had conversion at interferon-gamma values greater than 4.00 IU/mL were found to be at much higher risk of disease (28.0 per 100 person-years) compared with both nonconverters and children with interferon-gamma values between 0.35 and 4.00 IU/mL.
In addition to these findings, 91 QFT converters were given a repeat test. Fifty-eight percent reverted to a negative state, and this risk was inversely associated with interferon-gamma value at QFT conversion. Conversion was most likely for those with interferon-gamma values less than 4.00 IU/mL.
“The current recommended QFT threshold interferon-gamma value of 0.35 IU/mL might therefore be too low in this population, and a higher test threshold might be indicated for risk-targeted intervention,” researchers wrote. “If validated in other study populations, these findings justify revision of current international guidelines for use of IGRAs in young children.”— by Katherine Bortz
Disclosure: Dr. Landry reports an employee relationship with Aeras, the funder of the phase 2 study from which the data for the report were collected. All other researchers report no relevant financial disclosures.
