Rapid Test Successfully Discerns Active Tuberculosis From Other Causes of Persistent Cough

Tuberculosis (TB) prevention and control continues to be a global health priority amidst a mix of progress and challenges. Although there was a reduction of TB-related deaths from 2017, 1.5 million people still died of TB-related causes in 2018.

New study results indicate steps forward for TB detection, as a new rap`id triage test for active pulmonary tuberculosis may help identify the condition in patients who present symptoms that may mimic those of other diseases.

In research published in Science Translational Medicine, an international team of experts relied on data from 3 adult cohorts of patients with chronic cough across Africa, Asia, and South America. Specific locations included Peru, the Philippines, South Africa, Tanzania, and Vietnam. Using a machine learning algorithm, investigators identified 4 host blood proteins associated with active TB infection.

The research team then created an ultra-sensitive immunoassay that screened for the 4 proteins.

“Bead-based immunoassay and machine learning algorithms identified the blood proteins interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor, that

distinguished [active TB] from other TB-like disease,” investigators reported.

The test successfully identified active TB in XX samples “with receiver operator characteristic—area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%),” authors wrote in the study. “When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity.”

Study authors explained that “although some of these 4 proteins have also previously been individually described as associated with TB (24—29), it is only when combined in a predictive algorithm that they gain sufficient power to distinguish adults with [active TB] from those with TB-like symptoms because of other etiologies.”

Investigators noted several limitations and areas for future research. “Follow-up data collection across the discovery cohort was not logistically tractable but would have been helpful in at least two ways: First, in demonstrating appropriate clinical resolution of patients with OTD, and second, in determining whether any patients predicted to have (but not diagnosed with) TB went on to develop active disease,” they said.

Investigators also hoped future studies could reduce the cost per test from approximately $10 to a target of $2. They hypothesized that future studies, which would expand the diagnostic with additional informative markers, would yield further improved performance.

Investigators expressed optimism on the grounds that “results approach the WHO [World Health Organization] [target product profile] for accuracy and pave the way for the development and eventual deployment of a much-needed blood-based [point-of-care] triage test for [active TB].”

Tuberculosis is one of the world’s most daunting infectious disease challenges, and despite progress health care systems are off target to reach WHO goals of ending TB by 2035. Steps toward more effectively narrowing down a diagnosis in patients with persistent cough are thus vital to intensifying efforts.