Researchers identified evidence of tuberculosis in hospitalized patients in a low-incidence area, suggesting the disease may be more prevalent than previously recognized.
Researchers at Boston University identified an unexpectedly high prevalence of Mycobacterium tuberculosis (TB) DNA in hospitalized patients in Boston, suggesting that the disease may be significantly underdiagnosed in the US.
The study, published in Nature Communications, used an ultrasensitive molecular assay to detect TB DNA in 12% to 16% of respiratory samples from predominantly US-born patients. These findings occurred in a region known for a low TB incidence rate, according to the researchers.
The team utilized the Totally Optimized polymerase chain reaction TB assay, known as the TOP TB assay, which targets a gene involved in M tuberculosis cell wall assembly. The assay proved more sensitive than standard mycobacterial cultures and other molecular tests, identifying TB DNA in samples that previously tested negative through conventional diagnostic methods.
“Our ultrasensitive test is detecting Mycobacterium tuberculosis DNA in patients who are unlikely to be diagnosed with TB using current methods,” says Guillermo Madico, scientist at Boston University’s National Emerging Infectious Diseases Laboratories and co-inventor of the TOP TB assay, in a release. “This opens the possibility that there could be thousands of Americans infected with forms of tuberculosis disease that remain hidden from our current diagnostic tools, putting them at risk of developing more serious complications or potentially transmitting the disease to others.”
Link to Sickle Cell Complications
The research, led by Madico and Edward C Jones-Lopez, involved testing 297 respiratory samples over six years. One of the most notable findings was a potential association between TB DNA and acute chest syndrome, a life-threatening complication of sickle cell disease. All three patients diagnosed with the syndrome during the study period tested positive for TB DNA.
The study also found that 75% of TB DNA-positive patients were age 50 or older. This is consistent with US TB epidemiology, where most cases result from the reactivation of latent infections. Many of these patients had previously tested negative on standard TB infection tests, such as tuberculin skin tests or interferon-gamma release assays.
“These findings suggest we may be missing a significant burden of TB disease, particularly in older Americans and in patients with certain underlying conditions,” says Jones-Lopez, a researcher who conducted the work while at Boston Medical Center and Boston University Chobanian and Avedisian School of Medicine, in a release. “Most concerning is the potential association with acute chest syndrome in sickle cell patients. If confirmed and expanded upon in larger studies, this finding could lead to better health outcomes for patients with this potentially life-threatening condition.”
Challenges in TB Diagnostics
The researchers noted that current diagnostic strategies may be limited by an over-reliance on mycobacterial cultures. These cultures require viable, actively growing bacteria to produce a positive result. Because the TOP TB assay can detect very low levels of DNA, it may identify earlier stages of the disease or variants that do not fit traditional clinical definitions.
While the TOP TB assay has been validated in more than 400 patients across the US, Brazil, and Uganda, it is currently a research-use-only tool pending regulatory clearance. The researchers emphasize that these preliminary findings require confirmation through larger, prospective multicenter studies that include clinical, radiological, immunological, and microbiological correlation.
The study authors argue that the evidence warrants immediate dissemination due to the potential implications for public health and medical care. In 2023, TB killed nearly 600 people and sickened more than 9,600 in the US, while an estimated 13 million people in the country carry latent infections.
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