Researchers at Boston University announced on Apr. 14 that they have found a higher-than-expected presence of Mycobacterium tuberculosis DNA in patients hospitalized in Boston. The discovery was made using an ultrasensitive molecular test called the Totally Optimized PCR (TOP) TB assay, and the findings were published in Nature Communications.
This research could have important implications for how tuberculosis (TB) is detected and managed in the United States. Despite ongoing efforts to eliminate TB, recent years have seen an increase in new infections, highlighting challenges with current diagnostic tools.
The study involved testing 297 respiratory samples from patients at Boston Medical Center and St. Elizabeth's Medical Center over six years. The TOP TB assay detected TB DNA in 12-16 percent of samples from mostly U.S.-born patients—a rate much higher than expected given Boston’s low incidence of TB. Notably, all three patients diagnosed during the study period with acute chest syndrome, a serious complication related to sickle cell disease, tested positive for TB DNA.
"We began this research with the intent of sourcing respiratory samples to support the ongoing development of a new molecular assay for TB," said Dr. Guillermo Madico, scientist at Boston University's National Emerging Infectious Diseases Laboratories and co-inventor of the TOP TB assay. "What we found was completely unexpected. Our ultrasensitive test is detecting Mycobacterium tuberculosis DNA in patients who are unlikely to be diagnosed with TB using current methods. 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."
Tuberculosis remains a leading cause of death worldwide due to infectious disease. In 2023 alone, nearly 600 people died from it and more than 9,600 became ill in the United States.
The researchers observed that most individuals who tested positive for TB DNA were age 50 or older and often had negative results on standard infection tests such as tuberculin skin tests or interferon-gamma release assays—a phenomenon not fully understood but associated with advanced age and worse outcomes.
"These findings suggest we may be missing a significant burden of TB disease, particularly in older Americans and in patients with certain underlying conditions," said Dr. Edward C. Jones-López, who led parts of this research while at Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine. "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."
The team emphasized that these results are preliminary and require confirmation through larger studies involving multiple centers as well as thorough clinical evaluation.
The TOP TB assay has been validated among over 400 suspected cases across Uganda, Brazil, and the United States but remains limited to research use pending regulatory approval.
