Unexpected detection of Mycobacterium tuberculosis DNA in US-born patients in putative association with clinical syndromes

Sequential inflammatory stages characterizing early tuberculosis (TB) disease and reports of differentially culturable M. tuberculosis have compounded existing gaps in the detection of paucibacillary TB disease, threatening global elimination goals. Here we report unanticipated results we encountered while conducting early development work for an ultrasensitive molecular TB assay that has been validated in various cohorts of patients with suspected TB disease. Detection of M. tuberculosis DNA (TB-DNA) was confirmed by an alternate molecular target and sequencing. Over a six-year period, we conducted three separate clinical studies (N = 297) that tested two sets of anonymized respiratory samples from patients hospitalized in two Boston hospitals, and a longitudinal observational study to determine clinical associations and outcomes. We found an unexpectedly high prevalence of TB-DNA in US-born patients and a potential association with acute chest syndrome in patients with sickle cell disease. These results are preliminary and will require further study in prospective studies that include clinical, radiological, immunological, and microbiological correlation.