Does Disseminated Nontuberculous Mycobacterial Disease cause False-positive Determine TB-LAM Lateral Flow Assay Results?

BACKGROUND: The Determine TB-LAM (LF-LAM) can detect lipoarabinomannan, a glycolipid found in mycobacteria, in the urine of HIV-infected patients with disseminated TB. Whether disseminated nontuberculous mycobacterial (NTM) infection causes false-positive results has not been adequately assessed. METHODS: We retrospectively reviewed the LF-LAM results and the evidence for tuberculosis (TB) coinfection among HIV-infected subjects with microbiologically confirmed disseminated NTM infection seen by the infectious diseases consultation service at a tertiary hospital in Johannesburg, South Africa. RESULTS: 26 patients had disseminated NTM infection, and 83 mycobacterial cultures and Xpert MTB/RIF assays were performed on these patients. All patients had specimens collected from a minimum of two different sites (e.g., blood and sputum), and the median number of specimens taken per patient was three. On the basis of this, three subjects were diagnosed with TB-NTM coinfection. LF-LAM was performed on 23 out of 26 subjects with disseminated NTM disease, and was positive in 21 cases (91.3%, 95% CI 73.2–97.6). Excluding subjects in whom TB coinfection was diagnosed, LF-LAM was positive in 19/21 cases (90.5%, 95% CI 71.1–97.4). CONCLUSION: Our study revealed an unexpectedly high rate of LF-LAM positivity in patients with disseminated NTM infection. While it cannot be definitively determined whether these findings represent undiagnosed concomitant disseminated TB infection, cross-reactivity with NTM antigens, or a combination of the two, it is plausible that NTM cross-reactivity may account for at least some of the positive LF-LAM results seen in this study. In vitro studies have suggested this possibility, but previous studies assessing LF-LAM’s specificity have enrolled patients whose median CD4 counts were too high to have been at substantial risk for disseminated NTM infection. To the degree that these findings can be confirmed in similar high-burden TB-HIV coinfection settings, they suggest that positive LF-LAM results should be interpreted with caution in patients with very low CD4 counts. DISCLOSURES: All authors: No reported disclosures.