Application of metagenomic next-generation sequencing in HIV-negative hematogenous disseminated tuberculosis

Hematogenous disseminated tuberculosis (Hematogenous disseminated tuberculosis, HDTB) is a rare, critical form of tuberculosis with a high case fatality ratio and is uncommon in HIV-negative patients. Early recognition of this disease is difficult, and limitations of traditional testing methods often lead to delayed diagnosis. This study aims to investigate the value of metagenomic Next-Generation Sequencing (metagenomic Next-Generation Sequencing, mNGS), as a promising tool, in the diagnosis of hematogenous disseminated tuberculosis in HIV-negative (Human Immunodeficiency Virus, HIV) patients.

A retrospective analysis was conducted of the clinical data of 10 HIV-negative patients with hematogenous disseminated tuberculosis confirmed by mNGS.

All patients had pre-existing diseases that could lead to impaired immune function. Common symptoms included hyperpyrexia, cough, and dyspnea, and 6 patients developed respiratory failure. C-reactive protein (C-reactive protein, CRP) and procalcitonin (procalcitonin, PCT) levels were both elevated, and PCT was markedly elevated in more than half of the patients, using 0.5 ng/mL as the cutoff value. Most patients had markedly elevated D-dimer levels accompanied by thrombotic events, including 3 patients with concomitant pulmonary embolism. Chest imaging showed patchy pulmonary opacities, and 2 patients had atypical bilateral pleural effusion; these nonspecific findings were easily confused with those of other diseases. Blood mNGS detected Mycobacterium tuberculosis within 2 to 3 days. According to the presence or absence of concomitant pulmonary tuberculosis, the patients were divided into the pulmonary tuberculosis subgroup (pulmonary tuberculosis subgroup, PTB) and the non-pulmonary tuberculosis subgroup (non-pulmonary tuberculosis subgroup, non-PTB). The oxygenation index was significantly lower in the pulmonary tuberculosis subgroup than in the non-pulmonary tuberculosis subgroup (P = 0.037). All cases of pulmonary embolism occurred in the pulmonary tuberculosis subgroup, but the difference was not statistically significant.

HIV-negative patients with hematogenously disseminated tuberculosis have atypical clinical manifestations and are prone to incorrect diagnosis. The application of mNGS helps shorten diagnostic delays and accelerate disease control, providing an effective supplementary diagnostic pathway when conventional testing methods cannot identify the pathogen.