Congenital tuberculosis transmitted via the placenta: identification by metagenomic next-generation sequencing

Congenital tuberculosis (CTB) is a rare disease with high mortality in neonates. Early diagnosis is crucial but often delayed due to atypical clinical and imaging manifestations.

We report a 36-day-old female infant presenting with recurrent fever. Laboratory data showed leukocytosis and neutrophilia with mildly elevated C-reactive protein. Chest computed tomography revealed extensive ground-glass opacities, multiple subpleural nodules, and necrotic hilar and mediastinal lymphadenopathy. The asymptomatic mother was subsequently found to have diffuse miliary nodules on chest CT. Conventional tuberculosis tests (acid-fast smear, culture, GeneXpert, T-SPOT.TB) were negative in both the infant and mother. Metagenomic next-generation sequencing (mNGS) of the placental tissue detected 10 specific Mycobacterium tuberculosis sequences, and Ziehl-Neelsen staining confirmed acid-fast bacilli. Both mother and infant responded well to anti-tuberculosis therapy.

CTB should be considered in neonates with persistent pulmonary infection unresponsive to broad-spectrum antibiotics. Examination of placental tissue using mNGS is a valuable diagnostic tool for confirming transplacental tuberculosis transmission.