Diagnosis of osteoarticular tuberculosis via metagenomic next-generation sequencing: A case report

Abstract

Osteoarticular tuberculosis (OAT) may cause severe complications and disability. Due to its indolent nature, OAT is difficult to diagnose in the early stages. Diagnosis by conventional culture is time-consuming and insensitive, and polymerase chain reaction-based molecular diagnostic methods are incapable of excluding co-infections. Metagenomic next-generation sequencing (mNGS) may identify a broad spectrum of microorganisms, including Mycobacterium, bacteria and fungi, in clinical specimens. Therefore, the diagnosis of OAT may be rapidly performed using mNGS. The present study reports on a case of OAT. The patient presented with right knee swelling and pain for 1 year; his C-reactive protein levels and erythrocyte sedimentation rate were markedly elevated. Although multiple pre-operative cultures were negative, mNGS was finally used to successfully detect the underlying pathogen. The result was confirmed by other molecular biology methods and Mycobacterium culture. Anti-tuberculosis therapy was administered accordingly and the patient finally recovered. In conclusion mNGS, with the ability to detect Mycobacterium and other microorganisms in a single assay, is an emerging approach for rapidly and accurately diagnosing OAT. This method may provide significant support to guide physicians in selecting the appropriate pharmacotherapy and surgical treatments.

Keywords: metagenomic next-generation sequencing; mycobacterium tuberculosis; osteoarticular tuberculosis.

Figure 1.

Magnetic resonance imaging scans revealing effusion of the suprapatellar bursa (white arrow) in T2-weighted images.

Figure 2.

Anterior and lateral plain images of the right knee revealing that the tibiofemoral joint space was intact and contained a small number of osteophytes.

Figure 3.

Histopathological examination with hematoxylin and eosin revealing an inflammatory reaction, including a massive granuloma with central necrosis, lymphocytic infiltration and a small amount of neutrophil infiltration. Magnification, ×200.

Figure 4.

Taxonomic classification of sequencing reads from synovial fluid by a bioinformatics pipeline. (A) A total of 32,990,757 reads were detected by mNGS, including 188 microbial reads. (B) A total of 120 reads of bacteria were detected in the synovial fluid (63.83% of bacterial reads). (C) MTCP with 9 reads were detected in the synovial fluid (7.38% of bacterial reads). MTCP, Mycobacterium tuberculosis complex group.