Tuberculosis-Specific Antigen/Phytohemagglutinin Ratio Combined With GeneXpert MTB/RIF for Early Diagnosis of Spinal Tuberculosis: A Prospective Cohort Study

Abstract

Spinal tuberculosis (TB), the most common form of musculoskeletal tuberculosis, is an infection-related disease globally, with paraplegia occurring in severe cases. Therefore, identification of spinal TB at an early stage is important for early intervention and eventual therapy. In this study, we conducted a prospective cohort study in routine clinical practice to investigate the diagnosis of different TB tests. A total of 519 patients were recruited based on the radiology of spinal TB. The diagnostic model was computed by regression analysis and was determined by receiver operating characteristic (ROC) curve analysis. Specificity, sensitivity, predictive value, likelihood ratio, and accuracy were also computed and compared. GeneXpert MTB/RIF showed a higher positive rate compared to that in the acid-fast bacilli smear and Mycobacterium culture. The results also showed that the Mycobacterium tuberculosis-specific antigen/phytohemagglutinin ratio in the T-SPOT assay had a good performance in the preoperative diagnosis and prediction of spinal TB. The diagnostic model based on the ratio of tuberculosis-specific antigen/phytohemagglutinin combined with GeneXpert MTB/RIF showed better efficiency for spinal TB diagnosis. In summary, the tuberculosis-specific antigen/phytohemagglutinin ratio combined with GeneXpert MTB/RIF could provide an early diagnosis of spinal TB.

Keywords: GeneXpert MTB/RIF; T-SPOT; spinal infection; spinal tuberculosis; tuberculosis diagnosis.

Figure 1

Typical spinal tuberculosis cases. Marginal erosions, bone destruction, soft tissue infection (abscesses), and spinal cord compression were shown on CT or MRI images. (A–F) Typical lumbar tuberculosis. (G–L) Typical thoracic tuberculosis. (M–R) Typical cervical tuberculosis.

Figure 2

ROC curve of different tuberculosis tests and establishment of a diagnostic model in the Tongji Hospital cohort. (A) ROC analysis showing the performance of T-SPOT, AFBS, GeneXpert MTB/RIF, and TBAg/PHA ratio. (B) ROC analysis displaying models for the diagnosis of spinal tuberculosis based on the TBAg/PHA ratio or in combination with AFBS or GeneXpert MTB/RIF. (C) Scatter plots showing the ratio of TBAg/PHA in spinal tuberculosis patients (n = 110) and no spinal tuberculosis patients (n = 209). Orange dotted lines representing the median value. Red dotted lines indicating the cutoff value in distinguishing these two groups. ***p < 0.001 (Mann–Whitney U-test). (D) Scatter plots showing the score of the diagnostic model based on TBAg/PHA ratio combined with AFBS in spinal tuberculosis patients (n = 110) and no spinal tuberculosis patients (n = 209). Orange dotted lines representing the median. Red dotted lines indicating the cutoff value in distinguishing these two groups. ***p < 0.001 (Mann–Whitney U-test). (E) Scatter plots showing the score of the diagnostic model based on TBAg/PHA ratio combined with GeneXpert MTB/RIF in spinal tuberculosis patients (n = 110) and no spinal tuberculosis patients (n = 209). Orange dotted lines representing the median. Red dotted lines indicating the cutoff value in distinguishing these two groups. ***p < 0.001 (Mann–Whitney U-test). ROC, receiver operating characteristic; AUC, area under the curve; AFBS, acid-fast bacilli smear; MTB, Mycobacterium tuberculosis; RIF, rifampicin resistance; TBAg, Mycobacterium tuberculosis-specific antigen; PHA, phytohemagglutinin.

Figure 3

Validation of ROC curve of different tuberculosis tests and diagnostic models in the Sino-French New City Hospital cohort. (A) ROC analysis showing the performance of T-SPOT, AFBS, GeneXpert MTB/RIF, and TBAg/PHA ratio. (B) ROC analysis displaying models for the diagnosis of spinal tuberculosis based on the TBAg/PHA ratio or in combination with AFBS or GeneXpert MTB/RIF. (C) Scatter plots showing the ratio of TBAg/PHA in spinal tuberculosis patients (n = 93) and no spinal tuberculosis patients (n = 107). Orange dotted lines representing the median value. Red dotted lines indicating the cutoff value in distinguishing these two groups. ***p < 0.001 (Mann–Whitney U-test). (D) Scatter plots showing the score of the diagnostic model based on TBAg/PHA ratio combined with AFBS in spinal tuberculosis patients (n = 93) and no spinal tuberculosis patients (n = 107). Orange dotted lines representing the median. Red dotted lines indicating the cutoff value in distinguishing these two groups. ***p < 0.001 (Mann–Whitney U-test). (E) Scatter plots showing the score of the diagnostic model based on TBAg/PHA ratio combined with GeneXpert MTB/RIF in spinal tuberculosis patients (n = 93) and no spinal tuberculosis patients (n = 107). Orange dotted lines representing the median. Red dotted lines indicating the cutoff value in distinguishing these two groups. ***p < 0.001 (Mann–Whitney U-test). ROC, receiver operating characteristic; AUC, area under the curve; AFBS, acid-fast bacilli smear; MTB, Mycobacterium tuberculosis; RIF, rifampicin resistance; TBAg, Mycobacterium tuberculosis-specific antigen; PHA, phytohemagglutinin.