Xpert MTB/RIF: a New Pillar in Diagnosis of Extrapulmonary Tuberculosis?

Abstract

Approximately 10 to 15% of tuberculosis (TB) cases in India are estimated to have extrapulmonary disease, and due to a lack of diagnostic means, they often remain untreated. The early detection of Mycobacterium tuberculosis and multidrug resistance is a priority in TB diagnosis to improve the successful treatment rate of TB and reduce transmission. The Xpert MTB/RIF (Xpert) test, recently endorsed by the World Health Organization for the detection of pulmonary TB, was evaluated to test its utility in 547 patients with suspected extrapulmonary tuberculosis. Five hundred forty-seven extrapulmonary specimens were split and processed simultaneously for both culture (solid and liquid) and Xpert testing. For culture, the sensitivity was low, 53% (150/283 specimens). Xpert sensitivity and specificity results were assessed in comparison to a composite reference standard made up of smear and culture results and clinical, radiological, and histological findings. The sensitivity of the Xpert assay was 81% (228/283 specimens) (64% [89/138] for smear-negative cases and 96% [139/145] for smear-positive cases), with a specificity of 99.6%. The sensitivity was found to be high for the majority of specimen types (63 to 100%) except for cerebrospinal fluid, the sensitivity of which was 29% (2/7 specimens). The Xpert test correctly identified 98% of phenotypic rifampin (RIF)-resistant cases and 94% of phenotypic RIF-susceptible cases. Sequencing of the 6 discrepant samples resolved 3 of them, resulting in an increased specificity of 98%. In conclusion, the results of this study suggest that the Xpert test also shows good potential for the diagnosis of extrapulmonary TB and that its ease of use makes it applicable for countries where TB is endemic.India has the world's largest burden of tuberculosis (TB), accounting for one-fifth of the global TB incidence. The global annual incidence estimate is 9.4 million cases, of which 1.98 million cases are from India (10). TB remains the largest infectious killer disease affecting adults in developing countries (1). In India, TB disproportionately involves the young. Almost 50% of multidrug-resistant TB (MDR-TB) (resistant to at least rifampin [RIF] and isoniazid) cases worldwide are estimated to occur in China and India (21). TB manifests clinically as pulmonary or extrapulmonary tuberculosis (EPTB), with the former being more common. In India, 10 to 15% of TB cases are estimated to be cases of EPTB (which affects mainly the lymph nodes, meninges, kidney, spine, and growing ends of the bones), with a 25 to 50% case mortality rate within months. In this situation, not only rapid TB case detection but also the early determination of MDR status is important. The major challenge in the diagnosis of EPTB is the frequently atypical clinical presentation simulating other inflammatory and neoplastic conditions, which frequently results in a delay or deprivation of treatment. Therefore, a high index of suspicion is necessary to make an early diagnosis, and quite often, more than one procedure is ne...

Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis

“…When considering the overall sensitivity ( fig. 1) and specificity, our results did not differ significantly either from the ones obtained by VADWAI et al [12], in their survey in India (p50.36) or from those reported by HILLEMANN et al [11], in Germany (p50.53). Diagnostic accuracy values better than ours were reported for body fluids and pus, in the first study, and for urine and gastric aspirates, in the second.…”

“…As reported by others [12] it is possible that the decontamination step, required for performing the culture of non-sterile samples, has determined the lowering of bacillary load and consequently the reduction of test sensitivity.…”

“…ersjournals.com/site/misc/statements.xhtml Present study HILLEMANN et al [11] VADWAI et al [12] Present study HILLEMANN et al [11] VADWAI et al [12] Present study HILLEMANN et al [11] Present study HILLEMANN et al [11] Present study VADWAI et al [12] Present study VADWAI et al [12] Sensitivity …”

“…The first study, similar to ours for the epidemiological background, omitted in the evaluation the clinical diagnosis [11], while the other was carried out in a high prevalence TB country [12]. In addition, both studies did not target the paediatric population.…”

Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis: Table 1–

“…Pleural tissue was finely ground and re-suspended in 1 mL of sterile saline [8]. The Xpert ''sample reagent'' was added (2:1 ratio for both pleural fluid and pleural tissue samples) and, after incubation, 2 mL were transferred into a G4 cartridge.…”