The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues

Abstract

The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3–99.7) and a specificity of 95.7% (95% CI: 78.1–99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis.

Autopsy Prevalence of Tuberculosis and Other Potentially Treatable Infections among Adults with Advanced HIV Enrolled in Out-Patient Care in South Africa

“…Combining BAL Xpert® MTB/RIF with BAL mycobacterial culture would have detected nine of our TB cases; adding mycobacterial culture of lung tissue would add a further two; and histological examination of lung tissue a further three; accounting for 88% of the TB seen in our decedents. The role of Xpert® MTB/RIF as part of the autopsy process is not established: a recent study testing post mortem liver, lung, and brain tissue found that it detected TB in 7/8 (87.5%) cases, although the gold standard used was another PCR technique, rather than liquid culture [21]. In our study, only 5/14 (35.7%) decedents with BAL specimens and evidence of TB had a positive Xpert® MTB/RIF, though this test was done only on BAL specimens, whereas culture and histology were conducted on specimens from many other anatomical sites, many of them extrapulmonary.…”

“…There is growing evidence that minimally invasive autopsy (MIA) can provide useful information relevant to cause of death, particularly with regards to TB and other infectious diseases [20,21]; one study, involving 96 HIV-positive adults in Uganda, compared histology from MIA to that from full autopsy and found that MIA was 71% sensitive and 100% specific in detecting TB [18]. Adding culture and/or other bacteriological modalities to MIA would likely improve its sensitivity in this regard.…”

A Three-Year Experience with GeneXpert MTB/RIF Assay in Tuberculosis Control Programme (RNTCP)- A Clinical Study

“…For individual and public health benefits, there is a need to develop and more widely apply new methods to reliably estimate TB mortality. [17] Since children below 6 years are not able to expectorate the sputum, specimens like gastric lavage aspirate (GLA), induced sputum (IS), bronchoalveolar lavage (BAL) are used and each one will have its own advantages and disadvantages. In a study by Pang et al, the authors highlight limitations of their study and emphasize that Xpert MTB/RIF assay is not ideal for GA samples due to its low negative predictive value, which means overall low (70.1%) specificity.…”

Effect of Xpert MTB/RIF testing introduction and favorable outcome predictors for tuberculosis treatment among HIV infected adults in rural southern Mozambique. A retrospective cohort study

“…[9] Mozambique is one of the World Health Organization´s (WHO) 30 high TB burden countries and faces many challenges in its successful control, especially among persons living with HIV (PLHIV). [10,11] In 2017, WHO estimated Mozambique's TB prevalence to be 551/100,000 people. However, only 52% of estimated cases were diagnosed and reported to the National TB Program (NTP), which is the agency of the Ministry of Health responsible for combating TB in the country.…”