The diagnostic performance of Xpert MTB/RIF Ultra on Pericardial, Pleural and Ascitic cohort study fluids for diagnosis of extra-pulmonary Tuberculosis at a referral hospital in Malawi

Background Extra-pulmonary tuberculosis (EPTB) accounts for 15% of the 1.4 million patients with TB notified in 2019. EPTB carries a high risk of mortality and so early diagnosis and treatment are important to reduce this risk. Diagnosis of EPTB in low- and middle-income countries is challenging. This study investigated the diagnostic performance of Xpert MTB Ultra for the diagnosis of EPTB (pericardial, pleural, and ascitic fluid) in adults at a referral hospital in Malawi. Methods Adults with suspected extra-pulmonary TB were screened for evidence of extra-pulmonary fluid and tested for TB using Xpert MTB Ultra, mycobacterial culture, and a Focused Abdominal Sonography in HIV-associated TB (FASH scan). The diagnostic performance of the Xpert MTB Ultra was compared to mycobacterial culture and a composite reference standard defined as a positive FASH scan or a positive mycobacterial culture or a clinical TB diagnosis (constitutional symptoms not otherwise explained with response to empirical TB treatment). Results There were 174 patients recruited: 99/174 (57%) pleural, 70/174 (40%) ascitic and 5/174 (3%) pericardial. Overall, 10/174 (6%) had bacteriologically confirmed TB and 30/174 (17%) were started on TB treatment based on a positive FASH scan or a clinical TB diagnosis. The sensitivity and specificity of Xpert ultra compared to culture was 83% (95%CI:36%-100%) and 98% (95%CI:94%99%), respectively. Compared to the composite reference standard, the sensitivity of Xpert Ultra was 17% (95%CI:7%-34%) and specificity was 98% (95%CI:94%-100%). Conclusion Xpert MTB Ultra provides good diagnostic performance on pleural, pericardial and ascitic fluid with reference to mycobacterial culture. Improved EPTB diagnostic tests are required to improve patient outcomes. We recommend larger multi-centre studies to corroborate our findings.