{"doi":"10.1101/2021.06.11.21258751","title":"Xpert MTB/RIF Ultra is highly sensitive for the diagnosis of tuberculosis lymphadenitis in an HIV-endemic setting","abstract":"Abstract Background Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary TB (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but performance data for TBL, including on non-invasive specimens, are limited. Methods Fine needle aspiration biopsies (FNABs) from outpatients (≥18 years) with presumptive TBL (n=135) underwent: 1) routine Xpert (later Ultra once programmatically available), 2) a MGIT960 culture (if Xpert- or Ultra-negative, or rifampicin-resistant), and 3) study Ultra. Concentrated paired urine underwent Ultra. Primary analyses used a microbiological reference standard (MRS). Results In a head-to-head comparison (n=92) of FNAB study Ultra and Xpert, Ultra had increased sensitivity [91% (95% confidence interval 79, 98) vs. 72% (57, 84); p=0.016] and decreased specificity [76% (61, 87) vs. 93% (82, 99); p=0.020], and detected patients not on treatment. HIV nor alternative reference standards affected sensitivity and specificity. In patients with both routine and study Ultras, the latter detected more cases [+20% (0, 42); p=0.034] and, further indicative of potential laboratory-based room-for-improvement, false-negative study Ultras had more PCR inhibition than true-positives. Study Ultra “false-positives” had less mycobacterial DNA than “true-positives” [trace-positive proportions 59% (13/22) vs. 12% (5/51); p<0.001]. Exclusion or recategorization of “traces” removed potential benefits offered over Xpert. Urine Ultra had low sensitivity [18% (7, 35)]. Conclusions Ultra on FNABs is highly sensitive and detects more TBL than Xpert. Patients with FNAB Ultra-positive “trace” results, most of whom will be culture-negative, may require additional clinical investigation. Urine Ultra could reduce the number of patients needing invasive sampling.","journal":"medRxiv","year":2021,"id":221552,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.915,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":660389,"name":"Byron W P Reeve","orcid":"0000-0002-3332-3477","position":1,"is_corresponding":false},{"id":821657,"name":"Loren Rockman","orcid":"0000-0002-7882-2157","position":2,"is_corresponding":false},{"id":660387,"name":"Georgina Nyawo","orcid":"0000-0001-7251-2097","position":3,"is_corresponding":false},{"id":660386,"name":"C Naidoo","orcid":"0000-0003-0822-3180","position":4,"is_corresponding":false},{"id":821658,"name":"Natasha Kitchin","orcid":"0000-0003-4295-6222","position":5,"is_corresponding":false},{"id":751772,"name":"Cornelia Rautenbach","orcid":null,"position":6,"is_corresponding":false},{"id":300202,"name":"Colleen A. Wright","orcid":null,"position":7,"is_corresponding":false},{"id":589255,"name":"Andrew Whitelaw","orcid":"0000-0001-9070-5247","position":8,"is_corresponding":false},{"id":298554,"name":"Pawel Schubert","orcid":"0000-0003-4422-7349","position":9,"is_corresponding":false},{"id":89652,"name":"Robin M. Warren","orcid":"0000-0001-5741-7358","position":10,"is_corresponding":false},{"id":244855,"name":"Grant Theron","orcid":"0000-0002-9216-2415","position":11,"is_corresponding":false},{"id":523476,"name":"Stephanie Minnies","orcid":"0000-0003-2877-2419","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:53:55.215284Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}