{"doi":"10.1093/jpids/piaf041","title":"A Prospective Evaluation of a Three-Gene Host Response Signature to Classify Tuberculosis Severity in Children","abstract":"BACKGROUND: Children with non-severe TB may benefit from short-course treatment, but point-of-care tools are needed to stratify disease severity. We prospectively evaluated the Cepheid Xpert MTB-Host Response (HR) prototype cartridge for distinguishing TB severity in children with pulmonary TB (PTB) in The Gambia and Uganda. METHODS: We included children <15 with microbiologically confirmed or clinically diagnosed unconfirmed PTB. Severity was defined using the World Health Organization (WHO) guidelines for a four-month, drug-susceptible regimen. Capillary or venous blood was tested with the HR cartridge for PCR-based detection of 3 mRNA genes and calculation of a TB score from cycle thresholds. We generated receiver operating characteristic curves with the TB score to classify severe TB and assessed if Xpert-HR could achieve the WHO target accuracy for treatment optimization (≥90% sensitivity, ≥70% specificity). RESULTS: Among 106 children, the median age was 4 years (IQR 1-7), 56.6% were female, and 13.2% were living with HIV. In all children with PTB, Xpert-HR achieved an AUC of 0.67 (95% CI 0.55-0.78), with 89.3% sensitivity (95% CI 71.8-97.7) and 29.5% specificity (95% CI 19.7-40.9, cutoff ≤ -0.60). By confirmation status, Xpert-HR approached the target accuracy in children with Confirmed TB, with 62.5% specificity (95% CI 24.5-91.5) at 91.7% sensitivity (95% CI 61.5-99.8, cut-off ≤ -1.349). Among children with Unconfirmed TB, specificity was lower (24.3%, 95% CI 14.8-36.0) at 93.8% sensitivity (95% CI 69.8-99.8, cutoff ≤ -0.450). Target accuracy was almost achieved in children 5-9 regardless of confirmation status (100% sensitivity [95% CI 71.5-100], 66.7% specificity [95% CI 43.0-85.4], cutoff ≤ -1.35), but specificity (28.2%, 95% CI 18.6-39.5) was lower for children < 5 (92.9% sensitivity, 95% CI 76.5-99.1, cutoff ≤ -0.550). CONCLUSIONS: Xpert-HR approached the target accuracy to stratify PTB severity in older children and those with Confirmed TB but had lower specificity in children with Unconfirmed TB. Child-specific signatures may be needed to improve performance in younger children with paucibacillary disease.","journal":"Journal of the Pediatric Infectious Diseases Society","year":2025,"id":565353,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9458,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":634219,"name":"Esin Nkereuwem","orcid":"0000-0001-9606-9069","position":1,"is_corresponding":false},{"id":1388273,"name":"Jascent Nakafeero","orcid":null,"position":2,"is_corresponding":false},{"id":434920,"name":"Marie P Gomez","orcid":null,"position":3,"is_corresponding":false},{"id":1331883,"name":"Peter Wambi","orcid":"0000-0002-9195-0778","position":4,"is_corresponding":false},{"id":1398284,"name":"Moses Nsereko","orcid":null,"position":5,"is_corresponding":false},{"id":378255,"name":"Alfred Andama","orcid":"0000-0003-0526-0007","position":6,"is_corresponding":false},{"id":8685,"name":"J. Ernst","orcid":"0000-0001-9951-6207","position":7,"is_corresponding":false},{"id":315466,"name":"Adithya Cattamanchi","orcid":"0000-0002-6553-2601","position":8,"is_corresponding":false},{"id":231920,"name":"Beate Kampmann","orcid":"0000-0002-6546-4709","position":9,"is_corresponding":false},{"id":378252,"name":"Devan Jaganath","orcid":"0000-0002-8555-5667","position":10,"is_corresponding":false},{"id":475682,"name":"Eric Wobudeya","orcid":"0000-0001-9574-5539","position":11,"is_corresponding":false},{"id":1397737,"name":"Brittney Sweetser","orcid":"0000-0001-8655-2639","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:28.709936Z","pmid":"40319382","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":[]}