{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:05:25Z","timestamp":1753891525050,"version":"3.41.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Accurate diagnosis of <jats:italic>Pneumocystis jirovecii<\/jats:italic> pneumonia (PJP) in HIV patients remains challenging. This study compares metagenomic next-generation sequencing (mNGS) with PCR, GMS staining, and serum \u03b2-D-glucan (BG) assays for PJP detection and co-infection identification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BALF samples from 34 HIV-positive PJP patients and 50 non-PJP controls were analyzed. Diagnostic performance metrics (sensitivity, specificity, NPV, AUC) and co-pathogen profiles were evaluated for mNGS versus conventional methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>mNGS and PCR both achieved 100% sensitivity. mNGS showed higher specificity (91.3% vs. 88%) and AUC (0.898 vs. 0.940 for PCR). Co-infections were detected in 67.6% of PJP cases by mNGS, including cytomegalovirus (41.2%), Epstein\u2013Barr virus (29.4%), and non-tuberculous mycobacteria (14.7%). GMS and BG assays exhibited lower sensitivity (64.7% and 76.5%, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>mNGS offers superior specificity, accuracy, and co-infection detection compared to traditional methods. Its high NPV (100%) supports clinical utility in ruling out PJP. While resource-intensive, mNGS is a promising first-line diagnostic tool for HIV-associated PJP, particularly in polymicrobial infection settings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1567484","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T05:37:27Z","timestamp":1742967447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic value of metagenomic next-generation sequencing in detecting Pneumocystis jirovecii pneumonia in HIV-infected patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiawen","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuxiu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingli","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1513\/pats.201009-062WR","article-title":"HIV-associated Pneumocystis pneumonia","volume":"8","author":"Huang","year":"2011","journal-title":"Proc Am Thorac Soc"},{"key":"ref2","first-page":"466","article-title":"Projecting the medical costs of AIDS and ARC in the United States","volume":"988","author":"Hay","year":"1988","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1164\/ajrccm.151.6.7767533","article-title":"Suspected Pneumocystis carinii pneumonia with a negative induced sputum examination. Is early bronchoscopy useful?","volume":"151","author":"Huang","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1056\/NEJMra032588","article-title":"Pneumocystis pneumonia","volume":"350","author":"Thomas","year":"2004","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/mmy\/myaa024","article-title":"Diagnosing Pneumocystis jirovecii pneumonia: a review of current methods and novel approaches","volume":"58","author":"Bateman","year":"2020","journal-title":"Med Mycol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1378\/chest.108.2.415","article-title":"Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia, tuberculosis, and bacterial pneumonia","volume":"108","author":"Quist","year":"1995","journal-title":"Chest"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.3978\/j.issn.2072-1439.2015.12.27","article-title":"Diagnosis of Pneumocystis pneumonia using serum (1-3)-\u03b2-D-glucan: a bivariate meta-analysis and systematic review","volume":"7","author":"Li","year":"2015","journal-title":"J Thorac Dis"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/j.cmi.2020.05.024","article-title":"Diagnostic accuracy of serum (1-3)-\u03b2-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis","volume":"26","author":"Del Corpo","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.diagmicrobio.2006.08.015","article-title":"Performance of a molecular viability assay for the diagnosis of Pneumocystis pneumonia in HIV-infected patients","volume":"57","author":"de Oliveira","year":"2007","journal-title":"Diagn Microbiol Infect Dis"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1056\/NEJMoa1803396","article-title":"Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis","volume":"380","author":"Wilson","year":"2019","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"941930","DOI":"10.3389\/fcimb.2022.941930","article-title":"Metagenomic next-generation sequencing: a promising tool for diagnosis and treatment of suspected pneumonia in rheumatic patients with acute respiratory failure: retrospective cohort study","volume":"12","author":"Shi","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jinf.2021.01.029","article-title":"Metagenomic next-generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients","volume":"82","author":"Peng","year":"2021","journal-title":"J Infect"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41576-019-0113-7","article-title":"Clinical metagenomics","volume":"20","author":"Chiu","year":"2019","journal-title":"Nat Rev Genet"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1026739","DOI":"10.3389\/fcimb.2022.1026739","article-title":"The diagnostic value of metagenomic next-generation sequencing for identifying Pneumocystis jirovecii infection in non-HIV immunocompromised patients","volume":"12","author":"Zhao","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jinf.2018.08.013","article-title":"A cluster of cases of Pneumocystis pneumonia identified by shotgun metagenomics approach","volume":"78","author":"Zhang","year":"2019","journal-title":"J Infect"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1007\/s40121-021-00482-y","article-title":"Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia in non-HIV-infected patients: a retrospective study","volume":"10","author":"Jiang","year":"2021","journal-title":"Infect Dis Ther"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"413","DOI":"10.5582\/bst.2021.01514","article-title":"Clinical guidelines for the diagnosis and treatment of HIV\/AIDS in China: their potential benefits and impact on public health","volume":"15","author":"He","year":"","journal-title":"Biosci Trends"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"761788","DOI":"10.3389\/fmed.2021.761788","article-title":"Development of a droplet digital polymerase chain reaction for sensitive detection of Pneumocystis jirovecii in respiratory tract specimens","volume":"8","author":"Yi","year":"2021","journal-title":"Front Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"784236","DOI":"10.3389\/fcimb.2021.784236","article-title":"Clinical performance of BAL metagenomic next-generation sequence and serum (1,3)-\u03b2-D-glucan for differential diagnosis of Pneumocystis jirovecii pneumonia and Pneumocystis jirovecii colonisation","volume":"11","author":"Liu","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3201\/eid1903.121151","article-title":"Increasing Pneumocystis pneumonia, England, UK, 2000\u20132010","volume":"19","author":"Maini","year":"2013","journal-title":"Emerg Infect Dis"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1001\/jama.286.19.2450","article-title":"New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia","volume":"286","author":"Kovacs","year":"2001","journal-title":"JAMA"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.2147\/IDR.S257587","article-title":"Metagenomic next-generation sequencing in diagnosis of a case of Pneumocystis jirovecii pneumonia in a kidney transplant recipient and literature review","volume":"13","author":"Chen","year":"2020","journal-title":"Infect Drug Resist"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s11904-020-00514-1","article-title":"Application of pathogen discovery\/metagenomic sequencing in CNS HIV","volume":"17","author":"Thakur","year":"2020","journal-title":"Curr HIV\/AIDS Rep"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ijid.2021.04.057","article-title":"Clinical usefulness of metagenomic next-generation sequencing for the diagnosis of central nervous system infection in people living with HIV","volume":"107","author":"Chen","year":"2021","journal-title":"Int J Infect Dis"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1378\/chest.06-1467","article-title":"Serum indicators for the diagnosis of Pneumocystis pneumonia","volume":"131","author":"Tasaka","year":"2007","journal-title":"Chest"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1128\/JCM.05267-11","article-title":"Diagnostic accuracy of serum 1,3-\u03b2-D-glucan for Pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis","volume":"50","author":"Onishi","year":"2012","journal-title":"J Clin Microbiol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.2147\/IDR.S350047","article-title":"Metagenomic next-generation sequencing for the diagnosis of suspected opportunistic infections in people living with HIV","volume":"15","author":"Xu","year":"2022","journal-title":"Infect Drug Resist"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"541092","DOI":"10.3389\/fcimb.2021.541092","article-title":"Application of metagenomic next-generation sequencing in the diagnosis of pulmonary infectious pathogens from bronchoalveolar lavage samples","volume":"11","author":"Chen","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s12890-019-1022-4","article-title":"Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis","volume":"19","author":"Wang","year":"2019","journal-title":"BMC Pulm Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"607","DOI":"10.2147\/IDR.S394265","article-title":"Diagnostic value of metagenomic next-generation sequencing for multi-pathogenic pneumonia in HIV-infected patients","volume":"16","author":"Xie","year":"","journal-title":"Infect Drug Resist"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"100256","DOI":"10.1016\/j.jfp.2024.100256","article-title":"Targeted next-generation sequencing assay for direct detection and serotyping of Salmonella from enrichment","volume":"87","author":"Lin","year":"2024","journal-title":"J Food Prot"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13073-022-01054-6","article-title":"Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing","volume":"14","author":"Sibandze","year":"2022","journal-title":"Genome Med"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e0260522","DOI":"10.1128\/spectrum.02605-22","article-title":"Development and assessment of a novel whole-gene-based targeted next-generation sequencing assay for detecting the susceptibility of Mycobacterium tuberculosis to 14 drugs","volume":"10","author":"Wu","year":"2022","journal-title":"Microbiol Spectr"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1567484\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T05:37:40Z","timestamp":1742967460000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1567484\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":33,"alternative-id":["10.3389\/fmed.2025.1567484"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1567484","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2025,3,26]]},"article-number":"1567484"}}