{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:48:25Z","timestamp":1787161705078,"version":"build-2736575974"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100013479","name":"Bay Area Lyme Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21AI119457-01"],"award-info":[{"award-number":["1R21AI119457-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Laboratory confirmation of early Lyme borreliosis (LB) is challenging. Serology is insensitive during the first days to weeks of infection, and blood polymerase chain reaction (PCR) offers similarly poor performance. Here, we demonstrate that detection of Borrelia burgdorferi (B.b.) cell-free DNA (cfDNA) in plasma can improve diagnosis of early LB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>B.b. detection in plasma samples using unbiased metagenomic cfDNA sequencing performed by a commercial laboratory (Karius Inc) was compared with serology and blood PCR in 40 patients with physician-diagnosed erythema migrans (EM), 28 of whom were confirmed to have LB by skin biopsy culture (n = 18), seroconversion (n = 2), or both (n = 8). B.b. sequence analysis was performed using investigational detection thresholds, different from Karius\u2019 clinical test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>B.b. cfDNA was detected in 18 of 28 patients (64%) with laboratory-confirmed EM. In comparison, sensitivity of acute-phase serology using modified 2-tiered testing (MTTT) was 50% (P = .45); sensitivity of blood PCR was 7% (P = .0002). Combining B.b. cfDNA detection and MTTT increased diagnostic sensitivity to 86%, significantly higher than either approach alone (P \u2264 .04). B.b. cfDNA sequences matched precisely with strain-specific sequence generated from the same individual\u2019s cultured B.b. isolate. B.b. cfDNA was not observed at any level in plasma from 684 asymptomatic ambulatory individuals. Among 3000 hospitalized patients tested as part of clinical care, B.b. cfDNA was detected in only 2 individuals, both of whom had clinical presentations consistent with LB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first report of B.b. cfDNA detection in early LB and a demonstration of potential diagnostic utility. The combination of B.b. cfDNA detection and acute-phase MTTT improves clinical sensitivity for diagnosis of early LB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaa858","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T15:42:19Z","timestamp":1592840539000},"page":"e2355-e2361","source":"Crossref","is-referenced-by-count":28,"title":["Detection of\n                    <i>Borrelia burgdorferi<\/i>\n                    Cell-free DNA in Human Plasma Samples for Improved Diagnosis of Early Lyme Borreliosis"],"prefix":"10.1093","volume":"73","author":[{"given":"John A","family":"Branda","sequence":"first","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob E","family":"Lemieux","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Blair","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim A","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Hong","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivan","family":"Bercovici","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A","family":"Blauwkamp","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree","family":"Hollemon","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Ho","sequence":"additional","affiliation":[{"name":"Karius Inc, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemen","family":"Strle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin S","family":"Damle","sequence":"additional","affiliation":[{"name":"South County Internal Medicine Inc, Wakefield, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Lepore","sequence":"additional","affiliation":[{"name":"Nantucket Cottage Hospital, Nantucket, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nira R","family":"Pollock","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"2021100523245590500_CIT0001","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1086\/589242","article-title":"Prospective study of serologic tests for Lyme disease","volume":"47","author":"Steere","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2021100523245590500_CIT0002","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/clind\/15.5.788","article-title":"Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease","volume":"15","author":"Feder","year":"1992","journal-title":"Clin Infect 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