{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:36:05Z","timestamp":1768077365803,"version":"3.49.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Indonesia Ministry of Health"},{"name":"UK Wellcome Trust"},{"DOI":"10.13039\/501100001722","name":"Royal Netherlands Academy of Arts and Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Since their emergence in Indonesia in 2005, 200 human infections with clade 2.1 highly pathogenic avian influenza A\/H5N1 virus have been reported, associated with exceptionally high mortality (84%) compared to regions affected by other genetic clades of this virus. To provide potential clues towards understanding this high mortality, detailed clinical virological analyses were performed in specimens from 180 H5N1 patients, representing 90% of all Indonesian patients and 20% of reported H5N1-infected patients globally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>H5N1 RNA was quantified in available upper- and lower-respiratory tract specimens as well as fecal and blood samples from 180 patients with confirmed infection between 2005 and 2017. Mutations in the neuraminidase and M2 genes that confer resistance to oseltamivir and adamantanes were assessed. Fatal and nonfatal cases were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High viral RNA loads in nasal and pharyngeal specimens were associated with fatal outcome. Mortality increased over time during the study period, which correlated with increasing viral RNA loads on admission. Furthermore, the prevalence of amantadine resistance\u2013conferring M2 mutations increased over time, and viral loads were higher in patients infected with viruses that harbored these mutations. Compared to observations from other regions, viral RNA was detected more frequently in feces (80%) and particularly in blood (85%), and antiviral responses to oseltamivir appeared less pronounced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These observations confirm the association of viral load with outcome of human H5N1 infections and suggest potential differences in virulence and antiviral responses to oseltamivir that may explain the exceptionally high mortality related to clade 2.1 H5N1 infections in Indonesia.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz328","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T11:56:38Z","timestamp":1556106998000},"page":"1139-1146","source":"Crossref","is-referenced-by-count":11,"title":["Viral Factors Associated With the High Mortality Related to Human Infections With Clade 2.1 Influenza A\/H5N1 Virus in Indonesia"],"prefix":"10.1093","volume":"70","author":[{"given":"Hana A","family":"Pawestri","sequence":"first","affiliation":[{"name":"National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Eggink","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siti","family":"Isfandari","sequence":"first","affiliation":[{"name":"National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tran Tan","family":"Thanh","sequence":"first","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Rogier van Doorn","sequence":"first","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivi","family":"Setiawaty","sequence":"first","affiliation":[{"name":"National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menno D","family":"de Jong","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"2020030303394809400_CIT0001","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1086\/519692","article-title":"Epidemiology of cases of H5N1 virus infection in Indonesia, July 2005\u2013June 2006","volume":"196","author":"Sedyaningsih","year":"2007","journal-title":"J Infect Dis"},{"key":"2020030303394809400_CIT0002","author":"influenza OSRfa"},{"key":"2020030303394809400_CIT0003","unstructured":"World Health Organization. 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