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Phylogenetic analysis of hepatitis B virus full-length genomes reveals evidence for a large nosocomial outbreak in Belgium
Authors:Mahmoud Reza Pourkarim   Jannick Verbeeck   Mustafizur Rahman   Samad Amini-Bavil-Olyaee   An-Marie Forier   Philippe Lemey   Piet Maes  Marc Van Ranst  
Affiliation:1. Laboratory of Clinical Virology, Rega Institute for Medical Research, Leuven, Belgium;2. Research Center, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran;3. International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh;4. Biotechnology Department, Pasteur Institute of Iran, 13164 Tehran, Iran;5. Infectious Disease Control Unit, Division of Public Health Surveillance, Flemish Agency for Care and Health, Hasselt, Belgium;1. Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, Suzhou, Jiangsu, China;2. Suzhou Industrial Park Centers for Disease Control and Prevention, Suzhou 215123, China;1. “L. Spallanzani” National Institute for Infectious Diseases, Rome, Italy;2. Research & Development, Bristol-Myers Squibb, Wallingford, CT, United States;3. Research & Development, Bristol-Myers Squibb, Princeton, NJ, United States;1. Islamic Azad University, Shahrekord Branch, Shahrekord, Iran;2. Department of Microbiology, Faculty of Basic Sciences, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran;3. Department of Microbiology, Faculty of Veterinary Medicine, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran;1. Division of Viral Diseases, Center for Laboratory Control and Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea;2. Division of Viral Diseases Research, Center for Research of Infectious Diseases, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea;3. Division of Infectious Disease Control, Center for Infectious Disease Control, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea;1. Department of Biomedical and Clinical Sciences L Sacco, University of Milan, Via GB Grassi 74, 20157, Milan, Italy;1. Institute for Medical Informatics and Biometry, Technische Universität Dresden, 01307 Dresden, Germany;2. University of Heidelberg, Department of Infectious Diseases, Molecular Virology, 69120 Heidelberg, Germany;3. Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;4. Department of Evolutionary Biology, Evolutionary Biology Centre (EBC), Uppsala University, 75236 Uppsala, Sweden;5. Department of Internal Medicine 2/Molecular Biology, University Hospital Freiburg, 79106 Freiburg, Germany;6. Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA;7. Zoological Institute, University of Basel, 4051 Basel, Switzerland;8. Institute for Bioinformatics, University Medicine Greifswald, 17487 Greifswald, Germany;9. Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Abstract:BackgroundHepatitis B virus (HBV) is primarily transmitted from mother to child, by sexual contact, intravenous drug abuse, or unsafe health care-related injection practices. Despite increased safety efforts, nosocomial acquired hepatitis B infection remains problematic.ObjectivesA large HBV outbreak was investigated comprising 36 patients with acute HBV infection in a primary care physician's practice.Study designIn a retrospective study (2003–2008), 36 serum samples from patients with acute HBV infection were collected. They had received several injections by the same physician at least 3 months before the onset of clinical symptoms. As a control group, sera were collected from HBV patients from other physicians from the same province. Full-length HBV genomes were amplified and were phylogenetically analysed.ResultsHBV complete genomes of 32 patients were successfully amplified and sequenced, and clustered together with the reference genotype A, subgenotype A2 strains. We also analysed 26 control HBV genotype A samples. All 32 HBV strains from the patient group clustered in a monophyletic branch with a bootstrap value of 100, whereas the control samples branched separately in another clade. The genetic distance value showed small differences within the patients group, whereas the rate within the control group was seven times higher. These observations confirm that the source of transmission was clearly different in both groups.ConclusionMaximum likelihood analysis and genetic distance calculations based on the full-length genomes of HBV strains isolated from patients and controls provided strong evidence for a common nosocomial source of infection for all 32 patient cases.
Keywords:Hepatitis B virus   Nosocomial outbreak   Phylogenetic analysis   Maximum likelihood algorithm   Full-length genome   Belgium
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