Virology, Erasmus MC

Influenza news letter

The Dutch Influenza News letter is published in Dutch and appears at regular intervals during the influenza season.

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Testing for HPAIV H7N7

The Department for Virology of the ErasmusMC in Rotterdam, the Netherlands, is one of the laboratories that offers testing samples for suspected or probable HPAIV H7N7 infected individuals. We prefer that, before samples are sent to our laboratory, the referring physician or microbiologist contact the virologist on duty by phone (+31(0)10.4633431) to discuss the necessity of the laboratory testing. We like to be informed on the following points.

Information on the referring institute: name and phone number, contact person
Information concerning the patiënt
- name, gender and date of birth
- doctor in charge of the patient
- risk factors such as contact with a poultry farm
- clinical findings such as conjunctivitis and influenza-like symptoms
Specimens to be collected
- nasal washing
- throat swab in virus transport medium
- bronchoalveolar lavage
- serum
Observe guidelines on collecting, handling and transport of specimens obtained from probable, suspected or proven cases of infection with HPAIV H7N7.
It is recommended that specimens inoculated on cell cultures will be handled under biosafety level 2 conditions. However, this is the minimum level of containment under which it specimens will be handled. Under circumstances where handling of a high virus concentration can be expected or production of an aerosol is not excluded, a biosafety level three is recommended.
In the Netherlands the specimens must be transported according to the guidelines Reglement Vervoer over Land van Gevaarlijke Stoffen (VLG). More Information can be obtained at the site of the 'Inspectie Verkeer en Waterstaat'.
The boxes with the specimens can be sent by courier to:
Tests to be performed.

Cell culture on HPAIV H7N7 and other respiratory viruses.
PCR on the presence of HPAIV H7N7 directly on the clinical specimen. An interim-report can be given within three to four hours after arrival of the specimens at the laboratory before 13.00 hours on working days.
PCR testing for influenzavirus A and influenzavirus B, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) will be carried out later.

Interpretation of the test results
- Positive test results: positive test results indicate that the patient was infected with the HPAIV H7N7.
- Negative test results: a negative test results does not excluded the possibility that the patients is infected with the HPAIV H7N7.

It is recommended that specimens inoculated on cell cultures will be handled under biosafety level 2 conditions. We propose that the avian influenza A virus H7N7 will be classified as a biological agent risk group 2, for which a biosafety level two is required, when handling specimens that are received for diagnostic reasons. However, this is the minimum level of containment under which it specimens will be handled. Under circumstances where handling of a high virus concentration can be expected or production of an aerosol is not excluded, a biosafety level three is recommended.

This implicates that patients suspected for infection with avian influenza A virus H7N7 must be cared for under isolation measures preventing both contact transmission and aerosol transmission. Diagnostic specimens can be collected and transported following safety measures applicable for hazard group two. Procedures that have a high probability of aerosol production and handling of virus isolates must be conducted under biosafety three circumstances.

	Research topics
	Anti-viral drug development
	Epidemiology
	Host defence mechanisms
	Molecular biology
	Pathogenesis
	Vaccine development
	Zoonoses

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	Useful links
	Centre for Disease Control (CDC) - influenza information
	European Influenza Surveillance Scheme (EISS)
	European Scientific Working Group on Influenza (ESWI)
	FluNet (WHO/OMS)
	Influenza bibliography
	International Influenza Educational Panel
	MSNBC - influenza research over time
	National Institute for Public Health and the Environment(RIVM)
	Netherlands Institute for Health Services Research NIVEL
	WHO - emerging and communicable diseases
	World Health Organization (WHO)


	Publications
	Geurtsvankessel CH, Willart MA, van Rijt LS, Muskens F, Kool M, Baas C, Thielemans K, Bennett C, Clausen BE, Hoogsteden HC, Osterhaus AD, Rimmelzwaan GF, Lambrecht BN. Clearance of influenza virus from the lung depends on migratory langerin+CD11b-but not plasmacytoid dendritic cells. .J Exp Med. Jun 30:- (2008)
	Russell CA, Jones TC, Barr IG, Cox NJ, Garten RJ, Gregory V, Gust ID, Hampson AW, Hay AJ, Hurt AC, de Jong JC, Kelso A, Klimov AI, Kageyama T, Komadina N, Lapedes AS, Lin YP, Mosterin A, Obuchi M, Odagiri T, Osterhaus AD, Rimmelzwaan GF, Shaw MW, Skepner E, Stohr K, Tashiro M, Fouchier RA, Smith DJ. The global circulation of seasonal influenza A (H3N2) viruses. Science Apr 18;320(5874):340-6 (2008)
	Girard MP, Osterhaus A, Pervikov Y, Palkonyay L, Kieny MP. Report of the third meeting on "influenza vaccines that induce broad spectrum and long-lasting immune responses", World Health Organization, Geneva, Switzerland, 3-4 December 2007. Vaccine May 12;26(20):2443-50 (2008)
	Keawcharoen J, van Riel D, van Amerongen G, Bestebroer T, Beyer WE, van Lavieren R, Osterhaus AD, Fouchier RA, Kuiken T. Wild ducks as long-distance vectors of highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis Apr;14(4):600-7 (2008)
	Kreijtz JH, de Mutsert G, van Baalen CA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol. Jun;82(11):5161-6 (2008)
	Baras B, Stittelaar KJ, Simon JH, Thoolen RJ, Mossman SP, Pistoor FH, van Amerongen G, Wettendorff MA, Hanon E, Osterhaus AD. Cross-protection against lethal H5N1 challenge in ferrets with an adjuvanted pandemic influenza vaccine. PLoS ONE. Jan 2;3(1)::e1401- (2008)
	Scharpé J, Evenepoel P, Maes B, Bammens B, Claes K, Osterhaus AD, Vanrenterghem Y, Peetermans WE. Influenza vaccination is efficacious and safe in renal transplant recipients. Am J Transplant. Feb;8(2):332-7 (2008)
	Ruat C, Caillet C, Bidaut A, Simon J, Osterhaus AD. Vaccination of macaques with adjuvanted formalin-inactivated influenza A virus (H5N1) vaccines: protection against H5N1 challenge without disease enhancement. J Virol. Mar;82(5):2565-9 (2008)
	Ruat C, Caillet C, Bidaut A, Simon J, Osterhaus AD Vaccination of macaques with adjuvanted formalin-inactivated influenza A virus (H5N1) vaccines: protection against H5N1 challenge without disease enhancement. J Virol Mar;82(5):2565-9 (2008)
	Stittelaar KJ, Tisdale M, van Amerongen G, van Lavieren RF, Pistoor F, Simon J, Osterhaus AD. Evaluation of intravenous zanamivir against experimental influenza A (H5N1) virus infection in cynomolgus macaques. Antiviral Res Jul 21:- (2008)
	van der Vries E, van den Berg B, Schutten M Fatal oseltamivir-resistant influenza virus infection N Engl J Med. 359:1074-1076 (2008)
	Osterhaus AD Pre- or post-pandemic influenza vaccine? Vaccine Jun 28;25(27):4983-4984 (2007)
	Osterhaus AD, Vanlangendonck C. Chapter III. The second European Influenza Conference--lessons learnt and actions to take. The urgent need for a European influenza task force. Vaccine Mar 1;25(11)::2155-2160 (2007)
	Rimmelzwaan GF, Fouchier RA, Osterhaus AD Influenza virus-specific cytotoxic T lymphocytes: a correlate of protection and a basis for vaccine development. Curr Opin Biotechnol Dec;18(6):529-536 (2007)
	de Jong JC, Rimmelzwaan GF, Donker GA, Meijer A, Fouchier RA, Osterhaus AD [The 2006/'07 influenza season in the Netherlands and the vaccine composition for the 2007/'08 season] Ned Tijdschr Geneeskd Sep 29;151(39):2158-2165 (2007)
	de Jong JC, Rimmelzwaan GF, Donker GA, Meijer A, Fouchier RA, Osterhaus AD [The 2006/'07 influenza season in the Netherlands and the vaccine composition for the 2007/'08 season] Ned Tijdschr Geneeskd Sep 29;151(39):2158-2165 (2007)
	van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD,Kuiken T Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals Am J Pathol Oct;171(4):1215-1223 (2007)
	Rimmelzwaan GF, Nieuwkoop NJ, de Mutsert G, Boon AC, Kuiken T, Fouchier RA,Osterhaus AD Attachment of infectious influenza A viruses of various subtypes to live mammalian and avian cells as measured by flow cytometry Virus Res Nov;129(2):175-181 (2007)
	Ducatez MF, Olinger CM, Owoade AA, Tarnagda Z, Tahita MC, Sow A, De Landtsheer S, Ammerlaan W, Ouedraogo JB, Osterhaus AD, Fouchier RA, Muller CP Molecular and antigenic evolution and geographical spread of H5N1 highly pathogenic avian influenza viruses in western Africa J Gen Virol Aug;88(Pt 8):2297-2306 (2007)
	Munster VJ, de Wit E, van Riel D, Beyer WE, Rimmelzwaan GF, Osterhaus AD, Kuiken T, Fouchier RA The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses J Infect Dis Jul 15;196(2):258-260 (2007)
	Ducatez MF, Tarnagda Z, Tahita MC, Sow A, de Landtsheer S, Londt BZ, Brown IH, Osterhaus DM, Fouchier RA, Ouedraogo JB, Muller CP Genetic characterization of HPAI (H5N1) viruses from poultry and wild vultures, Burkina Faso Emerg Infect Dis Apr;13(4):611-3 (2007)
	Wallensten A, Munster VJ, Latorre-Margalef N, Brytting M, Elmberg J, Fouchier RA, Fransson T, Haemig PD, Karlsson M, Lundkvist A, Osterhaus AD, Stervander M, Waldenström J, Björn O. Surveillance of influenza A virus in migratory waterfowl in northern Europe Emerg Infect Dis Mar;13(3):404-411 (2007)
	Munster VJ, Baas C, Lexmond P, Waldenström J, Wallensten A, Fransson T, Rimmelzwaan GF, Beyer WE, Schutten M, Olsen B, Osterhaus AD, Fouchier RA Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds PLoS Pathog May 11;3(5):e61- (2007)
	Kreijtz JH, Suezer Y, van Amerongen G, de Mutsert G, Schnierle BS, Wood JM, Kuiken T, Fouchier RA, Lower J, Osterhaus AD, Sutter G, Rimmelzwaan GF. Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1 J Infect Dis Jun 1;195(11):1598-1606 (2007)
	Berkhoff EG, Geelhoed-Mieras MM, Jonges M, Smith DJ, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. An amino acid substitution in the influenza A virus hemagglutinin associated with escape from recognition by human virus-specific CD4+ T-cells Virus Res Jun;126(1-2):282-287 (2007)
	Philippa J, Baas C, Beyer W, Bestebroer T, Fouchier R, Smith D, Schaftenaar W, Osterhaus A Vaccination against highly pathogenic avian influenza H5N1 virus in zoos using an adjuvanted inactivated H5N2 vaccine Vaccine May 10;25(19):3800-3808 (2007)
	de Wit E, Spronken MI, Vervaet G, Rimmelzwaan GF, Osterhaus AD, Fouchier RA A reverse-genetics system for Influenza A virus using T7 RNA polymerase J Gen Virol Apr;88(Pt 4):1281-1287 (2007)
	Berkhoff EG, Geelhoed-Mieras MM, Verschuren EJ, van Baalen CA, Gruters RA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. The loss of immunodominant epitopes affects interferon-gamma production and lytic activity of the human influenza virus-specific cytotoxic T. lymphocyte response in vitro Clin Exp Immunol May;148(2):296-306 (2007)
	de Jong JC, Smith DJ, Lapedes AS, Donatelli I, Campitelli L, Barigazzi G, Van Reeth K, Jones TC, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. Antigenic and genetic evolution of swine influenza A (H3N2) viruses in Europe. J Virol Apr;81(8):4315-22 (2007)
	Berkhoff EG, Geelhoed-Mieras MM, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virus-specific CD8+ T-cell clones. J Gen Virol Feb;88(Pt 2):530-5 (2007)
	Martina BE, Verjans GM, Kuiken T, van Amerongen G, Osterhaus AD In vitro and in vivo replication of seal gammaherpesviruses in cells of multiple species. Microbes Infect Jan;9(1):40-6 (2007)
	de Wit E, Bestebroer TM, Spronken MI, Rimmelzwaan GF, Osterhaus AD, Fouchier RA Rapid sequencing of the non-coding regions of influenza A virus J Virol Methods Jan;139(1):85-9 (2007)
	Kreijtz JH, Bodewes R, van Amerongen G, Kuiken T, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine Jan 8;25(4):612-20 (2007)
	van Riet E, Adegnika AA, Retra K, Vieira R, Tielens AG, Lell B, Issifou S, Hartgers FC, Rimmelzwaan GF, Kremsner PG, Yazdanbakhsh M. Cellular and humoral responses to influenza in gabonese children living in rural and semi-urban areas. J Infect Dis. Dec 1;196(11):1671-8 (2007)
	Gelinck LB, Teng YK, Rimmelzwaan GF, van den Bemt BJ, Kroon FP, van Laar JM. Poor serological responses upon influenza vaccination in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. Oct;66(10):1402-3 (2007)
	van Gils JA, Munster VJ, Radersma R, Liefhebber D, Fouchier RA, Klaassen M. Hampered foraging and migratory performance in swans infected with low-pathogenic avian influenza A virus. PLoS ONE Jan 31;2(1):e184- (2007)
	de Beukelaar JW, Sillevis Smitt PA, Hop WC, Kraan J, Hooijkaas H, Verjans GM, Gratama JW. Imbalances in circulating lymphocyte subsets in Hu antibody associated paraneoplastic neurological syndromes. Eur J Neurol Dec;14(12):1383-91 (2007)
	Gooskens J, Kuiken T, Claas EC, Harinck HI, Thijssen JC, Baelde HJ, Kroes AC. Severe influenza resembling hemorrhagic shock and encephalopathy syndrome. J Clin Virol Jun;39(2):136-40 (2007)
	de Jong JC. Influenza vaccination in health-care workers: an effective method to reduce the consequences of influenza in health care users Ned Tijdschr Geneeskd Sep 29; 151 (39):2143-2146 (2007)
	Rimmelzwaan GF, de Jong JC, Donker GA, Meijer A, Fouchier RA, Osterhaus AD [The 2005-2006 influenza season in the Netherlands and the vaccine composition for the 2006-2007 season] Ned Tijdschr Geneeskd Oct 7;150(40):2209-2214 (2006)
	de Wit E, Bestebroer TM, Spronken MI, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. Rapid sequencing of the non-coding regions of influenza A virus. J Virol Methods Oct 20;:- (2006)
	Osterhaus AD, Vanlangendonck C. Editorial Vaccine Nov 10;24(44-46):6575- (2006)
	Berkhoff EG, de Wit E, Geelhoed-Mieras MM, Boon AC, Symons J, Fouchier RA, Osterhaus AD, Rimmelzwaan GF Fitness costs limit escape from cytotoxic T lymphocytes by influenza A viruses Vaccine Nov 10;24(44-46):6594-6596 (2006)
	de Wit E, Spronken MI, Rimmelzwaan GF, Osterhaus AD, Fouchier RA Evidence for specific packaging of the influenza A virus genome from conditionally defective virus particles lacking a polymerase gene Vaccine Nov 10;24(44-46)::6647-6650 (2006)
	Hampson AW, Osterhaus AD, Pervikov Y, Kieny MP Report of the second meeting on the development of influenza vaccines that induce broad-spectrum and long-lasting immune responses, World Health Organization, Geneva, Switzerland 6-7 December 2005 Vaccine Jun 5;24(23)::4897-4900 (2006)
	Wallensten A, Munster VJ, Karlsson M, Lundkvist A, Brytting M, Stervander M, Osterhaus AD, Fouchier RA, Olsen B High prevalence of influenza A virus in ducks caught during spring migration through Sweden Vaccine Nov 10;24(44-46):6734-6735 (2006)
	Munster VJ, Veen J, Olsen B, Vogel R, Osterhaus AD, Fouchier RA Towards improved influenza A virus surveillance in migrating birds Vaccine Nov 10;24(44-46):6729-6733 (2006)
	Boon AC, de Mutsert G, Fouchier RA, Osterhaus AD, Rimmelzwaan GF The hypervariable immunodominant NP418-426 epitope from the influenza A virus nucleoprotein is recognized by cytotoxic T lymphocytes with high functional avidity. J Virol Jun;80(12):6024-6032 (2006)
	Olsen B, Munster VJ, Wallensten A, Waldenstrom J, Osterhaus AD, Fouchier RA Global patterns of influenza a virus in wild birds Science Apr 21;312(5772):384-388 (2006)
	Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RA, Osterhaus AD, Kuiken T Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts Am J Pathol Jan;168(1):176-183 (2006)
	Kreijtz JH, Bodewes R, van Amerongen G, Kuiken T, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine Sep 7:- (2006)
	Berkhoff EG, de Wit E, Geelhoed-Mieras MM, Boon AC, Symons J, Fouchier RA, Osterhaus AD, Rimmelzwaan GF Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J Virol Sep;79(17):11239-11246 (2005)
	de Jong JC, Osterhaus AD. The threatening influenza pandemic: a national store of oseltamivir is necessary [Article in Dutch] Ned Tijdschr Geneeskd. Jul 16;149(29):1618-1618 (2005)
	Fouchier R, Kuiken T, Rimmelzwaan G, Osterhaus A. Global task force for influenza. Nature May 26;435(7041):419-420 (2005)
	Rimmelzwaan GF, Berkhoff EG, Nieuwkoop NJ, Smith DJ, Fouchier RA, Osterhaus AD Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J Gen Virol. Jun;86(Pt 6)::1801-1805 (2005)
	Wallensten A, Munster VJ, Elmberg J, Osterhaus AD, Fouchier RA, Olsen B. Multiple gene segment reassortment between Eurasian and American lineages of influenza A virus (H6N2) in Guillemot (Uria aalge). Arch Virol. Aug;150(8):1685-1692 (2005)
	Fouchier RA, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, Rimmelzwaan GF, Olsen B, Osterhaus AD. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol Mar;79(5):2814-2822 (2005)
	Fouchier RA, Rimmelzwaan GF, Kuiken T, Osterhaus AD. Newer respiratory virus infections: human metapneumovirus, avian influenza virus, and human coronaviruses. Curr Opin Infect Dis 18:141-146 (2005)
	Bosis S, Esposito S, Niesters HGM, Crovari P, Osterhaus ADME, Principi N Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses J Med Virol 75:101-104 (2005)
	Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, Vennema H, Meijer A, van Steenbergen J, Fouchier R, Osterhaus A, Bosman A. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands The Lancet Feb 21;363(9409)::587-593 (2004)
	Boon AC, de Mutsert G, van Baarle D, Smith DJ, Lapedes AS, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF Recognition of homo- and heterosubtypic variants of influenza a viruses by human CD8(+) T lymphocytes J Immunol. Feb 15;172(4):2453-2460 (2004)
	Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, Koch G, Bosman A, Koopmans M, Osterhaus AD. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome Proc Natl Acad Sci U S A Feb 3;101(5):1356-1361 (2004)
	Boon AC, De Mutsert G, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF Preferential HLA usage in the influenza virusspecific CTL response J Immunol Apr 1;172(7):4435-4443 (2004)
	N.P.J. Vogtländer, A. Brown, R.M. Valentijn, G.F. Rimmelzwaan, A.D.M.E. Osterhaus. Impaired response rates, but satisfying protection rates to influenza vaccination in dialysis patients Vaccine 22:2199-2201 (2004)
	G. F. Rimmelzwaan, A. C. M. Boon, J. T. M. Voeten, E. G. M. Berkhoff, R. A. M. Fouchier and A. D. M. E. Osterhaus Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes Virus Research 103; Issues 1-2, Jul:97-100 (2004)
	Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier RA, Amonsin A, Payungporn S, Noppornpanth S, Wattanodorn S, Theambooniers A, Tantilertcharoen R, Pattanarangsan R, Arya N, Ratanakorn P, Osterhaus DM, Poovorawan Y. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis. Dec;10(12):2189-2191 (2004)
	Bueving HJ, van der Wouden JC, Raat H, Bernsen RM, de Jongste JC, van Suijlekom-Smit LW, Osterhaus AD, Rimmelzwaan GF, Molken MR, Thomas S. Influenza vaccination in asthmatic children: effects on quality of life and symptoms. Eur Respir J. Dec;24(6)::925-931 (2004)
	Thijs Kuiken,Ron A.M. Fouchier, Martin Schutten, Guus F. Rimmelzwaan, Geert van Amerongen, Debby van Riel, Jon D. Laman, Ton de Jong, Gerard van Doornum, Wilina Lim, Ai Ee Ling, Paul K.S. Chan, John S. Tam, Maria C. Zambon, Robin Gopal, Christian Drosten, Sylvie van der Werf, Nicolas Escriou, Jean-Claude Manuguerra, Klaus Stöhr, J.S. Malik Peiris, Albert D.M.E. Osterhaus Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. The Lancet 362:263-270 (2003)
	Rimmelzwaan GF, Kuiken T, van Amerongen G, Bestebroer TM, Fouchier RA, Osterhaus AD A primate model to study the pathogenesis of influenza A (H5N1) virus infection Avian Diseases 47(3 Suppl):931-933 (2003)
	Gog JR, Rimmelzwaan GF, Osterhaus AD, Grenfell BT Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A Proc Natl Acad Sci U S A Sep 16;100(19):11143-11147 (2003)
	Bueving HJ, Bernsen RM, De Jongste JC, Van Suijlekom-Smit LW, Rimmelzwaan GF, Osterhaus AD, Rutten-Van Molken MP, Thomas S, Van Der Wouden JC. Influenza vaccination in asthmatic children: randomised double-blind placebo-controlled trial. Am J Respir Crit Care Med Dec 4:- (2003)
	Fouchier RA, Olsen B, Bestebroer TM, Herfst S, van der Kemp L, Rimmelzwaan GF, Osterhaus AD. Influenza A virus surveillance in wild birds in Northern Europe in 1999 and 2000 Avian Dis 47(3 Suppl):857-860 (2003)
	de Jong JC, Rimmelzwaan GF, Bartelds AI, Wilbrink B, Fouchier RA, Osterhaus AD [The 2002/2003 influenza season in the Netherlands and the vaccine composition for the 2003/2004 season] Ned Tijdschr Geneeskd Oct 4;147(40):1971-1975 (2003)
	de Jong JC, Osterhaus AD [Avian influenza and oseltamivir; a retrospective view] Ned Tijdschr Geneeskd Aug 23;147(34):1663- (2003)
	Fouchier RA, Osterhaus AD, Brown IH. Animal influenza virus surveillance. Vaccine May 1;21(16):1754-1757 (2003)
	Beyer WEP, Palache AM, De Jong JC, Osterhaus ADME. Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. Vaccine 20:1340-1353 (2002)
	Heijnen MLA, Rimmelzwaan GF, Bartelds AIM, Jong JC de, Wilbrink B Winter 2001/2002 in Nederland: een rustig influenzaseizoen Infectieziekten Bulletin. 13:156-157 (2002)
	Boivin G, Osterhaus AD, Gaudreau A, Jackson HC, Groen J, Ward P. Role of picornaviruses in flu-like illness of adults enrolled in an Oseltamivir treatment study who had no evidence of influenza virus infection. J. Clin. Microbiol. 40:330-334 (2002)
	Boon ACM, De Mutsert G, Graus YMF, Fouchier RAM, Sintnicolaas K, Osterhaus ADME, Rimmelzwaan GF. Sequence variation in a newly identified HLA-B35-restricted epitope in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. J. Virol. 76:2567-2572 (2002)
	Boon ACM, De Mutsert G, Graus YMF, Fouchier RAM, Sintnicolaas K, Osterhaus ADME, Rimmelzwaan GF. The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype. J. Virol. 76:582-590 (2002)
	Boon ACM, Vos AP, Graus YMF, Rimmelzwaan GF, Osterhaus ADME. In vitro effect of bioactive compounds on influenza virus specific B and T cell responses. Scan. J. Immunol. 55:24-32 (2002)
	Ljungberg K, Kolmskog C, Wahren B, Van Amerongen G, Baars M, Osterhaus A, Linde A, Rimmelzwaan G. DNA vaccination of ferrets with chimeric influenza A virus hemagglutinin (H3) genes. Vaccine 20:2045-2052 (2002)
	Osterhaus ADME, De Jong JC, Rimmelzwaan GF, Claas ECJ. H5N1 influenza in Hong Kong: virus characterizations. Vaccine 20:S82-S83 (2002)
	Rimmelzwaan GF, Osterhaus ADME. Flu in the limelight. Vaccine 20:2153-2154 (2002)
	Rimmelzwaan GF, Osterhaus ADME. Erratum to "Flu in the limelight" Vaccine 20:3042- (2002)
	Kitler ME, Lavanchy D, Osterhaus ADME (eds). Options for the control of influenza IV. Proceedings "Fifty years of influenza surveillance: A challenge for the 21st century"; WHO, 17-19 February 1999, Geneva. Vaccine 20 suppl. 2: S90- (2002)
	Boon ACM, Fringuelli E, Graus YMF, Fouchier RAM, Sintnicolaas K, Iorio AM, Rimmelzwaan GF, Osterhaus ADME. Influenza A virus specific T cell immunity in humans during aging. Virology 299:100-108 (2002)
	Voeten JTM, Rimmelzwaan GF, Nieuwkoop NJ, Fouchier RAM, Osterhaus ADME. Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B-lymphoblastoid cells. Clin. Exp. Immunol. 125:423-431 (2001)
	Rimmelzwaan GF, Osterhaus ADME. Influenza vaccines: New developments. Current Opinion in Pharmacology 1:491-496 (2001)
	Heijnen MLA, Bartelds AIM, Jong JC de, Rimelzwaan GF, Wilbrink B. Influenza en RS-virusinfecties in winter 2000/2001. Stand van zaken op 12 februari 2001. Infectieziekten Bulletin. 12:50-51 (2001)
	Feron EJ, Klaren VNA, Wierenga EA, Verjans GMGM, Kijlstra A Characterization of Toxoplasma gondii-specific T cells recovered from vitreous fluid of patients with ocular toxoplasmosis Invest Ophthalmol Vis Sci. 42:3228-3232 (2001)
	Rimmelzwaan GF, Kuiken T, Van Amerongen G, Bestebroer TM, Fouchier RAM, Osterhaus ADME. Pathogenesis of influenza A (H5N1) virus infection in a primate model. J. Virol. 75:6687-6691 (2001)
	De Jong JC, Rimmelzwaan GF, Bartelds AIM, Wilbrink B, Fouchier RAM, Osterhaus ADME. Het influenzaseizoen 2000/'01 en de vaccinsamenstelling voor het seizoen 2001/'02. Ned. Tijdschr. Geneeskd. 145:1945-1950 (2001)
	Penn CR, Osterhaus ADME. Zanamivir: a rational approach to influenza B. Scand. J. Infect. Dis. 33:33-40 (2001)
	De Jong JC, Heinen PP, Loeffen WLA, Van Nieuwstadt AP, Claas ECJ, Bestebroer TM, Bijlsma K, Verweij C, Osterhaus ADME, Rimmelzwaan GF, Fouchier RAM, Kimman TG. Antigenic and molecular heterogeneity in recent swine influenza A(H1N1) virus isolates with possible implications for vaccination policy. Vaccine 19:4452-4464 (2001)
	Lavanchy D, Osterhaus ADME. Recommendations for the use of inactivated influenza vaccines and other preventive measures. Conference report. Vaccine 19:1849-1853 (2001)
	Rimmelzwaan GF, Baars M, Van Amerongen G, Van Beek R, Osterhaus ADME. A single dose of an ISCOM influenza vaccine induces long-lasting protective immunity against homologous challenge infection but fails to protect cynomolgus macaques against distant drift variants of influenza A (H3N2) viruses. Vaccine 20:158-163 (2001)
	Rimmelzwaan GF, De Jong JC, Bestebroer TM, Van Loon AM, Claas ECJ, Fouchier RAM, Osterhaus ADME. Antigenic and genetic characterization of swine influenza A (H1N1) viruses isolated from pneumonia patients in The Netherlands. Virol. 282:301-306 (2001)
	Barnett JM, Cadman A, Gor D, Dempsey M, Walters M, Candlin A, Tisdale M, Morley PJ, Owens IJ, Fenton RJ, Lewis AP, Claas ECJ, Rimmelzwaan GF, De Groot R, Osterhaus ADME. Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies Antimicrob. Agents Chemother. 44:78-87 (2000)
	Beyer WEP. Routine influenza vaccination for healthy children - old concept, new technologies. Archives of Disease in Childhood. 83:461-462 (2000)
	Smirnov YA, Lipatov AS, Van Beek R, Gitelman AK, Osterhaus ADME, Claas ECJ. Characterization of adaptation of an avian influenza A (H5N2) virus to a mammalian host. Acta Virologica 44:1-8 (2000)
	Smirnov YA, Lipatov AS, Gitelman AK, Claas ECJ, Osterhaus ADME. Prevention and treatment of bronchopneumonia in mice caused by mouse-adapted variant of avian H5N2 influenza A virus using monoclonal antibody against conserved epitope in the HA stem region. Arch.Virol. 145:1733-1741 (2000)
	Osterhaus ADME, Hedrick JA, Henrickson KJ, Mäkelä MJ, Webster A, Keene O. Clinical efficacy of inhaled zanamivir for the treatment of patients with influenza B virus infection. A pooled analysis of randomised, placebo-controlled studies. Clin. Drug Invest. 20:223-228 (2000)
	Snacken R, Osterhaus A, Rotheray A, Middleton A, Pregliasco F, Vidal Tort J, El Sawy A, Boucher L, Cohen JM, Boussac J, Fuchs R, Leo G, Carewicz O, Whitsitt P. Managing influenza in primary care: a practical guide to clinical diagnosis. Disease Management Health Outcomes 8:79-85 (2000)
	Heijnen MLA, Bartelds AIM, Rimmelzwaan GF. Influenza in winter 1999/2000. Infectieziekten Bulletin. 11:24-26 (2000)
	Fouchier RAM, Bestebroer TM, Herfst S, Van der Kemp L, Rimmelzwaan GF, Osterhaus ADME. Detection of influenza A viruses from different species by PCR amplification of conserved sequences in the matrix gene. J. Clin. Microbiol. 38:4096-4101 (2000)
	Soesman NMR, Rimmelzwaan GF, Nieuwkoop NJ, Beyer WEP, Tilanus HW, Kemmeren MH, Metselaar HJ, De Man RA, Osterhaus ADME. Efficacy of influenza vaccination in adult liver transplant recipients. J. Med. Virol. 31:85-93 (2000)
	De Jong JC, Rimmelzwaan GF, Fouchier RAM, Osterhaus ADME. Influenza virus: a master of metamorphosis. J.Infection 40:218-228 (2000)
	De Jong JC, Beyer WEP, Palache AM, Rimmelzwaan GF, Osterhaus ADME. Mismatch between the 1997/1998 influenza vaccine and the major epidemic A (H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly. J.Med. Virol. 61:94-99 (2000)
	Voeten JTM, Bestebroer TM, Nieuwkoop NJ, Fouchier RAM, Osterhaus ADME, Rimmelzwaan GF. Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J. Virol. 74:6800-6807 (2000)
	De Jong JC, Rimmelzwaan GF, Fouchier RAM, Osterhaus ADME. Influenza: vóórkomen en voorkómen. Modern Medicine 10:877-882 (2000)
	Rimmelzwaan GF, De Jong JC, Bartelds AIM, Dorigo-Zetsma JW, Fouchier RAM, Osterhaus ADME. Het influenzaseizoen 1999/2000 en de vaccinsamenstelling voor het seizoen 2000/'01. Ned. Tijdschr. Geneeskd. 144:1968-1971 (2000)
	Osterhaus ADME, Rimmelzwaan GF, Martina BEE, Bestebroer TM, Fouchier RAM. Influenza B virus in seals. Science 288:1051-1053 (2000)
	Nicholson K, Aoki F, Osterhaus A, Trottier S, Carewicz O, Rode A, Kinnersley N, Ward P, the Neuraminidase Inhibitor Flu Treatment Investigator Group. Treatment of acute influenza: efficacy and safety of the oral neuraminidase inhibitor oseltamivir. The Lancet 355:1845-1850 (2000)
	De Jong JC, Rimmelzwaan GF, Fouchier RAM, Osterhaus ADME. Influenzapandemieën: verleden en toekomst. Tijdschrift van de Belgische Vereniging van Labora 27:5-11 (2000)
	Osterhaus ADME, De Jong JC. The control of influenza: antivirals as an adjunct to vaccines. Vaccine 18:779-780 (2000)
	Osterhaus ADME. Shortage in influenza vaccine supply: Can we reduce its antigenic mass? Vaccine 19:1007- (2000)
	Rimmelzwaan GF, Nieuwkoop N, Brandenburg A, Sutter G, Beyer WEP, Maher D, Bates J, Osterhaus ADME. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOMTM vaccines and conventional vaccines. Vaccine 19:1180-1187 (2000)
	Voeten JTM, Rimmelzwaan GF, Nieuwkoop NJ, Lövgren-Bengtsson K, Osterhaus ADME. Introduction of the haemagglutinin transmembrane region in the influenza virus matrix protein facilitates its incorporation into iscom and activation of specific CD8+ cytotoxic T lymphocytes. Vaccine 19:514-522 (2000)
	Beyer WEP. Is subcutane influenzavaccinatie even effectief als intramusculaire toediening? Vademecum. 36:1-2 (1999)
	Beyer WEP, De Bruijn IA, Palache AM, Westendorp RGJ, Osterhaus ADME. Protection against influenza after annually repeated vaccination. A meta-analysis of serologic and field studies. Arch. Intern. Med. 159:182-188 (1999)
	Smirnov YA, Lipatov AS, Gitelman AK, Okuno Y, Van Beek R, Osterhaus ADME, Claas ECJ. An epitope shared by the hemagglutinins of H1, H2, H5 and H6 subtypes of influenza A virus. Acta virologica 43:237-244 (1999)
	Rimmelzwaan GF, Baars, MMJW, De Lijster P, Fouchier R, Osterhaus ADME. Inhibition of influenza virus replication by nitric oxide. J. Virol. 73:8880-8883 (1999)
	Rothbarth PH, Groen J, Bohnen AM, De Groot R, Osterhaus ADME.. Influenza virus serology - a comparative study. J. Virol. Meths. 78:163-169 (1999)
	De Jong JC, Rimmelzwaan GF, Fouchier RAM, Osterhaus ADME. Influenzapandemieën: verleden en toekomst. Ned. Tijdschr. Geneeskd. 143:1988-1991 (1999)
	Rimmelzwaan GF, De Jong JC, Bartelds AIM, Dorigo-Zetsma JW, Fouchier RAM, Osterhaus ADME. Het influenzaseizoen 1998/'99; vaccinsamenstelling voor 1999/2000. Ned. Tijdschr. Geneeskd. 143:2015-2018 (1999)
	Rimmelzwaan GF, Osterhaus ADME. Universeel influenzavaccin nog ver weg. Ned. Tijdschr. Geneeskd. 143:2305-2307 (1999)
	Osterhaus ADME. Epidemiologische en macro-economische aspecten van influenza. De winst van vaccinatie. Pharmaceutisch Weekblad. 134:1512-1516 (1999)
	Osterhaus ADME. Medische apsecten van influenza. Een scala van complicaties. Pharmaceutisch Weekblad. 134:1517-1520 (1999)
	Osterhaus ADME. Influenza. Succesverhaal door voorlichting en participatie. Pharmaceutisch Weekblad. 134:1538-1539 (1999)
	De Jong JC, Van Nieuwstadt AP, Kimman TG, Loeffen WLA, Bestebroer TM, Bijlsma K, Verweij C, Osterhaus ADME, Claas ECJ. Antigenic drift in swine influenza H3 haemagglutinins with implications for vaccination policy. Vaccine 17:1321-1328 (1999)
	Rimmelzwaan GF, Baars M, Van Beek R, De Lijster P, De Jong JC, Claas ECJ, Osterhaus ADME. Influenza virus subtype cross-reactivities of haemagglutination inhibiting and virus neutralising serum antibodies induced by infection or vaccination with an ISCOM-based vaccine. Vaccine 17:2512-2516 (1999)
	Rimmelzwaan GF, Claas ECJ, Van Amerongen G, De Jong JC, Osterhaus ADME. Iscom vaccine induced protection against a lethal challenge with a human H5N1 influenza virus. Vaccine 17:1355-1358 (1999)
	Voeten JTM, Brands R, Palache AM, Van Scharrenburg GJM, Rimmelzwaan GF, Osterhaus ADME, Claas ECJ. Characterization of high-growth reassortant influenza A viruses generated in MDCK cells cultured in serum-free medium. Vaccine 17:1942-1950 (1999)
	Huisman W, Karlas JA, Siebelink KHJ, Huisman RC, De Ronde A, Francis MJ, Rimmelzwaan GF, Osterhaus ADME. Feline immunodeficiency virus subunit vaccines that induce virus neutralizing antibodies but no protection against challenge infection. Vaccine 16:181-187 (1998)
	Beyer WEP, Palache AM, Osterhaus ADME. Comparison of serology and reactogenicity between influenza subunit vaccines and whole virus or split vaccines. A review and meta-analysis of the literature. Clin. Drug Invest. 15:1-12 (1998)
	Beyer WEP, De Bruijn IA, Palache AM, Westendorp RGJ, Osterhaus ADME. The plea against annual influenza vaccination? "The Hoskins' Paradox" revisited. Vaccine 16:1929-1932 (1998)
	Kroon FP, Rimmelzwaan GF, Roos MTL, Osterhaus ADME, Hamann D, Miedema F, Van Dissel JT. Restored humoral immune response to influenza vaccination in HIV-infected adults treated with highly active antiretroviral therapy. AIDS 12:F217-F223 (1998)
	De Jong JC, Claas ECJ, Osterhaus ADME. Humane influenza A/H5N1 in Hong Kong: een analyse. Analyse 7:201-205 (1998)
	Voeten JTM, Claas ECJ, Brands R, Palache AM, Van Scharrenburg GJM, Rimmelzwaan GF, Osterhaus ADME. Generation and characterization of reassortant influenza A viruses propagated in serum-free cultured MDCK-SF1 cells. NIBSC Meeting on Inactivated Influenza Vaccines Prepared in Cell Culture, 26-27 September 1997, Potters Bar, United Kingdom. Dev. Biol. Stand. 98:77-87 (1998)
	De Jong JC, Claas ECJ, Osterhaus ADME. Influenza A/H5N1 in Hong Kong: augury of an impending pandemic of just an event of scientific interest and a useful exercise in pandemiology? ESCV Newsletter 3:34-36 (1998)
	Osterhaus ADME. Influenza A (H5N1) in Hong Kong: A pandemic threat? ESWI Newsletter 8:1- (1998)
	Remarque EJ, De Bruijn IA, Boersma WJA, Masurel N, Ligthart GJ. Altered antibody response to influenza H1N1 vaccine in healthy elderly people as determined by HI, ELISA and neutralization assay. J Med Virol 55:82-87 (1998)
	Voeten JTM, Groen J, Van Alphen D, Claas ECJ, De Groot R, Osterhaus ADME, Rimmelzwaan GF. Use of recombinant nucleoproteins in enzyme-linked immunosorbent assays for the detection of virus-specific Immunoglobulin A (IgA) and IgG antibodies in influenza virus A- or B-infected patients. J. Clin. Microbiol. 36:3527-3531 (1998)
	Groen J, Claas ECJ, Balentien E, Braakman D, Osterhaus ADME. High influenza morbidity and mortality in unvaccinated elderly people in Curaçao. J. Infect. 36:241-242 (1998)
	Rimmelzwaan GF, Baars M, Claas ECJ, Osterhaus ADME. Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J. Virol. Meths. 74:57-66 (1998)
	Claas ECJ, Osterhaus ADME, Van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, Krauss S, Shortridge KF, Webster RG. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351:472-477 (1998)
	Claas ECJ, Osterhaus ADME. New clues to the emergence of flu pandemics. Nature Medicine 4:1122-1123 (1998)
	Claas ECJ, Osterhaus ADME. Influenzavirussen, continu in verandering. Ned. T. Med. Microbiol. 6:99-102 (1998)
	Claas ECJ, Bartelds AIM, Dorigo-Zetsma JW, Rimmelzwaan GF, De Jong JC, Osterhaus ADME. Het influenzaseizoen 1997/'98 en de vaccinsamenstelling voor 1998/'99. Ned. Tijdschr. Geneeskd. 142:2423-2427 (1998)
	De Jong JC, Claas ECJ, Osterhaus ADME. Influenza A(H5N1) in Hong Kong: voorbode van een pandemie of alleen een wetenschappelijk interessant verschijnsel en een nuttige oefening in pandemiologie? Ned. Tijdschr. Geneeskd. 142:1252-1256 (1998)
	De Jong JC, Claas ECJ, Osterhaus ADME. Influenza A(H5N1) in Hong Kong: voorbode van een pandemie of alleen een wetenschappelijk interessant verschijnsel en een nuttige oefening in pandemiologie? Tijdschr. Diergeneesk. 123:278-282 (1998)
	Claas ECJ, De Jong JC, Van Beek R, Rimmelzwaan GF, Osterhaus ADME. Human influenza virus A/HongKong/156/97 (H5N1) infection. Vaccine 16:977-978 (1998)

	Introduction on Influenza research
The Influenza team at the department of Virology runs an extensive experimental research program that studies the epidemiology, pathogenesis, prevention and treatment of infections with human and animal influenza viruses. The department houses the National Influenza Centre for the WHO in the Netherlands, performing and reporting serology and virology based surveillance of influenza. Recent performance of the group includes H5N1 virus identification, vaccine and anti-viral drug development. Fundamental studies on mechanisms involved in immune-mediated protection against influenza are carried out with the help of animal models, and as part of phase I/II/III clinical trials in humans. The latter are conducted to evaluate the potential of newly developed vaccination and anti-viral drug strategies against influenza. Primary research interest of the immunology branch of the influenza group is the T-cell mediated immune response in natural infections and upon vaccination. Recently, molecular biological strategies to study aspects of the immunology, pathogenesis, zoonosis, epidemiology and prevention of influenza, were initiated. In addition, we have set up, and are currently expanding, new assay systems for influenza surveillance in wild-life and subsequent analyses of pathogenic properties and potential of cross-species transmission of virus isolates.

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