Influenza Updates. The newsletter of the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne

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Influenza Updates The newsletter of the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne Volume 5, Issue 1, April 016 Preparation for the Southern Hemisphere influenza season As winter and the influenza season approach in many countries in the southern hemisphere, we expect that the number of samples submitted to the Centre will increase in the coming months in the lead up to the next WHO Consultation on the Composition of Influenza Vaccines for the Southern Hemisphere on 7 9 September 016. Please send us your samples on a regular basis as soon as possible after collection, as they are most useful when they have been collected recently we accept both viral isolates and/or original clinical specimens. We need to receive samples by the end of August in order to process them in time for the Consultation. The WHO Shipping Fund Project covers the cost of shipping samples by National Influenza Laboratories to WHO Collaborating Centres for up to a maximum of 3 shipments per laboratory per year. If you have any questions about shipping samples or would like information about accessing the WHO Shipping Fund, please contact us at whoflu@influenzacentre.org. Timing for sending samples to a WHO Collaborating Centre Figure adapted from FluNet: http://www.who.int/influenza/gisrs_laboratory/flunet/en/; circulation of influenza viruses, Western Pacific Region of WHO 1

Upcoming meetings and conferences Look out for staff from our Centre who will be attending and presenting posters and talks at the following meetings during 016. Please contact us if you would like to meet us there. 15th National Immunisation Conference 7 9 June 016; Brisbane, Australia https://www.phaa.net.au/events/event/15th -national - immunisation-conference Organised by the Public Health Association of Australia, this year s conference will have the theme Immunisation: the jigsaw fitting the pieces two decades on, with broad discussion of current and future immunisation practices in Australia and the region, and in comparison to the United Kingdom. Australian Society for Microbiology Annual Scientific Meeting 3 6 July 016; Perth, Australia http://asmmeeting.theasm.org.au/ This meeting will cover a wide variety of topics, including infectious diseases microbial infections and resistance, the microbiome, viruses, zoonotic infections, vaccines and emerging treatment options. Options IX for the Control of Influenza 4 8 August 016; Chicago IL, USA http://016.isirv.org/ This is the largest international conference that focuses exclusively on influenza. The meeting is aimed for people working across all facets of influenza, including basic and applied researchers and scientists, clinicians, epidemiologists, policy makers, vaccine experts, public health workers, medical and scientific media, and government officials. 16th International Congress of Immunology 1 6 August 016; Melbourne, Australia http://ici016.org/ This triennial conference is the largest international meeting in the field of immunology, and in 016 will be held in our Centre s hometown of Melbourne. Dr Ian Barr, Acting Director of the Centre, is part of the organising committee. The main theme of this year s meeting is Immunotherapy: Harnessing the Power of the Immune System, while other topics to be discussed include advances in the development of vaccines for infectious diseases, microbiome-host interactions, new i n n a t e c e l l s u b s e t s a n d immunoregulatory pathways. The program will include over 800 oral presentations, of which over 100 will be from invited speakers. Australian Influenza Symposium Due to the similar timing of two major international meetings in this August of this year - Options IX for the Control of Influenza (Chicago IL, USA) and the 16th International Congress of Immunology (Melbourne) - it has been decided not to hold an Australian Influenza Symposium during 016. The next Symposium is scheduled for October 017 and potential locations are in Brisbane or Sydney. Please contact us at symposium@influenzacentre.org if you would like to stay informed about the Australian Influenza Symposium in future years. PhD students at the Centre We are pleased to welcome Ms Rubaiyea Farrukee (left) and Ms Annika Suttie (right), who have recently commenced their PhD candidatures at the Centre. Rubaiyea s project will investigate the replication, transmission and fitness of antiviralresistant viruses. In a collaboration between the Centre, Institut Pasteur du Cambodge, and Federation University, Annika will undertake a project characterising the molecular epidemiology of influenza viruses in Cambodia.

B/Yamagata Untyped B lineage undetermined B/Yamagata A (unsubtyped) Recent activity at the Centre (1 January 31 March 016) Below is a summary of surveillance activities at the Centre from 1 January to 31 March. We anticipate that the next few months will be an increasingly busy time for the Centre as the Southern Hemisphere influenza season commences. Samples received The Centre received 557 influenza samples from the laboratories and institutions listed below during the period 1 January 31 March, 016. AUSTRALIA: Canberra Hospital, Royal Darwin Hospital, Westmead Hospital, Queensland Health Forensic and Scientific Services, SA Pathology, Royal Hobart Hospital, Austin Health, Royal Children's Hospital (Molecular Microbiology Dept.) CAMBODIA: Institut Pasteur du Cambodge FIJI: Fiji Centre for Communicable Disease Control MALAYSIA: Insitute for Medical Research NEW CALEDONIA: Institut Pasteur PHILIPPINES: Research Institute for Tropical Medicine SINGAPORE: National Public Health Laboratory SOLOMON ISLANDS: National Referral Hospital SRI LANKA: Medical Research Institute THAILAND: Thai National Influenza Center Antigenic analysis: A total of 60 influenza isolates were analysed by HI assay. Neuraminidase inhibitor susceptibility: A total of 89 influenza isolates were tested by neuraminidase inhibition (NAI) assay for susceptibility to oseltamivir, zanamivir, peramivir and laninamivr. No. of viruses analysed by HI assay * No. of viruses tested by NAI assay * Country of submitting laboratory Australia 71 35 15 6 15 14 1 115 15 159 56 Cambodia 6 16 5 0 Fiji 4 5 55 7 4 5 55 Malaysia 16 5 1 3 16 5 1 3 New Caledonia 1 1 55 9 11 1 55 9 New Zealand 4 3 1 Papua New Guinea 1 3 Philippines 7 8 1 4 4 Singapore 31 33 16 18 31 41 16 18 Solomon Islands 17 Sri Lanka 9 18 1 13 5 15 1 Thailand 1 9 1 9 8 1 9 Total 146 130 1 14 133 47 1 198 59 60 175 * Subtypes and lineages are based on analysis of HA and in some cases confirmed by genetic analysis of NA. 3

Number of samples Recent activity at the Centre (1 Jan 31 Mar 016, continued) Country of submitting laboratory Genetic analysis: Sequencing was performed on 90 HA, 47 NA, 9 MP and 6 NS genes from 91 viruses by Sanger sequencing. Next Generation Sequencing (NGS) techniques were used to sequenced the HA, NA and MP genes of an additional 89 viruses, as well as the full genomes of 64 viruses. In total, 4 sequences from 45 human viruses received for surveillance purposes were deposited with the GISAID EpiFlu TM database (http://www.gisaid.org). No. of viruses with individual genes (HA/ NA/MP/NS) analysed by Sanger sequencing or NGS A(H1N1) pdm09 B/Vic B/Yam No. of viruses analysed by full genome sequencing using NGS techniques A(H1N1) pdm09 B/Vic B/Yam Australia 0 100 11 8 8 6 6 7 Cambodia 1 3 1 4 1 1 Fiji 1 1 3 1 1 1 Macau SAR 1 1 Malaysia 1 1 1 1 1 New Caledonia 3 1 1 1 New Zealand 1 3 3 Papua New Guinea 1 Philippines 1 1 1 Solomon Islands 3 South Africa 1 1 Sri Lanka 3 1 1 1 Thailand 1 1 1 1 Total 9 11 0 19 13 16 16 19 Isolation of viruses in eggs The Centre undertakes primary isolation of selected viruses in eggs to obtain potential vaccine strains. From 1 January to 31 March 016, 8 and one virus were successfully isolated in eggs at the Centre. Surveillance update: Virus activity 1 January 31 March 016 The data below are results for viruses collected between 1 January and 31 March 016 that have been analysed at the Centre as of 0 April 016. Virus types/subtypes The type and subtype/lineage of 110 viruses have been determined. The predominant type/subtype amongst viruses analysed to date was (68.%). 100 80 60 B/Yamagata Subtypes and lineages are based on analysis of the HA and in some cases confirmed by genetic analysis of NA. ^ The Pacific region comprises countries in Polynesia, Melanesia and Micronesia. 40 0 0 Australasia Australia New Zealand Pacific^ Solomon Islands 4

B/Yamagata A(H1N1)pdm9 Surveillance update: Virus activity 1 Jan 31 Mar 016 (continued) Antigenic analysis Haemagglutination inhibition (HI) assays indicate that with the exception of a small number of viruses, all isolates were antigenically similar to the 016 Southern Hemisphere and 016-017 Northern Hemisphere vaccine strains. * indicates strains included in the 016 Southern Hemisphere and 016-017 Northern Northern Hemisphere WHO vaccine recommendations. ^ Indicates strains included in the WHO quadrivalent vaccine recommendations A/California/7/009* A/Hong Kong/4801/014* B (Victoria lineage) B/Brisbane/60/008* B (Yamagata lineage) B/Phuket/3073/013^ 8 5 53 7 8 43 3 13 9 0% 0% 40% 60% 80% 100% % of isolates analysed by HI assay 4-fold or more higher -fold higher equal -fold lower 4-fold lower 8-fold lower Genetic analysis: focus on Sequencing and phylogenetic analysis of haemagglutinin (HA) genes indicate that viruses circulating during January March 016 contained some genetic changes compared to the vaccine reference strain A/California/7/009, although these changes do not affect the antigenic behaviour of the viruses. Christchurch/16/10e Victoria/918/10 CALIFORNIA/07/09e Darwin/11/16 feb Tasmania/6/16 mar Singapore/GP1911/15e nov Canberra/4/16 feb Newcastle/65/15e dec South Australia/5/016 feb Sydney/15/16 feb Darwin/3/16 jan Darwin/17/15 oct Brisbane/1/16 jan Brisbane/0/15 dec 6B.1 Singapore/GP1908/15e nov Scotland/P/15e nov Singapore/TT1307/15e nov Michigan/45/15e sep Philippines/3/15 oct Brisbane/181/15 oct Townsville/1/16 jan nphlsingapore/gp043/15 dec nphlsingapore/kk1074/15 dec Solomon Islands/7/16 feb Solomon Islands/5/16 feb Solomon Islands/1/16 feb Singapore/KK915/15e oct Tasmania/1/16 jan Malaysia/1335/15 jun Newcastle/5/15 apr Cambodia/Z110510/15 sep Sydney/15/15 nov Brisbane/3/15e mar South Australia//15e mar Philippines/7/15 mar Christchurch/538/14e aug Tasmania/4/14e jul Victoria/90/14 jul New Caledonia/58/14e may Goroka/1/15 jan Malaysia/507/15 Tasmania/17/15 jun Tasmania/7/15 jul Cambodia/AD05543/15 jun nphlsingapore/tt14/15 sep Cambodia/FSS39385/15 jun Singapore/KK967/15e nov Malaysia/09707/15 aug Victoria/900/16 feb Canberra/1/16 jan Townsville/41/15 dec Shanghai/Putuo/SWL1860/15e oct Brisbane/3/16 feb Sth Australia/1003/15 jun Brisbane/137/15e jul LR Darwin/19/15 nov Perth/103/15 aug Fiji/17/15 nov Malaysia/71614/15 nov cdcminnesota/3/15 jul nphlsingapore/en750/15 nov Newcastle/1004/15 aug Brisbane/05/15 dec Darwin/14/15 sep Brisbane/196/15e nov Darwin/0/15 dec SthAustralia/17/13e cnicbeijing Xicheng/SWL11631/14e apr Townsville/1/15 jan Singapore/KK517/14e jun Christchurch/6/14e jan Brisbane/70/14 mar 6C Brisbane/96/1 Darwin/56/13 cnicliaoning Yinzhou/SWL1177/14e mar 7 4 0.000 Legend Reference strains CURRENT VACCINE STRAIN Viruses collected in 016 } Brackets indicate clades Scale bar represents 0.% nucleotide sequence difference between viruses 6B. 6B Neuraminidase inhibitor susceptibility Viral isolates are routinely tested for their susceptibility to the antiviral drugs oseltamivir (Tamiflu), zanamivir (Relenza), peramivir and laninamivir using the neuraminidase inhibition (NAI) assay. Of 11 viruses tested, none showed highly reduced inhibition to any of the neuraminidase inhibitors. Viruses that demonstrate reduced inhibition by antiviral drugs in the NAI assay undergo genetic analysis of the neuraminidase gene to detect known or novel mutations associated with the f u n c t i o n a l c h a n g e. T h e relationship between reduced inhibition and the clinical effectiveness of a neuraminidase inhibitor is not well understood. Further studies would be required to determine whether a virus with reduced inhibition in the NAI assay is clinically resistant. Type/ subtype No. viruses tested 78 17 8 9 Number of viruses with highly reduced inhibition Oseltamivir 0 0 0 0 Peramivir 0 0 0 0 Zanamivir 0 0 0 0 Laninamivir 0 0 0 0 5 WHO Collaborating Centre for Reference and Research on Influenza Peter Doherty Institute for Infection and Immunity 79 Elizabeth Street, Melbourne VIC 3000, Australia ph: +61 3 934 9300 Fax: +61 3 934 939 Email: whoflu@influenzacentre.org http://www.influenzacentre.org