Global and Regional Situation of Zoonotic Influenza in Humans, and Pandemic Preparedness Takato Odagiri Director WHO Collaborating Center on Influenza, Tokyo and Influenza Virus Research Center, National Institute of Infectious Diseases, Japan
Influenza A Viruses All influenza A virus subtypes are detected in aquatic birds H1 - H16 N1 - N9 Aquatic birds Poultry Humans Pigs Horses Aquatic mammals Pandemic potential routes Cats Dogs
Zoonotic Influenza A viruses currently detected in Animals and Humans in the World (since Sept 2016) Avian viruses H5Nx : H5N1 (poultry, wild birds, human(6))(860) H5N2 (poultry, wild birds) H5N5 (wild birds) H5N6 (poultry, wild birds, human (16)) H5N8 (poultry, wild birds) H7N9 : (poultry, human(758), environment) (1564) H7N2 : (poultry) H9N2 : (environment, human(4)) Swine viruses H1N1v (pig) H1N2v (human(2), pig) H3N2v (human(31), pig) Since 2003, Since 2013, http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Zoonotic Influenza A viruses currently detected in Animals and Humans in the World (since Sept 2016) Avian viruses H5Nx : H5N1 (poultry, wild birds, human(6))(860) H5N2 (poultry, wild birds) H5N5 (wild birds) H5N6 (poultry, wild birds, human (16)) H5N8 (poultry, wild birds) H7N9 : (poultry, human(758), environment) (1564) H7N2 : (poultry) H9N2 : (environment, human(4)) Swine viruses H1N1v (pig) H1N2v (human(2), pig) H3N2v (human(31), pig) Since 2003, Since 2013, http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Evolution of A(H5) HA genes China, China HK SAR, Vietnam, Laos, Korea 2.3.4.3 2.3.4.2 2.3.4.4 H5N6 H5N8 H5N2 Bangladesh, India Cambodia, China, Vietnam, Cote d Ivoire, Ghana, Nigeria 2.3.3 2.3.4.1 2.3.2.1 2.3.2.1a 2.3.2.1c 2.3.2.1b 2.3.2 2.3.1 2.2.1.1a Egypt 2.5 2.1.2 2.2 2.4 2.1.1 1 2.2.1 2.2.2 2.2.1.1 2.2.2.1 2.1.3.1 and 2.1.3.3 1.1 2.2.1.2 2.1.3.2b 2.1.3.2a 1.1.2 1.1.1 8 6 9 5 7.2 7 7.1 3 0 4
Global distribution of H5Nx virus clades A(H5) activity birds 2.3.4.4 2.3.2.1c Non GS/GD 2.2.1.2 2.3.2.1a 2.3.2.1c 2.3.2.1c Mar Apr May Jun Jul Aug Sep WHO VCM for 2018 Southern H, Sept 28 Melbourne
A(H5) activity - birds since 27 September 2016 2.3.2.1a 2.3.4.4 2.2.1.2 2.3.2.1c 2.3.2.1c WHO VCM for 2017-2018 Northern H, Mar 2 Geneva
http://www.who.int/influenza/human_animal_interface/2017_07_25_tableh5n1.pdf?ua=1
Recent human infection cases with A(H5Nx) viruses Sept. 2016~Feb. 2017 4 new reported cases, China Egypt Sept Oct Nov Dec Jan Feb Mar. ~Sept. 2017 2 new A(H5N1) cases Egypt 860 A(H5N1) cases/453 fatal 16 A(H5N6) cases/11 fatal Indonesia Mar Apr May Jun Jul Aug Sept WHO VCM for 2017-2018 Northern H, Fen Mar 2 Geneva WHO VCM for 2018 Southern H, Sept 28 Melbourne
Zoonotic Influenza A viruses currently detected in Animals and Humans in the World (since Sept 2016) Avian viruses H5Nx : H5N1 (poultry, wild birds, human(9))(859) H5N2 (poultry, wild birds) H5N5 (wild birds) H5N6 (poultry, wild birds, human (4)) H5N8 (poultry, wild birds) H7N9 : (poultry, human(758), environment) (1564) H7N2 : (poultry) H9N2 : (environment, human(9)) Swine viruses H1N1v (pig) H1N2v (human(5), pig) H3N2v (human(18), pig) Since 2003, Since 2013, http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Data provided by China CDC
Recent human cases infected with LPAI and HPAIV A(H7N9) viruses A(H7N9) activity birds
Data provided by China CDC Pandemic potential with H7N9 viruses is not low Sustained H-to-H transmission is limited so far
Phylogenetic relationships of H7N9 virus HA genes Other Region 13 Genotypes Pearl River Delta 33 Genotypes Yangtze River Delta 36 Genotypes JS537 AnH1 JS18828 JX9530 JS1 SH7 AnH1887 GD2 GD1 GD8423 DG397 GX8970 Data provided by China CDC
Import cases of A(H7N9) infection in Canada, Malaysia and Taiwan Wang DY et al, J Virol, 2016
Summary of A(H7N9) human cases reported to WHO since 27 September 2016 758 human cases of A(H7N9) virus infection (288 fatal) in 5th W Total cases since 2013 = 1564 with 610 deaths Chinese Taipei, Hong Kong Special Administrative Region and Macau Special Administrative Region reported travelassociated cases CFR in reported cases = 39% 68% exposed to live poultry or contaminated environments 40 clusters confirmed, but not sustained human-to-human transmission The majority of A(H7N9) viruses detected in poultry and in humans are low pathogenic Since 2016 high pathogenic A(H7N9) viruses were detected in poultry and in human (28 cases) Most of H7N9 viruses recovered from patients were susceptible to antivirals of NA inhibitors
Candidate vaccine viruses (CVVs) for zoonotic influenza
Process of CVV selection and update for Zoonotic influenza WHO Vaccine Composition Meetings (VCM) held twice in a year (Northern and Southern Hemispheres) CCs (6)/ERLs (4) NICs (144 Labs) H5 Reference Labs (13) (seasonal influenza) Sharing information OIE / OFFLU (zoonotic)
Available H5Nx CVVs provided by WHO CCs/ERLs http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Available H7N9 CVVs provided by WHO CCs/ERLs Yangtze river delta-lineage viruses (predominant-lineage) High-path virus Low-path virus http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Available CVVs of A(H1)v and A(H3N2)v provided by WHO CCs/ERLs http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Pandemic influenza preparedness framework (PIP-FW) in WHO
http://www.who.int/influenza/pip/en/
WHO PIP-Framework is for; Virus sharing Equally access to vaccines and other benefits To get PIP-CVVs and reference viruses, members and stakeholders need to contract with WHO by S MTA2 (https://youtu.be/rmsr9zbyn7i) Under the S MTA2, members and stakeholders are required to response partnership contribution Partnership contribution is used for equal access of pandemic vaccine and for strengthen of pandemic preparedness (https://youtu.be/7m031gg1anq)
Novel virus detection system for pandemic preparedness at alert phase by Japanese government (MOHLW and HIID)
Rapid preparation of novel virus detection system by PCR at all local PHLs and quarantine labs in alert phase Government project supported by MOHLW and NIID Systematic collection of zoonotic influenza viruses as a library in NIID (supported by zoonotic sectors, e.i., NIAH, Hokkaido U, Kagoshima U, Kyoto S.U.) PCR-positive control prep from library viruses and rapid distribution to local PHLs and quarantine labs for immediate setup of PCR-detection system
Primers/Probes distributed to local PHLs and quarantine Labs for discrimination of novel virus Primers and probes Type/subtype Gene Primer Sequence fragment Influenza type A Matrix MP-39-67For CCMAGGTCGAAACGTAYGTTCTCTCTATC (M) MP-183-153Rev TGACAGRATYGGTCTTGTCTTTAGCCAYTCCA MP-96-75ProbeAs 5'-(FAM)-ATYTCGGCTTTGAGGGGGCCTG-(MGB)-3' Influenza A HA NIID-swH1 TMPrimer-F1 AGAAAAGAATGTAACAGTAACACACTCTGT H1N1 pandemic NIID-swH1 TMPrimer-R1 TGTTTCCACAATGTARGACCAT virus NIID-swH1 Probe2 5 -(FAM)-CAGCCAGCAATRTTRCATTTACC-(MGB)-3' Former seasonal HA NIID-H1 TMPrimer-F1 CCCAGGGYATTTCGCYGACTATGAG A(H1N1) NIID-H1 TMPrimer-R1 CATGATGCTGAYACTCCGGTTACG NIID-H1 Probe1 5'-(FAM)-TCTCAAAYGAAGATACTGAACT- (MGB)-3' A(H3N2) viruses HA NIID-H3 TMPrimer-F1 CTATTGGACAATAGTAAAACCGGGRGA NIID-H3 TMPrimer-R1 GTCATTGGGRATGCTTCCATTTGG NIID-H3 Probe1 5'-(FAM)-AAGTAACCCCKAGGAGCAATTAG-(MGB)-3' A(H5N1) viruses HA H5HA-205-227v2-For CGATCTAGAYGGGGTGAARCCTC (Clade 1, 2, 3) H5HA-326-302v2-Rev CCTTCTCCACTATGTANGACCATTC H5HA-205-227-For(2010) 1 CGATCTAAATGGAGTGAAGCCTC H5HA-326-302-Rev(2010) 1 CCTTCTCTACTATGTAAGACCATTC H5-Probe-239-RVa 2 5'-(FAM)-AGCCAYCCAGCTACRCTACA-(MGB)-3' H5-Probe-239-RVb 2 5'-(FAM)-AGCCATCCCGCAACACTACA-(MGB)-3' Influenza type B NS NIID-TypeB TMPrimer-F1 GGAGCAACCAATGCCAC NIID-TypeB TMPrimer-R1 GTKTAGGCGGTCTTGACCAG NIID-TypeB Probe1 5'-(FAM)-ATAAACTTTGAAGCAGGAAT-(MGB)-3' Procedure
New CVV of A/H5N6 (cl 2.3.4.4) from zoonotic virus library in NIID is available for distribution WHO-new CVV
Thank you Mt. Fuji from Murayama-campus, NIID, Tokyo