One Flu over the Cuckoo s nest Dr Rachel Jones Department of Virology NPHS Microbiology Cardiff Whistlestop tour through Flu The virus Some history The Novel Virus Recent events The disease The control measures The laboratory tests The Future Disease which sound like flu have been described since 400 BC Influenza comes from the word Influentia because it was believed that diseases were caused by bad heavenly fluids or influence. Diseases were described as influenza di catarro was a bad head cold with lots of catarrah. Segments 1,3,4,5 and 6 code for single proteins 1 and 3 = parts of transcription complex 4 = Haemaglutinin (16) H1,H2,H3 H5, H7, H9 5 = Nucleoprotein Capsid 6 = Neuraminidase (9) N1,N2 N3 Segments 2 codes for PB1 + PB1-F2 PB1 = Transcription complex PB1-F2 apoptosis Segments 7 codes for M1 and M2 proteins (Matrix proteins) Segment 8 codes for NS1 (IFN antagonist) NS2 (Exporter or ribonucleoproteins out of nucleus) What makes the viruses more pathogenic? Multiple genes determine pathogenicity: HA receptors bindings sites widespread or localised to upper respiratory tract HA cleavage protease c PB1-F2 - (apoptosis) high virus titres production of cytokines = more severe infections NS1 modulates host cell innate immune response Point mutations can result in dramatic changes to pathogenicity 1
Lessons learnt from the past. 1918 Spanish Flu H1N1 1957 Asian Flu H2N2 1968 Hong Kong Flu H3N2?? Next pandemic H1N1 H2N2 H1N1 Avian Human Reassortment H3 H2N2 Avian Human Reassortment? All 8 RNA segments from birds 3 Avian 5 human (1918) 2 new Avian 5 human (1918) Swine influenza Viruses Triple reassortant swine flu viruses Found in pigs since 1998 (enzootic) in North American pigs Dec 2005- Feb 2009 11/12 sporadic humans infections 9 patients had exposure to pigs? 1 cases of humanhuman transmission. 11/12 recovered 4 hospitalised 50 human cases of swine flu reported since 1970 s worldwide (7 deaths) Triple Re-assortant virus - Pigs PB2 PB1 PA HA NP NA M NS Classic swine North America Avian North America Seasonal H3N2 Eurasian swine lineage Novel swine H1N1 Humans Found in Humans not pigs It is a NEW virus this combination of genes has not been seen before 11 th March 1 st case retrospectively ID 18 th March Mexican surveillance notes increase in flu like illness 28 th March 9 yr old girl OPD flu surveillance ( Imperial County Ca) 30 th March 10 year old boy admitted with fever ( San Diego) 1 st April found to be flu A not typable 6 th April news breaks of problem in Mexico 7 th April Mexican National Inst of Respiratory disease starts investigating clusters 10 th April Pan American Health notes news 11 th April WHO as pandemic alert response network - asks what s happening in Mexico 16 th April 10 year old boy confirmed as H1N1 27 th April Canada and Spain confirm cases 28 th April 7 countries confirm cases 29 th WHO raises pandemic to phase 5 1 st May 13 countries report cases 5 th May 1 st Death in America / 11 th March ID 13 th May WHO discuss severity index 15 th May 100,000 USA clinical cases far greater than those confirmed with H1N1 20 th May Vaccine production mid July 22 nd May WHO claims to be thinking pandemic phases more consideration given to severity of disease?? WHO to declare pandemic?? 2
What s Happening today? Why the Fuss? UK 405 confirmed cases 313 England 88 Scotland 2 Ireland 2 Wales Worldwide 21940 confirmed 125 deaths (103 Mexico 17 USA) H1N1 is a new virus; it hasn t been seen before in man or animals Mild pandemics cause disruption Concerns that virus may change Globalisation different countries affected differently Increase in chronic disease burden Pandemics what we know Shift in the Virus subtype Attacks / Death rates higher in younger people Higher transmissibility cf seasonal flu Different impact in different geographic regions Successive waves of infection What do we know so far Mexico, USA, Canada, Spain Male:female 50:50 Mild illness outside of Mexico Median age 20-30yrs Mortality 0.56% (Incl Mexico) 0.10% (Exc Mexico) (2.5 4% 1918) Mummy are we all going to die of Swine Flu? Hospitalised patients-california 30 patient (553cases) 26 confirmed 4 probable 50% San Diego Age range 27-89 Median 27.5 years 70% female 65% Hispanic MMWR 22/05/09 58 (19) 536-41 64% Chronic conditions 20% ITU (80% Ventilated) 17% (5/30)pregnant 2 lost fetus 27% Vaccinated 3
Pandemics what we know Containment What happening in the labs? Shift in the Virus subtype Attacks / Death rates higher in younger people Higher transmissibility cf seasonal flu Different impact in different geographic regions Successive waves of infection Time will tell! To buy time Vaccine development Ensure plans in place Gain understanding about the virus Has it worked? Problems Case definition Work load Compliance Testing Is it sustainable?? MITIGATION NAAT tests: NASBA Nucleoprotein (A) TAQMAN CDC Atlanta Matrix (A) CFI (Swine generic) CDC Atlanta (HSW) Neuraminidase N1 Seasonal Flu DIF POCT Immunity?Vaccination? MMWR 22 May 09 58(19) 521-534 6-9% adults (18-64) had some cross reactivity 33% >60yrs had some cross reactivity After vaccination 18-64 had 12-18x in titre to seasonal Flu but no real increase against Novel Virus Conclusion Susceptible population Severity of illness Where does that come in the plan? 4
Vaccination Vaccination Lessons learnt Benefit 4.9 billion doses can be available in 12 months USA 90 million UK 45 million people Risk Risk The dangers of a new vaccine Stopping the production of seasonal vaccine Monovalent plus triple valent Costs! Benefit Vaccine works how well? but Will it be in time Is the virus severe enough to warrant the risks? Is this the pandemic? Pandemics plans need to be tested Laboratory reserves stretched Transport issues Teamworking Communication Duration! goodwill only lasts for so long. Politics needs vs health protection International cooperation needs to continue. Rapidity of gaining knowledge, sharing knowledge A lot of the infrastructure was in place HPA The future 5
Acknowledgements Catherine Moore and Sally Corden Staff of the molecular lab Cardiff Staff of the virology lab Cardiff Quote from WHO The only certain thing about Influenza is that nothing is certain 6