Seventh Welsh Immunisation Conference: Pandemic influenza Professor Nick Phin University of Chester & HPA Centre for Infections London

Influenza virus A respiratory virus with a segmented genome containing eight RNA strands The virus is commonly categorized by two proteins on the surface of the virus Neuraminidase (9 subtypes) Haemagglutinin (16 subtypes)

Role of viral neuraminidase Neuraminidase causes the virus to be released from the cell wall Stress that because the antiviral stops the release of new virus into the lungs that the sooner treatment is started the more effective and the more successful it is likely to be. This is one of the reasons that we don’t use Tamiflu after 48 hours because by then so much virus is circulating that stopping anymore is not likely to make much difference. Antivirals like Tamiflu prevent the release of viruses from infected cells

Why are these two proteins important? Haemagglutinin binds to receptors on the cell Virus is engulfed into cell The virus turns the cell into a factory producing new viruses

Clinical course Respiratory virus that attacks the lining of the respiratory system Uncomplicated Influenza Virus affects the upper airways Illness lasting 5 to 7 days Complicated Influenza The virus affects the lower airways causing or permitting the development of a pneumonia. This is either a Viral pneumonia (direct effect) Bacterial pneumonia (indirect caused particularly by: S Aureus, S Pneumoniae, H Influenzae

Viral pneumonia The example on the left are normal lungs the example on the right are the lungs of some affected by viral pneumonia. The lungs become very stiff and lose their flexibility. There is also bleeding and fluid in the airways.

What makes a pandemic? Nature June 2009

So what happened in 2009? It is estimated that the first cases may have occurred as soon as September 2008 but it is probably more likely that this was in mid January 2009 Mid February - start of an outbreak of ARI in La Gloria, Veracruz. 28% of the 2,150 inhabitants affected from March 5 to April 10

The timeline 1 April Healthmap, a global disease alert system run by academics, flags a news story from Mexico about a strange respiratory outbreak in Veracruz State that has claimed two lives. 6 April Veratect, a US based company that scours news reports for emerging threats, reports in its subscription-only database that local Mexican health officials have declared an alert because of respiratory disease outbreak in La Gloria, Veracruz State

The timeline (cont) 11 April as per the International Health Regulations (IHR) PAHO, a regional office of WHO, asks the Mexican IHR “focal point” to verify the outbreak reported in the news. 12 April - Mexican PH authorities confirms to PAHO the existence of acute respiratory infections. Mexico’s focal point considers outbreak to be a “potential public health event of international importance” Clusters of severe progressive pneumonia in young adults identified in Mexico City and San Luis Potosi

The timeline (cont) 15 April - boy in San Diego, California identified with a novel swine influenza from specimen taken on 30 March 2009 17 April - girl in Imperial, California identified with a novel swine influenza from early April 22 April - Mexico reports atypical influenza behaviour associated with severe pneumonia in various cities 23 April more cases identified in southern California/Texas – no connection 23 April Public Health Agency of Canada and CDC identifies novel swine flu in Mexican samples

The timeline 24 April the WHO issues an international disease outbreak notice 27 April the WHO raised the global pandemic alert phase to 4

The timeline On 30 April the pandemic alert phase was raised to 5 This is the first influenza pandemic in four decades;

WHO global influenza preparedness plan, 2005-2009 January 2008

New WHO Pandemic Phases April/May 2009

The timeline On 11 June WHO raised the pandemic alert phase to 6

Current Global position All countries affected – most countries have experienced some mortality Cases now in the millions Estimates from the US suggest 63 million (21%) US citizens infected. Studies in the UK suggest similar numbers.

Clinical presentation and underlying risk factors Clinical picture consistent with seasonal influenza: Median reported duration of illness 7 days; mean 8.5 days (range 1 to 25 days) Generally considered a mild disease however, Causes a small but significant number of cases of severe pneumonitis resulting in ARDS requiring ITU admission Difficult to treat and requiring treatment modalities such as HFOV and ECMO Significant mortality in these cases

Age groups – Q Surveillance ILI rate (w/e 25 October 2010)

Hospitalisation

Objectives of vaccination in a pandemic Public health measure to prevent illness and reduce transmission in the population Personal health measure to reduce the likelihood of illness and severe disease Infection control measure to reduce the likelihood of infection in vulnerable people

Vaccine Production Image courtesy of GlaxoSmithKline plc

Other issues Vaccine safety Guillain Barré Syndrome

Future Forecast H5N1 H1N1 H3N2

No room for complacency – 1968/69 Use the current time to learn from the events of 2009 and refine the response Need to maintain heightened vigilance and response Remember the FSA!

Acknowledgements All my colleagues in the HPA in the: Centre for Infections Regional Microbiology Network Local and Regional Services In particular: Richard Pebody Estelle Mclean Laura Craig Colin Hawkins Hongxin Zhao Barry Evans Maria Zambon John Watson