Pandemic influenza: using the past to predict the future Alex Elliot Primary Care Scientist,

1. Pandemic influenza: using the past to predict the future Alex Elliot Primary Care Scientist, Royal College of General Practitioners Birmingham Research Unit AND West Midlands Regional Surveillance Unit Health Protection Agency

2. Increase knowledge of influenza viruses Describe the surveillance systems in place to monitor influenza in the community Pandemic influenza – what are the current issues? Objectives of talk

3. Part I: Etiology and clinical presentation

4. Influenza A Influenza B Influenza C

5. Influenza virus attaches to the epithelial cells of the respiratory tract The virusreplicates in the epithelial cells Virus neuraminidase releases progeny virus into the airway Influenza in the respiratory tract

6. 120 100 80 60 40 20 0 Frequency shedding (%) 0 1 2 3 4 5 6 7 8 Study day Virus shedding Gentile et al., 1998

7. Part II: Treatment and prevention

8. Prevention and treatment

9. Trivalent vaccines – A (H3N2), A (H1N1), B virus Split and subunit vaccines licensed in UK Annual production cycle starts Feb each year 6 months to produce vaccine 60 million eggs used Vaccination

10. Amantadine / rimantadine Influenza A viruses only M2 ion channel – transmembrane mutations High level resistance (~30-40%) Resistant viruses transmissible Anti-neuraminidase drugs Low level resistance Haemagglutinin mutations Resistant viruses reduced virulence Requires early diagnosis/treatment to be effective Anti-influenza drugs

11. Part III: Surveillance of influenza & influenza-like illness

12. World Health Organisation (WHO) reference laboratories London Atlanta Tokyo Melborne All liaise with National Influenza Laboratories European Influenza Surveillance Scheme (EISS) Worldwide influenzasurveillance

13. RCGP clinical (1964) Boarding School (1979) Integrated RCGP/HPA clinical and virological surveillance (1992) HPA local laboratory virological and clinical data (1994) NHS Direct syndromic surveillance (1997) QResearch clinical data (2004) Sources of influenza surveillance data in the UK

14. Mortality statistics (weekly - influenza, bronchitis or pneumonia) Laboratory reports (weekly) Outbreak reports (ad hoc) Spotter practice data (weekly rates per 100,000 population) Virological surveillance (weekly % specimens positive) Schools data (weekly rates per 1,000 pupils) Sickness absence data (ad hoc) Community studies (ad hoc) NHS Direct Influenza pyramid: sources of data for surveillance Deaths Hospitalised cases Community cases seen by a general practitioner Community cases not seen by a general practitioner

15. Royal College of General Practitioners founded in 1952 Birmingham Research Unit established in 1959 Record all new episodes of illness (first and new) Incidence per 100,000 population Monitor at national, regional and practice level Age and gender specific data RCGP Birmingham Research Unit

16. 73 practices Population of ~600,000 (2004) North Central South WRS regional surveillance:England & Wales

17. Part IV: Pandemic influenza

18. Genetic reassortment – “antigenic shift” Human influenza Avian influenza HA NA Mixed infection in pig Reassortant strain capable of infecting Man but containing new gene for HA to which Man has no immunity HA

19. HPAI (human cases)over the last few years

20. H5N1 - recent events *Laboratory confirmed cases 28th Jan 2004 – 13th May 05 *Source: WHO

21. Started in the Spring of 1918 Three waves occurred Infected nearly 500 million worldwide Mortality 20-100 million Killed more troops in one year than the whole of WW1 1918/19 influenza pandemic

22. Then and now… 1918 What happened Year 2005 What could happen World population 1.8 billion 5.9 billion Primary mode of transport Troop ships, railways Airplanes Time for virus to circle globe 4 months 4 days Preventative measures Gauze masks, disinfectants Vaccines Treatments Bed rest, aspirin Antiviral drugs Estimated dead 20-40 million >60 million

23. Part V: The influenza pandemic plan

24. What can we do to prepare? What do we look out for? What can we do during the pandemic? Questions

25. UK alert mechanisms

26. When might this happen?

27. How long will it take to spreadfrom the source country?

28. Students returning from high-risk areas Quarantine checks (ports) Fever ≥38°C Onset of fever delayed? Normal surveillance systems might not detect these cases First clinical cases

29. Incubation time of ~2 days (? pandemic virus) Students returning – if infected as they leave they might possibly get through strict quarantine measures They will present initially with high temp/fever/chills (no cough) Shedding of virus lasts for ~6 days (? pandemic virus) Clinical presentation

30. Pandemic plan Stockpile antiviral drugs (Oseltamivir) Prioritise use (prophylaxis/treatment?) Vaccine – who gets it? Current activities – United Kingdom

31. Healthcare workers (with patient contact) Providers of essential services Persons with co-morbidities (“at-risk” groups) 65+ years old Selected industries Selected age groups e.g. children Offer to all Pandemic vaccine – priority vaccination groups (according to gradually increasing availability of vaccine)

32. Monitor virus activity on a daily basis -Geographical spread across the UK -Age groups affected -Drug susceptibility -Vaccine uptake/effectiveness Restrictions on public gatherings Minimise social mixing Use of masks? Activities during pandemic

33. Prepare pandemic plans What to look out for? Students returning from high risk areas Notification of early cases Forward samples/specimens for virological testing Quarantine/isolation of early cases Once pandemic takes hold – damage limitation Higher Education Health Services

34. The pandemic virus may spread rapidly in educational establishments (up to 90%) If this is confirmed as a characteristic of the [pandemic] virus, Health Departments will inform Education Departments to advise local education authorities and the education sector about measures to be taken to slow down the virus These measures might include: Short-term closures Management of students travelling within, to and from the UK

35. We need good monitoring systems Can we integrate monitoring of student populations with current pandemic surveillance systems? Help monitor future spread of other viruses/infectious agents in the local community What can we do now?