The next influenza pandemic ?

1. The next influenza pandemic ? Centre for Infections Health Protection Agency London John Watson July 2005

2. Plan • Health protection • What is an influenza pandemic? • Impact of a pandemic • Risk of a future pandemic • Pandemic plans • Potential responses

3. Health Protection Roles • To reduce the dangers to health from infections, chemical hazards and poisons, radiological and other environmental hazards. • Preventing harm • Preparing for threats • Protecting people

4. Health Protection Agency

5. Health Protection Agency Divisions/Centres • Communicable Disease Surveillance • Specialist and Reference Microbiology • Emergency Response Division • Business Division • Local and Regional Services • Chemical and Toxicological Hazards • [Radiological Hazards] • [National Institute of Biological Standards and Control]

6. HPA Nationally FWE = Food, Water & Environment

7. Functions • Advice to Government on health protection • Delivery of services to the NHS and other agencies • Impartial, authoritative information and advice to the public and professionals • Rapid response to new threats and emergencies • Improved knowledge base through research and development, education and training

9. Influenza or 'flu' is a respiratory illness associated with infection by influenza virus. Symptoms frequently include headache, fever, cough, sore throat, aching muscles and joints. There is a wide spectrum of severity of illness ranging from minor symptoms through to pneumonia and death. The influenza virus was first identified in 1933. There are two main types that cause infection: Influenza A and influenza B. Influenza A usually causes a more severe illness than influenza B

10. Pre-requisites for pandemic influenza • ‘PAN’ (all) ‘DEMOS’ (people) = Epidemic that • affects all people • New influenza A sub-type: Haemagglutinin (HA) • unrelated to immediate (pre-pandemic) • predecessor. Could not have arisen by mutation. • Little or no pre-existing population immunity • Person to person spread, causing clinically apparent disease • Spread (rapid) beyond the community in which it was first identified

11. Influenza epidemiology - Pandemics 1889-1892 ? A/H2N2 1900 ? A/H3N8 mild pandemic 1918 A/H1N1 Spanish influenza 1957 A/H2N2 Asian influenza 1968 A/H3N2 Hong Kong influenza (1977* A/H1N1 re-emergence) Shortest interval = 11 years Longest interval = 39 years Current interval = 36 years

12. Geographic spread: 1968-69 09/68 01/69 09/68 09/68 07/68 09/68 08/68 06/69 09/68 C.W. Potter, Textbook of Influenza, 1998

13. Mortality in 20th century pandemics 1918-1919 (A/H1N1) – Spanish flu • USA, 500,000 excess deaths; UK 198,000 • Worldwide: Est. 40+ million deaths in three distinct waves 1957-1958 (A/H2N2) – Asian flu • USA, 80,000 excess deaths • Worldwide: Est. 1 million deaths 1968-1970 (A/H3N2) – Hong Kong flu • UK: 30,000 excess deaths (c/f 26,000 in 1989-90) • Worldwide: Est. 1 million deaths

14. Age specific influenza death rates among females in England & Wales during 1st and 4th quarters of 1918 4st quarter 1st quarter 160 140 120 100 80 60 40 20 0 0-4 5-9 85+ 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 Death Rate per 1,000 Ministry of Health, GB, 1919

15. Morbidity associated with pandemic influenza Persons who consult their GP 1968 25-30% 1918 Persons infected with symptoms 25% 1957 25-30% 50% Persons infected without symptoms

16. Impact in the UK Planning assumption • 25% ill (50% infected) over one or more waves of about 12 weeks • Range 10 – 50% ill

17. Range of excess deaths (E&W) CFR* Clinical attack rate 10% 25% 50% 0.37% 19,300 48,400 96,700 1.0% 51,700 129,200 258,400 1.5% 77,100 192,700 258,400 2.5% 129,200 323,000 645,900 *Case fatality rate

18. Pandemic warning

19. Influenza epidemiology – Pandemic warnings 1976 A/H1N1 swine-like virus, Fort Dix, NJ, USA 1977 A/H1N1 global re-introduction 1997 A/H5N1 avian influenza, Hong Kong 1999 A/H9N2 human cases, Hong Kong 2003/04 A/H7N7 human cases, Netherlands & British Columbia 2002/03 SARS outbreak, rapid global spread of novel resp. virus

21. 20 February 2003 • Chicken ‘flu (influenza A H5N1) in Hong Kong • Outbreak in a family linked to southern China • Two deaths among four ill • Two cases confirmed influenza virus infection

22. Influenza epidemiology – Pandemic warnings 1976 A/H1N1 swine-like virus, Fort Dix, NJ, USA 1977 A/H1N1 global re-introduction 1997 A/H5N1 avian influenza, Hong Kong 1999 A/H9N2 human cases, Hong Kong 2003/04 A/H7N7 human cases, Netherlands & British Columbia 2002/03 SARS outbreak, rapid global spread of novel resp. virus 2003/04 A/H5N1 further human cases, SE Asia (Thailand, Korea, Vietnam)

23. Outbreaks of H5 Avian Influenza in Asia In the period January-March 2004 (with first dates of animal outbreaks reporting)

24. Recent (since June 2004) outbreaks of H5 Avian Influenza in Asia  and confirmed Human casesAs of: 16 March 2005 (with first dates of animal outbreaks reporting)

25. Up to 28 June 2005

26. April 2005

27. WHO global influenza preparedness plan, 2005

28. WHO global influenza preparedness plan, 2005

30. H5N1 as a pandemic virus? • Genetic changes • Virulence in humans • Asymptomatic cases • Clusters ? Adaptation to humans

31. UK Alert Levels A pandemic is thought most likely to start outside the UK, and to become established in other countries before reaching the UK. For the UK, four alert levels are described in the DH and HPA Plans: Alert level 1Cases due to pandemic virus only outside the UK Alert level 2New pandemic virus isolated in the UK (pandemic imminent in the UK) Alert level 3Outbreak(s) due to new pandemic subtype in the UK Alert level 4Widespread pandemic activity across UK In terms of specific actions, both plans assume UK alert levels 1-4 will be triggered within WHO phase 2.

32. Current UK vigilance • International situation • Unexplained clusters of severe respiratory illness (esp in health care workers) • Returning travellers • Large numbers • Ordinary respiratory infections

33. Algorithm for the management of returning travellers from south-east Asia presenting with febrile respiratory illness: recognition, investigation and initial management.

34. DH and HPA influenza pandemic contingency planning Well advanced, but more to go…

35. UKHD and HPA plans in context • UKHD plan covers all of UK; this includes Scotland, Wales and Northern Ireland who now have separate Health Departments independent of DH England. • Considered to be the ‘Overarching UK Plan’ • Covers role of DH England as ‘lead government department’ • Covers National Health Service (NHS) and wider issues such as essential services (Civil Emergency Response) • Covers specific responsibilities for policy, practice and logistics regarding antiviral drugs (oseltamivir: Tamiflu®) and vaccine (when supplies available)

36. UKHD andHPAplans in context • HPA plan is an operational manual for the HPA • Supports the overarching UKHD plan • Covers role of each relevant Centre or Division • Contains more detailed projections of impact • Concentrates on HPA public health roles: - surveillance; - diagnostics; - modelling (and real-time prediction); - communications; - and operational support to NHS and DH England

37. Responses • Vaccine

38. Vaccine options Develop vaccine once new strain is identified to be causing pandemic • Specificity • Delay Develop vaccine in advance • Limited or no protection

39. Responses • Vaccine • Antivirals

40. A major decision on antivirals Health Secretary John Reid today announced the Department of Health is to procure 14.6 million courses of oseltamivir (Tamiflu®), an antiviral drug, as part of the UK's preparedness for an influenza pandemic. John Reid said: “The plan we are publishing today, together with our procurement of these antivirals, puts the UK in the forefront of international preparedness for a possible flu pandemic….. …..it makes sense to ensure we in the UK are as prepared as we can be and have drugs for use against an influenza pandemic here. That is why I have ordered 14.6 million courses of oseltamivir for delivery over the next two financial years. This will enable us to treat one in four of the UK population - the proportion which the WHO recommends we plan for.” 01 March 2005

41. Responses • Vaccine • Antivirals • Infection control (including masks)

42. Responses • Vaccine • Antivirals • Infection control (including masks) • Travel

43. Responses • Vaccine • Antivirals • Infection control (including masks) • Travel • “Social distancing” measures

44. Impact on working life • Employees sick • Employees caring for sick • Employees reluctant to travel to, or for, work • Disruption to national or international trade or commerce • Disruption to national infrastructure

45. www.hpa.org.uk

48. The next pandemic ? • maximum recorded interval between pandemics is 39 years • likely origin will be SE Asia, seasonality unknown • rapid global spread • several epidemic waves; first may be ‘milder’ than subsequent ones • excess mortality and morbidity difficult to predict but may be high • overall population clinical attack rate likely to be 25-30% • likely shift from current inter-pandemic pattern of disease, towards younger age • groups in terms of severity and mortality • impact on health services likely to be considerable • H5N1 avian influenza virus is changing but development into a pandemic strain is still not certain

49. A / Singapore / 6 / 86 (H1N1) A / Jhb / 82 / 96 (H1N1) Antigenic drift and shift DRIFT: random (small) change in antigenic structure Influenza A and B A / H3N2 SHIFT: non-random substitution of haemagglutinin (H) or haemagglutinin and neuraminidase (H and N). Influenza A ONLY A / H5N1