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

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

Health Protection Roles 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

Health Protection Agency

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]

HPA Nationally FWE = Food, Water & Environment

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

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 There are two main types that cause infection: Influenza A and influenza B. Influenza A usually causes a more severe illness than influenza B

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

Influenza epidemiology - Pandemics ? A/H2N2 1900? A/H3N8 mild pandemic 1918A/H1N1 Spanish influenza 1957A/H2N2 Asian influenza 1968A/H3N2 Hong Kong influenza (1977*A/H1N1re-emergence) Shortest interval = 11 years Longest interval = 39 years Current interval = 36 years

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

Mortality in 20 th century pandemics (A/H2N2) – Asian flu  USA, 80,000 excess deaths  Worldwide: Est. 1 million deaths (A/H3N2) – Hong Kong flu  UK: 30,000 excess deaths (c/f 26,000 in )  Worldwide: Est. 1 million deaths (A/H1N1) – Spanish flu  USA, 500,000 excess deaths; UK 198,000  Worldwide: Est. 40+ million deaths in three distinct waves

Death Rate per 1,000 4 st quarter 1 st quarter Age specific influenza death rates among females in England & Wales during 1st and 4th quarters of 1918 Ministry of Health, GB, 1919

Persons who consult their GP Persons infected with symptoms Persons infected without symptoms % 50 % % % Morbidity associated with pandemic influenza

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

Range of excess deaths (E&W) CFR*Clinical attack rate 10%25%50% 0.37%19,30048,40096, %51,700129,200258, %77,100192,700258, %129,200323,000645,900 *Case fatality rate

Pandemic warning

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

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

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

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

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

Up to 28 June 2005 CountryTotal casesDeaths Cambodia44 Thailand1712 Vietnam8738 TOTAL10854

April 2005

WHO global influenza preparedness plan, 2005

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

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. UK Alert Levels

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

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

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

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) UKHD and HPA plans 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 UKHD and HPA plans in context

Responses Vaccine

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

Responses Vaccine Antivirals

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

Responses Vaccine Antivirals Infection control (including masks)

Responses Vaccine Antivirals Infection control (including masks) Travel

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

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

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

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