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 RolesHealth 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

FunctionsFunctions

• 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 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

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

1889-1892 ? A/H2N21900 ? A/H3N8 mild pandemic

1918 A/H1N1 Spanish influenza1957 A/H2N2 Asian influenza1968 A/H3N2 Hong Kong influenza

(1977* A/H1N1 re-emergence)

Shortest interval = 11 yearsLongest interval = 39 yearsCurrent interval = 36 years

Geographic spread: 1968-69

07/68

08/68

09/68

09/68

09/68

09/68

06/69

09/68

01/69

C.W. Potter, Textbook of Influenza, 1998

Mortality in 20th century pandemics

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

1918-1919 (A/H1N1) – Spanish flu

USA, 500,000 excess deaths; UK 198,000

Worldwide: Est. 40+ million deaths in three distinct waves

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Age specific influenza death rates among females in England & Wales during 1st and 4th quarters of 1918

Ministry of Health, GB, 1919

Personswho consult

their GP

Persons infected withsymptoms

Persons infected without symptoms

1918 25%

50%

195725-30%

1968

25-30%

Morbidity associated with pandemic influenza

Impact in the UKPlanning 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% 19,300 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

Pandemic warning

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

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

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)

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

Country Total cases

Deaths

Cambodia 4 4

Thailand 17 12

Vietnam 87 38

TOTAL 108 54

April 2005

WHO global influenza preparedness plan, 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 1 Cases due to pandemic virus only outside the UKAlert level 2 New pandemic virus isolated in the UK (pandemic

imminent in the UK)Alert level 3 Outbreak(s) due to new pandemic subtype in the UKAlert level 4 Widespread 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.

Infection Control & Reporting

Does clinical severity warrant hospitalisation?

Unlikely to be Influenza A/H5N1. Treat as indicated.

Discuss case with HPA reference laboratory

(ERNVL) with view to H5 testing

Treat as appropriate AND remove from strict respiratory isolation if appropriate.

Discuss further investigations for or avian influenza with HPA reference laboratory at Colindale (ERNVL)8

CLINICALFever and respiratory symptoms OR other severe life-threatening illness* (see Box A)

EPIDEMIOLOGICALTravel to east or south east Asia in the last two weeks2 or Health Care Worker (HCW) who has been in contact with a case of severe unexplained respiratory illness.

SCREENING (E.g. at triage station, by telephone or a GP surgery

Consider oseltamivir

HOSPITAL INVESTIGATIONS (treat samples as “high risk”)

CXRBlood CultureRespiratory sample for influenza A & B **, (NPA OR Combined nose/ throat swab)Sputum culture ± gram stainLegionella and pneumococcal urinary antigensFBC with differentialSerology mycoplasma, influenza A &B, adenovirus, RSV & 20 mls reserve

Inform local Health

Protection Team

Inform hospital infection control5 & occupational health. Inform local laboratory of sample status.

**Perform Immunofluorescence or other rapid test for Influenza A in local laboratory (CL3).Please note that investigations at a local level should NOT involve virus culture if influenza A (H5N1) is suspected.7

REASSESSMENTOf hospitalised patients (Specialist assessment/reassessment at 48 hours)No alternative diagnosis within 48 hours AND CXR consistent with avian influenza AND Clinical course consistent with avian influenza.

Standard Respiratory Infection Precautions

YesNo

No

Yes

PositiveNegative

No Yes

Yes

Strict Respiratory Infection Precautions

Liaise with local Health

Protection team again.

Treat as indicated. Follow up by primary care/health protection team within 48 hours, preferably by phone, to confirm recovery. If patient deteriorates

consider hospitalisation. If the need for direct patient contact arises staff must wear clothing in accordance with strict respiratory infection precautions i.e.

correctly fitted high filtration mask (FFP34), gown, gloves and eye protection.

Hospital: Location: Side roomPatient to wear mask (surgical) Staff to wear mask (surgical), gown and gloves.

Primary Care/ Community: Location:At patient‘s home if possible.Patientto wear mask (surgical). Staff to wear mask (surgical), gown and gloves.

Patient: Strict respiratory isolation preferably in negative pressure room 6

Staff: Correctly fitted high filtration mask (FFP34), gown, gloves and eye protection

CLINICALFever ≥ 38°C OR history of fever AND respiratory symptom (cough or shortness of breath)

EPIDEMIOLOGICALWithin 7 days of onset of symptoms, travel to area of east or south east Asia with outbreaks of avian influenza AND close contact (within 1 metre) with live or dead domestic fowl, wild birds, or swine in any setting.3

OR Close contact (touching/speaking distance) with other case(s) of severe respiratory illness or unexplained death from above areas.OR Part of HCW cluster of severe unexplained respiratory illness.OR Laboratory worker with potential exposure to influenza A (H5N1).

ASSESSMENTInitial medical/nursing assessment (e.g. in side room, by telephone, at a GP surgery or at home)

3

Box A* If epidemiological criteria definitely fulfilled and patient severely unwell but with no respiratory symptoms: discuss with HPA CFI.

AND

AND

2

1

5. For Ambulance infection control guidelines see: http://www.asa.uk.net/document_archive/section10.pdf 6. If negative pressure facilities are unavailable an isolation room can be set up in accordance with WHO guidance.Transferring patients for this reason alone is not advised www.who.int/csr/disease/avian_influenza/guidelines/infectioncontrol/en/ .7. HSE guidelines www.hse.gov.uk/biosafety/diseases/avianflu.htm Microbiological guidelines: www.hpa.org.uk/infections/topics_az/avianinfluenza/pdfs/Micro_guidance.pdf

1. Full avian influenza guidance see www.hpa.org.uk/infections/topics_az/avianinfluenza/guidelines.htm 2.Includes the possibility of a long incubation and late presentation3.For current zones see www.hpa.org.uk/infections/topics_az/avianinfluenza/situation_update.htm 4.FFP3 standard masks, see HSE guidelines for SARS: www.hse.gov.uk/lau/lacs/68-7.htm#Appendix%204

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

www.hpa.org.uk

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