Mitigation strategies for the protection of health care workers and first responders Dr John Watkins Department of Primary Care and Public Health School of Medicine Cardiff University Consultant National Public Heath Service for Wales UK

Cases of laboratory confirmed swine-lineage influenza A H1N1 by day of report and travel history, United Kingdom, 06 May 2009 (n=32)

Properties of the Virus Swine Origin Influenza A H1N1 S-OIV HA and NA genes worldwide cases great homogeneity 99% Greater than 90% similar to HA and NA swine virus genes that have been circulating for past 20 years Less than 90% similarity with H1N1 Human seasonal virus

Swine Origin Influenza A H1N1 S-OIV

HA and NA genes worldwide cases great homogeneity 99%

Greater than 90% similar to HA and NA swine virus genes that have been circulating for past 20 years

Less than 90% similarity with H1N1 Human seasonal virus

Canada great experience with SARS in dealing with a highly contagious disease World leading policy on vaccination – Ontario introduction of universal vaccination against influenza –Susan Tamlyn

Canada great experience with SARS in dealing with a highly contagious disease

World leading policy on vaccination – Ontario introduction of universal vaccination against influenza –Susan Tamlyn

Pandemic vaccines

Vaccine supply Internationally 400 million doses – 1.2 Billion of monovalent vaccine UK 20 million doses World population 6-7 billion Production capacity with adjuvants and single component 3.6 billion doses Production plus licence takes 6 months Naive population needs two doses 12-14 billion doses

Internationally 400 million doses – 1.2 Billion of monovalent vaccine

UK 20 million doses

World population 6-7 billion

Production capacity with adjuvants and single component 3.6 billion doses

Production plus licence takes 6 months

Naive population needs two doses 12-14 billion doses

Vaccine Options Replace seasonal programme Produce a single valent vaccine Issue quadruple vaccine Replace H1N1 antigens in seasonal vaccine with Swine strains (need two doses) New technologies using substrates other than eggs UK DH has contract with Baxter for cell culture vaccine

Replace seasonal programme

Produce a single valent vaccine

Issue quadruple vaccine

Replace H1N1 antigens in seasonal vaccine with Swine strains (need two doses)

New technologies using substrates other than eggs UK DH has contract with Baxter for cell culture vaccine

Who is at risk?

Age specific attack rate confirmed cases reported by México 0.75 109,955,400 822 Total 3 No details 0.20 9,640,294 19 60 + 0.54 14,349,342 77 45 to 59 0.57 23,687,456 134 30 to 44 0.94 29,722,159 279 15 to 29 0.95 21,783,444 208 5 to 14 0.95 10,772,705 102 < 5 rate per 100,000 Population from US census office N° Age (years)

Vaccine issues Strategy vaccinate high risk and young Adjuvanted vaccine how safe are they FluAd from Novartis 50 million doses no increased events e.g. GBS, GSK clinical trials with adjuvanted H5N1 vaccine. International agreements about sharing vaccine Who speaks for Africa and other poor countries S-OIV antigen distributed to vaccine manufacturers this week

Strategy vaccinate high risk and young

Adjuvanted vaccine how safe are they FluAd from Novartis 50 million doses no increased events e.g. GBS, GSK clinical trials with adjuvanted H5N1 vaccine.

International agreements about sharing vaccine

Who speaks for Africa and other poor countries

S-OIV antigen distributed to vaccine manufacturers this week

Influenza Strongly seasonal Previous pandemics demonstrate a ‘Herald Wave’ phenomena Next few months in southern hemisphere crucial

Strongly seasonal

Previous pandemics demonstrate a ‘Herald Wave’ phenomena

Next few months in southern hemisphere crucial

Influenza Public Health Strategies Containment phase Epidemic/Pandemic phase Role of containment strategies e.g. social distancing, personal protective equipment (PPE), closure of schools and other public gatherings, masks.

Containment phase

Epidemic/Pandemic phase

Role of containment strategies e.g. social distancing, personal protective equipment (PPE), closure of schools and other public gatherings, masks.

Containment phase Case identification Epidemiological features Attack rate Vulnerable groups Virulence Transmissibility Case fatality rate Contact tracing and management Case Management

Case identification

Epidemiological features Attack rate Vulnerable groups Virulence Transmissibility Case fatality rate

Contact tracing and management

Case Management

Case Management Isolation Personal protective equipment for HCW –correctly fitted high filtrate mask FFP3, long sleeve gown, gloves, eye protection Antiviral therapy for lab test +ve cases and contacts and health care workers HCW who have provided direct care to case and not wearing PPE at the time

Isolation

Personal protective equipment for HCW –correctly fitted high filtrate mask FFP3, long sleeve gown, gloves, eye protection

Antiviral therapy for lab test +ve cases and contacts and health care workers HCW who have provided direct care to case and not wearing PPE at the time

From Rashid A. Chotani Just-in-Time Lecture

1918-MOST FATAL EVENT IN HUMAN HISTORY WORLDWIDE FATALITIES: 50-100 MILLION US FATALITIES: 675,000 U.S. LIFE EXPECTANCY AT BIRTH

Antivirals- Tamiflu

Kaiser et al , 2003 Reduction in complications Patients (%)  55%  52%  61% **, p<0.001 vs placebo Placebo (n=1063) Tamiflu ® (oseltamivir) (n=1350) 10.3 8.2 1.8 4.6** 3.9 0.7 n=109 n=87 n=19 n=62 n=53 n=9 Kaiser et al. Arch Intern Med 2003; 163: 1667-72.

Kaiser et al, 2003 Reduction in hospitalisations  59%  62%  50% 1.7 0.7* 0.8 0.3 3.2 1.6 n=18 n=9 n=5 n=3 n=13 n=6 Placebo (n=1063) Tamiflu  (n=1350) Placebo (n=662) Tamiflu  (n=982) Placebo (n=401) Tamiflu  (n=369) P=0.17 P=0.02 Patients (%) Placebo Tamiflu ® (oseltamivir) Kaiser et al. Arch Intern Med 2003; 163: 1667-72.

Earlier Treatment With Oseltamivir Maximises Clinical Benefits Reduction of Illness Duration ( Days) Compared With Intervention at 48 h Time From Symptom Onset to Treatment (h) Modeled time to treatment P < 0.0001. – 3.1 d – 1.2 d – 2.2 d 12 24 36 – 3.8 d 0

Epidemic/Pandemic Phase Containment strategy futile Move to treatment of symptomatic individuals with antiviral drugs. Cessation of contact tracing PPE for HCW in aerosol generating procedures Antiviral drugs reserved for all symptomatic cases including HCW In UK – National Flu line and population based primary healthcare delivery

Containment strategy futile

Move to treatment of symptomatic individuals with antiviral drugs.

Cessation of contact tracing

PPE for HCW in aerosol generating procedures

Antiviral drugs reserved for all symptomatic cases including HCW

In UK – National Flu line and population based primary healthcare delivery

Antiviral stockpile Purchased 15 million treatment doses (25% of pop) pre 2008/9 season Increased to 33 million doses (50% pop) in 2009 Now increased to cover 80% of population by next winter Stockpile of antibiotics to cover 30% of population by next winter Stockpile of masks gowns and other PPE

Purchased 15 million treatment doses (25% of pop) pre 2008/9 season

Increased to 33 million doses (50% pop) in 2009

Now increased to cover 80% of population by next winter

Stockpile of antibiotics to cover 30% of population by next winter

Stockpile of masks gowns and other PPE

Protection of HCW in a Pandemic Medical/surgical masks Hand hygiene In case of splashes gown, gloves and face protection/eye protection Aerosol generating procedures full PPE No seasonal prophylaxis Antivirals policy same as general population reserved for HCW who develop symptoms who will also be advised to stay at home. Rapid access to antiviral therapy

Medical/surgical masks

Hand hygiene

In case of splashes gown, gloves and face protection/eye protection

Aerosol generating procedures full PPE

No seasonal prophylaxis

Antivirals policy same as general population reserved for HCW who develop symptoms who will also be advised to stay at home.

Rapid access to antiviral therapy

Contentious issues Evidence base for the use of masks MacIntyre R et. Al. EID www.cdc.gov/EID 2009;15:233-241 Social distancing, school closure, bans placed on mass gathering Post exposure prophylaxis and the immune response- still develop immunity Lina B et.al. poster V4140 48 th annual ICAAC Washington DC Oct 2008

Evidence base for the use of masks MacIntyre R et. Al. EID www.cdc.gov/EID 2009;15:233-241

Social distancing, school closure, bans placed on mass gathering

Post exposure prophylaxis and the immune response- still develop immunity Lina B et.al. poster V4140 48 th annual ICAAC Washington DC Oct 2008

INDOOR CHURCH SERVICES WERE BANNED BY HEALTH DEPARTMENTS

Poem from a lady afflicted Cannot speak-got no voice Cannot walk-got no legs Cannot sleep-got too much head Cannot lie down-cough too much Cannot sit up-sneeze too much Cannot eat-got too big a throat Cannot write-got nothing to say. Why? INFLUENZA Lancet January 11 th 1890 p72