2010 TSANZ ANNUALSCIENTIFIC MEETING

pH1N1 Influenza in Transplantation

Professor Jim Bishop AOChief Medical Officer

Australian Government Department of Health and Ageing

Thursday 24 June 2010

PANDEMIC (H1N1) 2009

Overview

Epidemiology of Pandemic H1N1 09 Influenza

Severity indices

Influenza in Transplantation

Current Global Situation

The Australian Health Management Plan for Pandemic Influenza (AHMPPI)

•

The AHMPPI (2008): third edition of the national health management plan

•

Exercise Cumpston 06 recommended –

AHMPPI revision: policy gaps

–

Streamlined decision making–

More flexible policy

PANDEMIC POLICIES

and PLANNING

Pandemic H1N1 2009 Timeline

WHO announces novel human influenza24 Apr

WHO moves to Pandemic phase 427 Apr

Australia moves to Pandemic DELAY28 Apr

WHO moves to Pandemic phase 529 Apr

Australia moves to Pandemic CONTAIN22 May

Victoria moves to MODIFIED SUSTAIN3 Jun

WHO moves to Pandemic phase 611 Jun

Australia moves to Pandemic PROTECT17 Jun

H1N1 Influenza 09 Pandemic Phases

ALERT (pre 24 April 09)

DELAY (24 April 09)

CONTAIN (22 May 09)

SUSTAIN

Victoria moved to a MODIFIED SUSTAIN on 3 June 2009

CONTROL

RECOVER

PROTECT

17 June 2009

Evidence supports focusing efforts on protecting the

‘vulnerable’

Australia's response is continual informed by the emerging evidence around the virus and effectiveness of control measures

H1N1 Influenza 09, mild in most and severe in

some (the vulnerable)

KEY ELEMENTS OF

THE PROTECT PHASE

Identifying the vulnerable

Early treatment of those identified as vulnerable

Voluntary home isolation for those who are sick

Controlling outbreaks in special settings

Limited school action, limiting ILI

A re-focus of testing to the vulnerable, severe

Public Communications Plan

Laboratory confirmed cases of pandemic (H1N1) 2009 and total

influenza in Australia

OVERALL STATISTICS Australia 2009

37,000 laboratory confirmed cases, underestimate

4,500 hospitalisations

13% of laboratory confirmed cases, higher in ATSI

700 ICU admissions

336 cases of viral pneumonia (around 57 per year usually)

13% of hospitalisations were admitted to ICU

1/3 had no known risk factor

61 patients treated using ECMO, 2/3 survived

191 deaths

Median age 53 years (83 years usually)

1/3 of deaths occurred in people with no known risk

Deaths reduced by:-

Older Australians spared- Use of ECMO

Summary of severity indicators

AUSTRALIAN INFLUENZA SURVEILLANCE REPORT. No. 22, 2010, 29 May 2010 –

4 June 2010

Rate of deaths classified as influenza and pneumonia (NSW)

SEVERITY INDICES p H1N1 2009

Hospitalisations-

Chronic underlying medical condition

-

Higher proportion of Indigenous Australians (20%)-

Over 50% admitted within 48 hours of onset

Higher rate of ICU admissions than expected

The clinical syndrome in

intensive care was diffuse viral

pneumonitis

associated with

severe hypoxemia

Clinical Presentation

Chest Radiograph and Computed Tomogram of 2 Patients Successfully Treated

With ECMO for Confirmed 2009 Influenza A(H1N1)

Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome.

JAMA. 2009;302(17):1888-1895

Pathological Features

Consistent

histopathological

findings

-

diffuse alveolar

damage

-

hyaline membranes

-

septal

oedema

-

necrotizing bronchiolitis.

The 2009 H1N1 virus targets alveolar lining cells (type I and

II pneumocytes) as well as upper airway lining cells

Writing Committee of the WHO Consultation on Clinical Aspects of

Pandemic (H1N1) 2009 Influenza,

Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus Infection

N Engl

J Med 2010 362: 1708-1719

KEY FINDINGS FROM ANZICS

Infants and younger adults 25-64 predominated

Risk of death increased with age

Underlying risk factors were pregnancy, chronic lung disease, Indigenous or obese

1/3 had no pre-existing risk factors

Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand. The ANZIC Influenza InvestigatorsN Engl

J Med 2009;361:1925-34.

ANZICS Data

Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand. The ANZIC Influenza InvestigatorsN Engl

J Med 2009;361:1925-34.

ECMO Study

Influenza in Transplant Recipients

Infection in transplant recipients-

Harder to recognize as signs and symptoms may be diminished

-

Fever may result from allograft rejection [1].

Influenza-

is a common infection in solid organ transplant recipients

-

is associated with higher morbidity (viral pneumonia, secondary bacterial pneumonia) and mortality than in immunocompetent

hosts [2].

1. Jay Fishman New England Med 357, 25 Dec 20072. Ison, MG, Hayden, FG. Viral infections in immunocompromised

patients: what's new with respiratory viruses?. Curr

Opin

Infect Dis

2002; 15:355.

Influenza in Lung Transplant Patients

Influenza causes significant morbidity and mortality, including obliterative

bronchiolitis

Neuraminidase inhibitors shorten the duration of symptoms, virus shedding and fewer antibiotic complications

In lung transplant recipients

-

Oseltamivir

is well tolerated-

Infection resolved in all patients and there were no deaths

-

None of the patients had persistent abnormalities noted on chest imaging and most did not show significant changes on pulmonary function testing

Ison, M. G., A. Sharma, et al. (2008). "Outcome of Influenza Infection Managed With Oseltamivir in Lung

Transplant Recipients." The Journal of Heart and Lung Transplantation

27(3): 282-288.

REVIEW of pH1N1 in TRANSPLANTATION

115 Adult and paediatric solid organ transplants

76 adults (median age, 49 years) 39 children (median age, 8 years)

38 kidney, 23 liver, 22 heart, 18 lung, and 14 other

median time since transplant was 3.8 years ( 2 -

21.9 years)

American Transplant Congress (ATC) 2010: Abstract

5. Presented May

2, 2010 From http://www.medscape.com/viewarticle/721412

REVIEW of pH1N1 in TRANSPLANTATION

OUTCOMES:

91% received anti-viral therapy 65.2% of patients were hospitalized 61.1% of patients were lymphopenic 25.2% experienced pneumonia

13.0% were admitted into the intensive care unit (ICU)

One death

American Transplant Congress (ATC) 2010: Abstract

5. Presented May

2, 2010 From http://www.medscape.com/viewarticle/721412

A mulitvariate

analysis with hospitalization more likely with:

-

fever (P

< .001), -

recent antilymphocyte

globulin therapy (P

= .04)

-

or delayed antiviral therapy (P

= .03)

Antiviral treatment within 48 hours of symptom onset -

Less likely to be admitted to the ICU —

0 of 36

compared with 15 of 67 patients (22.4%) who received late antiviral treatment (P

= .005)

American Transplant Congress (ATC) 2010: Abstract

5. Presented May

2, 2010 From http://www.medscape.com/viewarticle/721412

REVIEW OF pH1N1 in TRANSPLANTATION

World Transplant Games

Held in Queensland -20 –

30 August 2009

2000 transplant recipients from 50 countries

At a single campus

No reported cases

No hospitalisations

No fatalities

GUIDANCE FOR TRANSPLANT RECIPIENTS

Endorsed by the American Society of Transplantation (ABT), The Transplantation Society (TSS) and the Canadian Society of Transplantation (CST):

Diagnosis

Treatment

Chronoprophylaxis

Recommendations for patients and family

Recommendations for health care workers

Kumar D et al

American Journal of Transplantation 2010; 10: 18-25

0

10

20

30

40

50

60

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53Week

Rat

e of

ILI p

er 1

,000

con

sulta

tions

ASPREN 2007ASPREN 2008ASPREN + NT + VIDRL 2009ASPREN + VIDRL 2010

First case of Pandemic

(H1N1) 2009 reported in Australia

Weekly rate of ILI GP surveillance systems -

1 January 2007 to 6 June 2010

Currently

Australia has low pH1N1 activity with no increase in Influenza A levels

Following first wave natural immunity 15-25% of the population

Vaccination induced immunity is high:

-

9 Million pandemic vaccine does (41%)

-

5 Million + seasonal vaccine doses (23%)

WHO Update May 30 2010

Northern Hemisphere–

Overall pandemic influenza activity remains low

–

Active but declining p H1N1 in the Caribbean and Southeast Asia

–

Seasonal influenza type B viruses in China

Southern Hemisphere–

Pandemic and seasonal influenza activity is low

–

ILI remains low in Australia and New Zealand –

Limited pandemic influenza virus in Chile.

–

Low levels of H3N2 viruses in Kenya and Tanzania.

WHO Summary as at 30 May 2010