global pandemic preparedness research efforts text klaus stöhr who global influenza programme 3...

Global Pandemic Preparedness Research Efforts

text Klaus Stöhr

WHO Global Influenza Programme

3

Today

Medium-term applied research linked to medical and public health interventions addressing the current pandemic situation in Asia

text Interpandemic period

Natural history Medical impact Effectiveness of interventions

- Vaccines; antivirals; non-pharmaceutical Economic impact Virological research

Pandemic Interpandemic period

Research to address long-term inter-pandemic and pandemic challenges WHO Global Influenza Programme

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Priority Public Health Interventions International

Generic Many possible interventions during an influenza pandemic

existesearch during pandemics and pre-pandemic phase - Risk assessment and communication - Several Medical interventions

- • sub-o ptimally effective- • are no t accessible in time- • Effectiveness is incompletely understoodeumonia (antimicrobials)

Non-pharmaceutical interventions Opportunities for research - Slowing down local spread of pandemic virus package of activities to reduce text local transmission/infection rate

- Aversion of pandemic package of activities aiming at eliminating a new subtype with increasing fitness

Combination might vary - Reducing morbidity or mortality or economical implications or societal

interruption WHO Global Influenza Programme

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Priority Public Health Interventions International

Generic - Surveillance - Research during pandemics and pre-pandemic phase - Risk assessment and communication

Medical interventions - Vaccines - Antivirals

- Treatment of viral and secondary bacterial pneumonia

(antimicrobials)

Non-pharmaceutical interventions

- Slowing down local spread of pandemic virus package of activities to reduce text local transmission/infection rate

- Aversion of pandemic package of activities aiming at eliminating a new subtype with increasing fitness

Combination might vary - Reducing morbidity or mortality or economical implications or societal

interruption WHO Global Influenza Programme

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Opportunities for research 1. Risk assessment

New developments - 1997: direct transmission of avian influenza virus to humans

– 2004: No reassortment despite• long + widespread presence of new influenza type of known human pathogenicity • multiple transmission to humans with co-circulation of human influenza virus

What is the likelihood and outcome of reassortment between H5N1 and currently circulating human or pig influenza A viruses?

- Lab trials (appropriate biosafety): viable reassortants; pathogenicity and

text transmissibility Studies on the infection rate in the general population in affected countries


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Opportunities for research 2. Control of source and pathways of transmission

New developments - Domestic ducks are (a potent?) reservoir for HPAI - H5N1 with increased pathogenicity in poultry and mice and found in • Pigs • Wild birds • Mammals (felines)

What is the role of various animal/bird species in the epidemiology of influenza viruses of pandemic potential?

- Vector and reservoir studies (domestic and wild animals/birds); text • Serological/virological studies in various animal/bird species in H5N1

affected/non-affected countries What are the best disease control options in animals in the

currently affected countries? WHO Global Influenza Programme

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Opportunities for research 3. Case management and hospital infection control

- 74 cases; 49 death (VTN: 55/35) • Two publications on the clinical course of the disease…. - Very little understanding of key clinical, epidemiological and virological

parameters of H5N1 infection in humans • Risk groups, IKP, Ab kinetics, excretion patterns; duration of infectivity • Efficacy of antiviral drugs; adapted diagnostic tests/protocolls

Coordinated clinical research and case management - Network of linked laboratories in affected countries; standardized

treatment and study protocols; mechanism of sample and information exchange; complementary analyses

text- International clinical research network on emerging infectious diseases in Asia (WHO and NIH initiative) • Strengthen national capacity and resources and facilitate international

collaboration and exchange • Concept paper developed; international partners/funding institution identified; next step: engagement of national partners and enrollment of hospitals


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Opportunities for research 4.1 Aversion of a pandemic

New developments - Possibility of early detection of new subtype with increasing

transmissibility - Antiviral and H5N1 vaccine stockpile feasible

Could massive prophylactic use of antivirals (vaccines) in/around an epi centre extinguish an emerging new subtype or at least buy time? - Modelling very foundation for any decision making - Particular large number of assumptions.

Research on H5N1 vaccine stockpile Could an international stockpile of respective size(?) be

established and maintained?


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Opportunities for research 4.2 Slowing down local spread

New developments - Recommendations available on non-pharmaceutical measures at the

international and national level during different phases of an influenza pandemic - Built on best available science

What effectiveness will non-pharmaceutical interventions have?

- Research package necessary • during pandemics

What are the pathways of transmission of influenza viruses? text - incompletely understood and their relative importance unknown. - Hospital infectious control; case management; non-pharmaceutical

interventions


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Opportunities for research 5. Clinical research on the immunogenicity of pandemic vaccines

New developments - Pandemic vaccine prototype strain available since April 2004

- Vaccine stockpile feasible Establish immunogenicity of H5N1 vaccines from currently

circulating strain and implement antigen sparing strategies

text


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Vaccine availability scenarios million doses

4000

3500

3000

2500

2000

1500

1000

500 text

0 1

Trivalent Monovalent Whole virus Adjuv. (4x) 2 doses

2 3 4 5

month

Projected daily vaccine production - 0.72 million - 2.17 million - 3.25 million - 13 million

6 7 8

R. Hehme GSK; Presentation Vaccine Meeting Lisbon, May 2004 WHO Global Influenza Programme

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Opportunities for research 5. Clinical research on the immunogenicity of pandemic vaccines

New developments - Pandemic vaccine prototype strain available since April 2004

- Vaccine stockpile feasible Establish immunogenicity of H5N1 vaccines from currently

circulating strain and implement antigen sparing strategies - Requires • research coordination between countries and companies to avoid duplication • Public funds to compensate for lack of commercial interest - Current status

text • Promising progress since Nov 2004• 2 clinical trials started (USA)

• 10 more companies in Australia, Canada, France, Germany, Japan, USAbefore the end of the year (all antigen sparing)

H5N1 registration=pandemic vaccine registration WHO Global Influenza Programme

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Pandemic influenza virus emergence and possible begin of pandemic vaccine production

Expected scenario today text

0 1 2 3 4 5 6 7 8 9 10 11 month

Pandemic strain emerges Reaches Europe/Australia Global distribution

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Pandemic influenza virus emergence and possible begin of pandemic vaccine production

Expected scenario today

text

0 1 2 3 4 5 6 7 8 9 10 11 month

Pandemic strain emerges Reaches Europe/Australia Global distribution

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Opportunities for research 6. Vaccine production: surge capacity

Current problems - Little to no surge capacity for seasonal and pandemic influenza vaccines

What alternative production systems exist and how could existing ones be improved?

- Cell-culture; recombinant vaccines - Improved Ag harvest from eggs

Should be assessed as part of a text package of an complete pandemic preparedness concept.


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Opportunities for research 7. Epidemiology and natural history: mid-long term

Current problems - Public health risk of emerging avian and mammalian viruses very

difficult to assess and to predict. - Determinants for human pathogenicity of influenza viruses ill

understood - Role of migratory birds as vector/reservoir of HPAI unclear

Studies on the ecology and molecular biology of animal influenza viruses

- Genetic foundation for host specificity and pathogenicitytext • Molecular studies on the genetic determination of pathogenicity and host

specificity • Laboratory trials on the susceptibility of domestic animals to H5 - Virological/serological studies on the prevalence and molecular

evolution of influenza viruses in animals/birds WHO Global Influenza Programme

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Opportunities for research 8. Vaccines: long-term

Current problems - Pandemic vaccines • Stockpiling not possible for all subtypes as current vaccines confer

protection only against small number of variant viruses • Surge capacity - Seasonal vaccines • Annual revaccination; costs

text


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Annual vaccine costs to health Annual seasonal vaccine

production - 300 million doses – Assumptions

• WS price 7.5 USD • 5% increase

Costs by 2015: 28.3 billion text

4 5 % increase vaccine price

3.5

3

2.5

2

1.5

1

0.5

0 6 7 8 9 10 11 12 13 14 15

If only 5% was taken/added for research: 1.41 billion. WHO Global Influenza Programme

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Opportunities for research 8. Vaccines: long-term

Current problems - Pandemic vaccines • Stockpiling not possible for all subtypes as current vaccines confer

protection only against small number of variant viruses • Surge capacity - Seasonal vaccines • Annual revaccination; costs

Cross-subtype specific influenza vaccines which confer long-lasting immunity

- Would address both pandemic and epidemic dilemmastext Estimated global investment into antiviral stockpiling

- 1.4 billion USD


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Research prioritization and coordination Identification of research priorities does not equal international coordination of research efforts Several research projects already initiated

- Many individual projects • Governments; academia; national research and philanthropic institutions. - WHO Global Influenza Network including WHO Animal

Influenza Network: operational research and direct support to control efforts

- Several loose ends text Need for an meeting on coordination of international

support to avian influenza surveillance and control in Asia (donor meeting with gap analyses) - Coordination meeting on research?!.


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global pandemic preparedness research efforts text klaus stöhr who global influenza programme 3...

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