Health or Disease The Balance of Environment, Policy, and Science

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Health or Disease?The Balance of Environment,
Policy, and Science

• Margaret A. Liu, M.D.
• First Joint Meeting of Ministers of Health and
  Environment from South East and East Asia
• August 9, 2007

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• Organization of talk
• Status quo
• What are the realities and challenges?
• What are the issues?
• Paradigms to support and emulate
• International Vaccine Institute

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Global Health in the 21st Century

• Impact of Infectious Diseases
• 13 million deaths annually
• 50 of all deaths in developing countries
• Despite progress (e.g., smallpox, polio)
• Failure to control certain diseases
• Inadequate usage of existing technologies
• Re-emergence of diseases
• Emergence of new diseases
• What is the role of the environment?

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The Impact of the Environment on Infectious
Diseases

• 5-6 million annual deaths from water- borne
  diseases and air pollution
• Poor environmental quality is a factor in 25 of
  all preventable illness
• Indoor air pollution a factor in 60 of the 2.2
  million deaths/yr in children 5 due to acute
  respiratory infections

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Paradigms for success

• Eradication of smallpox

Courtesy of T Sharrar, Smithsonian Institution
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Paradigms for success
Near-eradication of Polio
Courtesy of T Sharrar Smithsonian Institution
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Eradicating polio achievements
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Why do Infectious Diseases still kill so many
people?

• Poverty/Lack of infrastructure
• Lack of access to clean water, vaccines
• Inadequate eradication strategies
• Malnutrition

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Why do Infectious Diseases still kill so many
people?

• Biological Scientific challenges/Ecosystem
• Persistence of diseases
• failure to develop preventions,
• treatments
• Emergence of new diseases
• e.g. HIV

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Why do Infectious Diseases still kill so many
people?

• Biological Scientific challenges/Ecosystem
• Re-emergence of diseases
• 20 diseases have re-emerged or spread
  geographically
• e.g., malaria, Tuberculosis
• New forms of old diseases antibiotic- resistant
  bacteria
• MDR-Tb, XDR-Tb, MRSA

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Why do Infectious Diseases still kill so many
people?

• Interplay of many factors environmental,
  scientific, and political
• This complexity poses challenges, but also means
• There are many solutions
• Solutions can synergize so 11 can 3

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Scientific challenges that hinder conquering
infectious diseases

• Emergence of new diseases
• Novelty
• Rapidity of global transmission
• Diseases that mutate quickly
• Immune escape from vaccines
• Treatment escape drug resistance
• -also due to misuse of existing therapies
• Diseases requiring new technologies to conquer
• New type of vaccine Cell-based immunity

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Impact of environment on diseases

• Environment changes and lack of change
• Transmission
• Vectors
• Global warming
• Proximity of humans to animals/loss of habitat
• Globalization
• human travel
• Animal/insect/pathogen hitchhiking
• War
• Mistrust

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Impact of environment on diseasesTransmission
Polio reservoirs

• Sewage

Drinking water
Sewage
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Impact of environment on diseases Vector-borne
diseases (which have both Mortality and often
extensive Morbidity)
Malaria (1 million annual deaths) Dengue (50
million infections, including about 400,000
cases of dengue haemorrhagic fever ) Yellow
fever Encephalitis West Nile Virus
Japanese Encephalitis Eastern Equine
encephalitis Western Equine encephalitis
La Crosse encephalitis St. Louis
encephalitis Rift Valley fever
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Natural and Man-made Mosquito habitats
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Environmental factors in current Southeast Asian
dengue outbreak

• Increased mosquito breeding
• warmer weather
• heavy rains
• "Factors leading to the spread of dengue include
  population explosion, migration and rapid growth
  of urban areas, which place a heavy strain on
  public health services and access to drinkable
  water."
• John Ehrenberg, WHO regional adviser.

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The complexities of environment and health
interventions

• Some countries eliminated/controlled malaria by
  draining swamps and spraying for mosquitoes
• But potential link between DDT and breast cancer

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The complexities of environment and health (Part
2)

• Hygiene hypothesis
• Many infectious diseases have been largely
  controlled in countries with high standards of
  living
• These countries have noted increases in allergic
  and autoimmune diseases

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T Helper (TH)Subtypes
TH1
Help to generate CTL
IL-2, g-IFN, TNF b
1L-12
TH0
TH2
Help to Generate Antibodies
1L-4
IL-4, 5, 6, 10
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Impact of environment on diseases

• Environment changes and lack of change
• Transmission
• Vectors
• Malaria, dengue, encephalitides and the role of
  persistent mosquito breeding grounds
• Global warming
• Proximity of humans to animals/loss of habitat
• Globalization
• human travel
• Animal/insect/pathogen hitchhiking
• War
• Mistrust

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Impact of environment on diseases

• Proximity of humans to animals/loss of habitat
  Animal reservoirs of pathogens
• Pathogen transmission, jumps, and
  recombinations to form new strains

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Impact of environment on diseases

• Proximity of humans to animals/loss of habitat
  Animal reservoirs of pathogens
• Transmission
• HIV, Ebola
• Monkeypox (US pet stores) African rodents
  (source) ? pet prairie dogs ? humans
• Lyme disease (suburban housing developments)
  Deer ?ticks ?humans
• Jumps and Recombinations
• SARS, Avian/pandemic influenza

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Origins of Pandemic Influenza
Belshe, NEJM 2005
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Impact of environment on diseases

• Vectors
• Malaria, dengue, encephalitides and the role of
  persistent mosquito breeding grounds
• Global warming
• Proximity of humans to animals/loss of habitat
• Transmission
• Recombination to form new strains
• HIV, Ebola, Hanta virus, influenza
• Globalization
• human travel SARS and the cough heard around
  the world
• Animal/insect/pathogen hitchhiking
• War
• Mistrust

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Examples of Emerging and Re-emerging Infectious
Diseases
Multi-Drug Resistant TB
H5N1 Avian flu
Diptheria
E. Coli O157-H7
Lyme
E. Coli O157-H7
Typhoid
West Nile
Vancomycin-Resistant S. Aureus
Hanta
HIV
Ebola
Dengue HF
Plague
Cholera
Nipah virus
Drug-resistant Malaria
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Roadmap for conquering Infectious Diseases

• Scientific advances
• New paradigms
• Multi-disciplinary
• Scientific disciplines
• Policy makers
• Public and private sectors
• Multi-national
• Co-partnering of stakeholders

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Key elements of success

• Scientific advances
• Prioritization of health and prevention
• Public and private sector involvment
• Multinational/multisector engagement
  and cooperation
• Example Rapid identification of novel
  coronavirus as etiology of SARS

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• November 16, 2002
• Initial cases of SARS appear.
• March 17, 2003
• WHO forms global network to simultaneously
  determine the etiology of SARS and develop a
  diagnostic test. Investigators share results in
  real time via secure website.
• March 24, 2003
• Scientists at the CDC and in Hong Kong announce
  that a new coronavirus has been isolated from
  patients with SARS.
• April 12, 2003
• Canadian researchers announce successful
  sequencing of the coronavirus genome. Scientists
  from the CDC confirm report.
• This incredibly rapid identification of the
  causative agent of SARS was enabled by an
  unprecedented collaboration of 13 laboratories in
  10 countries

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International Vaccine Institute

• Founded on the belief that vaccine science is a
  key tool for closing the gap in health between
  rich and poor
• Worlds only international research organization
  dedicated exclusively to research on new
  vaccines for the worlds poorest people

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IVI Background and Governance

• In 1997 the IVI became an International
  Organization under the Vienna Convention
• The Institute is autonomous and independent
• The Institute is governed by a Board of Trustees
  - a majority of whom are chosen in their
  individual capacity

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IVI Modus Operandi

• IVI brings together countries, developing and
  industrialized
• IVI brings together public institutions,
  international organizations (such as WHO and
  GAVI), and companies in public-private
  partnerships

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Signatories to Establishment Agreement(As of
March 2007)

• Bangladesh Kazakhstan Netherlands Spain
• Bhutan Korea Oman Sri Lanka
• Brazil Kuwait Pakistan Sweden
• Cote DIvoire Kyrgyzstan Panama Tajikistan
• China Lebanon PNG Thailand
• Ecuador Liberia Peru Turkey
• Egypt Malta Philippines United Arab
  Emirates
• Indonesia Mongolia Romania Uzbekistan
• Israel Myanmar Senegal Vietnam
• Jamaica Nepal Slovakia WHO

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IVIs Strategy for Narrowing the Vaccine Gap
between Rich and Poor

• Lab science ? Make Vaccines
• In-country studies ? Provide data to Formulate
  policy

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IVIs Strategy for Narrowing the Vaccine Gap
between Rich and Poor

• Gather epidemiological and socio- economic data
  that provide evidence to address policy
  uncertainties, and which can be utilized for
  formulating and supporting vaccine usage policy

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IVIs Strategy for Narrowing the Vaccine Gap
between Rich and Poor

• Synergize individuals, organizations, and
  governments from around the globe
• Accelerate affordable vaccine introduction
• -into poor countries and
• -for diseases which are a global burden

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IVIs Strategy for Narrowing the Vaccine Gap
between Rich and Poor

• Bring together partners from all sectors to
  optimally benefit from, and synergize with,
  their differing expertise, capacities, and
  political and real capital.
• Mine the scientific capabilities of all partners
  to develop vaccines that address the needs and
  fit the realities of developing countries

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IVIs Encephalitis vaccine program

• Japanese encephalitis
• Mortality rates 35 in developing countries
• Worldwide 10,000 deaths/yr
• 33-50 of surviving symptomatic patients have
  major neurologic sequelae at 1 year
• Mosquito-borne
• Insufficient incidence data for certain regions
  for MOH to make decisions about immunization
  programs

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IVI impact on JE vaccination

• IVI demonstrated that incidence of JE in
  Balinese children is among the highest in the
  world
• These findings contradict previous assumptions
  of low incidence
• Outcomes of Nov. 2006 policymakers mtg held by
  IVI, Bali authorities, PATH, CDC
• Pilot introduction of JE vaccine in Bali
• JE control program under development

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IVI impact on JE vaccination

• IVI extending observations to other parts of
  Indonesia
• Bali mainly Hindu
• Other areas mainly Muslim
• Pigs are the reservoir and amplifying host for
  JE, so incidence may be different

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Lessons learnedRoadmap for successful outcome

• IVI generated needed epidemiologic data
• Clarified reality of human cost of disease
• Evaluating effect of environment
• Crucial relevant parties engaged
• Informed policy enacted
• Lives saved, debility prevented

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Diseases of the Most Impoverished

• The DOMI Program
• A program to accelerate the development and begin
  the introduction of new vaccines against cholera,
  shigellosis, and typhoid fever

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Industrialized Country Research and Technical
Institutions Participating in the DOMI Program

• Country
• Australia
• Canada
• France
• Sweden
• United Kingdom

• Institutions
• TGA
• University of Western Ontario
• Institut Pasteur
• Epicentre
• MSF
• University of Goteborg
• NIBSC
• Sanger Institute

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Industrialized Country Research Institutions
Participating in the DOMI Program

• Country
• United States

• Institutions
• Harvard University
• Johns Hopkins University
• NIH
• University of Maryland
• University of North Carolina
• Walter Reed Army Institute of Research
• Wayne State University
• West Virginia University

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The DOMI Network A Resource for Coordinated,
Multi-Country Field Studies

• Institutions
• ICDDR,B
• Chinese Academy of Preventive Medicine
• Guangxi Province Health Service
• All India Institute of Medical Sciences
• National Institute of Cholera and Enteric
  Diseases
• National Institute of Health Research and
  Development, Ministry of Health
• U.S. NAMRU-2
• MOH
• Aga Khan University
• Mahidol University
• NIHE

• Country or Setting
• Bangladesh
• China
• India
• Indonesia
• Mozambique
• Pakistan
• Thailand
• Vietnam

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Vaccine Producer/Developer Participationin the
DOMI Program

• Amson, Pakistan
• AVANT Immunotherapeutics, United States
• BioFarma, Indonesia
• Emergent Solutions, US/UK
• GlaxoSmithKline, Belgium
• IVAC, Vietnam
• Lanzhou Institute of Biological Products, China
• Sanofi Pasteur, France
• SBL Vaccins
• Shantha, India
• VaBiotech,Vietnam
• Wuhan Institute of Biological Products, China

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Expertise of IVIs Scientific Staff

• Epidemiology
• Clinical trials
• Computerized data management
• Geographic information systems
• Biostatistics
• Health economics
• Sociobehavioral studies
• Policy analysis
• Immunology
• Molecular microbiology
• Bioinformatics
• Polysaccharide-protein biochemistry
• Vaccine process and scale-up, and technology
  transfer

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IVI Resource Base

• Korean government
• Building 18,000 sq m with pilot plant
• 30 of operating budget
• KOICA
• Korean Science Foundation
• Government of Sweden
• Government of Kuwait
• U.S. National Institutes of Health
• U.S. National Science Foundation
• Rockefeller Foundation

• Bill and Melinda Gates Foundation
• UBS Foundation
• PATH
• Industry (Aventis, Berna Biotech, CJ, Novartis,
  Merck, Microscience, Nonghyup, Sartorius, GSK,
  Wyeth, LG, )
• Korean public

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Partners in the DOMI Program

• Broad inclusiveness
• WHO
• Ministries of Health

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Strategy to Enable Development and Access to
Vaccines

• Increase availability of low-cost vaccines
  (preferably with technology transfer for local
  production)
• Technical assistance and training for
  professionals in developing countries
• Vaccine demonstration projects
• Develop an investment case, based on evidence
• Burden of disease studies (including compilation
  analysis of existing data)
• Cost-effectiveness studies

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IVI DOMI Program
C
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Summary

• The IVI DOMI program is successfully making a
  reality of providing vaccines for diseases like
  cholera and typhoid for endemic regions
• Accomplished by partnerships with diverse
  entities globally
• IVI paradigm demonstrates
• multi-etiology problem ? multi-disciplinary,
  multi-partner solution

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Summary

• Vaccine science efforts would synergize with
  efforts to improve the environment and
  infrastructure
• 113

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Conclusions

• The environment and infectious diseases are
  inextricably linked
• A new era of innovative global multi- disciplinary
  approaches are providing solutions
• We must continue to be aggressive, creative, and
  comprehensive in our efforts

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What you have, Mrs. Jones, sounds highly
contagious. Youd better see another doctor.
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Recommendations

• Prioritization of education, training, research
• Ensure that specialists have a broad view and
  global understanding
• Involvement and integration of all sectors
  (public and private), levels (local, regional,
  global), and disciplines
• Health, environmental, and development efforts
  must be concerted

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