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

1. 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

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

3. 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?

4. 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

5. Paradigms for success Eradication of smallpox Courtesy of T Sharrar, Smithsonian Institution

6. Near-eradication of Polio Paradigms for success Courtesy of T Sharrar Smithsonian Institution

7. Eradicating polio: achievements

8. Why do Infectious Diseases still kill so many people? Poverty/Lack of infrastructure • Lack of access to clean water, vaccines • Inadequate eradication strategies • Malnutrition

9. 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

10. 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

11. 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 1+1 can = 3

12. 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 Scientific challenges that hinder conquering infectious diseases

13. 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

14. Impact of environment on diseases:Transmission Polio reservoirs Sewage Drinking water Sewage

15. 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

16. Natural and Man-made Mosquito habitats

17. 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.

18. 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

19. 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

20. 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

21. 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

22. Impact of environment on diseases Proximity of humans to animals/loss of habitat: Animal reservoirs of pathogens: • Pathogen transmission, “jumps,” and recombinationsto form new strains

23. 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

24. Origins of Pandemic Influenza Belshe, NEJM 2005

25. 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

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

27. 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

28. 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

29. 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

30. International Vaccine Institute • Founded on the belief that vaccine science is a key tool for closing the gap in health between rich and poor • World’s only international research organization dedicated exclusively to research on new vaccines for the world’s poorest people

31. 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

32. 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

33. Signatories to Establishment Agreement(As of March 2007) Bangladesh Kazakhstan Netherlands Spain Bhutan Korea Oman Sri Lanka Brazil Kuwait Pakistan Sweden Cote D’Ivoire 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

34. IVI’s Strategy for Narrowing the Vaccine Gap between Rich and Poor Lab science  Make Vaccines In-country studies  Provide data to Formulate policy

35. IVI’s 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

36. IVI’s 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

37. IVI’s 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

38. IVI’s 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

39. 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

40. 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

41. Lessons learned:Roadmap 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

42. 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

43. Country Australia Canada France Sweden United Kingdom Institutions TGA University of Western Ontario Institut Pasteur Epicentre MSF University of Goteborg NIBSC Sanger Institute Industrialized Country Research and Technical Institutions Participating in the DOMI Program

44. 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 Industrialized Country Research Institutions Participating in the DOMI Program

45. Country or Setting Bangladesh China India Indonesia Mozambique Pakistan Thailand Vietnam 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 The DOMI Network: A Resource for Coordinated, Multi-Country Field Studies

46. 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

47. Expertise of IVI’s 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

48. 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 IVI Resource Base

49. Partners in the DOMI Program • Broad inclusiveness: * WHO * Ministries of Health

50. 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