Strategic Considerations for Global Tropical Disease Research:

1. Symposium on Vector Biology, Ecology and Control:Celebration of Professor Mir Mulla's 50 Years at Riverside Strategic Considerations for Global Tropical Disease Research: Continued need for innovative vector research Robert Ridley (Director WHO/TDR)

2. Publications demonstrate need for: • Investment in health to alleviate poverty • Investment in Research to ensure advances in health and appropriate policy decisions • Investment in capacity building so research sustainable and can be driven by DEC's

3. Critical trends in global research environment Epidemiological Changes Infectious disease burden remains high Growing regional variation Enhanced research capabilities in DEC's Global research environment for tropical diseases Momentum through new players / initiatives Rise in pharmaceutical product development DEC's left behind in priority setting Complexity and fragmentation

4. Vision An effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role

5. Implications for TDR • To foster the vision • To focus activity where there is need and where TDR has a comparative advantage

6. Empowerment, pivotal role … EDCTP MMV GAELF Trachoma Grand Challenges Microbicides RBM New and improved tools New and improved tools New and improved tools StopTB DNDi New knowledge / discoveries GATB Global Fund NIH, Trust, Research councils, etc… IAVI FIND APOC Stewardship, effective global effort .. Modelling the system to address TDR's role New knowledge / discoveries New and improved tools New and improved interventions New and improved interventions New and improved strategies New and improved strategies

7. Implications New and improved strategies New and improved interventions New knowledge / discoveries New and improved tools Foster innovation for products, emphasizing DEC engagement Foster research to develop and evaluate interventions in real-life settings Foster research for access to interventions

8. Working with all stakeholders to achieve Innovation Interventions Access

9. Business Lines and Gaps Empowerment Capacity, Empowerment, led by BL 4: Innovation for PD in DEC BL 11: Integrated delivery strategies BL 9: Malaria/fever treatment policy BL 8: Treatment for HIV/TB BL 3: Discovery BL 7: Drugs for helminths BL 6: Diagnostics BL 10: VL elimination BL 5: Innovative vector control Effective global effort, Stewardship… Stewardship

10. Business Lines – vector related Empowerment Capacity, Empowerment, led by BL 4: Innovation for PD in DEC BL 11: Integrated delivery strategies BL 10: VL elimination BL 5: Innovative vector control Effective global effort, Stewardship… Stewardship

11. Outline of the presentation • Global perspectives, issues and challenges for control of vector-borne diseases • TDR contribution to vector-borne disease research • Some critical issues for future direction of vector research for tropical diseases

12. Global perspectives, issues and challenges for control of vector-borne diseases

13. Vector-borne diseases affect about half of world's population • They occur in more than 100 countries, affect nearly half of the world's population, and result in high morbidity and mortality • They are responsible for more than 500 million clinical cases per year (nearly one person in ten). Their total burden is about 56 million Disability Adjusted Life Years (DALYs). • Malaria remains the dominant disease globally

14. Climate Change and Human Health. 2002. by A.J. McMichael, D.H. Campbell-Lendrum, C.F. Corvalán, K.L. Ebi, A. Githeko, J.D. Scheraga and A. Woodward, 2003, 322 pages: http://www.who.int/globalchange/publications/climchange.pdf, p. 50

15. http://www.who.int/globalchange/en/

16. The Economist, 12 May 2007, p. 41

17. Progress in reducing the global burden of malaria has been slow .Cases: 550 million clinical cases annually .Disease burden: 44.99 DALYs) . At risk: 40% of the global population (>2.1 bn) GLOBAL STATUS .Deaths: 1.09 million annually (most deaths occur in children under the age of 5)

18. Continent-wide distribution of malaria burden http://rbm.who.int/wmr2005

20. Research Priorities • New tools (to address resistance) • Drugs, diagnostics, vaccines, insecticides (IRS, ITN, other) • How to use these tools effectively • Dosing, packaging, rotation, combination into packages • How to ensure interventions are accessed in poor settings • Distribution mechanisms, community approaches • Cost effectiveness of interventions and impact • Health economics, burden of disease measurements etc.. ,

21. Dengue: Annual DHF cases

23. African trypanosomiasis Chagas disease Leishmaniasis Lymphatic filariasis Onchocerciasis (Schistosomiasis) Other Vector-Borne Diseases

24. Human African Trypanosomiasis (HAT) • Control limited by reduced vector control efforts and inadequacy of other existing interventions e.g., drugs are not adequate. • Several vector control methods (traps, screens, application of insecticides on traps or livestock, sequential aerial application of insecticides, sterile insect technique, and community-based vector control interventions) were developed over the years, but … • Are they optimised? • Can they be scaled up cost-effectively and sustainably? • Opportunities for new tools?

25. Chagas disease • Successful vector control achieved in the Americas based on the application of insecticides to control domestic triatomine populations. • However, this approach has been ineffective against the invasion of bugs from peridomestic and sylvatic areas. • New tools and approaches needed that prevent re-infestations of triatomine populations. • genetically-engineered bacterial symbionts and biological control agents?

26. Need for integrated vector management approach • Integrates all available resources to achieve a maximum impact on vector-borne disease. • Evidence-based requiring capacity to generate local data on disease epidemiology and vector ecology. • Collaboration within the health sector and with other public and private sectors that impact on vectors. • Engagement with local communities and other stakeholders; • A public health regulatory and legislative framework.

27. Continued need for innovation • Environmental management for integrated vector control • Tool development (chemical and non-chemical) for vector control • Exploiting advances in biotechnologies for the development of improved vector control tools and strategies • Vector genetic transformation as a potential method for vector control • Research on cost-effective delivery • Translating research findings into policy and action • Building capacity in disease endemic countries for the exploitation of new technologies • Need for $$$$$$$$$$$?

28. Some TDR contributions and future perspectives on Vector Research www.who.int/tdr for more publications

29. Some contributions • 1982: Onchocerciasis - Bacillus thuringiensis israelensis H-14in disease control use for blackfly control of onchocerciasis at critical moment to counter pesticide resistance • 1989: African trypanosomiasis - Insecticide impregnated tse tse fly traps in disease control use. (biconical and monoconical) • 1990: Chagas disease - Fumigant canisters, insecticidal paints and Triatomine detection boxes in disease control use • 1991: Onchocerciasis - DNA probes for Onchocerca volvulus (OCP) in control use • 1991: Malaria – Tucson meeting initiates activity on genetically modified mosquitoes

30. Some contributions • 1994: Malaria - Insecticide-impregnated bednets in disease control use following results of large-scale trials in Africa showing 20% mortality reduction. • 2002: Malaria - Genome sequencing of Anopheles gambiae completed by TDR-fostered consortium and announced simultaneous to the sequencing of Plasmodium falciparum). • 2004: African trypanosomiasis -A TDR-led consortium of organizations form the International Glossina Genomics Initiative (IGGI) in an international effort to fully sequence the tsetse fly genome • 2005: Methodology to facilitate pupal surveys for dengue • 2006: Evidence that community directed provision of bednets can demonstrably enhance uptake

31. Genetically modified vectors Malaria (since 1994), Dengue (added in 1999) and HAT (added in 2006) Catteruccia, Nature, 2000: A. stephensi transformed using Minos TE Grossman et al., Insect Molec. Bio. 2001: A. gambiae transformed using piggyBac Ito et al., Nature, 2002; Ghosh et al., PNAS, 2001 Mosquitoes refactory to P. berghei

32. Training Courses and Consultation ICIPE – July 2004

33. Recent TDR publications on dengue

34. Achievement – Entomological sampling for Dengue • Pupal and demographic surveys enable assessment of dengue vector densities and threshold levels for Dengue transmission • Pupae serve as proxy for adult mosquitoes • Allows focus on most productive containers making surveys more cost effective • Multi-country study validates hypothesis Revised view: Round tanks Tyres main source Traditional view: Bottles main source

35. Insecticide Treated Curtains Can Reduce Dengue House index (% of infested houses) presented as an example from Mexico. Blue bars representing nearby control clusters "benefit" from intervention clusters . Far away external control clusters show unchanged vector densities.

36. Elimination of visceral leishmaniasis on Indian sub-continent

38. Integrated community directed interventions • Many (APOC) countries familiar with CDTivermectin • Takes 5 years for APOC to introduce sustainably • Over 100,000 communities engaged • 60 million reached • 100 million by 2010 • Can this CDI be expanded and more broadly utilised?

39. Community engagement and ownership of distribution

40. RBM target P<0.001

41. P<0.001 APOC target

42. Some critical issues for vector research • Impact of climate change and water management • Resistance to insecticides • Integration of vector control into combined, multi-disease interventions • Sustainability of vector control interventions • Entomology capabilities, especially in developing countries • Managing innovation through multi-disciplinarity of future research • Interface between research, control and policy

43. Vision An effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role