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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) Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 1 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 2 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 DEC's left behind in priority setting Complexity and fragmentation Momentum through new players / initiatives Rise in pharmaceutical product development Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 3 Vision An effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 4 Implications for TDR To foster the vision To focus activity where there is need and where TDR has a comparative advantage Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 5 Modelling the system to address TDR's role Empowerment, pivotal role … EDCTP GAELF MMV Grand Challenges New New knowledge / knowledge / discoveries NIH, Trust, discoveries Research councils, etc… Trachoma Microbicides New and DNDi improved tools GATB IAVI New and improved interventions RBM New and improved strategies StopTB Global Fund APOC FIND Stewardship, effective global effort .. Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 6 Implications New knowledge / discoveries New and improved tools Foster innovation for products, emphasizing DEC engagement New and improved interventions Foster research to develop and evaluate interventions in real-life settings New and improved strategies Foster research for access to interventions Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 7 Working with all stakeholders to achieve Innovation Interventions Access Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 8 Business Lines and Gaps Capacity,Empowerment 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 9 Business Lines – vector related Capacity,Empowerment 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 10 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 11 Global perspectives, issues and challenges for control of vector-borne diseases Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 12 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 13 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 14 http://www.who.int/globalchange/en/ Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 15 The Economist, 12 May 2007, p. 41 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 16 Progress in reducing the global burden of malaria has been slow GLOBAL STATUS .Deaths: 1.09 million annually (most deaths occur in children under the age of 5) .Cases: 550 million clinical cases annually .Disease burden: 44.99 DALYs) . At risk: 40% of the global population (>2.1 bn) Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 17 Continent-wide distribution of malaria burden Africa Asia Americas Estimated proportion of population at risk 66% 49% 14% Estimated contribution to the global burden of clinical cases 59% 38% 3% Estimated contribution to the global mortality burden 89% 10% <1% http://rbm.who.int/wmr2005 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 18 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 19 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.. , Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 20 Dengue: Annual DHF cases Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 21 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 22 Other Vector-Borne Diseases • African trypanosomiasis • Chagas disease • Leishmaniasis • Lymphatic filariasis • Onchocerciasis • (Schistosomiasis) Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 23 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? Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 24 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 reinfestations of triatomine populations. – genetically-engineered bacterial symbionts and biological control agents? Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 25 Need for integrated vector management approach • Integrates all available resources to achieve a maximum impact on vectorborne 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. Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 26 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 $$$$$$$$$$$? Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 27 Some TDR contributions and future perspectives on Vector Research www.who.int/tdr for more publications Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 28 Some contributions • 1982: Onchocerciasis - Bacillus thuringiensis israelensis H-14 in 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 29 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 30 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 31 Training Courses and Consultation ICIPE – July 2004 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 32 Recent TDR publications on dengue Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 33 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 Traditional view: Bottles main source Round tanks Tires Bottles Other tanks Trays Div. Medium Div. Small Div. Large Don't know Revised view: Round tanks Tyres main source Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 34 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. Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 35 Elimination of visceral leishmaniasis on Indian sub-continent Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 36 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 37 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? Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 38 Community engagement and ownership of distribution Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 39 Underfive children sleeping under an ITN the night before the interview Underfive children sleeping under an ITN last night (%) RBM target 60 P<0.001 50 40 35.1 30 20 9.1 10.7 10 0 Comparison district, classical ITN CDI district, but classical ITN ITN through CDI Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 40 Ivermectin Treatment Coverage P<0.001 Treated with ivermectin (%) 80 70 71 73.5 APOC target 61.1 60 50 40 30 20 10 0 Comparison districts CDI districts, Vitamin A + ITN CDI districts, HMM + DOTS Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 41 Some critical issues for vector research • Impact of climate change and water management • Resistance to insecticides • Integration of vector control into combined, multidisease 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 Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 42 Vision An effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role Symposium on VBEC HMI, Riverside, CA May 29-June 1, 2007 43