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2Title of Presentation footer Why Vector Control ? Vector Control is 60% of the RBM Global Malaria Action Plan Budget! 2011 Malaria Report Reduction of >50% in cases between 2000 and 2009: 11 African countries and 32 outside of Africa Vector Control is one cornerstone of historic success in malaria control.

3Title of Presentation footer Insecticide resistance is growing! 2010 data Already needs updating! Increasing in Incidence Intensity –100X resistance observed Scope –All four classes Are there really blank spaces?

4Title of Presentation footer The resistance frequency Tipping Point strikes rapidly ! Pyrethroid resistance in Mexico exploded in Tipping point theory matches the field observations.

5Title of Presentation footer Resistance and control failure KwaZulu Natal, South Africa

6Title of Presentation footer Recent data on resistance Resistance is increasing in incidence and intensity! Burkina Fasso 0% mortality to diagnostic doses of Pyrethroids and DDT. LT50 doubled in 4 months. Now Unable to reach 50% mortality even after 10 hour exposure. LLIN mortality of 100% on susceptible mosquitoes down to 40% on wild. Tiassale, Cote D’Ivoire population resistant to 4 classes ! Resistance ratios of 124 for Deltamethrin, 24 for Bendiocarb. Unpublished Data —not for circulation

7Title of Presentation footer The impact of pyrethroid resistance on the effectiveness of insecticide treated nets against Anopheline mosquitoes: a systematic review. Authors and affiliations: Clare Strode 1, Sarah Donegan 1, Paul Garner 1, Ahmada Enyati 2 and Janet Hemingway 1. 1 Liverpool School of Tropical Medicine, Liverpool, United Kingdom 2 School of Public Health and Health Sciences Research Center, Mazandaran University of Medical Science, Sari, Iran. Running Title: The impact of pyrethroid resistance on ITN efficacy.

8Title of Presentation footer Insecticide Resistance is an issue for many NTDs ! Table 2.2DeathsDALYsInsect VectorsVector Control InterventionInsecticide Resistance Malaria0.8 million 42 million Anopheles mosquitoes LLIN and IRS Widespread and rapidly emerging pyrethroid resistance and resistance to other available classes of insecticide. Dengue21, million Aedes mosquitoes larvicides, space sprays, IRS Lymphatic filariasis million Anopheles Culex & Aedes MDA plus vector control LLINs and IRS Leishmaniasis:51, million Sandflies (Phlembotominae) IRS DDT Resistance P. papatasi in India Human African Trypanosomiasis 48, million Tsetse flies (Glossinidae) Attractant traps and targets. Aerial insecticide space spray Not yet reported Chagas14, million Kissing Bugs (Triatominae) IRS (e.g. Southern Cone Countries) Reports of pyrethroid resistance, Onchocerciasis00.5 million Biting Blackflies (Simuliidae) MDA Larviciding with temephos,pyrethroids and Bti temephos and pyrethroid resistance

9Title of Presentation footer Challenges for Vector Control Product Development Insecticide Resistance Products for resistance management Protecting people from infection from resistant mosquitoes Managing the resistant populations Outdoor Transmission Bed nets and IRS only work inside the home Outdoor transmission is exposed by successful indoor campaigns Products that protect outside the home are required Cost of Implementation Durability Logistics Coverage User choice ‘The question is not why don't people use the products we make but why don't we make products that people will use ? Products for the Elimination Analytical Framework Pre-conditioning for MDA. EIR reduction Vector Barrier products. Targeted, Short Term, High Efficacy To be explored !

10Title of Presentation footer PDPs work across different diseases and modalities HIV/AIDSTBMalariaNTD 2 Diarrhea 3 Respiratory Diagnostics Microbicides & prevention Therapeutic product Vaccine Development Program Human hookworm vaccine initiative

11Title of Presentation footer ‘12‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22 IVCC Strategic Roadmap May 2013 New Active Ingredient Bayer Miniportfolio Information Systems and Diagnostics Spin Out New Active Ingredient Syngenta Miniportfolio New Active Ingredient Sumitomo Miniportfolio Resistance Breaking Bi-treated Net Formulations Crop Protection Product Development Opportunities Decision support information systems, and insecticide quantification kits spin out to delivery vehicles IRS Formulations Completed Long Lasting Non pyrethroid IRS Formulations New Paradigms (Outdoor Transmission) Species and Geographical Extension Vector Shield for Radical Cure Elimination

12Title of Presentation footer 4. lack of appropriate insecticides and formulations for sustainable long term IRS and LLIN programmes IVCC products: Novel insecticides to overcome resistance and reduce application costs of insecticide use Three new active ingredients to manage resistance New long lasting formulations Non-pyrethroid and bi-treated LLINs First new products launched in 2012 New insecticides

13Title of Presentation footer Agrochemical Industry Partners

14Title of Presentation footer Field Trials Sites

15Title of Presentation footer IVCC Public Health Insecticides Portfolio — March 2013 New Active Ingredients New Formulations Proof of Concept Data Mining Lead Generation Screening Lead Optimisation Development Toxicology RegistrationProof of Concept DevelopmentWHOPES Phase I Phase II Phase III Country Registration LLIRS Formulation Dupont Discovery Platform Bayer AI Library Screening Syngenta AI Library Screening Sumitomo AI Library Screening Dow/Scynexis LLIN Combination Vestergaard LLIN Combination Sumitomo LLIN Combination BASF LLIRS Formulation BASF LLIRS Formulation Syngenta LLIRS Formulation Bayer Agricultural AI Review LLIN Combination Dupont Project “ Venus ” Akzo Nobel Crop Protection development compounds Completed Active In preparation

16Title of Presentation footer New Paradigms in vector control Stages of development of a New Paradigm in vector control 1.Development of intervention concept and draft TPP 2.Proof of concept 3.Verification of epidemiological efficacy and confirmation of TPP 4.Policy endorsement and product category adoption Examples Insecticidal Medicines Insecticidal Lotions Repellents Clothing ( Insecticidal and / or Repellent) Odour Baited Traps etc

17Title of Presentation footer example of first stage requirements Development of an Intervention Concept and Draft TPP Entomology Definition of the key proxy measurements that will indicate entomological impact, according to mode of action. Review available chemistry and develop resistance management plan. Epidemiology Creation of a credible case that the new category will add a significant impact in disease control. epidemiological modelling / entomological impact. Economics Expected cost of protection per person (at scale) Potential demand. Is the impact worth the effort? Technology DevelopmentReview technical feasibility. Does this intervention require unachievable performance? Manufacturability Sustainability First discussions with potential manufacturers to explore issues and opportunities. Solve in principle at least resulting IP issues. User compliance/ acceptability Define target user groups and expected mode of application Collect initial user reactions to the product concept. Delivery and Implementability Identification of distribution routes and first discussions with potential distributors to identify issues to be resolved Regulatory / Safety / Environmental impact Identification of Safety / Environmental issues to be tested. Identification of new risk assessment models required. Target Product Profile A first draft of the TPP is created showing large numbers of gaps and unknowns to be filled in as the intervention matures. Policy / StrategyFirst notification to VCAG of the intervention in development, dissemination to broader vector control community. This stage is largely based on experimental work, possibly with a supporting paper or modelling exercise with key experiments to elucidate the key parameters of the model. These issues are retested at each stage with differing levels of requirement

18Title of Presentation footer 2. lack of diagnostics to support quality assurance of insecticide-based products at their point of use IVCC product: IQK Insecticide quantification kits (IQKs) developed for Pyrethroids Carbamates DDT Organophosphates Kits currently moving into operational use and commercial production South African manufacturer and distributor has been identified and is in the qualification stage of licensing Insecticide diagnostics

19Title of Presentation footer IVCC insecticide portfolio — the global health context The current IVCC portfolio is developing the new insecticides and formulations that will overcome resistance and provide sustainable long term suppression of transmission The new analytical framework calls for transmission suppression in preparation for Radical Cure Elimination and the vector shield to protect from re-infection In the mean time we need to continue to protect the at-risk populations from the growing threat of insecticide resistance These objectives continue to call for new insecticides and further innovation in vector control

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