SumiShield50WG. A Breakthrough for Resistance Management

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1 TM SumiShield50WG A Breakthrough for Resistance Management SumiShield 50WG is an Indoor Residual Spray (IRS) product containing a new mode of action active ingredient. SumiShield 50WG provides excellent control of malaria transmitting mosquitoes and is especially valuable when used in insecticide resistance management strategies.

2 Contents Clothianidin 50.0% w/w Water Dispersible Granule (WG) Table of Contents 1 Introduction 2 Product Concept 4 Directions for Use 6 Biological Efficacy 8 Mammalian Toxicity Breakthrough: There has been no new mode of action IRS product in over 30 years.

3 Introduction and Background There is a long history of using indoor residual spray (IRS) for malaria control and it has proved very effective in many countries; however the usefulness of IRS is under threat due to increasing resistance to all 4 classes of insecticides and the many products containing them. There has been a need for a new mode of action (MOA) product for many years and nothing has been introduced for more than 30 years resulting in the reintroduction of old active ingredients like DDT which presents many risks to the environment. Insecticide resistance is increasing in many parts of the world so there is a great need for an insecticide with a new MOA and one that can be used in resistance management and rotational programmes. Sumitomo Chemical researched its portfolio of active ingredients and identified the neonicotinoid clothianidin as an insecticide with good potential for use in IRS against malaria vectors. Laboratory and field trials have shown great promise resulting in Sumitomo submitting the product SumiShield 50WG to the WHO Pesticide Evaluation Scheme (WHOPES) for evaluation and recommendation. This process usually takes several years but since there is an urgent need for new tools to ensure that the malaria elimination plan does not fail because of resistance, Sumitomo Chemical have made SumiShield 50WG available before the WHOPES process has been completed, noting that Sumitomo Chemical already has extensive knowledge and experience of the environmental impact and toxicity profile of clothianidin as the chemistry is already used in agriculture. Because of increased resistance to existing insecticides there is a great need for an insecticide with a new mode of action. Sumitomo Chemical s SumiShield 50WG addresses this need. 1

4 Product Concept The major objective for Sumitomo Chemical was to develop a new IRS product that would not be resisted by mosquitoes which have developed resistance to one or all of the major classes of insecticides currently available for IRS. Key features & Benefits 1. New active ingredient in IRS and Public Health applications. 2. At least 7 months activity under field conditions. 3. New mode of Action A breakthrough for resistance management programmes. 4. Non-repellant formulation compared with pyrethroid and DDT based IRS products. 5. Submitted to WHO Pesticide Evaluation Scheme (WHOPES) to obtain recommendation. 6. Mortality rates which increase over time post exposure. 7. Low Toxicity. 8. Odourless. 9. Readily dilutes in water. 10. Small easy to handle sachets. 11. Easy to transport one per tank, up to 50 sachets per carton. SumiShield 50WG is odourless, has low toxicity, readily dilutes in water, and is easy to transport. New mode of action makes it a breakthrough for resistance management programmes. 2

5 Insecticide resistance in malaria vectors is one of the major issues concerning stakeholders today. SumiShield 50WG meets the changing needs of today s IRS programs. 3

6 Technical specifications Active Ingredient: Clothianidin 50.0% (w/w) Other Ingredients: 50.0% Total 100.0% O NH + O N N N H S N CI Nitroguanidine (neonicotinoid) IRAC MoA Group 4A Neonicotinoids IUPAC: (E)-N-[(2-chloro-1,3-thiazol-5-yl)methyl]-N-methyl-N-nitroguanidine Formula: C6H8ClN5O2S Easily mixed and transported one small 150g sachet for one 10 litre sprayer. 4

7 Directions for Use SumiShield 50WG is a product which has been developed for Indoor Residual Spraying (IRS) and can be sprayed to the inside of houses and residences on walls and other surfaces / substrates that serve as a resting place for mosquitoes. Mixing instructions Fill sprayer with required volume of water Tear open end of sachet and put entire contents directly into spray tank. Close sprayer, pressurize and mix by inverting spray tank before spraying. Application rates and method The target dose of SumiShield 50WG is 300 mg ai/m2. Dilute one 150 g sachet of SumiShield 50WG in 10 liters of water and apply to 250 m2 wall surface area. This must be applied with a pressure sprayer that has WHO specifications and should be fitted with a No. 8002E nozzle calibrated to deliver 760 ml/minute. The spray tip should be kept 45 cm from the surface being sprayed to give a swath width of cm wide. An area of 19 m² should be covered in one minute giving a target application rate of 25 m² per litre. Where sprayers are fitted with a pressure regulating device set at 1.5 bar (i.e. red Control Flow Valve): Mix contents of a 150g sachet in 7.5 litres of water to treat 250m2. Handling Use only in well ventilated areas. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Storage Recommendations Keep out of reach of children. Keep away from food, drink and animal feeding stuffs. Store only in original sachets in a safe place at temperatures not exceeding 35C. Diluted insecticide should never be kept; a fresh dilution should be prepared as necessary. 5

8 Biological efficacy Experimental Hut Trials with SumiShield 50WG 1. Wall Bioassay Results Experimental huts were used for the trials and SumiShield 50WG was applied with a compression sprayer according to standard WHO protocol. Laboratory bred mosquitoes from 3 different An. gambiae s.s. strains were used and exposed for 30 minutes using cone bioassays according to WHO protocol. The Kisumu strain is fully susceptible while the other two strains are resistant to insecticides. SumiShield 50WG has a prolonged mortality effect and therefore mortality readings were taken up to 168 hours (7 days). Comment It can be seen in Figure 1 that kill against susceptible Kisumu strain of mosquitoes was good and this was maintained against the two resistant strains shown in Figures 2 & 3 although there was a slight reduction in speed of action against these resistant mosquitoes 100% kill was achieved in all cases and was still continuing at 7 months post-spray. Trials continue and it is expected that data will continue to show good levels of residual efficacy beyond 7 months. % Mortality % Mortality Figure 1 Residual efficacy of SumiShield 50WG on hut walls 30 min exposure. Dose 300 mg ai/m2 An. gambiae Kismu strain Months Figure 2 Residual efficacy of SumiShield 50WG on hut walls 30 min exposure. Dose 300 mg ai/m2 An. gambiae KdrKis strain Months Figure 3 Residual efficacy of SumiShield 50WG on hut walls 30 min exposure. Dose 300 mg ai/m2 An. gambiae Acerkis strain 168 hr 120 hr 72 hr 48 hr 24 hr 168 hr 120 hr 72 hr 48 hr 24 hr Note: Data corrected for control mortality These experimental hut trials in Benin, West Africa were conducted by Insitut de Recherche pour le développement (IRD) C.R.E.C. Cotonou. (2014) % Mortality Months (note: no mosquitoes for months 5 & 6) 168 hr 120 hr 72 hr 48 hr 24 hr 6

9 Resistance to at least one insecticide has been identified in 64 countries with on-going malaria transmission.* 2. Wild Mosquitoes Entering Experimental Huts Comment The local wild mosquitoes are naturally resistant to most insecticides especially pyrethroids and bendiocarb. The results in Figure 4 reflect this resistance and while the organophosphate pirimiphosmethyl is still giving reasonable results Sumi- Shield 50WG achieved the best results over time, noting that delayed mortality has to be assessed to determine the true efficacy of SumiShield 50WG. % Mortality Figure 4 Experimental hut trials Mortality of An. gambiae wild strain 207 nights of collection 24hr 48hr 72hr 120hr 168hr Hours after capture SumiShield 50WG 300mg Pirimiphos-methyl CS 1000mg Deltamethrin WG 25mg Bendiocarb WG 400mg 3. Excito Repellency Tests were conducted to evaluate the excito repellency of the active ingredient in Sumishield 50WG compared with active ingredients commonly used for IRS. Results presented on Figure 5 show that mosquito resting behavior on clothianidin treated surfaces is not significantly different from controls. This is an important finding as excito repellency is believed to be one of the factors behind the development of resistance. This contrasts with the high levels of excito repellency observed with pyrethroid insecticides, to which high levels of resistance have been reported. WHOPES Submission Data on Biological Evaluation (Figure 5) generated at Sumitomo Health and Crop Sciences Laboratory 2014 Figure 5 Irritant properties of insecticides against An. gambiae Kisumu strain by WHO cone test Number of take-offs b 2 1.8b 0 7.4a Flying time (sec) in 3 min a b 27.2b 0 Untreated SumiShield Deltamethrin paper 50WG WG 200mg 25 mg Ai/m2 Al/m2 2.9b 3.2b 2.7b 29.7b 22.1b Bendiocarb WP 400 mg Ai/m2 Pirimiphosmethyl CS 1000mg Ai/m2 44.9b Fenitrothion WP 2000 mg Ai / m2 7.3a 86.0a Permethrin 0.75% paper * UNITAID Malaria Landscape Report

10 Mammalian Toxicity Mammalian Toxicity Acute oral LD50: LD50 is 3900mg/kg body weight (bw) for male rats and 4700mg/kg bw for female rats. Skin and eye: Slight (barely perceptible) transient skin irritation and an eye irritant for rabbits. Inhalation LC50 (4h): for male and female rats >2.3mg/L Other: Not mutagenic. Not oncogenic in rats and mice. Not teratogenic in rats and rabbits. Clothianidin is moderately toxic through oral exposure, but toxicity is low through skin contact or inhalation. Since contact of householders will be via treated walls the product should not cause any significant risk. While clothianidin may cause moderate eye irritation, it is not a skin sensitizer. Clothianidin does not damage genetic material nor is there evidence that it causes cancer in rats or mice; it is unlikely to be a human carcinogen. Aquatic life United States EPA assessment report (2003) states that clothianidin should not present a direct acute or chronic risk to freshwater and estuarine/marine fish, or a risk to terrestrial or aquatic vascular and nonvascular plants. Consistent with the majority of pesticide products clothianidin is considered to be toxic to aquatic invertebrates if disposal of wastes according to disposal instructions are not followed. Birds According to the EPA, clothianidin is practically non-toxic to selected test bird species that were fed relatively large doses of the chemical on an acute basis. Clothianidin is practically non-toxic to selected test bird species that were fed relatively large doses of the chemical. 8

11 87% of countries failed to rotate the class of insecticides used last year.* * UNITAID Malaria Landscape Report

12 TM SumiShield50WG 27-1, Shinkawa 2-chome Chuo-ku, Tokyo , Japan SumiShield 50WG is a trademark of Sumitomo Chemical Company Limited. Sumitomo Chemical October 2015