A Breakthrough for Resistance Management

Transcription

1 A Breakthrough for Resistance Management SumiShield 5WG is an Indoor Residual Spray (IRS) product containing a new mode of action active ingredient. SumiShield 5WG provides excellent control of malaria transmitting mosquitoes and is especially valuable when used in insecticide resistance management strategies.

2 Contents Clothianidin 5.% w/w Water Dispersible Granule (WG) Table of Contents 1 Introduction 2 Product Concept 4 Directions for Use 6 Biological Efficacy 8 Mammalian Toxicity 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 3 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 5WG 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 5WG 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 5WG addresses this need. First new mode of action IRS product in over 3 years. 1

3 Product Concept Insecticide resistance in malaria vectors is one of the major issues concerning stakeholders today. 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 months duration of activity under field conditions. 3. New mode of Action A breakthrough for resistance management programmes. 4. Non-repellent formulation, increasing exposure of mosquito to the active ingredient (unlike pyrethroids and DDT). 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. 1. Small easy to handle sachets. 11. Easy to transport one per tank, up to 5 sachets per carton. SumiShield 5WG 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. SumiShield 5WG meets the changing needs of today s IRS programs. 2 3

4 Directions for Use SumiShield 5WG 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 Technical specifications Active Ingredient: Clothianidin 5.% (w/w) Other Ingredients: 5.% Total.% O NH + O N N N H S N C 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 Nitroguanidine (neonicotinoid) IRAC MoA Group 4A Neonicotinoids IUPAC: (E)-N-[(2-chloro-1,3-thiazol-5-yl)methyl]-N-methyl-N-nitroguanidine Formula: C6H8ClN5O2S The target dose of SumiShield 5WG is 3 mg ai/m2. Dilute one 15 g sachet of SumiShield 5WG in 1 liters of water and apply to 25 m2 wall surface area. This must be applied with a pressure sprayer that has WHO specifications and should be fitted with a No. 2E nozzle calibrated to deliver 7 ml/minute. The spray tip should be kept 45 cm from the surface being sprayed to give a swath width of 65-7 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 15g sachet in 7.5 litres of water to treat 25m2. 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. Easily mixed and transported one small 15g sachet for one 1 litre sprayer. 4 5

5 Biological efficacy Experimental Hut Trials with SumiShield 5WG Resistance to at least one insecticide has been identified in 64 countries with on-going malaria transmission.* 1. Wall Bioassay Results 2. Wild Mosquitoes Entering Experimental Huts Experimental huts were used for the trials and SumiShield 5WG 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 3 minutes using cone bioassays according to WHO protocol. The Kisumu strain is fully susceptible while the other two strains are resistant to insecticides. SumiShield 5WG 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 % 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. Note: Data corrected for control mortality These experimental hut trials in Benin, West Africa were conducted by Insitut Recherche pour le développement (IRD) C.R.E.C. Cotonou. Figure 1 Residual efficacy of SumiShield 5WG on hut walls 3 min exposure. Dose 3 mg ai/m2 An. gambiae Kismu strain Months Figure 2 Residual efficacy of SumiShield 5WG on hut walls 3 min exposure. Dose 3 mg ai/m2 An. gambiae KdrKis strain Months Figure 3 Residual efficacy of SumiShield 5WG on hut walls 3 min exposure. Dose 3 mg ai/m2 An. gambiae Acerkis strain Months (note: no mosquitoes for months 5 & 6) 168 hr 1 hr 72 hr 48 hr 24 hr 168 hr 1 hr 72 hr 48 hr 24 hr 168 hr 1 hr 72 hr 48 hr 24 hr 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 5WG achieved the best results over time, noting that delayed mortality has to be assessed to determine the true efficacy of SumiShield 5WG. 3. Excito Repellency Tests were conducted to evaluate the excito repellency of the active ingredient in Sumishield 5WG 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 14 Figure 4 Experimental hut trials Mortality of An. gambiae wild strain 7 nights of collection 24hr 48hr 72hr 1hr 168hr Hours after capture SumiShield 5WG 3mg Pirimiphos-methyl CS mg Deltamethrin WG 25mg Bendiocarb WG mg Figure 5 Irritant properties of insecticides against An. gambiae Kisumu strain by WHO cone test Number of take-offs b 2 1.8b 7.4a Flying time (sec) in 3 min. 74.2a 22.9b 27.2b Untreated SumiShield Deltamethrin paper 5WG WG mg 25 mg Ai/m2 Al/m2 2.9b 3.2b 2.7b 29.7b 22.1b Bendiocarb WP mg Ai/m2 Pirimiphosmethyl CS mg Ai/m2 44.9b Fenitrothion WP mg Ai / m2 7.3a 86.a Permethrin.75% paper 6 * UNITAID Malaria Landscape Report 14 7

6 Mammalian Toxicity 87% of countries failed to rotate the class of insecticides used last year.* Mammalian Toxicity Acute oral LD5: LD5 is 39mg/kg body weight (bw) for males and 47mg/kg bw for females. Skin and eye: Very slight (barely perceptible) transient skin irritation and is an eye irritant. Inhalation LC5 (4h): for male and female rats >2.3mg/L Other: Not mutagenic. Not oncogenic in rats and mice. Not teratogenic in rats and rabbits. Reference: Pesticide Manual 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 slight eye irritation, it is not a skin sensitizer or irritant. 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 (3) 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. According to the EPA, Clothianidin is practically non-toxic to selected test bird species that were fed relatively large doses of the chemical. 8 * UNITAID Malaria Landscape Report 14 9

7 27-1, Shinkawa 2-chome Chuo-ku, Tokyo 14-82, Japan SumiShield 5WG is a registered trademark of Sumitomo Chemical Company Limited. Sumitomo Chemical 15