WO2018073161A1

WO2018073161A1 - Mosquito vector control compositions, methods and products utilizing same

Info

Publication number: WO2018073161A1
Application number: PCT/EP2017/076315
Authority: WO
Inventors: Ottmar Franz Hueter; Peter Maienfisch; Philip WEGE; Mark Hoppe; Andrew Bywater
Original assignee: Syngenta Participations Ag
Priority date: 2016-10-17
Filing date: 2017-10-16
Publication date: 2018-04-26

Abstract

The present inventions concerns use of a certain compound selected from thiocyclam, thiocyclam hydrogen oxalate, diflumetorim and fluazinam to control mosquitoes, and vector control products comprising the defined compound, in particular the invention relates to a substrate, to a composition, for controlling mosquitoes comprising the defined compound.

Description

MOSQUITO VECTOR CONTROL COMPOSITIONS. METHODS AND PRODUCTS UTILIZING SAME

The present invention is in the technical field of insect vector control, particularly mosquito control, with a certain compound selected from thiocyclam, thiocyclam hydrogen oxalate, diflumetorim, and fluazinam. More specifically, the present invention relates to methods of controlling mosquitoes and to substrates, products, compositions and and vector control management products for controlling mosquitoes, each comprising a mosquitocidally active compound selected from thiocyclam, thiocyclam hydrogen oxalate, diflumetorim, and fluazinam.

Mosquito control manages the population of mosquitoes to reduce their damage to human health, economies, and enjoyment. Mosquito control is a vital public-health practice throughout the world and especially in the tropics because mosquitoes spread many diseases, such as malaria (Wikipedia contributors, "Mosquito control", Wikipedia).

With the present invention, it has now been found that certain compounds are mosquitocidally active (compared to similar analogous compounds) and are surprisingly useful for controlling mosquitoes and for decreasing mosquito vector populations.

Accordingly, in a first aspect the present invention provides for the use of one or more compounds selected from thiocyclam, thiocyclam hydrogen oxalate, diflumetorim, and fluazinam for controlling mosquitoes.

In a second aspect, the present invention provides compositions, products, and treated articles (such as substrates or non-living materials) comprising one or more defined compounds in the first aspect.

In a third aspect, the present invention provides a vector control, preferably a mosquito control, management product comprising one or more defined compounds in the first aspect.

In a further aspect, a method of controlling mosquitoes, preferably mosquito vectors of pathogenic disease, comprises contacting a mosquito or its environment with a composition comprising a mosquitocidally effective amount of one or more defined compounds in the first aspect, is made available.

Compound thiocyclam and thiocyclam hydrogen oxalate are insecticides and thiocyclam hydrogen oxalate, has an lUPAC name of /V,/V-dimethyl-1 ,2,3-trithian-5-ylamine oxalate (1 : 1 );

whereas thiocyclam has an lUPAC name of /V,/V-dimethyl-1 ,2,3-trithian-5-ylamine It is an analogue or propesticide of the natural toxin nereistoxin, and is a selective insecticide with contact and stomach action, has limited systemic activity, with translocation acropetally. In each aspect of the present invention, thiocyclam hydrogen oxalate is preferred.

Compound diflumetorim is a fungicide with an lUPAC name of (RS)-5-chloro-N-[1-(4- difluoromethoxyphenyl)propyl]-6-methylpyrimidin-4-ylamine. It may inhibit complex 1 of respiration (NADH oxido-reductase), and is a protectant fungicide with penetrative action. Compound fluazinam is a fungicide with an lUPAC name of 3-chloro-N-(3-chloro-5- trifluoromethyl-2-pyridyl)-a,a,a-trifluoro-2,6-dinitro-p-toluidine. As a fungicide, it is with protective action, has little curative or systemic activity, but good residual effect and rain-fastness.

In summary, the technical teaching from these documents is primarily directed to use of these compounds for control of fungi or insects on plants and crops.

Many infectious diseases (e.g. , malaria, dengue and yellow fever, lymphatic filariasis, and leishmaniasis) that are responsible for debilitating or even killing humans and animals in many countries, especially in tropical countries, are transmitted by insect vectors. For example, the mosquito parasite, Plasmodium falciparum, accounts for greater than 25 percent of childhood mortality outside the neonatal period. In certain parts of Africa, malaria has been ranked first by the World Bank in terms of disability-adjusted life-years lost. A number of drugs are available to treat and/or prevent some insect-borne diseases. However, not all diseases transmitted by mosquitoes can be treated efficiently. For example, there is currently no chemotherapeutic drug or vaccine available against the Dengue virus. Furthermore, in the case of antimalarial drugs, treatment with the drugs currently available is becoming less effective due to increased resistance in some Plasmodium strains. Plasmodium enters the human bloodstream as a consequence of the insect bite and causes malaria. Therefore, one of the most effective ways to prevent mosquito vector-borne illnesses is by decreasing mosquito populations in areas of high pathogen transmission and/or preventing mosquito bites in the first place. More recently, efforts have been concentrated on controlling the transmitting mosquitoes.

The three medically important genera of insects which transmit diseases are the mosquitoes Anopheles, Culex and Aedes. The genera Culex and Aedes belong to the sub-family Culicinae, while the Anopheles belongs to the sub-family Anophelinae.

Examples of diseases or pathogens transferred by the key mosquitoes are:

• Anopheles: malaria, filariasis;

· Culex: Japanese encephalitis, other viral diseases, filariasis; and

• Aedes: yellow fever, dengue fever, chikungunya, other viral diseases (e.g. , Zika virus), and filariasis.

In an attempt to reduce the problems associated with disease-transmitting mosquitoes, a wide range of insecticides and insect repellents have been developed. Mosquitoes can be targeted with insecticides when they are in a larval state or once they have developed into adults. Accordingly, insecticides which are used to kill larvae are termed larvicides whereas insecticides that are used to specifically target adult insects are called adulticides. Most of the insecticides commonly used to prevent the spread of disease are targeted against the adult mosquito and in particular against the female adult mosquito.

The organochlorine DDT was the most widespread compound used worldwide as an adulticide until it was withdrawn from use in most areas. After that, organophosphates such as malathion, carbamates, e.g., propoxur were widely used in vector control programmes in most parts of the world and were steadily replaced by pyrethroids, which became the mostly used adulticide. Organophosphates, such as pirimiphos-methyl are now being used again due to the development of pyrethroid resistance in many important vector species.

One of the most important problems associated with pyrethroids, like their predecessors, is that resistance has already developed in many insect species in several parts of the world. Pyrethroid resistance, caused either by specific detoxification enzymes or an altered target site mechanism (kdr- type mutations in the sodium channels), has been reported in most continents in the majority of medically important mosquitoes species, such as Anopheles gambiae in Africa and Aedes aegypti in Asia. If resistance continues to develop and spread at the current rate, it may render such insecticides ineffective in their current form in the not too distant future. Such a scenario would have potentially devastating consequences in public health terms, since there are as yet no obvious alternatives to many of the uses of pyrethroids.

Therefore, there is an ongoing search for compounds for control of mosquitoes, especially for mosquitoes having developed resistance, such as against pyrethroids.

As well as the biological efficacy of the compounds of the present invention against mosquitoes and resistant strains of such mosquitoes, other considerations for selecting a suitable compound could include its safety (such as its toxicity, persistence) to the environment, including to the users of a vector control management method or product; its suitability for making a vector control management product (whether indoor residual spray formulation, mosquito net, or another type), its suitability for adherence and availability on a surface over a period of time (in the event the management method is an indoor residual spray), and also its suitability for incorporation into a polymer product (such as a net) so that the compound would be readily available to control mosquitoes on the surface of the net over a period of time and the nets can withstand multiple washings.

In an embodiment of each aspect of the present invention involving a vector control method, the development of vector-borne diseases may be reduced by the mosquito control. .

In an embodiment of each aspect of the present invention involving a vector control method or product, thiocyclam hydrogen oxalate, diflumetorim, and fluazinam are preferred.

The compounds useful in the methods and other aspects of the invention can be prepared using known procedures.

Mosquito control is any method to limit or eradicate mosquito species which transmit disease pathogens. The most frequent types of mosquito vector control employ a variety of strategies.

Mosquito vector control focuses on utilizing preventative methods to control or eliminate mosquito populations. Common preventative measures are

• habitat control - removing or reducing areas where mosquitoes can easily breed can help limit population growth. For example, stagnant water removal, destruction of old tires and cans which serve as mosquito breeding environments and good management of stored water can reduce areas of excessive mosquito incidence. • reducing contact - limiting exposure to mosquitoes can reduce infection risks significantly. For example, bed nets, window screens on homes, or protective clothing can help reduce the likelihood contact with mosquitoes. To be effective this requires education and promotion of methods among the population to raise the awareness of mosquito threats. · chemical control - insecticides, larvicides, and repellents can be used to control mosquitoes. For example, larvicides can be used in mosquito breeding zones; insecticides can be applied to house walls or bed nets, and use of personal repellents can reduce incidence of mosquitoes bites and thus infection. The use of pesticides for mosquito vector control is promoted by the World Health Organization (WHO) and has proven to be highly effective.

• biological control - the use of natural mosquito vector predators, such as bacterial toxins or botanical compounds, can help control mosquito populations. Using fish that eat mosquito larvae, has been demonstrated to have some success.

• population control through the release of sterilized, or genetically modified, male mosquitoes has also been shown to control mosquito vector populations and reduce infection risks.

A number of considerations is taken into account when determining which compound would be suitable for use in a particular mosquito vector control strategy, such as favourable safety profile, biological performance and affordability.

In one embodiment - the compound of the first aspect in accordance with the methods and other aspects of the present invention are useful in controlling mosquitoes, in particular mosquitoes selected from the genus Anopheles, Culex and Aedes. Examples include Aedes aegypti, Aedes albopictus, Aedes japonicas, Aedes vexans, Coquillettidia perturbans, Culex molestus, Culex pallens, Culex pipiens, Culex quinquefasciatus, Culex restuans, Culex tarsalis, Anopheles albimanus, Anopheles albitarsis, Anopheles annularis, Anopheles aquasalis, Anopheles arabiensis, Anopheles aconitus, Anopheles atroparvus, Anopheles balabacensis, Anopheles culicifacies, Anopheles coluzzii, Anopheles darlingi, Anopheles di s, Anopheles farauti, Anopheles flavirostris, Anopheles fluviatilis, Anopheles freeborni, Anopheles funestus, Anopheles gambiae s.l., Anopheles koliensis, Anopheles labranchiae, Anopheles lesteri, Anopheles leucosphyrus, Anopheles maculatus, Anopheles marajoara, Anopheles melas, Anopheles merus, Anopheles messeae, Anopheles minimus, Anopheles moucheti, Anopheles nili, Anopheles nuneztovari, Anopheles plumbeus, Anopheles pseudopunctipennis, Anopheles punctipennis, Anopheles punctulatus, Anopheles quadrimaculatus, Anopheles sacharovi, Anopheles sergentii, Anopheles sinensis, Anopheles stephensi, Anopheles subpictus, Anopheles sundaicus, Anopheles superpictus, and Mansonia titillans, Ochlerotatus stimulans, Ochlerotatus japonicas (each of which is an example of a mosquito capable of carrying or vectoring a pathogenic disease). By control is meant that a compound useful in the methods and other aspects of the invention is employed in a manner that kills or repels the mosquito such that biting does not occur or in a manner that decreases mosquito populations such that biting does not occur as frequently.

In an especially preferred embodiment, the compound of the first is useful in controlling a mosquito selected from the genus Anopheles, Culex and Aedes, in particular Aedes aegypti, Aedes albopictus, Aedes japonicas, Aedes vexans, Culex molestus, Culex pallens, Culex pipiens, Culex quinquefasciatus, Culex restuans, Culex tarsalis, Anopheles albimanus, Anopheles arabiensis, Anopheles coluzzii, Anopheles darlingi, Anopheles di s, Anopheles funestus, Anopheles gambiae s.l., Anopheles melas, Anopheles minimus, Anopheles sinensis, Anopheles stephensi, Mansonia titillans.

In an embodiment, each of the compounds defined in the first aspect are useful in the methods and other aspects of the invention to control adult mosquitoes.

In another embodiment each of the compound defined in the first aspect is especially useful in controlling one or more of the mosquitoes listed in table below:

Mosquito species

Compound no. Mosquito species Compound no.

thiocyclam hydrogen Aedes aegypti thiocyclam Aedes aegypti

oxalate

thiocyclam hydrogen Anopheles funestus thiocyclam Anopheles funestus

oxalate

thiocyclam hydrogen Anopheles gambiae thiocyclam Anopheles gambiae s.l. oxalate s.l.

thiocyclam hydrogen Anopheles thiocyclam Anopheles stephensi oxalate stephensi

thiocyclam hydrogen Anopheles thiocyclam Anopheles arabiensis oxalate arabiensis

thiocyclam hydrogen Aedes albopictus thiocyclam Aedes albopictus

oxalate

thiocyclam hydrogen Anopheles coluzzii thiocyclam

Anopheles coluzzii oxalate

diflumetorim Aedes aegypti

diflumetorim Anopheles funestus

diflumetorim Anopheles gambiae s.l.

diflumetorim Anopheles stephensi

diflumetorim Anopheles arabiensis

diflumetorim Aedes albopictus

diflumetorim Anopheles coluzzii

fluazinam Aedes aegypti

fluazinam Anopheles funestus

fluazinam Anopheles gambiae s.l. fluazinam Anopheles stephensi

fluazinam Anopheles arabiensis

fluazinam Aedes albopictus

fluazinam Anopheles coluzzii

Insecticide resistant mosquito species have also been detected and accordingly in an

embodiment, a compound useful in the methods and other aspects of the invention is suitable for controlling insecticide-resistant mosquitoes, such as pyrethroid and/or carbamate-resistant mosquitoes.

Pyrethroids are the only insecticides that have obtained WHO recommendation against malaria vectors on both Indoor Residuals Sprays (IRS) and Long Lasting Insecticidal Mosquito Nets (LLINs), in the form of alpha-cypermethrin, bifenthrin, cyfluthrin, permethrin, deltamethrin, lambda-cyhalothrin and etofenprox. It has been the chemical class of choice in agriculture and public health applications over the last several decades because of its relatively low toxicity to humans, rapid knock-down effect, relative longevity (duration of 3-6 months when used as IRS), and low cost. However, massive use of pyrethroids in agricultural applications and for vector control led to the development of resistance in major malaria and dengue vectors. Strong resistance has e.g. been reported for the pyrethroid deltamethrin (and permethrin) for the Anopheles gambiae Tiassale (from southern Cote d'lvoire) strain (Constant V.A. Edi et al., Emerging Infectious Diseases; Vol. 18, No. 9, September 2012). Pyrethroid resistance was also reported for Permethrin, Deltamethrin and Lambda-Cyhalothrin for the Aedes aegypti Cayman Island strain (Angela F. Harris et al., Am. J. Trap. Med. Hyg., 83(2), 2010) and alpha- cypermethrin, permethrin and lambda-cyhalothrin for certain Anopheles strains (Win Van Bortel, Malaria Journal, 2008, 7: 102).

In another embodiment of the invention, each of the compound defined in the first aspect can be suitable for use against insecticide-resistant mosquitoes that are selected from Anopheles gambiae RSPH, Anopheles gambiae Tiassale, Anopheles gambiae Akron, Anopheles gambiae Kisumi Rdl, Anopheles arabiensis NDjamina, Anopheles gambiae VK7, Anopheles funestus FUMOZ, Aedes aegypti Grand Cayman and Culex quinquefasciatus strain POO.

· Anopheles gambiae, strain RSPH is a multi-resistant mosquito (target-site and metabolic-resistance) that is described in the reagent catalogue of the Malaria Research and Reference Reagent Resource Center (www.MR4.org; MR4-number: MRA-334).

• Anopheles gambiae, strain Tiassale is a multi-resistant mosquito (target and metabolic-resistant strain) which shows cross-resistance between carbamates, organophosphates and pyrethroids and is described in Constant V.A. Edi et al., Emerging

Infectious Diseases; Vol. 18, No. 9, September 2012 and Ludovic P Ahoua Alou et al., Malaria Journal 9: 167, 2010).

• Anopheles gambiae, strain Akron is a multi-resistant mosquito (target and metabolic- resistant strain) and is described in Djouaka F Rousseau et al., BMC Genomics, 9:538; 2008. • Anopheles gambiae, strain VK7 is a target-resistant mosquito and is described in Dabire Roch Kounbobr et al., Malaria Journal, 7: 188, 2008.

• Anopheles funestus, strain FUMOZ is a metabolic-resistant strain and is described in Hunt et al., Med Vet Entomol. 2005 Sep; 19(3):271-5). In this article it has been reported that Anopheles funestus - as one of the major malaria vector mosquitoes in Africa - showed resistance to pyrethroids and carbamate insecticides in South Africa.

• Anopheles gambiae, strain Kisumi Rdl, a dieldrin resistant strain from Kenya.

• Anopheles arabiensis, strain NDjamina, a pyrethroid resistant from Chad.

• Aedes aegypti, strain Grand Cayman is a target-resistant mosquito and is described in Angela F. Harris, Am. J. Tro. Med. Hyg. 83(2), 2010.

• Culex quinquefasciatus (metabolic-resistant to DDT strain P00); received from Texchem, Penang, Malaysia.

Vector control management methods or products are means to control a vector, such as a mosquito. Examples of such means are compositions, products, and treated articles, which include a substrate or non-living material incorporating (e.g. coated or impregnated with) a compound defined in the first aspect, spray products (e.g. indoor sprays, and aerosol products) comprising a compound defined in the first aspect, paint compositions comprising a compound defined in the first aspect 1 , and products or treated articles comprising a compound defined in the first aspect.

Examples of vector control management methods & products of the invention, such as methods for controlling mosquito bites or decreasing relevant mosquito populations, include the use of compositions, products, treated articles and substrates at a locus of potential or known interaction between the mosquito vector and an animal, including a human, that is susceptible to a pathogenic disease infection transmitted by such vector. Suitable vector control management methods & products within the scope of the present invention also include identifying mosquito breeding sites and positioning compositions, products, treated articles and substrates of the invention at such sites.

The use of a compound in a substrate of the present invention (e.g., nets and weaves) achieves at least one of the following objects:

good insecticidal effect

fast-acting insecticidal efficacy

· long-lasting insecticidal efficacy

uniform release of active ingredient

long durability (including resisting multiple washings over an extended period) simple production

safe to the user

The nets and weaves (or textiles) of the invention that incorporate (e.g. , are coated or impregnated with) the compound of the first aspect are made up of a variety of natural and synthetic fibres, also as textile blends in woven or non-woven form, as knit goods or fibres. Natural fibres are, for example, raffia, jute, flax, sisal, hessian, wool, silk or hemp. Synthetic fibres may be made of polyamides, polyesters, polyacrylonitriles, polyolefines, for example polypropylene or polyethylene, Teflon, and mixtures of fibres, for example mixtures of synthetic and natural fibres. Polyamides, polyolefins and polyesters are preferred as fibre material. Polyester, such a polyethylene terephthalate, polyethylene and polypropylene are especially preferred. Most preferred are nettings made from polyethylene and/or polypropylene.

The art discloses methods suitable for incorporating (by way of coating) a compound onto nets and weaves (see for example, WO2003/034823, WO 2008/122287, WO 01/37662, US2009036547, WO 2007/036710), from dipping or submerging them into a formulation of the insecticide or by spraying the formulation onto their surfaces. After treating the nets and weaves of the invention, they may be dried simply at ambient temperatures (see also below for more background). Such methods are also suitable for incorporating (by way of coating) the compound of the first aspect.

Also disclosed in the art are methods suitable for incorporating (by way of impregnating) a pesticide compound within the net or weave by making polymer material in the presence of the compound, which is then extruded into fibres, threads or yarns, for making the nets and weaves (see for example, WO0800471 1 , WO2009/121580, WO201 1/128380, WO201 1/141260, WO2010/1 18743). Such nets and weaves having available at the surface of the net and weave an effective amount of the compound so as to control mosquito bites. Generally the compound is mixed with the molten polymer. Such methods are also suitable for incorporating (by way of impregnating) the compound of the first aspect. The term "incorporating" or "incorporated" in context of the compound of the invention, additives and other insecticides is meant that the substrate or non-living material comprises or contains the respectively defined compound, additive and/or insecticide, such as by coating or impregnation.

Preferably the substrate of the present invention is a net, which net is preferably a long lasting net, incorporated with the compound of the first aspect by way of coating the net with a composition comprising the compound of the first aspect, or by way of making a polymeric material in the presence of the compound of the first aspect and then processing the resultant polymeric material into an inventive net.

In accordance with the invention, when the compound of the first aspect is used within the polymer, then during use of the resulting net or weave made from the polymer, the compound of the first aspect is released to the surface of the net to control against mosquito bites - such control is sustained at adequate level and for adequate amount of time.

Examples of suitable polymers are polyamides, polyesters, polyacrylonitriles, polyolefines, such as polyethylene compositions that can be made from different polyethylene polymers; these may be LDPE, LLDPE, MDPE and HDPE. LLDPE (Linear low-density polyethylene) is a substantially linear polymer (polyethylene), with significant numbers of short branches, commonly made by copolymerization of ethylene with longer-chain olefins. MDPE is medium-density polyethylene is a substantially linear polymer of polyethylene with shorter chain length than HDPE. HDPE (High-Density PolyEthylene) or PolyEthylene High-Density (PEHD) is a polyethylene thermoplast. HDPE has little branching, giving it stronger intermolecular forces and tensile strength than lower-density polyethylene. It is also harder and more opaque and can withstand somewhat higher temperatures (120 degrees Centigrade / 248 degrees Fahrenheit for short periods, 1 10 degrees Centigrade /230 degrees Fahrenheit continuously). HDPE yarns are stronger than LDPE mixed polyethylene yarns. LLDPE differs structurally from conventional low- density polyethylene (LDPE) because of the absence of long chain branching. These polyethylene compositions (HDPE, LDPE, LLDPE and mixture thereof) are generally used for preparing yarns and polyethylene based textile products. Methods for incorporating an insecticide compound into the polymer without weakening its resulting properties are known in the art, such as using mixtures of HDPE and LDPE. Such methods can also be used to incorporate the compound of the first aspect into a polymer.

Examples of spray products of the present invention are indoor residual sprays or space sprays comprising the compound of the first aspect. Indoor Residual Spraying (IRS) is the technique of applying a residual deposit of an insecticide onto indoor surfaces where vectors rest, such as on walls and ceilings. The primary goal of indoor residual spraying is to reduce the lifespan of the mosquito vectors and thereby reduce or interrupt disease transmission. The secondary impact is to reduce the density of mosquitoes within the treatment area. IRS is a recognised, proven and cost-effective intervention method for the control of malaria and it is also used in the management of Leishmaniasis disease. Many malaria mosquito vectors are endophilic, resting inside houses after taking a blood meal. These mosquitoes are particularly susceptible to control through indoor residual spraying (IRS) comprising the compound of the first aspect. As its name implies, IRS involves coating the walls and other surfaces of a house with a residual insecticide. For several months, the compound of the first aspect will kill mosquitoes that come in contact with these surfaces. IRS does not directly prevent people from being bitten by mosquitoes. Rather, it usually kills mosquitoes after they have fed, if they come to rest on the sprayed surface. IRS thus prevents transmission of infection to other persons. To be effective, IRS must be applied to a very high proportion of households in an area (usually greater than 70 percent). Although the community plays a passive role in IRS programs, cooperation with an IRS effort is a key to its success. Community participation for IRS often consists of cooperating with the spray teams by removing food and covering surfaces prior to spraying and refraining from covering the treated surfaces with new paint or plaster. However, community or individual householder opposition to IRS due to the smell, mess, possible chemical exposure, or sheer bother has become a serious problem in some areas. Therefore, sprays in accordance with the invention having good residual efficacy and acceptable odour are particularly suited as a component of vector control management.

In contrast to IRS, which requires that the active compound of the first aspect is bound to surfaces of dwellings, such as walls, ceiling, space spray products of the invention rely on the production of a large number of small insecticidal droplets intended to be distributed through a volume of air over a given period of time. When these droplets impact on a target mosquito, they deliver a lethal dose of the compound of the first aspect. The traditional methods for generating a space-spray include thermal fogging (whereby a dense cloud of insecticide droplets is produced giving the appearance of a thick fog) and Ultra Low Volume (ULV), whereby droplets are produced by a cold, mechanical aerosol- generating machine. Since large areas can be treated at any one time this method is a very effective way to rapidly reduce the population of flying mosquitoes in a specific area. Since there is very limited residual activity from the application it must be repeated at intervals of 5-7 days in order to be fully effective. This method can be particularly effective in epidemic situations where rapid reduction in mosquito numbers is required. As such, it can be used in urban dengue control campaigns.

Effective space-spraying is generally dependent upon the following specific principles:

• Target insects are usually flying through the spray cloud (or are sometimes impacted whilst resting on exposed surfaces). The efficiency of contact between the spray droplets and target insects is therefore crucial. This is achieved by ensuring that spray droplets remain airborne for the optimum period of time and that they contain the right dose of insecticide.

These two issues are largely addressed through optimizing the droplet size.

• If droplets are too big they drop to the ground too quickly and don't penetrate vegetation or other obstacles encountered during application (limiting the effective area of application). If one of these big droplets impacts an individual insect then it is also 'overkill' since a high dose will be delivered per individual insect.

• If droplets are too small then they may either not deposit on a target insect (no impaction) due to aerodynamics or they can be carried upwards into the atmosphere by convection currents.

• The optimum size of droplets for space-spray application are droplets with a Volume Median Diameter (VMD) of 10-25 microns.

The compositions of the present invention may be made available in a spray product as an aerosol- based application, including aerosolized foam applications. Pressurised cans are the typical vehicle for the formation of aerosols. An aerosol propellant that is compatible with the compound of the first aspect is used. Preferably, a liquefied-gas type propellant is used. Suitable propellants include compressed air, carbon dioxide, butane and nitrogen. The concentration of the propellant in the composition is from about 5 percent to about 40 percent by weight of the composition, preferably from about 15 percent to about 30 percent by weight of the composition.

In one embodiment, the formulation of the invention comprising the compound of the first aspect can also include one or more foaming agents. Foaming agents that can be used include sodium laureth sulphate, cocamide DEA, and cocamidopropyl betaine. Preferably, the sodium laureth sulphate, cocamide DEA and cocamidopropyl are used in combination. The concentration of the foaming agent(s) in the composition is from about 10 percent to about 25 percent by weight, more preferably 15 percent to 20 percent by weight of the composition.

When the compound of the first aspect formulation is used in an aerosol application not containing foaming agents), the composition of the present invention can be used without the need for mixing directly prior to use. However, aerosol formulations containing the foaming agents do require mixing (i.e. shaking) immediately prior to use. In addition, if the formulations containing foaming agents are used for an extended time, they may require additional mixing at periodic intervals during use. A dwelling area may also be treated with composition comprising the compound of the first aspect by using a burning formulation, such as a candle, a smoke coil or a piece of incense containing the composition. For example, composition may be comprised in household products such as "heated" air fresheners in which insecticidal compositions are released upon heating, for example, electrically, or by burning.

The compositions of the present invention containing the compound of the first aspect may be made available in a spray product as an aerosol, a mosquito coil, and/or a vaporiser or fogger.

The concentration of the compound of the first aspect in the polymeric material, fibre, yarn, weave, net, or substrate, each of the invention, can be varied within a relatively wide concentration range from, for example 0.05 to 15 percent by weight, preferably 0.2 to 10 percent by weight, more preferably 0.4 to 8 percent by weight, especially 0.5 to 5, such as 1 to 3, percent by weight.

The percentages mentioned above are based on dry weight of the net or substrate or non-living material.

Similarly, the concentration of the compound of the invention in the composition (whether for treating surfaces or for coating a fibre, yarn, net, weave) can be varied within a relatively wide concentration range from, for example 0.1 to 70 percent by weight, such as 0.5 to 50 percent by weight, preferably 1 to 40 percent by weight, more preferably 5 to 30 percent by weight, especially 10 to 20 percent by weight.

The concentration shall be chosen according to the field of application such that the requirements concerning insecticidal efficacy, durability and toxicity are met. Adapting the properties of the material can also be accomplished and so custom-tailored textile fabrics are obtainable in this way.

The compound of the first aspect when used in the IRS methods of the invention is present on a surface of a dwelling at a coverage of from 0.01 to 2 grams of Al per m2, preferably from 0.05 to 1 grams of Al per m2, especially from 0.1 to 0.7 grams of Al per m2.

Accordingly an effective amount of the compound of the first aspect can depend on how it is being used, the mosquito against which control is most desired and the environment it is being used in.

Therefore, an effective amount of the compound of the first aspect is sufficient that control of a mosquito is achieved; in case of:

• use as a IRS formulation, the effective amount is such that coverage of the Al on the surface is from 0.01 to 2 grams of Al per m2, preferably from 0.05 to 1 grams of Al per m2, especially from 0.1 to 0.7 grams of Al per m2;

• use incorporated within a net or substrate, the effective amount is 0.05 to 15 percent by weight, preferably 0.2 to 10 percent by weight, more preferably 0.4 to 8 percent by weight, especially 0.5 to 5, such as 1 to 3, percent by weight.

Generally the compound of the first aspect when used in certain products of the invention is continuously distributed in a thread, yarn, net or weave, but can also be partially or discontinuously distributed in a thread, yarn, net or weave. For example, a net may contain certain parts which are coated or which is made-up of impregnated fibre, and certain other parts which are not; alternatively some of the fibres making up the net is impregnated, or is coated, with the compound of the invention, and some of the other fibres not or these other fibres are impregnated, or are coated, with another insecticide compound (see below).

Nets of the invention impregnated, or coated, with the compound of the first aspect can satisfy the criteria of the WHOPES directive (see "Guidelines for laboratory and field testing of long-lasting insecticidal mosquito nets", 2005, http://www.who.int/whopes/guidelines/en/) for insecticide-containing long-lasting mosquito nets up to 20 washes only, which means that such nets should not lose their biological activity after just 20 wash cycles or so.

In an embodiment, a net of the invention impregnated, or coated, with the compound of the first aspect can have biological activity in accordance with WHOPES directive of a knockdown after 60 minutes of between 95 percent and 100 percent or a mortality after 24 hours of between 80 percent and 100 percent after at least 20, such as 25, preferably at least 30 and even more preferably at least 35 washes.

The "WHOPES directive" is to be understood as meaning the directive "Guidelines for laboratory and field testing of long-lasting insecticidal mosquito nets", 2005). This directive is retrievable at the following interact address: http://www.who.int/whopes/guidelines/en/.

When a net is "impregnated with" the compound of the first aspect to prepare a net of the present invention, the fibres making up the net are made by melting a polymer, the compound of the first aspect and optionally other compounds, such as other insecticides, additives, stabilisers. When a net is impregnated with the compound of the first aspect, then the net of the invention contains synthetic fibres; whereas, a net of the invention coated with the compound of the first aspect contains synthetic fibres and/or natural fibres.

The polymeric materials useful in the compositions of the invention incorporating the compound of the first aspect can be produced by mixing the compound of the first aspect with the polymer in the liquid phase, and optionally other additives (such as binders and/or synergists), and other insecticidal compounds.

Methods of making suitable polymeric materials and then processing it are described in the art - see for example, WO09121580, WO201 1/141260.

For example, nets based on an insecticide-containing polymeric material are produced by the following steps:

a) melting the polymer to be used and one or more insecticidally active ingredients together or separately at temperatures between 120 and 250 degrees centigrade,

b) forming the melt of step a) into spun threads and cooling,

c) optionally leading the spun threads formed in step b) through a drawing system and drawing and then optionally setting out the threads,

d) knitting the spun threads to form a net,

e) subjecting the net to a heat-setting operation wherein the temperature for the heat- setting operation is chosen to be 20 degrees centigrade below the melting temperature of the polymer to be used. The heat setting in step e) of the production of the nets is preceded by a washing step. Water and a detergent is preferably used for this. The heat setting is preferably carried out in a dry atmosphere.

Although the manufacture of the nets incorporated with a compound can occur in a single location, it is also envisaged that the different steps can take place in different locations. So a composition comprising the compound of the first aspect may be made which can then be processed into a polymer. Accordingly, the present invention also provides a composition comprising the compound of the first aspect in a concentrated form, which composition may also contain additives (such as binders and/or synergists), and other insecticidal compound(s) (which composition had been prepared explicitly for making a polymer material impregnated with the compound of the first aspect (such a composition is often referred to as a "masterbatch")). The amount of the compound of the first aspect in the masterbatch would depend on the circumstances, but in general can be 10 to 95 percent by weight, such as 20 to 90 percent by weight, preferably 30 to 85 percent by weight, more preferably 35 to 80 percent by weight, especially 40 to 75 percent by weight.

Also made available in the present invention are compositions or formulations for coating walls, floors and ceilings inside of buildings and for coating a substrate or non-living material, which comprise the compound of the first aspect. The inventive compositions can be prepared using known techniques for the purpose in mind, which could contain a binder to facilitate the binding of the compound to the surface or other substrate. Agents useful for binding are known in the art and tend to be polymeric in form. The type of binder suitable for composition to be applied to a wall surface having particular porosities, binding characteristics would be different to a fibre, yarn, weave or net - a skilled person, based on known teachings, would select a suitable binder.

Typical binders are poly vinyl alcohol, modified starch, poly vinyl acrylate, polyacrylic, polyvinyl acetate co polymer, polyurethane, and modified vegetable oils. Suitable binders can include latex dispersions derived from a wide variety of polymers and co-polymers and combinations thereof. Suitable latexes for use as binders in the inventive compositions comprise polymers and copolymers of styrene, alkyl styrenes, isoprene, butadiene, acrylonitrile lower alkyl acrylates, vinyl chloride, vinylidene chloride, vinyl esters of lower carboxylic acids and alpha, beta-ethylenically unsaturated carboxylic acids, including polymers containing three or more different monomer species copolymerized therein, as well as post-dispersed suspensions of silicones or polyurethanes. Also suitable may be a polytetrafluoroethylene (PTFE) polymer for binding the active ingredient to other surfaces.

The formulation according to the present invention comprises the compound of the first aspect (or a pesticide (A), and a carrier, such as water (C), and optionally a polymeric binder (B) and further components (D).

The polymeric binder binds the compound of the first aspect to the surface of the non-living material and ensures a long-term effect. Using the binder reduces the elimination of the pesticide (A) out of the non-living material due to environmental effects such as rain or due to human impact on the non-living material such as washing and/or cleaning it. The further components can be an additional insecticide compound, a synergist, a UV stabiliser. The inventive compositions can be in a number of different forms or formulation types, such as suspensions, capsules suspensions, and a person skilled in the art can prepare the relevant composition based on the properties of the compound of the first aspect, its uses and also application type.

For example, the compound of the first aspect used in the methods and other aspects of the present invention may be encapsulated in the formulation. A encapsulated compound can provide improved wash-fastness and also longer period of activity. The formulation can be organic based or aqueous based, preferably aqueous based.

A microencapsulated compound suitable for use in the compositions and methods according to the invention are prepared by any suitable technique known in the art. For example, various processes for microencapsulating material have been previously developed. These processes can be divided into three categories-physical methods, phase separation and interfacial reaction. In the physical methods category, microcapsule wall material and core particles are physically brought together and the wall material flows around the core particle to form the microcapsule. In the phase separation category, microcapsules are formed by emulsifying or dispersing the core material in an immiscible continuous phase in which the wall material is dissolved and caused to physically separate from the continuous phase, such as by coacervation, and deposit around the core particles. In the interfacial reaction category, microcapsules are formed by emulsifying or dispersing the core material in an immiscible continuous phase and then an interfacial polymerization reaction is caused to take place at the surface of the core particles. The concentration of the compound of the first aspect present in the microcapsules can vary from 0.1 to 60% by weight of the microcapsule.

The formulation according to the invention may be formed by mixing all ingredients together with water optionally using suitable mixing and/or dispersing aggregates. In general, the formulation is formed at a temperature of from 10 to 70 degrees centigrade, preferably 15 to 50 degrees centigrade, more preferably 20 to 40 degrees centigrade

It is possible to use a pesticide (A), solid polymer (B) and optionally additional additives (D) and to disperse them in the aqueous component (C)

If a binder is present in a composition of the present invention, it is preferred to use dispersions of the polymeric binder (B) in water as well as aqueous formulations of the pesticide (A) in water which have been separately prepared before. Such separate formulations may contain additional additives for stabilizing (A) and/or (B) in the respective formulations and are commercially available. In a second process step, such raw formulations and optionally additional water (component (C)) are added.

Also combinations are possible, i.e. using a pre-formed dispersion of (A) and/or (B) and mixing it with solid (A) and/or (B).

A dispersion of the polymeric binder (B) may be a pre-manufactured dispersion already made by a chemicals manufacturer.

However, it is also within the scope of the present invention to use "hand-made" dispersions, i.e. dispersions made in small-scale by an end-user. Such dispersions may be made by providing a mixture of about 20 percent of the binder (B) in water, heating the mixture to temperature of 90 to 100 degrees centigrade and intensively stirring the mixture for several hours.

It is possible to manufacture the formulation as a final product so that it can be readily used by the end-user for the process according to the present invention.

However, it is of course also possible to manufacture a concentrate, which may be diluted by the end-user with additional water (C) to the desired concentration for use.

In an embodiment, a composition suitable for IRS application or a coating formulation containing the compound of the first aspect contains the active ingredient and a carrier, such as water, and may also one or more co-formulants selected from a dispersant, a wetter, an anti-freeze, a thickener, a preservative, an emulsifier and a binder or sticker.

The compound of the first aspect is generally milled to a desired particle size, such as the particle size distribution d(0.5) is generally from 3 to 20, preferably 5 to 15, especially 7 to 12, μηη.

Furthermore, it may be possible to ship the formulation to the end-user as a kit comprising at least

• a first component comprising the compound of the first aspect (A); and · a second component comprising at least one polymeric binder (B).

• Further additives (D) may be a third separate component of the kit, or may be already mixed with components (A) and/or (B).

The end-user may prepare the formulation for use by just adding water (C) to the components of the kit and mixing.

The components of the kit may also be formulations in water. Of course it is possible to combine an aqueous formulation of one of the components with a dry formulation of the other component(s). As an example, the kit can comprise

• one formulation of the compound of the first aspect (A) and optionally water (C); and

· a second, separate formulation of at least one polymeric binder (B), water as component (C) and optionally components (D).

Accordingly, in a further aspect the present invention provides a kit for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising: a first sachet comprising a pre-measured amount of the compound of the first aspect, and a second sachet comprising a pre-measured amount of at least one polymeric binder. The resulting treated fibre, yarn, net and weave has imparted thereto the insecticidal properties needed for vector control, such as to control vector-carrying mosquitoes.

The concentrations of the components (A), (B), (C) and optionally (D) will be selected by the skilled artisan depending of the technique to be used for coating/ treating.

In general, the amount of pesticide (A) may be up to 50, preferably 5 to 50, such as 10 to 40, especially 15 to 30, percent by weight, based on weight of the composition.

The amount of polymeric binder (B) may be in the range of 0.01 to 30, preferably 0.5 to 15, more preferably 1 to 10, especially 1 to 5, percent by weight, based on weight of the composition. If present, in general the amount of additional components (D) is from 0.1 to 20, preferably 0.5 to 15, percent by weight, based on weight of the composition. If present, suitable amounts of pigments and/or dyestuffs are in general 0.01 to 5, preferably 0.1 to 3, more preferably 0.2 to 2, percent by weight, based on weight of the composition.

A typical formulation ready for use comprises 0.1 to 40, preferably 1 to 30, percent of components (A), (B), and optionally (D), the residual amount being water (C).

A typical concentration of a concentrate to be diluted by the end-user may comprise 5 to 70, preferably 10 to 60, percent of components (A), (B), and optionally (D), the residual amount being water (C).

The formulation of the present invention may be applied to polymeric material before their formation into the required products, e.g. , while still a yarn or in sheet form, or after formation of the relevant products.

For the case of nets and/or weaves, a process for coating nets and/or weaves at least comprising the following steps:

a) treating the nets and/or weaves with the aqueous formulation according to the invention by any of the procedural steps selected from the group of

(a1 ) passing the material through the formulation; or

(a2) contacting the material with a roller that is partly or fully dipped into the formulation and drawing the formulation to the side of the material in contact with the roller, or

(a3) submerging the material into the formulation; or

(a4) spraying the formulation onto the material; or

(a5) brushing the formulation onto or into the material; or

(a6) applying the formulation as a foam; or

(a7) coating the formulation onto material.

b) optionally removing surplus formulation by squeezing the material between rollers or by means of a doctor blade; and

c) drying the material.

In case the raw materials containing residues of preceding production processes, e.g., sizes, spin finishes, other auxiliaries and/or impurities, it may be beneficial to perform a washing step before the coating.

Specifically, the following details are important for the steps a), b), and c).

Step a1 )

The formulation is applied by passing the material through the aqueous formulation. Said step is known by a person skilled in the art as padding. In a preferred embodiment the material is completely submerged in the aqueous formulation either in a trough containing the liquor or the material is passed through the formulation which is held between two horizontally oriented rollers. In accordance with the invention, the material may either be passed through the formulation or the formulation may be passed through the material. The amount of uptake of the formulation will be influenced by the stability of concentrated baths, the need for level distribution, the density of material and the wish to save energy costs for drying and curing steps. Usual liquor-uptakes may be 40 to 150 percent on the weight of material. A person skilled in the art is familiar with determining the optimum value. Step al) is preferred for coating open-width material which is later tailored into nets.

For small-scale production or re-coating of non-treated nets, use of a simple hand-held roller may be sufficient.

Step a2)

It is further possible to apply the aqueous formulation on the material by a roller that is partly dipped into the dispersion thus applying the dispersion to the side of the material in contact with the roller (kiss-rolling). By this method it is possible to coat only one side of the material which is advantageous if, e.g. , direct contact of the human skin with insecticide-treated material is to be avoided.

Coating of the material in step al), a2) or a3) is typically carried out at temperatures from 10 to 70 degrees centigrade, preferably 15 to 50 degrees centigrade, more preferably 20 to 40 degrees centigrade

Step a4)

The spray may be applied in continuous processes or in batch-wise processes in suitable textile machines equipped with a spraying device, e.g., in open-pocket garment washer/extractors. Such equipment is especially suitable for impregnating ready-made nets.

Step a6)

A foam comprises less water than the dispersion mentioned above. The drying process may therefore be very short. The treatment may be performed by injecting gas or blends of gas (e.g. , air) into it. The addition of surfactants, preferably with film-forming properties, may be required. Suitable surfactants and the required technical equipment are known to persons skilled in the art.

Step a7)

A coating process may preferably carried out in a doctor-blade process. The process conditions are known to a person skilled in the art.

Step b)

The surplus emulsion is usually removed by squeezing the material, preferably by passing the material through rollers as known in the art thus achieving a defined liquor uptake. The squeezed-off liquor may be re-used. Alternatively, the surplus aqueous emulsion or aqueous dispersion may be removed by centrifuging or vacuum suction.

Step c)

Drying may be performed at ambient temperatures. In particular, such a passive drying may be carried out in hot-dry climate. Of course, the drying process may be accelerated applying elevated temperatures. An active drying process would normally be performed during high scale processing. The drying is in general carried out temperatures below 200 degrees centigrade. Preferred temperatures are from 30 to 170 degrees centigrade, more preferably at room temperature. The temperature choice is determined by the thermal stability of the insecticide in the formulation and the thermal stability of the non-living material impregnated. For the method according to the invention aqueous formulation comprising at least one pigment and/or at least one dyestuff may be used so that the material is not only coated with the compound of the first aspect but in addition also coloured at the same time.

In a further aspect, the present invention provides a method for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising (i) preparing a treatment composition, which comprises the compound of the first aspect, (ii) treating said fibre, yarn, net and weave and (iii) drying the resulting treated a fibre, yarn, net and weave.

The polymeric binder (B) can be dispersed in an aqueous formulation and comprises one or more fluorinated acrylic copolymers useful in the water and oil resistant formulations includes copolymer prepared by the polymerization of a perfluoroalkyl acrylate monomer and a comonomer, especially an acrylate monomer. The binder may also be fluorocarbon resins (as described in WO 2006/128870.

Only water is used as solvent for the formulation. However, trace amounts of organic solvents miscible with water may be present. Examples of solvents comprise water-miscible alcohols, e.g., monoalcohols such as methanol, ethanol or propanol, higher alcohols such as ethylene glycol or polyether polyols and ether alcohols such as butyl glycol or methoxypropanol. Preferably the content of an organic solvent is no more than 5 percent by weight (based on component (C), more preferably no more than 1 percent by weight (based on component (C), in particular no more than 0.1 percent by weight, based on component (C).

Depending on the intended use of the non-living material to be treated the formulation according to the present invention may further comprise one or more components or additives (D) selected from preservatives, detergents, fillers, impact modifiers, anti-fogging agents, blowing agents, clarifiers, nucleating agents, coupling agents, fixative agents, cross-linking agents, conductivity-enhancing agents (antistats), stabilizers such as antioxidants, carbon and oxygen radical scavengers and peroxide decomposing agents and the like, flame retardants, mould release agents, agents having UV protecting properties, spreading agents, anti-blocking agents, anti-migrating agents, foam-forming agents, anti-soiling agents, thickeners, further biocides, wetting agents, plasticizers and film-forming agents, adhesive or anti-adhesive agents, optical brightening (fluorescent whitening) agents, pigments and dyestuffs.

A typical amount of the polymeric binder (B) is from 0.01 to 10 percent by weight (dry weight) of the (dry) weight of the material. As a general guideline, the weight ratio between insecticide and binder

(B) should approximately be constant with a value depending on the insecticidal and migratory ability of the insecticide, i.e. the higher the amount the insecticide the higher also the amount of binder (B).

Preferred amounts of binder (B) are from 0.1 to 5 percent by weight, more preferably 0.2 to 3 percent by weight of the (dry) weight of the material.

The coated material can comprise at least one pigment and/or at least one dyestuff. The amount of the at least one pigment and/or dyestuff is in general from 0.05 to 10 percent by weight, preferably

0.1 to 5 percent by weight, more preferably 0.2 to 3.5 percent by weight of the (dry) weight of the material. The method of coating or treating the non-living material is not limited to a specific technology. Coating may be performed by dipping or submerging the non-living substrate into the formulation or by spraying the formulation onto the surface of the non-living material. After treating the treated nonliving substrate may be dried simply at ambient temperatures.

Accordingly, no sophisticated technology is necessary for the coating, and therefore the coating process may be carried out by the end-user itself in at low-scale.

For instance, a typical end-user may coat/treat a net itself, e.g. , within its household, using the formulation according to the present invention. For this purpose, it is in particular advantageous to use a kit as herein defined.

In an embodiment, the present invention provides a polymer, a fibre, a thread, a yarn, a net or weave comprising one or more compounds M of the invention, where also incorporated can be one or more other customary materials used to make such a polymer, and the polymer, a fibre, a thread, a yarn, a net or weave optionally can further incorporate one or more other insecticides and/or synergists.

In an embodiment, the present invention provides a net or weave incorporated with one or more compounds M, which optionally further incorporates one or more other insecticides and/ or synergists.

As described in the art, a compound useful in the methods and other aspects of the present invention can be used alone or in combination with another insecticide, synergist, insect repellent, chemosterilant, flame retardant, UV protector/ absorber, and/or additives for controlling release characteristics.

When used in accordance with the invention, the compound of the first aspect may be used alone to control a mosquito or used in combination with one or other known insecticides and/or one or more additives (such as synergists) - in polymers for making non-living substrates, such as nets and weaves, for formulations for treating non-living substrates, such as nets and weaves, in IRS products and space-spraying products.

In an embodiment, the present invention provides a composition (useful for coating a polymeric material or a product therefrom, or a useful as a spray product) comprising one or more compounds of the invention, which optionally further comprises one or more other insecticide and/or synergists and one or more other additives.

Examples of synergists are piperonylbutoxide (PBO), sebacic esters, fatty acids, fatty acid esters, vegetable oils, esters of vegetable oils, alcohol alkoxylates and antioxidants.

Suitable sebacic esters are for example dimethyl sebacate, diethyl sebacate, dibutyl sebacate, dibenzyl sebacate, bis(N-succinimidyl)sebacate, bis(2-ethylhexyl)sebacate, bis(1-octyloxy-2, 2,6,6- tetramethyl-4-piperidyl)sebacate, bis(2,2,6,6-tetramethyl-4-piperidyl)sebacate and bis(1 ,2,2,6,6- pentamethyl-4-piperidinyl)sebacate (BLS292).

Suitable fatty acids are (preferably mono- or polyunsaturated) fatty acids having a chain length of 12 to 24 carbon atoms, for example palmitoleic acid, oleic acid, elaidic acid, vaccenic acid, icosenic acid, cetoleic acid, erucic acid, nervonic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, timnodonic acid, clupanodonic acid and cervonic acid. Particular preference is given to oleic acid, linoleic acid, alpha-linolenic acid and gamma-linolenic acid.

Suitable fatty acid esters are preferably methyl or ethyl esters of the above-recited fatty acids. Methyl esters are particularly preferred. Fatty acids and their esters can each also be present in mixtures.

Useful vegetable oils include all plant-derivable oils customarily usable in agrochemical compositions. As examples there may be mentioned sunflower oil, rapeseed oil, olive oil, castor oil, colza oil, maize kernel oil, cottonseed oil and soybean oil. Rapeseed oil is preferred.

Suitable esters of vegetable oils are methyl or ethyl esters of the above-recited oils. Methyl esters are preferred.

Antioxidants useful as additives include for example butylhydroxytoluene, butylhydroxyanisole and L-ascorbic acid.

Plant essential oils may also be used in an indoor residual spray compositions; examples are those selected from citronella, peppermint oil, d-limonene and Abies sibirica oil. These plant essential oil materials are known and used for other uses and can be prepared by a skilled artisan by employing known methods and also are available commercially.

In addition to the compound of the first aspect, the methods, compositions, polymer, product, substrate and/or vector control management methods/ products according to the invention may contain one or more further insecticidally active ingredients. Particularly examples are one or more active ingredients from the class of organophosphates, pyrethroids, carbamates or neonicotinoids, and also DDT, indoxacarb, nicotine, bensultap, cartap, spinosad, camphechlor, chlordane, endosulfan, gamma- HCH, HCH, heptachlor, lindane, methoxychlor, acetoprole, ethiprole, fipronil, pyrafluprole, pyriprole, vaniliprole, avermectin, emamectin, emamectin-benzoate, ivermectin, milbemycin, diofenolan, epofenonane, fenoxycarb, hydroprene, kinoprene, methoprene, pyriproxifen, triprene, chromafenozide, halofenozide, methoxyfenozide, tebufenozide, bistrifluoron, chlofluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluoron, teflubenzuron, triflumuron, buprofezin, cyromazine, diafenthiuron, azocyclotin, cyhexatin, fenbutatin-oxide, chlorfenapyr, binapacyrl, dinobuton, dinocap, DNOC, fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad, hydramethylnon, dicofol, rotenone, acequinocyl, fluacrypyrim, Bacillus thuringiensis strains, spirodiclofen, spiromesifen, spirotetramat, 3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl ethyl carbonate (alias: carbonic acid, 3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl ethyl ester, CAS-Reg.-No.: 382608-10-8), flonicamid, amitraz, propargite, flubendiamide, chloranthraniliprol, , thiosultap-sodium, azadirachtin, Bacillus spec, Beauveria spec, Metarrhizium spec, Paecilomyces spec, Thuringiensin, Verticillium spec, aluminium phosphide, metaflumizone, picoxystrobin, methylbromide, sulfurylfluoride, cryolite, flonicamid, pymetrozine, clofentezine, etoxazole, hexythiazox, amidoflumet, benclothiaz, benzoximate, bifenazate, bromopropylate, buprofezin, chinomethionate, chlordimeform, chlorobenzilate, chloropicrin, clothiazoben, cycloprene, cyflumetofen, dicyclanil, fenoxacrim, fentrifanil, flubenzimine, flufenerim, flutenzin, gossyplure, hydramethylnone, japonilure, metoxadiazone, petroleum, piperonylbutoxide, kaliumoleat, pyridalyl, sulfluramid, tetradifon, tetrasul, triarathene, verbutin, 4-(trifluoromethyl)pyridine-3-carboxamide. In an embodiment, a preferred mixing partner is a pyrethroid, such as alpha-cypermethrin, bifenthrin, cyfluthrin, permethrin, deltamethrin, lambda-cyhalothrin and etofenprox, or 4-(trifluoromethyl)pyridine- 3-carboxamide.

In a further aspect, a method of controlling mosquitoes, preferably mosquito vectors of pathogenic disease, which comprises contacting a mosquito or its environment with a composition comprising a mosquitocidally effective amount of the compound of the first aspect, is made available.

The present invention also provides a method, comprising: (i) identifying a locus of potential or known interaction between a mosquito vector and a mammal, including a human, susceptible to pathogenic disease infection when contacted by such vector and (ii) positioning a vector control management or control product at the locus, wherein the product includes a mosquitocidally effective amount of the compound of the first aspect.

In a further aspect, the present invention provides a method for protecting a mammal, including a human, against mosquitoes, the method comprising applying to the mosquito or to a locus of potential or known interaction between the mammal and the mosquito, a vector control management product comprising a mosquitocidally effective amount of the compound of the first aspect.

Another aspect of the invention is a method for controlling the spread of a vector-borne disease, comprising: identifying a mosquito vector; and contacting the mosquito vector or its environment with a vector control management method comprising a mosquitocidally effective amount of the compound of the first aspect.

An aspect of the invention also includes a mosquitocidal method which comprises contacting a mosquito or its environment with a vector control management product comprising a mosquitocidally effective amount of the compound of the first aspect.

The present invention through control of mosquitoes would also be expected to control the many viruses carried by such vectors. As an example, control of the mosquitoes of the genus Aedes by use of the compound of the first aspect, as part of a vector control management or control method/product, may control the Zika infections. Examples of mosquitoes reported to spread the Zika virus are the Aedes mosquitoes, such as Aedes aegypti and Aedes albopictus. Accordingly, in an aspect, the present invention provide a method of controlling Zika virus infection, the compound of the first aspect is present in a mosquitocidally effective amount in the vicinity of Aedes mosquitoes, such as Aedes aegypti and Aedes albopictus. In the vicinity of the mosquitoes is meant areas where mosquitoes are likely to be present, such as in the environment in general, specifically in a room, or at the site of a mosquito biting an individual or mammal, for example, on the skin surface.

In each of the methods according to present invention, the vector control management, preferably mosquito control management, is preferably one or more of a composition, a product and a treated article, at least one of which comprises the compound of the first aspect. Preferred further aspects of the present invention is a product, and a treated article (such as substrates or non-living materials) comprising the compound of the first aspect.

In an embodiment, the development of malaria can be reduced by the mosquito control defined in first aspect.

In an embodiment, the vector control management method is a net incorporated with the compound of the first aspect; in another embodiment, the vector control management product is a composition for coating a net, which composition comprises the compound of the first aspect; in further embodiment, the vector control management product is a composition for spraying surfaces of a dwelling, which composition comprises the compound of the first aspect.

The vector control management method product can comprise a further insecticide and/or synergist.

Another aspect is a polymeric material incorporated with the compound of the first aspect, which material is useful for making substrate or non-living material, such as threads, fibres, yarns, pellets, nets and weaves.

The present invention also makes available

a method of controlling mosquitoes, preferably mosquito vectors of pathogenic disease, with the compound of the first aspect;

a kit for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising: a first sachet comprising a pre-measured amount the compound of the first aspect, and a second sachet comprising a pre-measured amount of at least one polymeric binder;

a method for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising (i) preparing a treatment composition, which comprises the compound of the first aspect, (ii) treating said fibre, yarn, net and weave and (iii) drying the resulting treated a fibre, yarn, net and weave;

a method of preparing a polymeric material impregnated the compound of the first aspect, which material is useful for making substrate or non-living material, such as threads, fibres, yarns, pellets, nets and weaves, which method comprises mixing a polymer with the defined compound at a temperature between 120 to 250 °C;

a method for mosquito vector-control, in particular controlling mosquito vectors carrying pathogenic disease, which method comprises (a) applying an effective amount of a liquid composition comprising the compound of the first aspect, and a polymeric binder, and optionally, one or more other insecticides, and/or synergists, to a surface of a dwelling; and/or (b) placing a substrate or non-living material incorporated with the compound of the first aspect, and optionally an additive, one or more other insecticides, and/or synergists, within a dwelling; and

a net incorporated with the compound of the first aspect having a biological activity in accordance with the WHOPES directive of a knockdown after 60 minutes of between 95 percent and 100 percent and/or a mortality after 24 hours of between 80 percent and 100 percent after 20 washes.

The disclosure in the present application makes available each and every combination of embodiments disclosed herein.

In each aspect and embodiment of the invention, "consisting essentially" and inflections thereof are a preferred embodiment of "comprising" and its inflections, and "consisting of" and inflections thereof are a preferred embodiment of "consisting essentially of and its inflections.

A "fibre" as used in the present invention refers only to a fine, threadlike piece, generally made of natural material, such as cotton, or jute.

In each aspect and embodiment of the invention, "consisting essentially" and inflections thereof are a preferred embodiment of "comprising" and its inflections, and "consisting of and inflections thereof are a preferred embodiment of "consisting essentially of" and its inflections.

The following Examples serve to illustrate the invention. They do not limit the invention.

Temperatures are given in degrees Celsius; mixing ratios of solvents are given in parts by volume.

The Examples which follow serve to illustrate the invention. The compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples below, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of Al per m².

EXAMPLES BIOLOGY EXAMPLES:

Examples B1 and B2: activity against adult mosquitoes

The compounds were applied to the base of wells as solutions in ethanol. After the ethanol had evaporated five adult female mosquitoes, three to five days old and non-blood fed, were placed in a treated well, then a retaining lid was used to prevent escape. Lids of the tissue culture plates were modified to hold small sections of cotton wool over each well in order to allow air exchange. The infested plates were held with the base at an angle of 60 degrees to the horizontal in a controlled environment chamber at 26°C and 60% relative humidity. The mosquitoes were assessed for knockdown one hour after introduction. Then, a small quantity of 10% sucrose solution was pipetted onto the retaining cotton wool to provide a source of food and water. Mortality was assessed 24 and 48 hours after introduction and recorded as LC80's indicating the lowest concentration where at least 80% of the mosquitoes were dead. A mosquito was recorded as "dead" if it was unable to right itself when knocked onto its back or side.

Table 1 provides the 48 hour adulticidal results of certain compounds against insecticide susceptible strain of Aedes aegypti (Yellow fever mosquito), and Table 2 provides the adult knock- down activity and 24 hour adult mortality against the same Aedes aegypti tested in Table 1 , but also the adult knock-down and 24 & 48 hour mortality against Anopheles stephensi.

Tables 1 & 2 show that the compounds thiocyclam hydrogen oxalate, diflumetorim and fluazinam provide unexpected unexpected activity compared to compounds from their respective class.

Table 1 : 48 hour Adulticidal activity of compounds against Aedes aegypti

a⁾ LCso: Lowest applied dosage in mg Al litre^"1 which provides 80% or more mortality after 48 hours.

Concentrations tested: 200, 20, 2 and 0.2 mg Al litre^"1.

Tab!e 2: Activity of agrochemicais against Aedes aegypti and Anopheles stephensi

Compound Aedes aegypti ^d> Anopheles stephensi

KDeo LCeo LCeo

LCeo LCeo

Aduit knockdown Aduit mortality, 24 h Adult mortality, 48 a) b) Adult knockdown ^a) Adult mortality, 24 h ^b) c)

Thiocyclam hydrogen oxalate 200 20 20 20 20

Cartap 200 200 > 200 200 200

Indoxacarb (racemic) > 200 > 200 > 200 > 200 > 200 diflumetorim 20 200 20 20 20

Kresoxim-methyl 200 200 > 200 200 200

Flufenoxystrobin > 200 > 200 > 200 > 200 > 200

Orysastrobin > 200 20 > 200 > 200 > 200

Fluazinam > 200 > 200 200 20 20 ^a) KDeo: Lowest applied dosage in mg Al litre ¹ which provides at least 80% knock-down effects after 1 hour. Concentrations tested : 200, 20, 2 and 0.2 mg Al litre . ) LCeo: Lowest applied dosage in mg Al litre ¹ which provides at least 80% mortality after 24 hours. Concentrations tested: 200, 20, 2 and 0.2 mg Al litre ¹.

c⁾ LCao: Lowest applied dosage in mg Al litre ¹ which provides at least 80% mortality after 48 hours. Concentrations tested: 200, 20, 2 and 0.2 mg A I litre .

d⁾ Adult mortality against Aedes aegypti after 48 h is shown in Table 1

Claims

I . Use of one or more compounds selected from thiocyclam, thiocyclam hydrogen oxalate, diflumetorim and fluazinam in mosquito control.

2. The use according to claim 1 wherein the compound is selected from diflumetorim and

fluazinam.

3. The use according to either claim 1 or claim 2 wherein the development of vector-borne diseases are reduced by the mosquito control defined in claim 1.

4. An vector control management product comprising one or more compounds defined in either claim 1 or 2.

5. The product according to claim 4 wherein the product is a net incorporated with the one or more compounds as defined in either claim 1 or 2.

6. The product according to claim 4 wherein the product is a composition for coating a net, which composition comprises one or more compounds defined in either claim 1 or 2.

7. The product according to claim 4, wherein the product is a composition for spraying surfaces of a dwelling, which composition comprises one or more compounds as defined in either claim 1 or 2.

8. The vector control management product according to any one of claims 4 to 7, wherein a further insecticide and/or synergist is present.

9. A polymeric material incorporated with a compound defined in either claim 1 or claim 2, which material is useful for making substrate or non-living material, such as threads, fibres, yarns, pellets, nets and weaves.

10. A method of controlling mosquitoes, preferably mosquito vectors of pathogenic disease, with one or more compounds defined in either claim 1 or claim 2.

I I . A kit for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising: a first sachet comprising a pre-measured amount of at least one compound defined in either claim 1 or claim 2, and a second sachet comprising a pre- measured amount of at least one polymeric binder.

12. A method for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising (i) preparing a treatment composition, which comprises at least one compound defined in either claim 1 or claim 2, (ii) treating said fibre, yarn, net and weave and (iii) drying the resulting treated a fibre, yarn, net and weave.

13. A method of preparing a polymeric material impregnated with a compound defined in either claim 1 or claim 2, which material is useful for making substrate or non-living material, such as threads, fibres, yarns, pellets, nets and weaves, which method comprises mixing a polymer with a compound defined in claim 1 at a temperature between 120 to 250 °C.

14. A method for mosquito vector-control, in particular controlling mosquito vectors carrying

pathogenic disease, which method comprises (a) applying an effective amount of a liquid composition comprising a compound defined in either claim 1 or claim 2, and a polymeric binder, and optionally, one or more other insecticides, and/or synergists, to a surface of a dwelling; and/or (b) placing a substrate or non-living material incorporated with a compound defined in either claim 1 or claim 2, and optionally an additive, one or more other insecticides, and/or synergists, within a dwelling.

15. A net incorporated with a compound defined in either claim 1 or claim 2 having a biological activity in accordance with the WHOPES directive of a knockdown after 60 minutes of between 95 percent and 100 percent and/or a mortality after 24 hours of between 80 percent and 100 percent after 20 washes.