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Background While Iran is on the path to eliminating malaria, the disease with 4.9 million estimated cases and 9300 estimated deaths in 2018 remains a serious health problem in the World Health Organization (WHO) Eastern Mediterranean Region. Anopheles stephensi is the main malaria vector in Iran and its range extends from Iraq to western China. Recently, the vector invaded new territories in Sri Lanka and countries in the Horn of Africa. Insecticide resistance in An. stephensi is a potential issue in controlling the spread of this vector. Methods Data were collated from national and international databases, including PubMed, Google Scholar, Scopus, ScienceDirect, SID, and IranMedex using appropriate search terms. Results Indoor residual spaying (IRS) with DDT was piloted in Iran in 1945 and subsequently used in the malaria eradication programme. Resistance to DDT in An. stephensi was detected in Iran, Iraq, Pakistan, and Saudi Arabia in the late 1960s. Malathion was used for malaria control in Iran in 1967, then propoxur in 1978, followed by pirimiphos-methyl from 1992 to 1994. The pyrethroid insecticide lambda-cyhalothrin was used from 1994 to 2003 followed by deltamethrin IRS and long-lasting insecticidal nets (LLINs). Some of these insecticides with the same sequence were used in other malaria-endemic countries of the region. Pyrethroid resistance was detected in An. stephensi in Afghanistan in 2010, in 2011 in India and in 2012 in Iran. The newly invaded population of An. stephensi in Ethiopia was resistant to insecticides of all four major insecticide classes. Different mechanisms of insecticide resistance, including metabolic and insecticide target site insensitivity, have been developed in An. stephensi. Resistance to DDT was initially glutathione S-transferase based. Target site knockdown resistance was later selected by pyrethroids. Esterases and altered acetylcholinesterase are the underlying cause of organophosphate resistance and cytochrome p450s were involved in pyrethroid metabolic resistance. Conclusions Anopheles stephensi is a major malaria vector in Iran and many countries in the region and beyond. The species is leading in terms of development of insecticide resistance as well as developing a variety of resistance mechanisms. Knowledge of the evolution of insecticide resistance and their underlying mechanisms, in particular, are important to Iran, considering the final steps the country is taking towards malaria elimination, but also to other countries in the region for their battle against malaria. This systematic review may also be of value to countries and territories newly invaded by this species, especially in the Horn of Africa, where the malaria situation is already dire.

In Iran, there are four pest domestic species of cockroaches: Periplaneta americana (Linnaeus, Blattodea: Blattidae), Blatta orientalis (Linnaeus, Blattodea: Blattidae), Blattella germanica (Linnaeus, Blattodea: Blattidae), and Supella longipalpa (Fabricius, Blattodea: Blattellidae). The aim of this study was to compile and review studies conducted on insecticide resistance of domestic cockroaches in Iran to assess the current knowledge and gaps. Twenty insecticides were used in susceptibility testing of cockroaches. The bioassay methods varied, and included surface contact (exposure tests), topical applications and feeding studies on baits. Resistance ratio (RR) stated in the reviewed studies showed that B. germanica was resistant (RR > 10) to DDT, permethrin, and cypermethrin, while P. americana and S. longipalpa were categorized as low levels of resistance (RR = 1-2). S. longipalpa is newly reported from houses in some areas of Iran, including Tehran, and there are very few studies on its' biology, ecology and insecticidal resistance. Most studies used adult cockroaches, while the susceptibility status of nymphs was evaluated only in few studies. Use of different test methods and lack of a World Health Organization (WHO) updated procedure, including revised/updated insecticide diagnostic dosages and test kits. The lack of susceptible strains of cockroaches was a major challenge in the assessment of data. A comprehensive national program for monitoring susceptibility of household pests to insecticides in Iran is of great concern and is highly recommended.

Background: Data on insecticide use for vector control are essential for guiding pesticide management systems on judicious and appropriate use, resistance management, and reduction of risks to human health and the environment. Objective: We studied the global use and trends of insecticide use for control of vector-borne diseases for the period 2000 through 2009. Methods: A survey was distributed to countries with vector control programs to request national data on vector control insecticide use, excluding the use of long-lasting insecticidal nets (LNs). Data were received from 125 countries, representing 97% of the human populations of 143 targeted countries. Results: The main disease targeted with insecticides was malaria, followed by dengue, leishmaniasis, and Chagas disease. The use of vector control insecticides was dominated by organochlorines [i.e., DDT (dichlorodiphenyltrichloroethane)] in terms of quantity applied (71% of total) and by pyrethroids in terms of the surface or area covered (81% of total). Global use of DDT for vector control, most of which was in India alone, was fairly constant during 2000 through 2009. In Africa, pyrethroid use increased in countries that also achieved high coverage for LNs, and DDT increased sharply until 2008 but dropped in 2009. Conclusions: The global use of DDT has not changed substantially since the Stockholm Convention went into effect. The dominance of pyrethroid use has major implications because of the spread of insecticide resistance with the potential to reduce the efficacy of LNs. Managing insecticide resistance should be coordinated between disease-specific programs and sectors of public health and agriculture within the context of an integrated vector management approach.

In this study, the activity of cyromazine was evaluated following WHO standard procedures against susceptible and resistant mosquito strains of Anopheles gambiae, Culex quinquefasciatus, and Aedes aegypti. The dose for 50% and 90% inhibition of adult emergence (IE50 and IE90) ranged from 0.028 mg/liter to 0.17 mg/liter and from 0.075 mg/liter to 0.42 mg/liter, respectively. The effects of cyromazine were closer to that of chitin synthesis inhibitors rather than that of juvenile hormone analogues, with only 10-20% pupal mortality. The toxicity of cyromazine was not strongly affected by the presence of common resistance mechanism, i.e., Kdr mutation and Ace.1(R) (resistance ratio from 0.5 to 2.3). The absence of cross resistance with common insecticides (pyrethroids, carbamates, organophosphates) makes cyromazine a potential candidate for disease vector control, especially for the management of insecticide resistance.

Most insecticides used against pests and vectors of human disease (e.g. fleas, flies and mosquitoes) are spin-offs from agrochemical research and development. The arsenal of safe and cost-effective public health insecticides is being depleted by restrictions for various reasons (e.g. insecticide resistance, unacceptable side effects and non re-registration) and the number of new products launched is dwindling. Mobilizing public resources and establishment of partnerships to support research and development of public health insecticides is crucial in the post-DDT and post-pyrethroid era.

Tablet (40 mg a.i./tablet) and granular (2% a.i.) formulations of diflubenzuron, a chitin synthesis inhibitor, insect growth regulator, were evaluated for larvicidal efficacy against the larvae of Aedes aegypti (L.) in water-storage containers under field conditions in Thailand. Each formulation was applied to 200-1 clay jars at 5 different dosages (0.02, 0.05, 0.1, 0.5 and 1 mg/l a.i.). The jars were covered with solid celocrete sheets and placed in the shade under a roof. Another experiment was also carried out using 3 different dosages (0.1, 0.5 and 1 mg/l) where half the water in each treated jar and the control was removed and refilled weekly. Each treatment was replicated four times. The treatments were challenged by adding 25 3rd instar larvae/jar weekly. Assessments were made of each treatment through emergence inhibition (%EI) by removing and counting pupal skins one week after larval addition. Using these assessment techniques, a high degree of larvicidal efficacy (96-100%EI) was achieved with 4 dosages (0.05, 0.1, 0.5 and 1 mg/l) of both (tablet and granular) formulations for a period of 23 weeks post-treatment. The efficacy of the lowest dosage (0.02 mg/l) of tablet and granular formulations lasted for 21 and 22 weeks post-treatment, respectively. Under the conditions of water removal and weekly refilling, a high degree of larvicidal efficacy (96-100%El) at the 3 dosages was obtained with the tablet formulation 18 to 21 weeks post-treatment, whereas the efficacy of the granular formulation persisted 15 to 23 weeks post-treatment depending on the dosage. This study clearly demonstrates a high level of residual activity with both formulations of diflubenzuron against larvae of Ae. aegypti in water-storage containers. Considering environmental factors and water-use conditions, it is likely that dosages of 0.05 to 0.1 mg a.i./l are effective dosages providing long-lasting control for 3 to 4 months in the field.

Toxic and feeding inhibition effect of cyfluthrin treated nets was assessed and compared with the activity of deltamethrin impregnated nets, before and after 2 and 4 washes against Phlebotomus papatasi. Impregnated cyfluthrin nets (50, 25, 12.5 mg active ingredient (a.i.)/m2) caused knock down and mortality rates higher than 90%, being of 100% at the highest dose, while the nets impregnated with deltamethrin (25, 12.5, 6.25 mg a.i./m2) showed low mortality rates (13.3-43.5%). Also after washing cyfluthrin at the dose of 50 mg a.i./m2 provided higher activity than deltamethrin (25 mg a.i./m2), being mortality rates within 24 hs of 66.7 and 48.9% for cyfluthrin and 38.0 and 2.1% for deltamethrin, respectively after 2 and 4 washes. Before washing, cyfluthrin (50 mg a.i./m2) significantly prevented blood feeding, with respect to both untreated (88.6%) and deltamethrin impregnated nets (56.8%). Deltamethrin (25 mg a.i./m2) showed low feeding inhibition (48.4%), although it was significantly higher than control. The washing of cyfluthrin impregnated nets (50 mg a.i./m2) produced a decrease of the feeding inhibition, being the reduction of 26.6% and 41.3%, respectively after 2 and 4 washes. Two washes of deltamethrin impregnated nets (25 mg a.i./m2) yielded a very high reduction of antifeeding inhibition (68.8%). These laboratory results if confirmed by field evaluation indicate cyfluthrin as good candidate for treatment of mosquito nets to be used against phlebotomine sandflies.

Two long-term experiments were carried out on the release profile and efficacy of temephos 1% GR (sand granules) against Aedes aegypti larvae in water-storage containers. In the first experiment, the efficacy of temephos 1% GR enclosed and tied in a muslin cloth and placed in water at the bottom of 200 L earthen water-storage jars was studied by exposing the packets for four to nine wk in one set ofjars and then transferring them sequentially to new sets ofjars four times successively. Temephos released slowly from the granules, the magnitude of release being adequate in the initial period of two to three wk after treatment. Following this period, the efficacy of the granules increased substantially where 92-100% inhibition of emergence even at the lowest dosage of 1 g/100 L (0.05 mg/L AI) was obtained for about another five mo or longer. On removal of the packets from a given set of jars, the released residues remaining in the jars and water lasted a maximum of one to six wk post-removal depending on the magnitude of prior release into the jars. This experiment provided clear evidence that temephos is released slowly over a long period of time in water-storage jars. In the second experiment, we compared the efficacy of temephos 1% GR at 1 and 10 g (0.05 and 0.5 mg/L AI) per 200-L water in jars painted and unpainted on the inside. The efficacy in the painted jars, although high, was consistently lower than that in the unpainted jars, where 99-100% control of larvae was achieved at both rates for a minimum of five mo after treatment. On the basis of this experimental evidence, it is desirable to study the efficacy of lower dosages of temephos than those currently used in Ae. aegypti control programs. The use of controlled release formulations or sachets that are retrievable during cleaning and washing will be more practical and desirable. Both of these interventions will make the program more cost effective.

Because pyrethroid, organophosphate, and carbamate resistance is more and more developed in mosquitoes of medical importance, there is an urgent need for alternative insecticides for vector control. Dinotefuran, a new neonicotinoid insecticide commercialized by Mitsui Chemicals (Tokyo, Japan), could be a useful candidate in public health because it shows low mammalian toxicity and great insecticidal activity against a broad range of pests. In this study, the intrinsic toxicity of dinotefuran was evaluated by larval bioassay and topical application against different mosquito strains of Anopheles gambiae Giles, Culex quinquefasciatus Say, and Aedes aegypti L. having none, one, or several resistance mechanisms, respectively, to insecticides. The results showed that dinotefuran was less toxic than most of the commonly used insecticides (e.g., deltamethrin, carbosulfan, and temephos) against the susceptible mosquitoes tested (between 6- and 100-fold at the LD50 level). However, the toxicity of dinotefuran was not strongly affected by the presence of common resistance mechanism, i.e., kdr mutation and insensitive acetylcholinesterase (resistance ratio [RR] from 1.3 to 2.3). More interestingly, the carbamate-resistant strain of Cx. quinquefasciatus was significantly more affected by dinotefuran than the susceptible strain (RR = 0.70), probably because the insensitive acetylcholinesterase is less efficient to degrade nicotinic substrates than normal acetylcholinesterase. Despite the relatively low toxicity of dinotefuran against susceptible mosquitoes, the absence of cross-resistance with common insecticides (pyrethroids, carbamates, and organophosphates) makes neonicotinoids potential candidates for disease vector control, especially in area where mosquitoes are resistant to insecticides.

Novaluron, a new chitin synthesis inhibitor type of insect growth regulator, was evaluated in the laboratory and field against larvae of the mosquito Aedes aegypti (L.). In the laboratory, the technical material showed a high level of activity against 2nd and 4th instar larvae. The inhibition of emergence (IE) was 100% at concentrations of 0.25 to 1.0 microg/L. Second instars were slightly more susceptible than fourth instars. At the high concentration (1 ppb), most of the mortality occurred in the larvae, but at sublethal concentrations (for larvae) mortality also occurred in pupae and adults (incomplete eclosion). An EC10 (emulsifiable concentrate containing 10% active ingredient) formulation of novaluron was evaluated against Ae. aegypti in water-storage containers in the field in Thailand. Two tests at high (0.05 to 1 mg/L) and low (1 to 20 microg/L) concentrations were carried out in clay jars (200 L) and plastic pails (75 L). At high concentrations in clayjars, we obtained 86-96% inhibition of emergence (IE) for about 190 d, but the mortality declined at low concentrations after 190 d. At much lower concentrations, in jars and plastic pails in the second experiment, the IE was 80-100% for 2 mo. The highest concentrations of this series (10 microg/L in jars and 20 microg/L in pails) were active for 75 and 68 d respectively, losing efficacy by 82 d post-treatment. In the experiment using low concentrations, all treatments in jars and plastic pails failed to provide adequate control 90 d after treatment. These studies show that novaluron, even as EC10, has exceptional long-term activity against Ae. aegypti in water-storage containers, with higher concentrations yielding greater long-term control than low concentrations.

Limited laboratory and field studies have indicated that the insect growth regulator (IGR) novaluron exhibits good activity against larvae of pest species in the orders Coleoptera, Hemiptera (suborder Heteroptera), and Lepidoptera by both ingestion and contact. We completed laboratory and field studies to evaluate activity and efficacy of novaluron against Culex mosquitoes. In laboratory studies, novaluron was highly active against Cx. quinquefasciatus, as indicated by low levels of inhibition of emergency (IE), at the 50% level, IE50 (0.159 ppb for 2nd-stage larvae and 0.118 ppb for 4th-stage larvae) and IE90, at the 90% level, (0.604 ppb for 2nd-stage larvae and 0.595 ppb for 4th-stage larvae). In outdoor microcosm and mesocosm studies against natural populations, novaluron yielded excellent control of immature Culex mosquitoes for up to 14 days at 1.25, 2.5, and 5 ppb in microcosms, and for up to 7 days at the dosages of 1, 5, and 10 mg/m2 in mesocosms. Based on qualitative observations, novaluron seemed to have a favorable margin of safety for nontarget aquatic invertebrates cohabiting with mosquito larvae. Further large-scale field studies are warranted to evaluate initial efficacy and longevity of novaluron against various mosquito species, as well as its safety for nontarget biota.

OBJECTIVE: To compare the efficacy of seven pyrethroid insecticides for impregnation of mosquito nets, six currently recommended by WHO and one candidate (bifenthrin), under laboratory conditions. METHODS: Tests were conducted using pyrethroid-susceptible and pyrethroid-resistant strains of Anopheles gambiae and Culex quinquefasciatus. Knock-down effect, irritancy and mortality were measured using standard WHO cone tests. Mortality and blood-feeding inhibition were also measured using a baited tunnel device. FINDINGS: For susceptible A. gambiae, alpha-cypermethrin had the fastest knock-down effect. For resistant A. gambiae, the knock- down effect was slightly slower with alpha-cypermethrin and much reduced following exposure to the other insecticides, particularly bifenthrin and permethrin. For susceptible C. quinquefasciatus, the knock-down effect was significantly slower than in A. gambiae, particularly with bifenthrin, and no knock-down effect was observed with any of the pyrethroids against the resistant strain. Bifenthrin was significantly less irritant than the other pyrethroids to susceptible and resistant A. gambiae but there was no clear ranking of pyrethroid irritancy against C. quinquefasciatus. In tunnels, all insecticides were less toxic against C. quinquefasciatus than against A. gambiae for susceptible strains. For resistant strains, mortality was significant with all the pyrethroids with A. gambiae but not with C. quinquefasciatus. Inhibition of blood-feeding was also high for susceptible strains of both species and for resistant A. gambiae but lower for resistant C. quinquefasciatus; bifenthrin had the greatest impact. CONCLUSIONS: Efficacy for impregnation of mosquito nets against A. gambiae was greatest with alpha-cypermethrin. Bifenthrin is likely to have a significant comparative advantage over other pyrethroids in areas with pyrethroid resistance because of its much stronger impact on the nuisance mosquito, C. quinquefasciatus, despite its slower knock-down effect and irritancy. Selection of pyrethroids for mosquito vector control and personal protection should take into account the different effects of these insecticides, the status of pyrethroid resistance in the target area, and the importance of nuisance mosquitoes, such as C. quinquefasciatus.

Effectiveness and residual activity tests of granular formulations of 2 insect growth regulators (IGRs), s-methoprene and pyriproxyfen, against laboratory-reared larvae of 5 colonized mosquitoes, Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles quadrimaculatus, and Culex nigripalpus, were conducted in the laboratory and outdoors in plastic tubs. Culex quinquefasciatus was exposed to these two IGRs in the laboratory only. Each IGR formulation was applied at 0.02 and 0.05 ppm active ingredient (Al) against 5 of the 6 mosquito species both in the laboratory and the outdoor evaluations, whereas Cx. quinquefasciatus was exposed to 0.2 and 0.4 ppm AI of s-methoprene, and 0.1 and 0.2 ppm AI of pyriproxyfen in the laboratory. s-Methoprene at 0.02 and 0.05 ppm AI resulted in variable levels (39-100%) of inhibition of adult emergence in the 5 species monitored for 6 weeks after treatment under both test conditions. Aedes taeniorhynchus was the most susceptible to s-methoprene in terms of initial and residual activity. Culex quinquefasciatus and Ae. albopictus were the most tolerant to s-methopene, with maximum emergence inhibitions amounting to 84% in Cx. quinquefasciatus at 0.4 ppm and 44.3% in Ae. albopictus at 0.05 ppm during the 1st week in the laboratory. Pyriproxyfen at comparable treatment rates to s-methoprene caused very high levels (80-100% in most cases) of initial and residual emergence inhibitions of the tested species in the laboratory as well as outdoors. In several species, pyriproxyfen induced complete inhibition of adult emergence for several weeks after treatment, even at the lower rate of 0.02 ppm. The World Health Organization has recently recommended the use of pyriproxyfen for the control of some mosquito species at specified rates in certain habitats.

Bifenthrin, a pyrethroid insecticide already used in agriculture was evaluated in laboratory conditions against susceptible and pyrethroid resistant mosquitoes, as a potential insecticide for treatment of mosquito nets. Two laboratory strains of Anopheles gambiae s.s. Giles, the major malaria vector in Africa, and two of Culex quinquefasciatus Say, a major pest mosquito in urban areas, were used. Compared with other pyrethroids such as permethrin and deltamethrin, the intrinsic toxicity of bifenthrin, measured by topical application with susceptible strains, was intermediate. By forced tarsal contact on filter papers (cylinder tests) or on netting materials (cone tests), bifenthrin was found slightly more effective against A. gambiae than against C. quinquefasciatus, in terms of mortality and knock-down effect. With free flying mosquitoes (tunnel tests), bifenthrin was very efficient in killing mosquitoes and inhibiting blood feeding. Against the two pyrethroid resistant strains, bifenthrin was relatively efficient against A. gambiae but the impact of resistance was greater with C. quinquefasciatus. In tunnel tests, blood feeding remained almost entirely inhibited with the two species despite resistance. The high mortality of susceptible mosquitoes and excellent blood feeding inhibition of susceptible and resistant strains makes bifenthrin a good candidate for treatment of netting materials, particularly in areas where C. quinquefasciatus, the main nuisance in urban areas, is resistant to pyrethroids. The slower knock-down and lower irritant effect also makes this insecticide especially attractive when a mass killing effect on mosquito populations is expected.

The use of insecticide treated nets (ITNs) for personal protection against malaria vector Anopheles mosquitoes (Diptera: Culicidae) has become popular during the past decade. With the precautions outlined in this paper, field use of pyrethroids--at concentrations recommended for treatment of mosquito nets--poses little or no hazard to people treating the nets or to users of the treated nets. With frequent exposure to low concentrations of pyrethroids, the risk of toxicity of any kind is remote. Pyrethroids entering the systemic circulation are rapidly metabolized to much less toxic metabolites. Toxicologically, pyrethroids have a useful characteristic--the production of skin paraesthesia--which gives an early indication of exposure. This reversible symptom of exposure is due to transient stimulation of peripheral sensory nerves and not a toxic effect. In the retail market, for home use, the provision of proper packaging and labelling, with clear instructions on safe and effective use of the product are most important. Because many domestic users of pyrethroid 'home treatment kits' for ITNs may not be fully literate, it is essential that 'instructions for use' should be portrayed via pictograms with supporting text in appropriate local language(s).