Morteza Zaim

Safety of pyrethroid-treated mosquito nets

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).

Alternative insecticides: an urgent need

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.

Exploiting the potential of vector control for disease prevention

Although vector control has proven highly effective in preventing disease transmission, it is not being used to its full potential, thereby depriving disadvantaged populations of the benefits of well tried and tested methods. Following the discovery of synthetic residual insecticides in the 1940s, large-scale programmes succeeded in bringing many of the important vector-borne diseases under control. By the late 1960s, most vector-borne diseases--with the exception of malaria in Africa--were no longer considered to be of primary public health importance. The result was that control programmes lapsed, resources dwindled, and specialists in vector control disappeared from public health units. Within two decades, many important vector-borne diseases had re-emerged or spread to new areas. The time has come to restore vector control to its key role in the prevention of disease transmission, albeit with an increased emphasis on multiple measures, whether pesticide-based or involving environmental modification, and with a strengthened managerial and operational capacity. Integrated vector management provides a sound conceptual framework for deployment of cost-effective and sustainable methods of vector control. This approach allows for full consideration of the complex determinants of disease transmission, including local disease ecology, the role of human activity in increasing risks of disease transmission, and the socioeconomic conditions of affected communities.

Global Trends in the Use of Insecticides to Control Vector-Borne Diseases

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.

Long-lasting treated mosquito nets: a breakthrough in malaria prevention

Editor – Regardless of views expressed recently in the Bulletin (1–2), insecticide-treated mosquito nets are currently the only viable option to prevent malaria transmission in large parts of Africa. To be effective, mosquito nets have to be treated by dipping them in suitable insecticides at least once a year. Less than 5% of the nets currently used in Africa are properly treated or retreated. Looking for practical solutions, WHO stimulated industry to produce long-lasting insecticide-treated mosquito nets (LLNs), using new bioactive fabric technologies. Long-lasting nets are treated only once, at factory level. The insecticide can resist multiple washes and is released over time to the surface of the netting fibres. The major criteria for LLNs is that efficacy should last as long as the average lifespan of the net, i.e. 4–5 years. Compared with nets treated by conventional dipping, LLNs have several important advantages: no need for re-treatment; reduced insecticide consumption; and minimum potential environmental impact: release of insecticide in natural water bodies during washing is greatly reduced. There are two LLNs commercially available, currently being evaluated through the WHO Pesticide Evaluation Scheme (WHOPES). R&D is crucial in further improving the technology. Second-generation LLNs are now emerging with even better performance. They are major technical breakthroughs, significantly changing prospects for successful implementation of ITN programmes, especially in Africa. To protect the most vulnerable groups in Africa (children under five, pregnant women and people living below the poverty line) and to meet the objective set by the Heads of State of African countries in Abuja (60% of net coverage by 2005), it is estimated that a total of 115 million nets will be needed. To reach full coverage, ideally by the year 2007, an additional 97 million nets will be needed and maintenance of this coverage after 2007 will require 28 to 30 million nets per year. Protection of the whole population at risk of malaria in Africa would require about twice these numbers. When envisaging further development of LLNs, it is important to involve the net industry in Africa and to facilitate technology transfer. Strengthening production capacity of LLNs in Africa and further reducing the price through well-targeted public– private partnerships will be an effective way to go to scale, reduce the malaria burden, and contribute to poverty alleviation. It also offers an opportunity to African countries to develop a profitable ITN economy and to play an increasing role in …

Dinotefuran: A Potential Neonicotinoid Insecticide Against Resistant Mosquitoes

Abstract 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.

Bifenthrin: A Useful Pyrethroid Insecticide for Treatment of Mosquito Nets

Abstract 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.

Comparative performances, under laboratory conditions, of seven pyrethroid insecticides used for impregnation of mosquito nets

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.

Insecticide‐treated plastic tarpaulins for control of malaria vectors in refugee camps

Abstract Spraying of canvas tents with residual pyrethroid insecticide is an established method of malaria vector control in tented refugee camps. In recent years, plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian shelter material for displaced populations in complex emergencies. Advances in technology enable polythene sheeting to be impregnated with pyrethroid during manufacture. The efficacy of such material against mosquitoes when erected as shelters under typical refugee camp conditions is unknown. Tests were undertaken with free‐flying mosquitoes on entomological study platforms in an Afghan refugee camp to compare the insecticidal efficacy of plastic tarpaulin sprayed with deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin impregnated with deltamethrin (initially ≥ 30 mg/m2) during manufacture, and a tent made from the factory impregnated tarpaulin material. Preliminary tests done in the laboratory with Anopheles stephensi Liston (Diptera: Culicidae) showed that 1‐min exposure to factory‐impregnated tarpaulins would give 100% mortality even after outdoor weathering in a temperate climate for 12 weeks. Outdoor platform tests with the erected materials (baited with human subjects) produced mosquito mortality rates between 86–100% for sprayed or factory‐impregnated tarpaulins and tents (average ˜40 anophelines and ˜200 culicines/per platform/night), whereas control mortality (with untreated tarpaulin) was no more than 5%. Fewer than 20% of mosquitoes blood‐fed on human subjects under either insecticide‐treated or non‐treated shelters. The tarpaulin shelter was a poor barrier to host‐seeking mosquitoes and treatment with insecticide did not reduce the proportion blood‐feeding. Even so, the deployment of insecticide‐impregnated tarpaulins in refugee camps, if used by the majority of refugees, has the potential to control malaria by killing high proportions of mosquitoes and so reducing the average life expectancy of vectors (greatly reducing vectorial capacity), rather than by directly protecting refugees from mosquito bites. Mass coverage with deltamethrin‐sprayed or impregnated tarpaulins or tents has strong potential for preventing malaria in displaced populations affected by conflict.

Status of Legislation and Regulatory Control of Public Health Pesticides in Countries Endemic with or at Risk of Major Vector-Borne Diseases

Background: Legislation and regulation of pesticides used in public health are essential for reducing risks to human health and the environment. Objective: We assessed the global situation on legislation and regulatory control of public health pesticides. Methods: A peer-reviewed and field-tested questionnaire was distributed to 142 member states of the World Health Organization (WHO); 113 states completed the questionnaire. Results: Legislation on public health pesticides was absent in 25% of the countries. Where present, legislation often lacked comprehensiveness, for example, on basic aspects such as labeling, storage, transport, and disposal of public health pesticides. Guidelines or essential requirements for the process of pesticide registration were lacking in many countries. The capacity to enforce regulations was considered to be weak across WHO regions. Half of all countries lacked pesticide quality control laboratories, and two-thirds reported high concern over quality of products on the market. National statistics on production and trade of pesticides and poisoning incidents were lacking in many countries. Despite the shortcomings, WHO recommendations were considered to constitute a supportive or sole basis in national registration. Also, some regions showed high participation of countries in regional schemes to harmonize pesticide registration requirements. Conclusions: Critical deficiencies are evident in the legislative and regulatory framework for public health pesticides across regions, posing risks to human health and the environment. Recent experience in some countries with situational analysis, needs assessment, action planning, and regional collaboration has signaled a promising way forward.