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).     

Efficacy of mosquito nets treated with permethrin in Suriname

In the rain-forest of Suriname, where malaria is endemic, 95% of the Maroons (who call themselves bush-negroes) and all Amerindians use mosquito nets made of cotton cloth or, less frequently, nylon or cotton gauze over their hammocks or beds. Bush-negroes usually wash their nets weekly; Amerindians wash nets at 1-4 month intervals. Females of the principal local malaria vector, Anopheles darlingi Root, were seen blood-feeding through cotton cloth netting (at 22.30-23.30 hours) on a person sleeping in a hammock; others fed successfully after the net was opened in the morning. Cotton cloth impregnated with permethrin at a rate of 0.5 g/m2 killed all An. darlingi females exposed for 2 min, but after the material had been washed twice in soapy water the bioassay mortality fell to only 21.4%. Exit traps on a hut with a single sleeper protected by a permethrin-impregnated net yielded 185 An. darlingi females (12% blood-fed) in 74 nights, compared with 276 females (19% blood-fed) from another hut with a sleeper using an untreated net on the same nights (P less than 0.001). No An. darlingi females remained resting alive indoors in these huts during the daytime, and very few were found dead on the floor in the mornings (one treated, seven untreated). The 24 h mortality rate for those collected in exit traps was 58.4% for the test hut and 27.1% for the control hut (P less than 0.001). Bioassays of permethrin-treated cotton cloth using laboratory-reared sugar-fed Culex quinquefasciatus Say females showed that sprayed nets were less effective than nets impregnated by soaking (at equivalent dosages of 0.16-1.34 g/m2 measured by chemical assay) and confirmed that washing causes severe decline in insecticidal activity. The feasibility of local mass treatment of mosquito nets is discussed.     

Combined pyrethroid and carbamate 'two-in-one' treated mosquito nets: field efficacy against pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus

A new approach is proposed in the treatment of mosquito nets, using a 'two-in-one' combination of pyrethroid and non-pyrethroid insecticides applied to different parts of bednets. The objectives are mainly to overcome certain limitations of pyrethroid-impregnated bednets currently recommended for malaria control purposes. Apart from developing alternatives to pyrethroid dependency, we sought to counteract pyrethroid irritant effects on mosquitoes (excito-repellency) and resistance to pyrethroids. The idea takes advantage of the presumed host-seeking behaviour of mosquitoes confronted by a net draped over a bed, whereby the mosquito may explore the net from the top downwards. Thus, nets could be more effective if treated on the upper part with residual non-irritant insecticide (carbamate or organophosphate) and with a pyrethroid on the lower part. Sequential exposure to different insecticides with distinct modes of action is equivalent to the use of a mixture as a potential method of managing insecticide resistance. We also intended to improve the control of nuisance mosquitoes, especially Culex quinquefasciatus Say (Diptera: Culicidae) that often survive pyrethroids, in order to encourage public compliance with use of insecticide-treated nets (ITNs). Polyester bednets were pretreated with residual pyrethroid (bifenthrin 50 mg/m2 or deltamethrin 25 mg/m2) on the lower half and with carbamate (carbosulfan 300 mg/m2) on the upper half to minimize contact with net users. Unreplicated examples of these 'two-in-one' treated nets were field-tested against wild mosquitoes, in comparison with an untreated net and bednets treated with each insecticide alone, including PermaNet wash-resistant formulation of deltamethrin 50 mg/m2. Overnight tests involved volunteers sleeping under the experimental bednets in verandah-trap huts at Yaokofikro, near Bouaké in C te d'Ivoire, where the main malaria vector Anopheles gambiae Giles, as well as Culex quinquefasciatus Say, are highly resistant to pyrethroids. Efficacy of these ITNs was assessed in the huts by four entomological criteria: deterrency and induced exophily (effects on hut entry and exit), blood-feeding and mortality rates (immediate and delayed). Overall, the best impact was achieved by the bednet treated with carbosulfan alone, followed by 'two-in-one' treatments with carbosulfan plus pyrethroid. Blood-feeding rates were 13% An. gambiae and 17% Cx. quinquefasciatus in huts with untreated nets, but only 3% with carbosulfan ITNs, 7-11% with combined ITN treatment, 6-8% An. gambiae and 12-14% Cx. quinquefasciatus with pyrethroid alone. Mosquitoes that entered the huts were killed sooner by nets with combined treatment than by pyrethroid alone. Mortality-rates in response to ITNs with carbosulfan (alone or combined with pyrethroid) were significantly greater for Cx. quinquefasciatus, but not for An. gambiae, compared to ITNs with only pyrethroid. About 20% of sleepers reported potential side-effects (headache and/or sneezing) from use of ITN treated with carbosulfan alone. Further development of this new 'two-in-one' ITN concept requires a range of investigations (choice of effective products, cost-benefit analysis, safety, etc.) leading to factory production of wash-resistant insecticidal nets treated with complementary insecticides.     

Field trial of the effectiveness of indoor-spraying with pirimiphos-methyl emulsion for malaria control in a tribal area of Phulbani district, Orissa State, India

A field trial of malaria vector control was conducted in Phulbani district, Orissa, during 1984 and 1985. Indoor-spraying of pirimiphos-methyl emulsion formulation was undertaken at an application rate of 2 g/m2 in two sections (population 14,692) of Nuagaon Primary Health Centre. Houses in two adjacent sections (population 21,450) were sprayed with DDT a water dispersible powder (wdp) formulation at 1 g/m2 for comparison purposes. Operational problems in this area come from the tendency of tribal people to re-plaster over wdp applications. Pre-spray malariological indices in the trial area were 38% slide positivity rate, 37% slide falciparum rate and 12.1% annual parasite incidence. Densities of Anopheles annularis Van der Wulp, An. culicifacies Giles, An. fluviatilis Theobald and other potential malaria vectors were reduced in the pirimiphos-methyl trial area 2-35-fold more than in the area sprayed with DDT. Malariological indices were reduced by 65-68% in the pirimiphos-methyl sprayed area compared with only 26-35% reduction in the DDT sprayed area. Spraymen and villagers experienced no adverse side-effects from residual house-spraying with pirimiphos-methyl emulsion and it is concluded that this organophosphate product has advantages for malaria vector control, especially in operationally difficult situations.     

Behavioural and insecticidal effects of organophosphate‐, carbamate‐ and pyrethroid‐treated mosquito nets against African malaria vectors

Three insecticides – the pyrethroid deltamethrin, the carbamate carbosulfan and the organophosphate chlorpyrifos‐methyl – were tested on mosquito nets in experimental huts to determine their potential for introduction as malaria control measures. Their behavioural effects and efficacy were examined in Anopheles gambiae Giles s.s. (Diptera: Culicidae) and Anopheles funestus Giles s.s. in Muheza, Tanzania, and in Anopheles arabiensis Patton and Culex quinquefasciatus Say in Moshi, Tanzania. A standardized dosage of 25 mg/m² plus high dosages of carbosulfan (50 mg/m², 100 mg/m² and 200 mg/m²) and chlorpyrifos‐methyl (100 mg/m²) were used to compare the three types of insecticide. At 25 mg/m², the rank order of the insecticides for insecticide‐induced mortality in wild An. gambiae and An. funestus was, respectively, carbosulfan (88%, 86%) > deltamethrin (79%, 78%) > chlorpyrifos‐methyl (35%, 53%). The rank order of the insecticides for blood‐feeding inhibition (reduction in the number of blood‐fed mosquitoes compared with control) in wild An. gambiae and An. funestus was deltamethrin > chlorpyrifos‐methyl > carbosulfan. Carbosulfan was particularly toxic to endophilic anophelines at 200 mg/m², killing 100% of An. gambiae and 98% of An. funestus that entered the huts. It was less effective against the more exophilic An. arabiensis (67% mortality) and carbamate‐resistant Cx quinquefasciatus (36% mortality). Carbosulfan deterred anophelines from entering huts, but did not deter carbamate‐resistant Cx quinquefasciatus. Deltamethrin reduced the proportion of insects engaged in blood‐feeding, probably as a consequence of contact irritancy, whereas carbosulfan seemed to provide personal protection through deterred entry or perhaps a spatial repellent action. Any deployment of carbosulfan as an individual treatment on nets should be carried out on a large scale to reduce the risk of diverting mosquitoes to unprotected individuals. Chlorpyrifos‐methyl was inferior to deltamethrin in terms of mortality and blood‐feeding inhibition and would be better deployed on a net in combination with a pyrethroid to control insecticide‐resistant mosquitoes.     

Multi-country field trials comparing wash-resistance of PermaNet and conventional insecticide-treated nets against anopheline and culicine mosquitoes

Insecticide-treated bednets (ITNs) are commonly used as a means of personal protection from malaria transmission by anopheline mosquitoes (Diptera: Culicidae). Long-lasting insecticidal nets (LLINs) have special treatments intended to remain effective after many washes. The present trials assessed the efficacy and wash-resistance of several production batches of PermaNet (polyester net coated with polymer resin containing pyrethroid insecticide deltamethrin 55 mg ai/m2) against malaria vectors in Pakistan, Iran and Tanzania compared to ITNs conventionally treated with alphacypermethrin 15 or 20 mg ai/m2, or deltamethrin 25 or 50 mg ai/m2. Insecticidal efficacy of the nets before and after repeated washing (using W.H.O. recommended and traditional local washing procedures) was monitored through contact bioassays with Anopheles and by experimental hut and outdoor platform tests. Local washing regimes gradually reduced the insecticidal efficacy of conventionally treated nets, but they were not exhausted, even after 21 washes. Using a more rigorous laboratory washing method, insecticide was more readily stripped from conventionally treated nets. PermaNet retained high efficacy after 21 washes, giving more than 97% mortality of Anopheles in contact bioassays with 3-min exposure. Using the more sensitive bioassay criterion of 'median time to knockdown', PermaNet showed no loss of insecticidal activity against Anopheles after washing repeatedly in 2 out of 6 trials; whereas in a further three trials knockdown activity of PermaNet and conventional ITNs declined at comparable rates. Higher mortality levels of Anopheles in contact bioassays did not always translate to superiority in experimental hut or enclosed platform trials. In only one of four comparative field trials did PermaNet out-perform conventional ITNs after washing: this was in the trial of PermaNet 2.0--the product with improved quality assurance. Because PermaNet and conventionally treated nets were both quite tolerant of local washing procedures, it is important in field trials to compare LLINs with conventional ITNs washed an equivalent number of times. Our comparison of PermaNet 2.0 against conventionally treated deltamethrin nets (CTDN) in Pakistan demonstrated superior performance of the LLIN after 20 washes in phase I and phase II bioassays, and this was corroborated by chemical assays of residual deltamethrin. Although PermaNet 2.0 has received WHOPES interim recommendation for malaria control purposes, its performance should be monitored in everyday use throughout its lifespan in various cultural settings to assess its durability and long-term effectiveness for malaria prevention and control. As many millions of conventionally treated nets are already in routine use, and these will require regular re-treatment, programme strategies should be careful to preserve the effectiveness of ITNS before and after establishing the reliability of LLINs in long-term use.     

Experimental hut comparisons of nets treated with carbamate or pyrethroid insecticides, washed or unwashed, against pyrethroid-resistant mosquitoes

Abstract. The efficacy against mosquitoes (Diptera: Culicidae) of a bednet treated with carbamate insecticide [carbosulfan capsule suspension (CS) 200 mg/m²] was compared with four types of pyrethroid‐treated nets in veranda‐trap huts at Yaokoffikro near Bouaké, Côte d'Ivoire, where the malaria vector Anopheles gambiae Giles carries the kdr gene (conferring pyrethroid resistance) at high frequency and Culex quinquefasciatus Say is also pyrethroid resistant. Pyrethroids compared were lambdacyhalothrin CS 18 mg/m², alphacypermethrin water dispersible granules (WG) 20 mg/m², deltamethrin 50 mg/m² (Permanet?) and permethrin emulsifiable concentrate (EC) 500 mg/m². Insecticidal power and personal protection from mosquito bites were assessed before and after the nets were used for 8 months and hand washed five times in cold soapy water. Before washing, all treatments except permethrin significantly reduced blood‐feeding and all had significant insecticidal activity against An. gambiae. The carbosulfan net gave significantly higher killing of An. gambiae than all pyrethroid treatments except the Permanet. Against Culex spp., carbosulfan was more insecticidal and gave a significantly better protective effect than any of the pyrethroid treatments. After washing, treated nets retained various degrees of efficacy against both mosquito genera – but least for the carbosulfan net. Washed nets with three types of pyrethroid treatment (alphacypermethrin, lambdacyhalothrin, permethrin) gave significantly higher mortality rates of Culex than in huts with the same pyrethroid‐treated nets before washing. After five washes, the Permanet?, which is sold as a long‐lasting insecticidal product, performed no better than the other nets in our experimental conditions.     

Impact of permethrin-impregnated mosquito nets compared with DDT house-spraying against malaria transmission by Anopheles farauti and An.punctulatus in the Solomon Islands

Abstract. In villages of northern Guadalcanal in the Solomon Islands, where the predominant malaria vector is An.farauti No. 1 and An. puctulatus is also involved, malaria transmission rates were compared for three zones: (1) non-intervention: 438 people in seventeen villages; (2) residual DDT house-spraying two cycles per year: 644 people in thirty villages; (3) bednets impregnated with permethrin 0.5 g/m² twice per year, used by 580 people in sixteen villages. Regular DDT spraying in zones 1 and 3 had been withdrawn 18 months previously. Malariological blood smear surveys of children aged 1-9 years in August 1986 to January 1987 showed a mean-baseline malaria parasite rate of 38% (32/84). By February 19 88 , 18 months after introduction of impregnated bednets, the Plasmodium falciparum infection rate in children was lowest in the zone using impregnated bednets (21% of 29), intermediate in the untreated zone (29% of 34) and highest in the DDT zone (46% of 53), but these differences were not statistically significant. P.vivax infection rates were 9–14%. Using ELISA tests for malaria circumsporozoite antigen in the vectors, overall positivity rates were 0.7% of 49 ,902 An.farauti and 2.54% of 118 An.punctulatus, comprising 228 P.falciparum and 124 P. vivax infections. In the study zones, vector positivity rates were 0.93% of 31 ,615 An.farauti in the untreated zone; 0.32% of 16, 883 An.farauti in the DDT zone; 0.07% of 1404 An.farauti and 2.54% of 118 An.puctulatus in the impregnated bednet zone. There was no significant correlation between malaria parasite rates in the vectors and the children. Entomological inoculation rates were consistently highest in the untreated zone (1.6–2.8 infective bites/night), intermediate in the DDT zone (0.8– 1.1/night) and significantly lowest in the bednet zone (0.03-0.23/night). Geometric mean densities of P.falciparum sporozoites were also significantly higher in the DDT zone (50% > 10,000 sporozoites/mosquito compared with 20% in untreated zone). The highest individual infection density was an estimated 52,080 sporozoites of P.falciparum in a specimen of An.punctulatus from the bednet zone. P.vivax sporozoite densities were not significantly different between zones, and both species of vector had similar mean sporozoite loads for both species of malaria. It is concluded that permethrin-impregnated mosquito nets exerted significantly more impact on vector infectivity and the inoculation rate than resulted from DDT spraying. Even so, the inoculation rate for people in the bednet zone remained at one infective bite every 4–32 days, an insufficient reduction to control malaria without additional countermeasures. Ineffectiveness of house-spraying and the limited impact of impregnated bednets are attributed to exophily and other behavioural aspects of An. farauti.     

Comparison of three pyrethroid treatments of top-sheets for malaria control in emergencies: entomological and user acceptance studies in an Afghan refugee camp in Pakistan

Insecticide-treated bedding materials (sheets and blankets) could be protective against vectors of malaria and leishmaniasis--especially in complex emergencies, epidemics and natural disasters where people are more likely to sleep in exposed situations. Comparison of cotton top-sheets impregnated with different pyrethroids (permethrin 500 mg/m2, deltamethrin 25 mg/m2 or alphacypermethrin 25 mg/m2) for effectiveness against mosquitoes (Diptera: Culicidae) was undertaken in a refugee camp in Pakistan. Predominant species encountered were Anopheles stephensi Liston, An. pulcherrimus Theobald, An. nigerrimus Giles, Culex quinquefasciatus Say, Cx. tritaeniorhynchus Giles and other culicine mosquitoes. All three pyrethroid treatments performed significantly better than the untreated sheets in deterrence and killing of mosquitoes. No significant differences were found between the three insecticides tested in terms of entomological effect. Washing of the treated sheets greatly reduced their effectiveness. In a user acceptance study conducted among 88 families (divided into four groups), six families complained of irritation of the skin and mucous membranes. Of these reports, one was from the placebo group (using untreated sheets) and the other five (5/22=23%) from families using deltamethrin-treated sheets. All families allocated to permethrin and alphacypermethrin groups declared an appreciation for the intervention and reported no side-effects. Ten of the placebo group disliked the intervention, citing no prevention of mosquito biting as the reason. Side-effects associated with deltamethrin indicate that alphacypermethrin and permethrin are more appropriate first choice insecticides for treatment of sheets and blankets.