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The activity of the pyrrole insecticide chlorfenapyr in mosquito bioassay: towards a more rational testing and screening of non-neurotoxic insecticides for malaria vector control.

Oxborough RM, N'Guessan R, Jones R, Kitau J, Ngufor C, Malone D, Mosha FW, Rowland MW - Malar. J. (2015)

Bottom Line: The efficacy of WHO recommended cone, cylinder and tunnel tests was compared for pyrethroids and chlorfenapyr.The endogenous circadian activity rhythm of anophelines results in inactivity by day and raised metabolism and flight activity by night.A model which explains improved toxicity of chlorfenapyr ITN when tested at night, and during the day at higher ambient temperature, is that activation of chlorfenapyr and disruption of respiratory pathways is enhanced when the insect is more metabolically and behaviourally active.

View Article: PubMed Central - PubMed

Affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK. oxandbull@hotmail.com.

ABSTRACT

Background: The rapid selection of pyrethroid resistance throughout sub-Saharan Africa is a serious threat to malaria vector control. Chlorfenapyr is a pyrrole insecticide which shows no cross resistance to insecticide classes normally used for vector control and is effective on mosquito nets under experimental hut conditions. Unlike neurotoxic insecticides, chlorfenapyr owes its toxicity to disruption of metabolic pathways in mitochondria that enable cellular respiration. A series of experiments explored whether standard World Health Organization (WHO) guidelines for evaluation of long-lasting insecticidal nets, developed through testing of pyrethroid insecticides, are suitable for evaluation of non-neurotoxic insecticides.

Methods: The efficacy of WHO recommended cone, cylinder and tunnel tests was compared for pyrethroids and chlorfenapyr. To establish bioassay exposure times predictive of insecticide-treated net (ITN) efficacy in experimental hut trials, standard three-minute bioassays of pyrethroid and chlorfenapyr ITNs were compared with longer exposures. Mosquito behaviour and response to chlorfenapyr ITN in bioassays conducted at night were compared to day and across a range of temperatures representative of highland and lowland transmission.

Results: Standard three-minute bioassay of chlorfenapyr produced extremely low levels of mortality compared to pyrethroids. Thirty-minute day-time bioassay produced mortality closer to hut efficacy of chlorfenapyr ITN but still fell short of the WHO threshold. Overnight tunnel test with chlorfenapyr produced 100% mortality and exceeded the WHO threshold of 80%. The endogenous circadian activity rhythm of anophelines results in inactivity by day and raised metabolism and flight activity by night. A model which explains improved toxicity of chlorfenapyr ITN when tested at night, and during the day at higher ambient temperature, is that activation of chlorfenapyr and disruption of respiratory pathways is enhanced when the insect is more metabolically and behaviourally active.

Conclusions: Testing according to current WHO guidelines is not suitable for certain types of non-neurotoxic insecticide which, although highly effective in field trials, would be overlooked at the screening stage of evaluation through bioassay. Testing methods must be tailored to the characteristics and mode of action of each insecticide class. The WHO tunnel test on night-active anophelines is the most reliable bioassay for identifying the toxicity of novel insecticides.

No MeSH data available.


Related in: MedlinePlus

Predicted mortality ofAnopheles gambiaeKisumu by treatment between 21 and 29°C.
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Fig6: Predicted mortality ofAnopheles gambiaeKisumu by treatment between 21 and 29°C.

Mentions: In the second series, the bioassay mortality was compared at testing intervals of 2°C in a range of 21-29°C. Chlorfenapyr 200 mg/sq m samples showed a strong positive temperature coefficient, with mortality increasing with every increment of 2°C. Focusing on the WHOPES recommended testing range of 27°C ± 2°C, there was an odds ratio of 10.4 (95% CI = 5.5-19.6, P <0.001) associated with the 4°C increase in temperature from 25-29°C for chlorfenapyr ITN compared with only 1.7 for alphacypermethrin (95% CI = 0.9-3.1, P = 0.075). The alphacypermethrin net of 100 mg/sq m killed 100% of pyrethroid-susceptible An. gambiae Kisumu at all temperatures. To improve the prospect of discriminating between temperature intervals, lower dosages of alphacypermethrin at 0.5 and 1 mg/sq m were tested. While this had the desired effect of killing less than 100%, the proportions killed across the 21-29°C range were similar at all intervals (Figure 5). Predicted mean mortality projections for chlorfenapyr showed strong evidence (odds ratio = 1.8; 95% CI 1.5-2.1, P <0.001) of a mortality-temperature response for every 1°C increase in temperature. There was little evidence of a mortality gradient with temperature for alphacypermethrin (odds ratio = 1.1; 95% CI 1.0-1.3, P = 0.075) (Figure 6).Figure 5


The activity of the pyrrole insecticide chlorfenapyr in mosquito bioassay: towards a more rational testing and screening of non-neurotoxic insecticides for malaria vector control.

Oxborough RM, N'Guessan R, Jones R, Kitau J, Ngufor C, Malone D, Mosha FW, Rowland MW - Malar. J. (2015)

Predicted mortality ofAnopheles gambiaeKisumu by treatment between 21 and 29°C.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4390098&req=5

Fig6: Predicted mortality ofAnopheles gambiaeKisumu by treatment between 21 and 29°C.
Mentions: In the second series, the bioassay mortality was compared at testing intervals of 2°C in a range of 21-29°C. Chlorfenapyr 200 mg/sq m samples showed a strong positive temperature coefficient, with mortality increasing with every increment of 2°C. Focusing on the WHOPES recommended testing range of 27°C ± 2°C, there was an odds ratio of 10.4 (95% CI = 5.5-19.6, P <0.001) associated with the 4°C increase in temperature from 25-29°C for chlorfenapyr ITN compared with only 1.7 for alphacypermethrin (95% CI = 0.9-3.1, P = 0.075). The alphacypermethrin net of 100 mg/sq m killed 100% of pyrethroid-susceptible An. gambiae Kisumu at all temperatures. To improve the prospect of discriminating between temperature intervals, lower dosages of alphacypermethrin at 0.5 and 1 mg/sq m were tested. While this had the desired effect of killing less than 100%, the proportions killed across the 21-29°C range were similar at all intervals (Figure 5). Predicted mean mortality projections for chlorfenapyr showed strong evidence (odds ratio = 1.8; 95% CI 1.5-2.1, P <0.001) of a mortality-temperature response for every 1°C increase in temperature. There was little evidence of a mortality gradient with temperature for alphacypermethrin (odds ratio = 1.1; 95% CI 1.0-1.3, P = 0.075) (Figure 6).Figure 5

Bottom Line: The efficacy of WHO recommended cone, cylinder and tunnel tests was compared for pyrethroids and chlorfenapyr.The endogenous circadian activity rhythm of anophelines results in inactivity by day and raised metabolism and flight activity by night.A model which explains improved toxicity of chlorfenapyr ITN when tested at night, and during the day at higher ambient temperature, is that activation of chlorfenapyr and disruption of respiratory pathways is enhanced when the insect is more metabolically and behaviourally active.

View Article: PubMed Central - PubMed

Affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK. oxandbull@hotmail.com.

ABSTRACT

Background: The rapid selection of pyrethroid resistance throughout sub-Saharan Africa is a serious threat to malaria vector control. Chlorfenapyr is a pyrrole insecticide which shows no cross resistance to insecticide classes normally used for vector control and is effective on mosquito nets under experimental hut conditions. Unlike neurotoxic insecticides, chlorfenapyr owes its toxicity to disruption of metabolic pathways in mitochondria that enable cellular respiration. A series of experiments explored whether standard World Health Organization (WHO) guidelines for evaluation of long-lasting insecticidal nets, developed through testing of pyrethroid insecticides, are suitable for evaluation of non-neurotoxic insecticides.

Methods: The efficacy of WHO recommended cone, cylinder and tunnel tests was compared for pyrethroids and chlorfenapyr. To establish bioassay exposure times predictive of insecticide-treated net (ITN) efficacy in experimental hut trials, standard three-minute bioassays of pyrethroid and chlorfenapyr ITNs were compared with longer exposures. Mosquito behaviour and response to chlorfenapyr ITN in bioassays conducted at night were compared to day and across a range of temperatures representative of highland and lowland transmission.

Results: Standard three-minute bioassay of chlorfenapyr produced extremely low levels of mortality compared to pyrethroids. Thirty-minute day-time bioassay produced mortality closer to hut efficacy of chlorfenapyr ITN but still fell short of the WHO threshold. Overnight tunnel test with chlorfenapyr produced 100% mortality and exceeded the WHO threshold of 80%. The endogenous circadian activity rhythm of anophelines results in inactivity by day and raised metabolism and flight activity by night. A model which explains improved toxicity of chlorfenapyr ITN when tested at night, and during the day at higher ambient temperature, is that activation of chlorfenapyr and disruption of respiratory pathways is enhanced when the insect is more metabolically and behaviourally active.

Conclusions: Testing according to current WHO guidelines is not suitable for certain types of non-neurotoxic insecticide which, although highly effective in field trials, would be overlooked at the screening stage of evaluation through bioassay. Testing methods must be tailored to the characteristics and mode of action of each insecticide class. The WHO tunnel test on night-active anophelines is the most reliable bioassay for identifying the toxicity of novel insecticides.

No MeSH data available.


Related in: MedlinePlus