detoxification. Finally it is worth noting that pyrethroid resistance in nontarget
organisms may be difficult to identify because not all populations will evolve due
to the genetic and functional constraints of variation within the population in
question, and further, not all populations will evolve in the same way [58]. Some
of the most pronounced evolved resistance results when insecticides select for
otherwise rare genotypes that confer resistance. Without the genetic background to
allow for adaptation, acutely affected populations may be likely to move or experience local extinction.
4.2.1 Mosquitoes
Evidence that pyrethroid application is capable of driving resistance in aquatic
environments comes somewhat surprisingly from studying resistance in pest species.
In Africa, where malaria is a prominent public health threat, decreased sensitivity to
pyrethroids in Anopheles gambiae s.l., the primary malaria vector, has been attributed to, in part, agricultural or urban pyrethroid applications not specifically
targeting mosquitoes. This is of particular concern because the World Health
Organization (WHO) relies heavily on the use of pyrethroid-treated bed nets to
reduce malaria transmission in humans, and if mosquitoes are becoming resistant
from nontarget exposures, it may render these bed nets less effective for protecting
human health. While it can be difficult to determine the relative contributions of
resistance drivers for pests that are targeted with pyrethroids for human health [132],
mosquito larvae taken from aquatic breeding grounds near agricultural fields and
some urban areas then reared and challenged with pyrethroids and other insecticides
in a controlled setting consistently exhibit increased pyrethroid resistance compared
to those from reference sites [56, 59, 63]. Most of these studies rely on the methods
of resistance screening recommended by the WHO. These methods involve challenging adult mosquitoes with insecticide-impregnated paper treated with a prescribed amount of pesticide (e.g., 1% permethrin) and monitoring the time to
impairment (“knockdown”/immobilization) [133]. As a result, the resistance phenotypes for mosquitoes are often reported in a time-to-knockdown phenotype (KDT 50 )
for 50% of the population or in mosquito survival or mortality after a 1 h insecticideimpregnated filter paper exposure and subsequent 24 h recovery period.
The challenge in determining whether pyrethroids are responsible for adaptive
resistance in some populations of less sensitive mosquitoes is rooted in the use of
another pesticide, the organochlorine DDT, that also targets the Vgsc to elicit its
toxic action. Historically, DDT has been used in urban and agricultural settings in
much of Africa. However, its use has been restricted to necessary public health uses
when other insecticides are not available following a resolution by the United
Nations Stockholm Convention in 2001 [134]. Still, DDT presence or use in the
environment could potentially select for prominent adaptive resistance mechanisms
in pyrethroids, such as the leucine-to-phenylalanine amino acid substitution at
position 1014 (L1014F, M. domestica numbering) kdr mutation, located in the S6
transmembrane segment of the domain II of the para sodium channel (Fig. 4). This
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organisms may be difficult to identify because not all populations will evolve due
to the genetic and functional constraints of variation within the population in
question, and further, not all populations will evolve in the same way [58]. Some
of the most pronounced evolved resistance results when insecticides select for
otherwise rare genotypes that confer resistance. Without the genetic background to
allow for adaptation, acutely affected populations may be likely to move or experience local extinction.
4.2.1 Mosquitoes
Evidence that pyrethroid application is capable of driving resistance in aquatic
environments comes somewhat surprisingly from studying resistance in pest species.
In Africa, where malaria is a prominent public health threat, decreased sensitivity to
pyrethroids in Anopheles gambiae s.l., the primary malaria vector, has been attributed to, in part, agricultural or urban pyrethroid applications not specifically
targeting mosquitoes. This is of particular concern because the World Health
Organization (WHO) relies heavily on the use of pyrethroid-treated bed nets to
reduce malaria transmission in humans, and if mosquitoes are becoming resistant
from nontarget exposures, it may render these bed nets less effective for protecting
human health. While it can be difficult to determine the relative contributions of
resistance drivers for pests that are targeted with pyrethroids for human health [132],
mosquito larvae taken from aquatic breeding grounds near agricultural fields and
some urban areas then reared and challenged with pyrethroids and other insecticides
in a controlled setting consistently exhibit increased pyrethroid resistance compared
to those from reference sites [56, 59, 63]. Most of these studies rely on the methods
of resistance screening recommended by the WHO. These methods involve challenging adult mosquitoes with insecticide-impregnated paper treated with a prescribed amount of pesticide (e.g., 1% permethrin) and monitoring the time to
impairment (“knockdown”/immobilization) [133]. As a result, the resistance phenotypes for mosquitoes are often reported in a time-to-knockdown phenotype (KDT 50 )
for 50% of the population or in mosquito survival or mortality after a 1 h insecticideimpregnated filter paper exposure and subsequent 24 h recovery period.
The challenge in determining whether pyrethroids are responsible for adaptive
resistance in some populations of less sensitive mosquitoes is rooted in the use of
another pesticide, the organochlorine DDT, that also targets the Vgsc to elicit its
toxic action. Historically, DDT has been used in urban and agricultural settings in
much of Africa. However, its use has been restricted to necessary public health uses
when other insecticides are not available following a resolution by the United
Nations Stockholm Convention in 2001 [134]. Still, DDT presence or use in the
environment could potentially select for prominent adaptive resistance mechanisms
in pyrethroids, such as the leucine-to-phenylalanine amino acid substitution at
position 1014 (L1014F, M. domestica numbering) kdr mutation, located in the S6
transmembrane segment of the domain II of the para sodium channel (Fig. 4). This
124
K. M. Major and S. M. Brander