Chemical Control of Mosquitoes and the Pesticide Treadmill: A Case for Photosensitive Insecticides as Larvicides

Abstract

Insecticides reduce the spread of mosquito-borne disease. Over the past century, mosquito control has mostly relied on neurotoxic chemicals-such as pyrethroids, neonicotinoids, chlorinated hydrocarbons, carbamates and organophosphates-that target adults. However, their persistent use has selected for insecticide resistance. This has led to the application of progressively higher amounts of insecticides-known as the pesticide treadmill-and negative consequences for ecosystems. Comparatively less attention has been paid to larvae, even though larval death eliminates a mosquito's potential to transmit disease and reproduce. Larvae have been targeted by source reduction, biological control, growth regulators and neurotoxins, but hurdles remain. Here, we review methods of mosquito control and argue that photoactive molecules that target larvae-called photosensitive insecticides or PSIs-are an environmentally friendly addition to our mosquitocidal arsenal. PSIs are ingested by larvae and produce reactive oxygen species (ROS) when activated by light. ROS then damage macromolecules resulting in larval death. PSIs are degraded by light, eliminating environmental accumulation. Moreover, PSIs only harm small translucent organisms, and their broad mechanism of action that relies on oxidative damage means that resistance is less likely to evolve. Therefore, PSIs are a promising alternative for controlling mosquitoes in an environmentally sustainable manner.

Keywords: Culicidae; Diptera; insect control; insecticide resistance; pest management; photoactive; photodynamic; reactive oxygen species.

Figure 1

Neurotoxic insecticides can be classified as axonic poisons or synaptic poisons. Axonic poisons (AP) bind voltage gated sodium channels (VGSC) and their inactivation loop (IL), thereby altering the movement of sodium ions and disrupting the transmission of action potentials. Synaptic poisons (SP) either prevent enzymes from degrading neurotransmitters or interfere with the binding of neurotransmitters to their post-synaptic terminal receptors, thereby disrupting the communication between presynaptic neurons and post-synaptic cells.

Figure 2

Insects utilize four primary strategies to evolve resistance against insecticides: metabolic sequestration and elimination, target site modification, cuticle thickening, and behavioral avoidance. (A) Metabolic sequestration and elimination results from the upregulation of enzymes that intercept and degrade the insecticide before it reaches the target site. (B) Target site modification results from the changing of a target site such that it cannot interact with the insecticide. (C) Cuticle thickening results from an increase in cuticular thickness and a decrease in cuticular permeability, thereby preventing an insecticide from entering the body. (D) Behavioral avoidance results from the changing of behavior such that the insect avoids encountering an insecticide.

Figure 3

A model of accumulation and resistance of insecticides, known as the pesticide treadmill. (A) Resistance evolves (open circles) against classical insecticides following their repeated application (closed circles) because of selective pressure on their highly specific neurological targets. Therefore, to achieve the same level of insect control, higher dosages are progressively applied as the populations gain resistance. (B) Classical insecticides persist in the environment and require increased dosage application to manage resistant populations. Therefore, classical insecticides accumulate over time and eventually lead to ecological damage.

Figure 4

Controlling larval populations relies on three general strategies: source reduction, chemical control, and biological control. (A) Source reduction decreases mosquito access to standing water, preventing both oviposition and larval development. (B) Chemical control kills larvae via toxic insecticides. (C) Biological control introduces an organism, such as a larval predator, bacteria, or fungi, that kills larvae.

Figure 5

Photosensitive molecules are activated by light to produce reactive oxygen species. Reactive oxygen species produced by the photoactivation (asterisk) of a photosensitive insecticide irreversibly damage biomolecules, harming the organism in numerous ways.

Figure 6

Photosensitive insecticides (PSIs) are ingested by larvae and kill them via oxidative damage. Photosensitive insecticides are applied to bodies of water (1), and once ingested by larvae (2), the PSIs are activated by natural light (asterisk) to produce reactive oxygen species (ROS; 3–6). These ROS irreversibly damage macromolecules in their vicinity, killing the larvae (7, 8). Any PSI that is not consumed is degraded by sunlight (9).

Figure 7

Photosensitive insecticides avoid the pesticide treadmill and environmental accumulation. (A) Resistance evolves (open orange circles) against classical insecticides following their repeated application (closed orange circles) because of selective pressure on their highly specific neurological targets whereas the evolution of resistance against PSIs following their repeated application (closed blue circles) is unlikely because of their broad mechanism of action that relies on oxidative damage. Therefore, to achieve the same level of insect control with classical insecticides, higher dosages are progressively applied as the populations gain resistance, whereas this is unnecessary for PSIs. (B) Classical insecticides persist longer in the environment and require increased dosage application to manage resistant populations. Therefore, classical insecticides accumulate over time and eventually lead to environmental damage, whereas PSIs do not.

Figure 8

Photosensitive insecticides are broken down by photodegradation. Images of various concentrations of the PSIs, methylene blue and rose bengal, that have been maintained in the dark or exposed to 5000 Lumens of LED light for 2 h. Photodegradation is evident by the increased clarity and translucency following light irradiation.