Insecticide resistance and management Flashcards
Which insecticide is used on bednets?
Pyrethroids
What are some mechanisms of resistance?
- Behavioural changes
- Target site modification
- Reduced permeability e.g. of cuticle
- Metabolic resistance: Increased excretion or detoxification
How can penetration be reduced?
Increasing cuticle thickness
What is required for excretion to be able to occur?
In order for excretion to occur the insecticides need to be made soluble
Most insecticides are not soluble as they are?
Hydrophobic/lipophilic
How can insecticides be made soluble?
By conjugation to another molecule which is more soluble
What is an example of a chemical which can allow excretion of insecticides?
GST
Glutathione transferases
GST?
Glutathione transferases
Glutathione transferases do what?
Glutathione transferases conjugate xenobiotic substances to glutathione which allows them to be excreted
What are xenobiotic substances?
A chemical foreign to the body
How do glutathione transferases metabolise insecticides?
Conjugation of the insecticide (a xenobiotic substance) to glutathione to make it more soluble and readily excretred
How can resistance occur through excretion? How can the level of GST be increased?
Gene duplication
Promoter mutations which result in increased gene expression of glutathione transferase
What other chemicals are involved in detoxification and excretion?
P450
Esterases
What is P450?
Cytochrome P450 dependent monoxygenases
What is P450?
Cytochrome P450 dependent monoxygenases
How do monoxoygenases function?
They are involved in hydroxylation reactions by introduction of an oxygen atom to a xenobiotic substance
What is the role of cytochrome P450 dependent monoxygenases?
They add an oxygen atom to xenobiotic compounds and are involved in hydroxylation reactions. The addition of an oxygen allows the insecticides to become more polar= more soluble= more readily excreted
What are glutathione transferases involved in?
Increased excretion of insecticides
What are cytochrome P450 dependent monoxygenases involved in?
Increased excretion
Detoxification
Esterases are involved in?
Detoxification
What do esterases do?
They hydrolyse ester bonds
Example of a target site modification which confers resistance to DDT and pyrethroids?
Resistance to pyrethroids and DDT
Single amino acid substitution in the sodium ion channel makes it have a lower affinity for the insecticides
This is known as knock down resistance allele= kdr allele
A single amino acid substitution in the transmembrane voltage gated ion channel can confer resistance to?
Pyrethroids and DDT
What are two examples of target site mutations?
kdr= knock down resistance allele MACE= modified acetycholinesterase
MACE modification provides resistance to?
Organophosphates and carbamates
kdr allele provides resistance to?
DDT
Pyrethroids
What is the disadvantage of the MACE mutation?
MACE- the modified acetylcholinesterase does not have an activity as high as the original acetylcholinesterase= resistance has an associated fitness cost
How does a modified acetylcholinesterase provide resistance to organophosphates and carbamates?
It provides resistance as it no longer binds to them, it is able to then degrade acetylcholine and function can proceed as normal, even with its decreased activity
What are the current strategies against malaria?
- Rapid diagnostic tests
- Artemisinin Combination Therapy
- Insecticide treated nets= ITNs and LLINs- long lasting insecticide nets
- Indoor residual spraying
What are some strategies of resistance management?
- Only using insecticides when required
- Rotations, mosaic
- Combination of insecticides at one time
- Stop using them for a while
- Monitor resistance, as soon as it occurs use a different method
- Use of synergistic molecules
Use of synergistic molecules?
Molecules that can enhance the efficacy of the insecticides. Molecules capable of binding the enzymes which may increase excretion/detoxification of the insecticide e.g. glutathione transferases, esterases or cytochrome P450 dependent monoxygenases
What are the benefits of synergistic molecules?
- Allows the use of lower doses of insecticides
- Makes the insects more susceptible or hypersusceptible
What are some barriers to resistance management?
- Usage of insecticides in the agricultural industry
- Pollutants selecting for resistance
- Reproductive isolation, if there is none then the resistance genes may rapidly spread
- Some insecticides may be very persistent in the environment which prevents rotations occurring
- Funding
- Lack of available insecticides… pyrethroids are the only insecticides we can currently use on bednets
- Cross resistance. Resistance may confer resistance to insecticides of a whole class rather than a specific insecticide
- If the insecticide is applied for a long period of time then the fitness cost associated with resistance may disappear due to the development of contingency mutations
Due to cross resistance?
We should consider the same class of insecticide as an individual insecticide… therefore, combination approaches require insecticides of different classes to be used as they all act in different ways
What should we do to ensure proper management?
- Try not to use insecticides of the same class
- Ensure we are not overdosing as this is costly and may have other consequences on human health/environment, and ensure we are not underdosing as this can harm the environment
- Ensure we use a combination of insecticides
- Ensure we are rotating our insecticide use
- Mosaics
- As soon as resistance develops we should switch to another insecticide
- More research and development into alternatives
- Only use insecticides where and when they are required
