Insecticide resistance and management

Question 1

Which insecticide is used on bednets?

Answer 1

Pyrethroids

Question 2

What are some mechanisms of resistance?

Answer 2

• Behavioural changes
• Target site modification
• Reduced permeability e.g. of cuticle
• Metabolic resistance: Increased excretion or detoxification

Question 3

How can penetration be reduced?

Answer 3

Increasing cuticle thickness

Question 4

What is required for excretion to be able to occur?

Answer 4

In order for excretion to occur the insecticides need to be made soluble

Question 5

Most insecticides are not soluble as they are?

Answer 5

Hydrophobic/lipophilic

Question 6

How can insecticides be made soluble?

Answer 6

By conjugation to another molecule which is more soluble

Question 7

What is an example of a chemical which can allow excretion of insecticides?

Answer 7

GST

Glutathione transferases

Question 8

GST?

Answer 8

Glutathione transferases

Question 9

Glutathione transferases do what?

Answer 9

Glutathione transferases conjugate xenobiotic substances to glutathione which allows them to be excreted

Question 10

What are xenobiotic substances?

Answer 10

A chemical foreign to the body

Question 11

How do glutathione transferases metabolise insecticides?

Answer 11

Conjugation of the insecticide (a xenobiotic substance) to glutathione to make it more soluble and readily excretred

Question 12

How can resistance occur through excretion? How can the level of GST be increased?

Answer 12

Gene duplication

Promoter mutations which result in increased gene expression of glutathione transferase

Question 13

What other chemicals are involved in detoxification and excretion?

Answer 13

P450

Esterases

Question 14

What is P450?

Answer 14

Cytochrome P450 dependent monoxygenases

Question 15

What is P450?

Answer 15

Cytochrome P450 dependent monoxygenases

Question 16

How do monoxoygenases function?

Answer 16

They are involved in hydroxylation reactions by introduction of an oxygen atom to a xenobiotic substance

Question 17

What is the role of cytochrome P450 dependent monoxygenases?

Answer 17

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

Question 18

What are glutathione transferases involved in?

Answer 18

Increased excretion of insecticides

Question 19

What are cytochrome P450 dependent monoxygenases involved in?

Answer 19

Increased excretion

Detoxification

Question 20

Esterases are involved in?

Answer 20

Detoxification

Question 21

What do esterases do?

Answer 21

They hydrolyse ester bonds

Question 22

Example of a target site modification which confers resistance to DDT and pyrethroids?

Answer 22

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

Question 23

A single amino acid substitution in the transmembrane voltage gated ion channel can confer resistance to?

Answer 23

Pyrethroids and DDT

Question 24

What are two examples of target site mutations?

Answer 24

kdr= knock down resistance allele
MACE= modified acetycholinesterase

Question 25

MACE modification provides resistance to?

Answer 25

Organophosphates and carbamates

Question 26

kdr allele provides resistance to?

Answer 26

DDT | Pyrethroids

Question 27

What is the disadvantage of the MACE mutation?

Answer 27

MACE- the modified acetylcholinesterase does not have an activity as high as the original acetylcholinesterase= resistance has an associated fitness cost

Question 28

How does a modified acetylcholinesterase provide resistance to organophosphates and carbamates?

Answer 28

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

Question 29

What are the current strategies against malaria?

Answer 29

- Rapid diagnostic tests - Artemisinin Combination Therapy - Insecticide treated nets= ITNs and LLINs- long lasting insecticide nets - Indoor residual spraying

Question 30

What are some strategies of resistance management?

Answer 30

- 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

Question 31

Use of synergistic molecules?

Answer 31

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

Question 32

What are the benefits of synergistic molecules?

Answer 32

- Allows the use of lower doses of insecticides | - Makes the insects more susceptible or hypersusceptible

Question 33

What are some barriers to resistance management?

Answer 33

- 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

Question 34

Due to cross resistance?

Answer 34

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

Question 35

What should we do to ensure proper management?

Answer 35

- 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