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Parasitology > Insecticide resistance and management > Flashcards

Insecticide resistance and management Flashcards

1
Q

Which insecticide is used on bednets?

A

Pyrethroids

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2
Q

What are some mechanisms of resistance?

A
  • Behavioural changes
  • Target site modification
  • Reduced permeability e.g. of cuticle
  • Metabolic resistance: Increased excretion or detoxification
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3
Q

How can penetration be reduced?

A

Increasing cuticle thickness

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4
Q

What is required for excretion to be able to occur?

A

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

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5
Q

Most insecticides are not soluble as they are?

A

Hydrophobic/lipophilic

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6
Q

How can insecticides be made soluble?

A

By conjugation to another molecule which is more soluble

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7
Q

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

A

GST

Glutathione transferases

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8
Q

GST?

A

Glutathione transferases

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9
Q

Glutathione transferases do what?

A

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

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10
Q

What are xenobiotic substances?

A

A chemical foreign to the body

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11
Q

How do glutathione transferases metabolise insecticides?

A

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

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12
Q

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

A

Gene duplication

Promoter mutations which result in increased gene expression of glutathione transferase

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13
Q

What other chemicals are involved in detoxification and excretion?

A

P450

Esterases

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14
Q

What is P450?

A

Cytochrome P450 dependent monoxygenases

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15
Q

What is P450?

A

Cytochrome P450 dependent monoxygenases

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16
Q

How do monoxoygenases function?

A

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

17
Q

What is the role of cytochrome P450 dependent monoxygenases?

A

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

18
Q

What are glutathione transferases involved in?

A

Increased excretion of insecticides

19
Q

What are cytochrome P450 dependent monoxygenases involved in?

A

Increased excretion

Detoxification

20
Q

Esterases are involved in?

A

Detoxification

21
Q

What do esterases do?

A

They hydrolyse ester bonds

22
Q

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

A

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

23
Q

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

A

Pyrethroids and DDT

24
Q

What are two examples of target site mutations?

A 
kdr= knock down resistance allele
MACE= modified acetycholinesterase
25
Q

MACE modification provides resistance to?

A

Organophosphates and carbamates

26
Q

kdr allele provides resistance to?

A

DDT

Pyrethroids

27
Q

What is the disadvantage of the MACE mutation?

A

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

28
Q

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

A

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

29
Q

What are the current strategies against malaria?

A
  • Rapid diagnostic tests
  • Artemisinin Combination Therapy
  • Insecticide treated nets= ITNs and LLINs- long lasting insecticide nets
  • Indoor residual spraying
30
Q

What are some strategies of resistance management?

A
  • 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
31
Q

Use of synergistic molecules?

A

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

32
Q

What are the benefits of synergistic molecules?

A
  • Allows the use of lower doses of insecticides

- Makes the insects more susceptible or hypersusceptible

33
Q

What are some barriers to resistance management?

A
  • 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
34
Q

Due to cross resistance?

A

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

35
Q

What should we do to ensure proper management?

A
  • 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

Parasitology (17 decks)

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