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3/21/2016 1 Chemical control & insectiside resistance Fiocruz Instituto Oswaldo Cruz Ademir J Martins Jr Maceió, march 13 th 2016 Suppression X Substitution Target population Control of insect populations

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Page 1: Chemical control & insectiside resistance...3/21/2016 1 Chemical control & insectiside resistance Fiocruz Instituto Oswaldo Cruz Ademir J Martins Jr Maceió, march 13th 2016 Suppression

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Chemical control & insectiside resistance

FiocruzInstituto Oswaldo Cruz

Ademir J Martins Jr

Maceió, march 13th 2016

Suppression

XSubstitution

Target population

Control of insect populations

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Wolbachiatransgenesis

Avoid larval breeding sites

Mechanical control

SIT genetic shiftingparatransgenesisBiological control

Chemical control insecticides

predators/ parasites

Suppression

Substitution

Control of Aedes aegyptipopulations

Wolbachiatransgenesis

Avoid larval breeding sites

Mechanical control

SIT genetic shiftingparatransgenesisBiological control

Chemical control insecticides

predators/ parasites

Suppression

Substitution

Control of Aedes aegyptipopulations

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Bass et al 2014 – Insect Biochem Mol Biol

The Brazilian National Program for Dengue Control only applies insecticides approved by the WHO Pesticide Evaluation Scheme (WHOPES)

Insecticides

updated 5 February 2016

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The Brazilian National Program for Dengue Control only applies insecticides approved by the WHO Pesticide Evaluation Scheme (WHOPES)

Insecticides

updated 5 February 2016

NNNN

IGRIGRIGR

N

Bio

The Brazilian National Program for Dengue Control only applies insecticides approved by the WHO Pesticide Evaluation Scheme (WHOPES)

Insecticides

updated 5 February 2016

Pyr

Pyr

Pyr

Pyr

OP

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The Brazilian National Program for Dengue Control only applies insecticides approved by the WHO Pesticide Evaluation Scheme (WHOPES)

Insecticides

updated 5 February 2016

Insecticides against Ae. aegypti In Brazil- Larvicide temephos (OP) and adulticides fenitrothion and malathion

(OPs) until 2009- Resistance to OPs started being detected in1998- Inauguration of a National Monitoring Network for Insecticide Resistance in

Aedes aegypti- Substitution of the larvicide to Bti (biol), JH and BPUs IGRs and the

adulticides to deltamethrin (Pyr)- Soon after, resistance to Pyr was detected and then we returned to the OP

malathion.

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Insecticides against Ae. aegypti In Brazil

Currently indicated by the Brazilian National Program for Dengue Control

Larvicide: pyriproxyfen (JH)Adulticides: malathion (OP) – spatial

bendiocarb (CA) – residual

- Larvicide temephos (OP) and adulticides fenitrothion and malathion(OPs) until 2009

- Resistance to OPs started being detected in 1998- Inauguration of a National Monitoring Network for Insecticide Resistance in

Aedes aegypti- Substitution of the larvicide to Bti (biol), JH and BPUs IGRs and the

adulticides to deltamethrin (Pyr)- Soon after, resistance to Pyr was detected and then we returned to the OP

malathion.

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Insecticide resistance can contribute to an increase in the incidence of arboviruses

0 5000 10000 15000 20000 2500030

40

50

60

70

cumulative dengue incidence

mo

rta

lity

(%) R2= 0.7372, p <0.0286

P. Prudente

Marília

CampinasRib. Preto

Santos

SJR Preto

Exemple: reduced mortality of Ae. aegypti to pyrethroids showed a significant correlation with dengue incidence in localities from São Paulo

Insecticide resistance can contribute to an increase in the incidence of arboviruses

Macoris, not published

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Insecticide resistance in dengue vectorsRanson et al 2010, TropiKanet

Insecticide resistance in dengue vectorsRanson et al 2010, TropiKanet

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2005 – 2015 published data on Anopheles resistance source: IR Mapper

How to evaluate insecticide resistance?

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How to evaluate insecticide resistance?

There is an increasing number of validated methods for evaluating insecticide resistance levels and their selected physiological mechanisms

CDC bottle bioassay

WHO tubes bioassay

How to evaluate insecticide resistance?

Bioassays

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Behavioral changes Reduced penetration

(cuticle)

Increase in enzymatic detoxificationTarget site

insensitivity

Main mechanisms selected for insecticide resistance

How to evaluate insecticide resistance?

Biochemical and molecular assays

Biochemical assays of enzymatic activity

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Mechanisms for insecticide resistance: metabolic resistance in Aedes aegypti from Brazil

High-throughput identification of resistance genes

Faucon et al 2015 – Genome Research

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Mechanisms for insecticide resistance: kdrmutations in Aedes aegypti from Brazil

Aedes aegypti SNP chipEvans et al 2015 – Genes,

Genomics, Genetics

- Wide genome analysis (GWAS) comparing susceptible and resistant individuals of several Brazilian populations

Bioasays with insecticide

Resistant Susceptible

- 32K biallelic, mendelian and validated SNPs for each individual in one reaction

Aedes aegypti SNP chip

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Worldwide insecticide resistance network in mosquito vectors of arbovirusesAcronym: WIN (Worldwide Insecticide-resistance Network)PI’s: Vincent Corbel (IRD, Thailand) and Jean-Philippe David (CNRS, France)

The WIN proposes to bring together 15internationally recognized institutions in vector research, providing a unique framework for trackinginsecticide resistance in mosquito vectors of arboviruses around the world. The network aims atidentifying the particular countries/regions where resistance could challenge vector controlinterventions and to provide the WHO and member states with key recommendations for improvementof insecticide resistance surveillance and deployment of alternative vector control tools.

Is it possible to revert to a susceptible stage?

Would we able to continue effectively using insecticides as one of the alternatives for vector control ???

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Selection pressureinsecticide

time

Is it possible to revert to a susceptible stage?

- Comparisons between Rock and Rock-kdr (R2R2)Time of larval development

Pupation rate

Adults longevity

Blood feeding

Fecundity: rate of inseminated females

Fecundity: number of eggs

Locomotor activity

Circadian rhythm

Fertility: eggs’ viability

Competition during larval development

Competition for copula

R2 kdr allele has a fitness cost

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- Comparisons between Rock and Rock-kdr (R2R2)Time of larval development

Pupation rate

Adults longevity

Blood feeding

Fecundity: rate of inseminated females

Fecundity: number of eggs

Locomotor activity

Circadian rhythm

Fertility: eggs’ viability

Competition during larval development

Competition for copula

R2 kdr allele has a fitness cost

Enough to diminish the frequency of the mutant allele in an

insecticide-free environment ?

0 3 6 9 12 15

0.0

0.2

0.4

0.6

0.8

1.0 cage 1 cage 2cage 3

A

generations (F)

10

16

Ile

(fre

qu

ec

y)

0 3 6 9 12 15

0.0

0.2

0.4

0.6

0.8

1.0 cage 4cage 5cage 6

B

generations (F)

10

16

Ile

(fre

qu

ec

y)

Kdr allele initial frequency(3 independent cages for each situation)

50%

75%

R2 kdr allele has a fitness cost

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0 3 6 9 12 15

0.0

0.2

0.4

0.6

0.8

1.0 cage 1 cage 2cage 3

A

generations (F)

10

16

Ile

(fre

qu

ec

y)

0 3 6 9 12 15

0.0

0.2

0.4

0.6

0.8

1.0 cage 4cage 5cage 6

B

generations (F)

10

16

Ile

(fre

qu

ec

y)

Kdr allele initial frequency(3 independent cages for each situation)

50%

75%

R2 kdr allele has a fitness cost

Awarenessmodifier genes

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- Insecticide resistance has become a serious threatento mosquito control. Merely switching insecticide whenthe current one no longer works is not effective.

- Good predictions of the dynamics of resistance innatural populations have to consider the knowledge ofgenetic, biologic and ecological aspects of the selectedmechanisms.

Conclusions

Challange #1 : knowledge of the selected mechanisms

- Metabolic- target site- cuticle thickening- behavioural

Challenge #2 : knowledge of the dynamics of resistance genes in the population

Avoid the increase and dispersion of resistance Avoid cross resistance among different class of insecticides Maintain insecticides as one of the possible strategies for mosquito control

- R allele frequencies- dominance relationships- epistatic effects on fitness

Remarks for studying a resistant population

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Thank you!

Ademir J [email protected]