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PRESENTATION DU PROJET ERC REVOLINCJeremy BOUYER Thierry BALDETUMR ASTRE Cirad/INRA

Journées EMBA, 13 juin 2018 UM

thierry.baldet@cirad.fr

Toxicity and ecotoxicity of insecticides

Reduction of authorizedinsecticides

(by 75% in Europe)

Impact of VectorControl?

Insecticide resistance

Biologicalinvasions

Vectors/PestsPathogens

Environmentalchanges

(local/global)

Diseases outbreaksNuisance

Health impactEconomical loses

2

THE CHALLENGE

Strong Need for INNOVATION

Source: Justin McBeath ISNTD Bites – March 19th 2015

… worse in Europe!

3

DDT

Pyrethroids

Pyrethroids

Pyrethroids

SIT Boosted SITBouyer & Lefrançois Trends Parasitol 2014

THE PRINCIPLE

INSECT MODELS

5

MosquitoesAedes albopictus

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PUBLIC HEALTH

2010 2015

7

An invasive species in EuropeNuisance in Late Summer & AutumnRisk of Oubreaks of Aedes-borne viral diseasesChikungunya : Italy (2007, 2017) & France (2010 Var, 2014 Herault, 2017 Var) Dengue Croatia (2010) & France (2010 Nice, 2014 Var+BdR, 2015 Gard)

8

Moustique tigre: « Appel à la vigilance » dans 42 départements métropolitains il y a 4 jours par la Direction Général de la Santé

Situation au 1er Janvier 2018

« surveillance renforcée »

Tsetse fliesGlossina palpalis gambiensis

Fruit fliesCeratitis capitata

9

AGRICULTURE PUBLIC & ANIMAL HEALTH

Other Targets

VectopoleSud

LISIS

.

10

Research Partners

WHAT IS NEEDED TO RUN BOOSTED SIT?WHAT WILL WE ADDRESS?

11

Contamination technique of males

Resilience on males & transfer to females during mating

Impact on female fertility (+ transfer to breeding sites)

+

Transfer of biocides during matingand impact on female fertility

(PP & Densovirus)

12

Pipeline of R & D for vector control tools/strategies

Source: B. Mosqueira

Laboratory Evaluation ISurvival of sterile males

of Glossina palpalis gambiensistreated with a new formulation of PP (F15)

0

10

20

30

40

50

60

70

80

90

100

0H 6H 48H 4j 7j 9j 13j 15j 17j 21j

Su

rviv

alo

f st

eril

em

ales

(%

)

Time after treatment

Master2 Lison LarocheNo impact of PP (F15) on male survival

Control F15

35mg F15 + Pyriproxyfen

Control

Laboratory Evaluation IIPersistency of PP (F15) on treated males

of Glossina palpalis gambiensis

0

200

400

600

800

1000

1200

1400

Am

ou

nt

of

PP

per

tse

tse

(ng

)

Time after treatment

0H 3H 6H 24H 48H 72H 4J 6J 8J 10J

Fast initial decline of PP followed by a level off around 100ng during 10 days

Master2 Lison Laroche

1,35

15,35 17,82 17,65 18,26

42,78

71.45

0

10

20

30

40

50

60

70

80A

mount

of

py

ripro

xy

fen

per

fem

ale

(ng)

Nb of contacts without mating

Laboratory Evaluation IIITransfer of PP from males* to females

of Glossina palpalis gambiensis

Master2 Lison Laroche

*3h after treatment by PP (F15)

To be followed: Impact of PP transferred on female fertility…

Laboratory Evaluation ISurvival of males of Aedes albopictus

treated with a new formulation of PP (F15)

Reduced survival of treated males (+50% mortality in 14 days)

183,48

132,01

107,67

62,01

42,03

16,76

-40

0

40

80

120

160

200

240

T0 (0 heure) T1 (3heures)

T2 (6heures)

T3 (24heures)

T4 (48heures)

T5 (4 jours)

Am

ou

nt

of

PP

pe

r in

div

idu

al (

ng)

Time after treatment

Laboratory Evaluation IIPersistency of PP (F15) on treated males

of Aedes albopictus

What about associating SIT to DENSOVIRUSES?

18

Drawn by Steve Higgs 19

Copyright © 2016 Bouyer et al. Open Access article distributed under the terms of CC BY-NC-ND Terms and Conditions

The Lancet Global Health 2016 4, DOI: (10.1016/S2214-109X(16)00082-6)

Mosquito DensovirusesHigh specificity

Carlson et al. 2006 Advances in virus research

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Mosquito DensovirusesOn-going trials

DVs moustiques Origine des DVs

Production en cellules

(virus équivalent génome –veg/µl) sécrétion dans le

surnageant

Test d’infectionen larves

Aedes albopictus

Densovirus 2

AalDV2

C6/36P chroniquement infectées

Jousset et al., 1993

Récolte des surnageants de culture

2,4 x 108 En cours

Aedes aegypti

Densovirus 1

AaeDV1

Clone viral origine: synthèse de

genes

Production de virus par transfection de culture de

cellules de moustiques

C6/36 3,4x106

AAG2 1,2x103

Clone viral origine : clonage génome

viral

Production de virus par transfection de cultures

de cellules de moustiques

C6/36 1,3 x 101

AAG2 3,8x106 En cours

Survival curve for Ae. albopictus larvae (Italian strain)

infected with AalDV2 virus

Survival curve for Ae. aegypti larvae (Bora strain)

infected with AalDV2 virus

Protocol:

• 1 larvae L1, P96 well, +/- virus

• Transfert 48hpi in P24 well plate + food

Protocol:

• 1 larvae L1, P96 well, +/- virus

• Virus +/- FB28 0,1%

• Transfert 48hpi in P24 well plate + food

Aedes albopictus Densovirus 2 produced from infectious plasmid Infection in Aedes albopictus and Aedes aegypti larvae

Aedes albopictus Densovirus 2 producedfrom C6/36 chronically infected cell line

Infection in Aedes albopictus larvae

Ind

ivid

ual

s n

um

ber

at

14

dp

i

Protocol:

• 100 larvaes L1, 5 ml cell culture

• Transfert 48hpi in 300 ml water + food

• Analysis 14 dpi AalDV2 effects : • ↗ mortality• ↘ development• ↗ cannibalism

25

Semi-field trials Experimental field trials

Impact of boosted SIT in semi-field and field trials with the best biocide

(Ae. albopictus & C. capitata)

Deterministic models Individual-based models

Relative impacts of SIT and boosted-SIT on population dynamics and resilience

26

Preliminary models with Pyriproxyfen

27

Elimination with minimised Rtotal: RSIT opt = 2528RBSIT opt = 1214

David Pleydell

Preliminary models with Pyriproxyfen

28David Pleydell

Modèle

Observation

Spatial modelAccounting for ClimateValidated on entomological dataUsed by Agence Régionale de Santé (ARS) to target monitoring and control

Population dynamics of Ae. albopictus in La Réunion (AlboRun)

PhD Marion Haramboure

First results of integrating SIT to the model

Perspectives

200,000 sterile males released weekly for 3 months

With a constant climate, return to equilibrium only 1.5 month after releases

Boosted SITStudy various release scenariosImpact of Climate on vector control

PhD Marion Haramboure

31

Mass rearing and irradiation procedures

32

Sexing of mosquitoes and handling procedures

2 genetic strategies to be compared to Tragsa Laser sorter:- Development of non-transgenic GSS- RNAi sexing

Quality control of produced strains

Sex separation method (female elimination) and quality control

PhD student (Start in July 2018)

33

Development of an automatic release machine

Photo WeRobotics

Successful trial of the drone release system in Brazil on Aedes aegypti in March 2018 (https://www.iaea.org/newscenter/pressreleases/iaea-conducts-successful-test-of-drones-in-fight-against-disease-transmitting-mosquitos)

34

Risk assessment Regulatory issues

Regulatory issues and social acceptability of boosted SIT

Social acceptability

Review of regulatory issues, technical constraints and social acceptability of genetic control in Europe

35

Revolinc & Regulatory issues

Audition des expertsSaisines en phase finale de rédactionPrésentation des saisines pour décision auprès HCSP & AFB (fin juin 2018)

Revolinc & social sciences

• La Reunion island

• 29 Jan - 16 Feb. 2018

• Survey by observations

• Meeting of scientific actors from CIRAD, Revolinc, IRD, TIS-La Réunion, ARS and collaborators on CYROI platform of Saint-Denis in the context of phase 2 preparation meeting of TIS-project

PhD Kamil Ghouati

• Vienna, Seibersdorf(Austria)

• 26 - 29 mar. 2018

• Survey by interviews & observations

• Meeting of members fromInsect Pest Control Lab ( FAO / IAEA Programme on Nuclear Techniques in Food and Agriculture )

Revolinc & social sciences

PhD Kamil Ghouati

• Vienna, Seibersdorf (Austria)

• 23 - 30 April 2018

• Survey by interviews & observations

• Meeting with European stakeholders in charge of mosquito control during a meeting on stakeholder engagement in mosquito SIT projects organized by IAEA

Revolinc & social sciences

PhD Kamil Ghouati

1. Identification of actors in the different sites: project leaders, stakeholders, collaborators, funding agencies, civil society, public(s), beneficiaries…

2. Identification of actors logics, categories involved to account for the action & social dimension of SIT projects, on scientific & technical thematics in the society, on technical democracy and on research participation: education, sensitization, communication, vulgarization, etc.

3. Study of social relationships and their dynamics along with ongoing projects deployment

Revolinc & social sciencesPreliminary results

PhD Kamil Ghouati

Thanks!

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