Environmental Science – Vector Control

Fostering healthy
environments where
we live, work and play
////////////////////////////////////

Rio Reyno Elia S.Tp.

Market Development Manager ID
&
Dr. Tee Hui Siang, Ph.D.
Market Development Manager MY

1 /// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

Environmental Science

Together, we care
for millions.
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/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///
/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///
/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///
/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///
/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///
/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///
 Bayer 360º Vector Control
Together, we care for millions

Our experience has shown us that Vector Control needs a

holistic approach if it is to be truly effective in saving lives.

With our 360° activities, we provide an innovative product

portfolio, interdisciplinary partnerships, training and
education programs as well as global advocacy.

We partner to fight vector-borne diseases and protect

millions of people around the world.

5 fold increase
in our investment into vector control over
the last 10 years

/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

Bayer 360º Vector Control
Vector Control

* Please contact a Bayer representative to find out

Partners more about the solutions available in your country.

Public authorities, UN agencies, contractors of USAID-PMI

Ministry of Health & Municipalities Private pest control
companies

Main Challenges
Insecticide resistance
Long-term stability of funding Registration hurdles
Timeframes associated with WHO recommendations

Portfolio
Indoor Residual Sprays (IRS) such as Ficam® and Fludora®
Fusion
Targeted Outdoor Residual Spray - K-Othrine® Polyzone
Space Sprays such as Aqua Resigen® and Aqua K-Othrine®
Larvicide – Barcelo®

/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

Environmental Science

Vector Control in Asia

Pacific
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/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

 Who are the stakeholders in vector control in APAC?

NGO/Policy
Global stakeholders
• WHO – WPRO (PH)
• Global Fund • WHO – SEARO (Delhi)
• WHO • APMEN (SG)
• IVCC • APLMA (SG)
• USAID • Malaria Consortium Asia
• AUSAID (Bangkok)
• UKAID • Malaria Consortium Imyanmar,
• UNDP Phnom Penh)
• UNICEF • Pasteur Institute (Laos, Cambodia,
Vietnam)
• Abt Associates
• Psi (MM)
Ministry/Governmental • ACT Malaria (PH)
Researchers/Universities
• CHAI (IN)
agencies
• Air Force Research Institute of
• MOH (MY,ID, PH, VN, TH, Medical Sciences (TH) Private
BD, PK, AF, BT, NP, • Naval Medical Research Unit-2 (SG,
• IMR (MY) KH) • International SOS (ID)
• NIMPE (VN) • Kasetsart University (TH) • Myanmar Health Development
• RITM (PH) • Shoklo Malaria Research Unit (TH) Consortium (MM)
• National Malaria Program • University Sains Malaysia (MY)
(ID) • Institut Teknologi Bandung ITB (ID)
• EHI (SG) • Institut Pertanian Bogor (ID)
• NEA (SG) • Gadjah Mada University (ID)
• CDC (CN) • Eijkman-Oxford University (ID)
• KCDCP (KR) • B2P2VRP (ID)
• JICA (MM)

/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

 Stakeholder engagement activities
Vector Control Expert Meeting (VCEM)

BACKGROUND
The Bayer Vector Control Expert Meeting (VCEM) provides vector control experts from
research institutions, academia and government agencies with a platform where we
encourage and facilitate the exchange of information and ideas on subjects related to
improved methods for vector control.

WHY
Continue to be a facilitator to drive dialogue and cross border collaborations.

Generate insight of needs and gaps from stakeholders via direct engagement.

KEY MILESTONES

DLL + 1st VCEM, PDOH 5th Year +

1st DEM IMR-KOPZ NIMPE+KOPZ + MOU KEMENKES SOA GOV
OUR Global Vector Control
2013 2015 2016 2017 2018 2019 ASPIRATION Expert Meeting

13 /// Vector Control Segment Strategy (APAC) 2019 /// Say Piau /// June 2019
 Advocacy and Communication for Disease Control
Bayer Dengue Media Briefing
*@ 2017 and 2018 Actual respective rates)

20 20
ABOUT 17 18
In line with ASEAN Dengue Day
on 15 June and World Mosquito
Day on 20 August, ES organizes a
yearly “Dengue Media Briefing” for
journalists. Vector Control Experts
who are part of the VCEM will
share their expertise and
knowledge on mosquitoes and
mosquito-borne diseases with
journalists, specifically dengue.
Panel experts (L-R): Nadim Mohr (Bayer), Dr Panel experts (L-R): Public Health Official
Sebastian Horstmann (Bayer), Dr Enrique A. Tayag, (KEMENKES), Dr Michael Bangs (International
FORMAT (Philippine Department of Health) and Dr Jeffrey Hii SOS), Dr Sebastian Horstmann (Bayer), and
Presentations, followed by a panel (Malaria Consortium) Jason Nash (Bayer)
discussion and ending with a Q&A
session.

14 /// Vector Control Segment Strategy (APAC) 2019 /// Say Piau /// June 2019
Commemorating the region’s efforts on Vector Control
ASEAN Dengue Day and World Mosquito Day

About Calling journalists to join us in

the battle against mosquitoes
In line with ASEAN Dengue Day on 15 June
and World Mosquito Day on 20 August, ES
organises a yearly “Dengue Media Briefing”
for journalists.
It is an hour-long media briefing where
prominent experts will share their expertise
and knowledge on mosquitoes and mosquito-
borne diseases with journalists, specifically on
Dengue.
Speakers are part of the Bayer Vector Control
Expert Meeting; in which the session will
Panel experts at the 2017 Dengue Media Briefing in Manila (L-R):
feature presentations and a panel discussion Nadim Mohr (Bayer), Dr Sebastian Horstmann (Bayer), Dr Enrique A.
at the end to allow Q & A from attendees. Tayag, (Philippine Department of Health) and Dr Jeffrey Hii (Malaria
Consortium)

/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

Advocating the role of the community in
reducing mosquito breeding sites
Public outreach to support national campaigns

Raising public awareness is critical to

educate communities on the importance of
their role in managing source reduction in
and around their homes.

Bayer Mosquito Learning Lab

A global online learning platform developed
by Bayer to raise awareness about dengue
and zika and the relevant control measures
to manage these diseases.

Bayer Mosquito Quest

A 3D virtual reality experience developed by
Bayer that complements the Mosquito
Learning Lab to test user’s skills at finding
potential mosquito breeding sites inside a
home. Teck Peng Lee at a Bayer Science Festival talking to primary
school children in Kajang, Malaysia about the dangers of Dengue.

/// ES APAC_Introduction to Vector Control in Asia // Seoul, September 2019 ///

Fludora® Co-Max
A new space spray combination
for mosquito resistance
management programs.

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 Topics

Background - resistance management situation

What is Fludora® Co-Max? Field trial results

Conclusion

1
8
 Background

Resistance
Management

1
9
 Urgent need for resistance-breaking active ingredients
Apart from introduction of Clothianidin in 2017, nothing much has changed in the WHOPES recommended
list of insecticides for 30 years

2
0
 Our approach to resistance management
We constantly look at the new active ingredients we
develop for agriculture to identify any that might serve
a purpose in public health:

// Do these active ingredient’s have the adequate activity?

// Do these chemical families bring a new mode of action in

vector control?

// Can we increase the impact on the target pest by

combining them?

// Can we reduce dose rates to meet the requirement for

use in public health through combinations of active
ingredients with different mode of action?

2
1
 Fludora Co-Max

What is it?

2
2
What is Fludora® Co-Max?
A new space spray specifically developed for areas where there is established or emerging
resistance of mosquitoes to conventional insecticides for indoor and outdoor uses.

/// The product combines 2 unique active ingredients, with 2 complementary modes of action – designed
by experts to control mosquitoes that have developed resistance to conventional insecticides.

Chemical name: Flupyradifurone Chemical Chemical name: Transfluthrin / Bayothrin®

family: butenolides Mode of action:
nAChR agonist
+ Chemical family:
Mode of action:
synthetic pyrethroids
Na+ channel modulator

/// It is a water based formulation, containing improved proprietary FFAST Technology:

• more visible fog
• more distant coverage
• no VOC’s.
• No PBO
Bayothrin® (Transfluthrin) is resistant to P450 enzymes

General pyrethroid degradation scheme Bayothrin® (Transfluthrin):

(e.g.Deltamethrin): NO binding = NO degradation = NO resistance
Flupyradifurone is a new class of insecticide

/// Butenolides - a new IRAC sub-class – 4D

- first time a butenolide has been introduced for vector control

- different to neonicotinoids, due to different chemical structure

and little cross-resistance

Controls resistant mosquitoes

Global Field
Trials
Global field trials
Fludora® Co-Max - evaluated across geographical areas and differents strains
Outdoor vehicle-mounted ULV in USA
An optimal droplet size for maximal efficacy and range

24-hr Mortality (%)

Average Droplet AVG Droplet
Distance Culex Anopheles
Treatment Aedes DVM Density Density
(feet) quinquefasci quadrimacul
aegypti (microns) (drops/mm2) (drops/mm2)
atus atus
100 100 100 100 1.45
Fludora®
200 100 100 100 18.73 1.17 1.38
Co-Max
300 100 100 100 1.51

/// Efficient control of local pyrethroid-resistant strains up to 100m distance from spray origin
/// Homogeneous droplet density over the whole spray distance
Outdoor hand-held ULV in Brazil
Good performance up to 100m distance against a pyrethroid-resistant strain

/// High efficacy up to 100m against pyrethroid-resistant Santos strain.

 Outdoor hand-held ULV & thermal fogging in Malaysia
Good performance against resistant mosquitoes and coverage at distance

ULV application Thermal application

Aedes Aegypti (lab) Aedes Aegypti (wild) resistant to Aedes Aegypti (lab) Aedes Aegypti (wild) resistant to
Susceptible Permethrin and Deltamethrin Susceptible Permethrin and Deltamethrin
Mortality (%)

Fludora Co-Max Aqua Resigen

/// Overall good mosquito control at label rate

/// 100m distance efficacy also with handheld foggers

 Conclusion

/// New insecticidal combination space spray introducing a new mode of action
for resistance management

/// Latest formulation technology to improve visibility and extended coverage

/// Flexible use for application by ULV, cold and hot fogging, outdoor and indoor uses.
- highly effective in a range of field situations around the globe.

The combination of two modes of action offers insecticide

resistance management that is robust and sustainable

16
 Thank you
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17
Insights from field trials
with Fludora Fusion, a
new combination IRS
product

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///////////
Justin McBeath
VCEM
Delhi
June 2019
 The robust
solution for your
malaria IRS
program

34 /// Bayer Environmental Science 16:9 Template 2010 /// April 2018
 Fludora Fusion – product basics
The first two-way mixture product designed for IRS use

Active substances and their 500 g/kg Clothianidin

concentrations 62.5 g/kg Deltamethrin

MoA class 4A - Neonicotinoids

Modes of action
MoA class 3A - Pyrethroids

Formulation type Wettable Powder in water soluble sachet (WP-SB)

100 g unit-dose sachet in 10 L sprayer

Packaging and pack size 80 g sachet for an 8 L sprayer
(200 mg/m2 of clothiandin and 25 mg/ m2 of deltamethrin)

35 /// Bayer Environmental Science 16:9 Template 2010 /// April 2018
 Determination of optimum dose rate – clothianidin
Early laboratory dose-finding studies demonstrated effectiveness across a range of dose rates
• No significant difference in mortality levels between 50 mg/m2 and 800 mg/2.
• Subsequent testing demonstrated 200 mg/m2 as achieving right balance of efficacy and cost-
effectiveness
• No increase in efficacy at dose rates above 200 mg/m2

36 /// Bayer Environmental Science 16:9 Template 2010 /// April 2018
 Understanding the combination approach
Two unrelated modes of action with complementary activity

Clothianidin
Is a selective agonist of nicotinic acetylcholine receptors
(nAChRs) and bind to these receptors on the post-synaptic
membrane (circled in blue).

Deltamethrin
Pyrethroids bind preferentially to the open (activated) state of
the sodium channels (circled in red).

Clothianidin triggers a general hyper-excitation of the

nervous system and this also causes overstimulation of
the voltage-dependent sodium channels - thereby
enhancing the binding probability and the efficacy of
pyrethroids in addition to having strong insecticidal
activity on its own.

This complementary effect has been demonstrated at the molecular level by Sodium channel
electrophysiological measurements on single neurons as well as by extracellular
recordings from a nerve cord preparation.
Source: Ralf Nauen, BSc, Phd, FRES

37 /// Bayer 16:9 Template 2010 /// November 2017

 Variability in residual life of IRS insecticides is normal
Well illustrated from observational analysis of operational IRS programs

Examples of observed
residual life:

1 – 10 months for
pyrethroids

2 – 9 months for
pirimiphos methyl CS

39 /// Delhi /// June 2019

 Factors contributing to
variability in residual life:

Susceptibility of mosquitoes

Achievement of dose rate

Surface type (eg. mud vs cement)

Ambient conditions

Properties of insecticide formulation

40
 Hypothesis
Combination products are used
in agriculture to achieve more
Insecticide Treated Bed Nets
consistent levels of control of
a mixed pest population or
when varying levels of
resistance are present in a
target pest population.
Can more consistent or
robust results be achieved
with a combination in Indoor
Residual Spraying?

41 /// Delhi /// June 2019

 Methodology
Observational comparison* of residual efficacy (months above 80% mortality) of
different products based on WHO cone bioassays across multiple field trials.

Target dose achievement measured but not reported here; the variation in dose
rate achieved reflected normal operational practice.

Formulations tested
Combination Clothianidin 500 g/kg & Deltamethrin 62.5 g/kg - wettable powder in
Neonicotinoid plus pyrethroid soluble sachets (200 mg/m2 + 25 mg/m2)
Neonicotinoid solo Clothianidin 700 g/kg - water dispersible granule (200 mg/m2)
Pyrethroid solo Deltamethrin 250 g/kg - water dispersible granule (25 mg/m2)
Positive control Pirimiphos-methyl 300 g/L - capsule suspension (1000 mg/m2)

*No statistical analysis performed to date – waiting until finalisation of all trials (8 remaining)

42 /// Delhi /// June 2019

 Results chosen from 9
countries where final
reports were available:

9 different spray teams

9 different types of mud and

cement surfaces

Susceptible mosquito strains (trials

with resistant strains were low in
number)

Countries included here:

Benin, Ghana, Senegal, Rwanda, Tanzania, Zambia, 24hr, 48hr and 72 hr mortalities
Zimbabwe, South Africa, Madagascar measured
Trial results pending:
43
Cote D’Ivoire, Ethiopia, Mozambique, Cameroon, Uganda
 Results: Susceptible strains – cement and mud surfaces
Lower and upper limits of residual efficacy on cement and mud surfaces based on 24 hr and 72 hr
mortality assessments in cone bioassays tests in multiple countries across Sub-Saharan Africa

44 /// Delhi /// June 2019

 Observations and Conclusions
(range)
• All products performed better on cement
than mud (greater variation between lower
and upperTreated
Insecticide limits on mud
Bed than cement).
Nets

• Delayed mortality assessments generally

benefited all products – this was most
notable on mud

• Higher lower and upper limits were achieved

for the combination compared to individual
components (except 24 hrs on mud)

• More consistent performance with the

combination than with the individual
components

45 /// Delhi /// June 2019

 Results: Susceptible strains – cement and mud surfaces
Mean and median number of months above 80% WHO Threshold for a range of results from small-
scale cone-bioassay residual efficacy assessments across various countries in Sub-Saharan Africa

46 /// Delhi /// June 2019

 Observations and Conclusions
(median and means)

• The combination generally performed more

reliably than either of the two individual
Insecticide
components.Treated Bed Nets

• When 72 hr mortality assessments were taken

into account the mean mortalities on cement
and mud exceeded 6 months in the Fludora
Fusion treatment.

Additional analysis to be performed when other results

47 /// Delhi ///available.
June 2019
 Overall:
This observational analysis suggests a
benefit of the combination compared to
either insecticide component applied alone.

Additional analysis (including with resistant

strains) will be completed when results
from other trials are received.

48 /// FoFD 2018 /// Sarah de Souza

 Acknowledgements: Institutions and Scientists which conducted the individual trials

RBMC

NIHR

Prof. M. Akogbeto; Dr S. Dadzie; M Diagne; M. Muleba; Dr E. Hakizimana;

Dr S. Randriamaherijaona; Dr Matt Kirby; Dr A. Makuwaza; Prof R. Maharaj

49 /// Delhi /// June 2019

 In conclusion

50 /// Bayer Environmental Science 16:9 Template 2010 /// April 2018
 Fludora Fusion is….

• WHO PQ listed since end-2018

• The robust and affordable solution for your malaria IRS program
• That provides reliable and consistent results relative to alternatives
• That has a perfect fit in an overall resistance management strategy
• That will provide overall savings in your program costs
• And which will allow you to protect more lives

51 /// Bayer 16:9 Template 2010 /// November 2017

 With all this data – how do
we best share it ?

Broad geography

Stakeholders with common

interests operating remotely

Large array of data being

generated.

Countries included here:

Benin, Ghana, Senegal, Rwanda, Tanzania, Zambia, Recognising what works best for
Zimbabwe, South Africa, Madagascar people with little time
Trial results pending:
52
Cote D’Ivoire, Ethiopia, Mozambique, Cameroon, Uganda
 We created a closed access data sharing platform
Invited participants given access to view trial results

• Allowed us to be more transparent

with trial data with targeted
stakeholder group

• Single repository of trial results

• Opportunity for interaction and direct

contribution from principal
investigators.

53 /// Bayer Environmental Science 16:9 Template 2010 /// April 2018
 Each trial in each individual country has its own entry point
Updates posted to the site as trial data points become available

• Chronology of results

• Interaction via questions posted to the

platform.

• Allows us to be more transparent than

we have been in the past.

54 /// Bayer Environmental Science 16:9 Template 2010 /// April 2018
More information, please reach us at :

Rioreyno.elia@bayer.com
Huisiang.tee@bayer.com

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