New Insecticides and Repellents for Use on Mosquitoes and Sand Flies

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New Insecticides and Repellents for Use on
Mosquitoes and Sand Flies

• Ulrich R. Bernier
• USDA-ARS-CMAVE
• Mosquito Fly Research Unit
• 352-374-5917
• uli.bernier_at_ars.usda.gov
• 2010 DWFP-OPMRA
• February 12, 2010
• Jacksonville NAS

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Research Projects

1. Development of Novel Repellents and Insecticides
   -SCA with Alan Katritzky (UF-Chemistry).
2. Bite Protection of Current Uniforms and Improved
   Repellent-Treated Military Uniforms -
   Reimbursable with NSRDEC. Collaboration with
   Kamal Chauhan (IIBBL), CDR Schoeler (JAX-NECE).
3. Attraction-Inhibitors - Collaboration with Kamal
   Chauhan (IIBBL), CDR Szumlas, CDR Hoel, LT Furman
   (NAMRU-3).

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Insecticide/Repellent Projects
Project dataset used from USDA archives

• 1608 Carboxamides carboxamide
  repellents
• 1757 Acylpiperidines best 7
  repellents
• 1665 Various insecticides house fly
• 1666 Various insecticides house fly
• 1668 Various insecticides anopheleines
• 1669 Various insecticides Ae.
  taeniorhynchus
• 1670 Various repellents Ae. aegypti

USDA, Agriculture Handbooks No 69 (1954), No 340
(1967), Technical Bulletin No 1549 (1977).
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Research strategy
USDA archives
Modeling (ANN, QSAR
Predictions
Synthesis
Bioassays
Katritzky AR et al. PNAS US. 2008, 21, 7359
Gupta RK, Bhattacharjee AK (2007) Insect
Repellents Principles, Methods, and Uses,
pp195228.
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Cloth patch assay UF IRB-01 636-2005
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Acylpiperidines top candidates from 1611
repellents (1757)
Complete protection time (CPT) of most active
acylpiperidines vs DEET using Cloth Patch assays
Protection time (days)
25 mmol/cm2
Concentration
2.5 mmol/cm2
Treatment
Katritzky AR et al. PNAS US. 2008, 21, 7359
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Acylpiperidines as mosquito repellents (1757)
Selected carboxamides vs DEET
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Carboxamides as mosquito repellents (1608)
Complete protection time (CPT) for selected
carboxamides and DEET at two concentrations using
Cloth Patch assays
Protection time (days)
25 mmol/cm2
Concentration
2.5 mmol/cm2
Treatment
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Carboxamides as mosquito repellents (1608)
Selected carboxamides vs DEET
12.0 days
13.0 days
15.0 days
22.0 days
DEET
5.0 days
7.0 days
2.5 days
25 and 2.5 ?mol/cm2
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House Fly, Contact Insecticides (1665)
Dataset Predicted /similarity eval 100 Mortality, mmol/L
159 (228) Musca domestica 390/30 8 3,5-dichloroaniline 4.6 Carbaryl 14.9 Propoxur 7.1
100 mortality
Concentration (mmol/L)
P/1.5 C/3.2
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House fly, Residual Insecticides (1666)
Dataset Dataset from archive Predicted /similarity Eval 100 Mortality, mmol/L
53 non-phosph. (out of 228) Musca domestica 125/25 25 Ethyl cis-3-iodoacrylate 0.075 Xanthene 0.005 Carbaryl 0.0149 Propoxur 0.0071
100 mortality
Concentration (mmol/L)
P/1.4 C/3
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Common Malaria MosquitoResidual Insecticides
(1668)
Dataset from archive Predicted /similarity eval 100 Mortality, mmol/L
62 non-phosph. (241) Anopheles 230 28 2-(3-fluorophenoxy)-benzoxazole 0.013088 2-(4-chlorophenoxy)-benzoxazole 0.006106 Carbaryl 0.0149 Propoxur 0.0071
100 mortality
Concentration (mmol/L)
P/1.2 C/2.5
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Evaluation of Permethrin-Treated Military
Uniforms

• August, 2003After Monrovia, Liberia mission,
  USMC requested assistance of MFRU to transition
  to factory-treated uniforms.
• May 20, 2006-March 09, 2007First Article
  Testing of Marine Corps Combat Utility Uniforms
  (MCCUUs).
• 2008-2009Evaluation of U.S. Army, USMC, U.S. Air
  Force, U.S. Navy uniforms.
• 2010First Article Testing of Factory Treated
  Fire-Resistant Army Combat Uniforms (FT FRACUs).

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Bite Protection Assay UF IRB-01 69-2006
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Summary of Bite Protection Evaluation of Twill
Uniforms(MCCUUs, FROG, ABUs, Abrams)
Specimen (Co)-Type-Treatment Air Perm (cfm) Bite Protection (SE) Bite Protection (SE) Bite Protection (SE)
Specimen (Co)-Type-Treatment Air Perm (cfm) 0x 20/25x 50x
AA-MCCUU-Trouser 6.8 99.1 0.3 97.5 0.7 93.7 1.0
EA-MCCUU-Trouser 6.8 98.4 0.5 99.2 0.4 96.0 0.8
CO-MCCUU-Trouser 6.8 96.0 0.7 98.3 0.6 97.6 0.6
PR-MCCUU-Trouser 6.8 95.9 0.9 96.8 0.7 90.3 1.7
MCCUU-Tr WK Rev Ord 6.8 90.8 2.0 n/a n/a
AA-MCCUU- Blouse 10.4 99.1 0.2 98.7 0.3 97.9 0.5
EA-MCCUU- Blouse 10.4 98.5 0.4 97.8 0.6 97.5 0.7
CO-MCCUU- Blouse 10.4 97.7 0.3 98.7 0.2 98.5 0.5
PR-MCCUU- Blouse 10.4 97.4 0.7 97.5 0.6 96.4 0.8
ABU IDA 10.8 94.5 1.5 92.3 1.6 82.8 3.0
Abrams V 23.0 97.0 0.4 97.4 0.4 97.4 0.5
Abrams Lite iCVC 37.5 95.6 0.7 94.5 0.9 84.9 3.3
FROG Sleeve 44.1 92.1 1.4 92.9 1.1 87.6 1.8
FROG Torso 114.0 71.3 3.6 49.9 4.6 49.3 4.1
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Summary of Bite Protection Evaluation of US Army
UniformsACUs, FRACUs, Nomex
Specimen (Co)-Type-Treatment Air Perm (cfm) Bite Protection (SE) Bite Protection (SE) Bite Protection (SE)
Specimen (Co)-Type-Treatment Air Perm (cfm) 0x 20/25x 50x
ACU IDA 6.1 99.9 0.1 98.8 0.5 95.1 0.9
BI-ACU-FT 6.1 98.9 0.4 99.5 0.3 tbd
FRACU IDA 55.9 91.2 0.9 n/a n/a
WK-FT-FRACU 55.9 95.9 0.5 87.4 1.9 74.9 2.6
BO-FT-FRACU 55.9 92.1 1.0 92.6 1.2 76.3 1.9
WK-S-FRACU Reform Bind 55.9 86.1 1.2 83.8 0.9 80.9 1.2
BO-R2-FRACU Reform Bind 55.9 91.8 0.9 87.2 1.9 78.3 2.5
Nomex iCVC/A2CU 96.5 89.0 1.7 58.6 3.4 48.9 3.4
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Comparison of Air Permeability (CFM) andBite
Through () of Twill and Ripstop Combat Uniforms
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Evaluation of NWU Field TreatmentHand Can,
Spray Can, IDA Kit(Collaboration with CDR
Schoeler,JAX-NECE)
Bite protection evaluation initiated 18 Nov
2009- Initial (0x laundered specimens) 3
volunteers control bite through 30.5 7.7
Hand Can (BP) Spray Can (BP) IDA Kit (BP)
Ae. aegypti 100.0 0.0 88.0 3.7 98.8 1.2
An. albimanus 96.6 2.0 90.8 1.0 100.0 0.0
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Treated Fabric Strips

• FRACU fabric obtained from Natick Soldier Center
• Single-ply fabric cut into (25.5 cm x 33.2 cm x
  21.0 cm side) trapezoids (691 cm2 area) and sewn
  into sleeves.
• Chemicals Permethrin on uniform plus additional
  fast-acting insecticides ( with Kamal
  Chauhan-IIBBL).

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Evaluation of untreated and permethrin treated
sleeves with a (20.5 cm x 2.6 cm) untreated,
several volatile pyrethroids, or volatile
insectide-treated fabric strips affixed with
Velcro to the wrist regionMaterial was the US
Army Fire Resistant Army Combat Uniform (FRACU)
(65 Rayon, 10 Nylon, 25 Para-aramid)
Sleeve (Treatment and Concentration) Ultrathon 12 hr repellent (34.34 DEET) applied on hand Ae. aegypti Strip (Treatment and Concentration) Fed () Bite Protection ()
Untreated (Control) Untreated 26.7 ----
Untreated TL-I-73 at 0.163 mg/cm2 38.8 -45
Permethrin 0.135 mg/cm2 Untreated 7.6 71.5
Permethrin 0.134 mg/cm2 TL-I-73 at 0.163 mg/cm2 1.5 94.5
Untreated UB-21 at 0.158 mg/cm2 2.9 89.2
Permethrin 0.134 mg/cm2 UB-21 at 0.158 mg/cm2 0.0 100.0
Permethrin 0.134 mg/cm2 TL-III-23 at 0.172 mg/cm2 0.5 98.1
Permethrin 0.134 mg/cm2 TL-III-25 at lt 0.090 mg/cm2 3.7 86.1
Permethrin 0.134 mg/cm2 TL-III-27 at 0.187 mg/cm2 0.5 98.2
Permethrin 0.134 mg/cm2 TL-III-29 at 0.211 mg/cm2 4.5 83.2
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Treated FRACU (0.134 mg/cm2)/treated strip
(0.158 mg/cm2)DEET-protected hand
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Anosmia (noun)

• Absence of odour sensitivity
• Absence/decrease of sense of smell
• Lack of or decrease in olfaction, either
  permanent or temporary
• On average used 2 times of 100 million spoken
  words in English (Websters Online)

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A typical repellent functions as a feeding
deterrent or contact irritant. The surface is
unappealing to land on, remain in contact with,
or feed through.
Adapted from Bernier, U.R., Laboratory Research
and Development of Attractants, Inhibitors and
Repellents, Tech. Bull. Florida Mosq. Control
Assoc., 2006, 99-16.
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An attraction-inhibitor decreases host-finding by
masking or cloaking the presence of kairomones
evident by anosmia exhibited by the insects.
?
Adapted from Bernier, U.R., Laboratory Research
and Development of Attractants, Inhibitors and
Repellents, Tech. Bull. Florida Mosq. Control
Assoc., 2006, 99-16.
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Non-competitive assays Addition of a small
amount of inhibitor to an attractant blend or to
human emanations results in decreased attraction
of Ae. aegypti
Data acquired 20-26 June 2000
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Non-competitive assays Candidate
attraction-inhibitors combined with the
attractant blend (Aedes aegypti) Tukeys HSD (P
0.05) (F45,287 59.6, P lt 0.001)
e
Efficient Inhibition
d
31.9
c
b
a
Data acquired 2 May 2005 23 July 2007
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Non-competitive assays Response of Anopheles
albimanus to a subset ofattraction-inhibitorsAtt
ractant L-lactic acid methylene
chlorideTukeys HSD (P 0.05) (F14,95 15.2, P
lt 0.001)
Efficient Inhibition
d
c
b
a
Data acquired 9 May 2006 -11 September 2007
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Evaluation of Selected Inhibitors in a
Single-Tube Two-Port OlfactometerPhlebotomus
papatasi
Compound () Captured on Inhibitor Side () Captured on Control Side () Remaining in Central Chamber
1-methylpiperazine I7 21.0 71.9 7.0
1-methylpyrrolidine I3 25.0 46.4 28.6
1-ethylpiperazine I11 25.0 60.4 14.6
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Evaluation of Inhibitors with MM-X Traps in
Aswan, Egypt Collaboration with NAMRU-3gt 93
Phlebotomus papatasi
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Release devices designed forgt 24 h protection
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Comparison-2007 vs. 2006 total sand flies Over 12
Trap Nights
2007
2006
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Technical StaffPhotos
Greg Allen Jesse Durrance Natasha
Elejalde Nathan Newlon Maia Tsikolia
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(No Transcript)
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Dan Kline, Jerry Hogsette--Honorary Members
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Probability that I would not mention Dan Kline in
a talk