Worldwide Developments of Worldwide Developments of Pesticides for Vector ControlPesticides for Vector Control

Graham Bruce White PhDGraham Bruce White PhDconsultant to theconsultant to the

Deployed War-Fighter Protection (DWFP) Deployed War-Fighter Protection (DWFP) Research ProgramResearch Program

from DDT to DWFP

AFPMB funding $5m/yr (W81XWH-FY04 recurrent) to upgrade DWFP

“Deployed War-Fighter Protection from Disease-Carrying Insects”

by R&D support for:• academic experts (universities etc)• industry (chemical & equipment cos.)• govt agencies (Fed & State & local)• international collaborations

Vectors of Human DiseasesVectors of Human Diseases

VECTORSVECTORS DISEASESDISEASES PREVALENCEPREVALENCE

mosquitoesmosquitoes malaria malaria >2 million deaths/year>2 million deaths/year

lymphatic filariasislymphatic filariasis >1 billion infected>1 billion infected

arboviruses: JE, DEN, WNV, YF etcarboviruses: JE, DEN, WNV, YF etc spreading & epidemics increasingspreading & epidemics increasing

flies & cockroachesflies & cockroaches dysenterydysentery Global & repetetiveGlobal & repetetive

Phlebotomine sandfliesPhlebotomine sandflies LeishmaniasesLeishmaniases focal <1million/yearfocal <1million/year

fleasfleas PlaguePlague widespreadwidespread

blackfliesblackflies OnchocerciasisOnchocerciasis focal <10 m casesfocal <10 m cases

tsetsetsetse African trypanosomiasesAfrican trypanosomiases focal < 5 m casesfocal < 5 m cases

Reduviid bugsReduviid bugs Chagas diseaseChagas disease 24m cases in 15 countries24m cases in 15 countries

Ticks & mitesTicks & mites Borrelioses, Ehrlichias etcBorrelioses, Ehrlichias etc widespreadwidespread

Mosquito Control:Mosquito Control:

Proven methods of control: Proven methods of control: environmental, biological, environmental, biological, CHEMICALCHEMICAL, physical, , physical,

physiological, trapping…management approachphysiological, trapping…management approach

Targetting in Targetting in airair, in , in waterwater, on , on substratessubstrates Possibilites for personal protection and/or Possibilites for personal protection and/or

mosquito population suppression/diversion, mosquito population suppression/diversion, intermittent or sustained……eliminationintermittent or sustained……elimination

Mosquito Target OptionsMosquito Target Options

Ovicides & habitat manipulationOvicides & habitat manipulation Larvicides – density dependent effectiveness Larvicides – density dependent effectiveness Adulticides & Repellents:Adulticides & Repellents:

– – reduction of vectorial capacity reduction of vectorial capacity

by combined impact on: by combined impact on: density density survival-rates survival-rates man-vector contact man-vector contact

Primary Manufacturers of PesticidesPrimary Manufacturers of PesticidesBASFBASF GermanyGermany

Bayer (Bayer (includes Agrevo, Aventis, Wellcomeincludes Agrevo, Aventis, Wellcome)) GermanyGermany

CheminovaCheminova DenmarkDenmark

DowDow USAUSA

FMCFMC USAUSA

MakteshimMakteshim IsraelIsrael

SumitomoSumitomo JapanJapan

Syngenta (Syngenta (includes ICI, Novartis, Zenecaincludes ICI, Novartis, Zeneca)) SwitzerlandSwitzerland

Innumerable generic producersInnumerable generic producers Argentina, China, India, Argentina, China, India,

Hungary, Italy, S Korea etc.Hungary, Italy, S Korea etc.

Insecticides for Vector Control (VC) approved by WHOPES

Class active ingredient Global use* for VC EPA statusOrganochlorines DDT, dieldrin Restricted by UNEP -

OrganoOrgano

phosphatesphosphatesFenitrothion Widespread R, S -

Fenthion Widespread L, S phase-out

malathion Widespread L, R, S (+)

naled - +

Pirimiphos-methyl Widespread L, R, S -

temephos Widespread L (+)

carbamates bendiocarb Widespread R -

propoxur Widespread, R, S -

pyrethroids natural pyrethrins Consumer/Domestic +

synthetics non-R Limited +

R non-α Widespread R, S +

R α-cyano Dominant R, S -/+

IGRs JH mimics Widespread +

chitin inhibitor Limited -

*L, larvicide; R, residual; S, space-spray

Novel insecticidesNovel insecticides

• Benzoylureas, e.g. novaluron (Makteshim)

• Neonicotinoids, e.g. imidacloprid (Bayer)

• Phenylpyrazoles, e.g. fipronil (BASF)

• Spinosins, e.g. spinosad (Dow)

Pesticide formulationsPesticide formulations

• EC, emulsifiable concentrate

• SC, suspension concentrate

• CS, capsule suspension

• EW, emulsion in water

• WG, wettable grain

• WP, wettable powder

• aerosol

product $/gal Rate* $/acre Cost ratio

Synergized Permethrin 2.0 <1

Malathion 96% tech 24 4.3 0.121 1

Naled (Dibrom™ 14) 87 1.2 0.123 ~1

Fenthion (Baytex™ LC) 138 2.4 0.388 3.2x

Synergised Resmethrin (Scourge™ 18-54)

250 3.6 1.050 8.7x

Adulticide Cost Comparison

*highest label rate: fl.oz./min. @ 10 mph

Mosquito RepellentsMosquito Repellentsprovide only transient personal protection inconvenientlyprovide only transient personal protection inconveniently

DMP (USDA/CMAVE)DMP (USDA/CMAVE) Deet (USDA/CMAVE)Deet (USDA/CMAVE) Ethyl hexanediolEthyl hexanediol Indalone Indalone Di-n-propylisocinchoronate Di-n-propylisocinchoronate Bicycloheptene dicarboximideBicycloheptene dicarboximide Tetrahydro furaldehyde Tetrahydro furaldehyde IR3535 (Bayrepel)IR3535 (Bayrepel) SS220 (USDA/CAIBL)SS220 (USDA/CAIBL) skin-so-softskin-so-soft™™ (Avon) (Avon) citronella & many others of dubious valuecitronella & many others of dubious value

from ITNs (Insecticide-Treated Nets)from ITNs (Insecticide-Treated Nets)to to LLINs (Long-Lasting Insecticidal Nets)LLINs (Long-Lasting Insecticidal Nets)

• Olyset™ − Sumitomo• Permanet™ − Vestergaard-Frandsen

Fifth update on Long Lasting Insecticidal NetsCurrent Status And Programmatic Issues: Geneva, 5/01/2004PermaNet 2.0, a New LLIN Recommended by WHO

The 7th WHOPES Working Group Meeting, held in WHO/HQ, Geneva, 2-4 December 2003,reviewed the results of laboratory and field studies of PermaNet and made the followingconclusions and recommendations:

“PermaNet 2.0 is a long lasting insecticidal mosquito net where the insecticide (deltamethrin 55 mg a.i./m2) is mixed in a resin coating the netting fibers so that the insecticide is progressively released from the resin and the net retains efficacy after repeated washings.

GOALS of DWFP: GOALS of DWFP:

retain/improve/acquire/invent retain/improve/acquire/invent safe & fast-acting chemicalssafe & fast-acting chemicals for: for:

better personal protection from mosquitoes & other biting arthropodsbetter personal protection from mosquitoes & other biting arthropods more effective community-wide vector control programsmore effective community-wide vector control programs improved targetting of vectors (enhanced formulations & equipment)improved targetting of vectors (enhanced formulations & equipment) overcoming vector resistance problems with new activesovercoming vector resistance problems with new actives

foster newly productive and growing collaborations, foster newly productive and growing collaborations, involving industry, academia & government agenciesinvolving industry, academia & government agencies

deliver new products for vector control deliver new products for vector control potentially benefitting mankind generallypotentially benefitting mankind generallyas well as particular interest groups as well as particular interest groups (military, industry, mosquito control workers) (military, industry, mosquito control workers)

DWFP steps towards better VC insecticides:DWFP steps towards better VC insecticides:

• USDA to boost PH insecticide R&D • EPA to allow RR status for PH pesticides• EPA to reassess risk/benefits of VC products• Re-motivate Pesticides Industry • Stimulate insecticide R&D:

discovery/development/production • New actives/formulations/manufacturers• Global VC spin-off to developing countries

Regulatory issues for Regulatory issues for Public Health PesticidesPublic Health Pesticides

European Commission – European Commission – Biocides DirectiveBiocides Directive

FQPA objective: EPA to considerFQPA objective: EPA to considerunique benefits of public health pesticidesunique benefits of public health pesticides

Definition of public health pesticide: Definition of public health pesticide: any minor use pesticide used predominantly any minor use pesticide used predominantly in public health programs for vector control in public health programs for vector control or other recognized health protection usesor other recognized health protection uses

Public Health Pesticides --Public Health Pesticides --Unreasonable Adverse EffectsUnreasonable Adverse Effects

EPA must consider the EPA must consider the risks and benefits of risks and benefits of public health pesticides public health pesticides separate from separate from

risks and benefits of risks and benefits of other pesticidesother pesticides

Risks of Risks of vector pesticides

Public Health Pesticides Public Health Pesticides FQPA considerationsFQPA considerations

Expedited registration of PHPsExpedited registration of PHPs

Data requirements commensurate with PH needsData requirements commensurate with PH needs

Waiver of feesWaiver of fees

Views of DHHS when canceling PHPsViews of DHHS when canceling PHPs

$12 million for DHHS testing of PHPs$12 million for DHHS testing of PHPs

EPA/DA/DHHS to develop program to EPA/DA/DHHS to develop program to control public health pestscontrol public health pests

AFPMB funding $5m/yr (W81XWH-FY04 recurrent) to upgrade DWFP

“Deployed War-Fighter Protection from Disease-Carrying Insects”

by R&D support for:• academic experts (universities etc)• industry (chemical & equipment cos.)• govt agencies (Fed & State & local)• international collaborations