Worldwide Developments of Pesticides for Vector Control Graham Bruce White PhD Graham Bruce White PhD consultant to the Deployed War-Fighter Protection (DWFP) Research 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 Diseases VECTORSDISEASESPREVALENCE mosquitoesmalaria >2 million deaths/year lymphatic filariasis >1 billion infected arboviruses: JE, DEN, WNV, YF etc spreading & epidemics increasing flies & cockroaches dysentery Global & repetetive Phlebotomine sandflies Leishmaniases focal <1million/year fleasPlaguewidespread blackfliesOnchocerciasis focal <10 m cases tsetse African trypanosomiases focal < 5 m cases Reduviid bugs Chagas disease 24m cases in 15 countries Ticks & mites Borrelioses, Ehrlichias etc widespread

Mosquito Control:  Proven methods of control: environmental, biological, CHEMICAL, physical, physiological, trapping…management approach  Targetting in air, in water, on substrates  Possibilites for personal protection and/or mosquito population suppression/diversion, intermittent or sustained……elimination

Mosquito Target Options  Ovicides & habitat manipulation  Larvicides – density dependent effectiveness  Adulticides & Repellents: – reduction of vectorial capacity – reduction of vectorial capacity by combined impact on:  density  survival-rates  man-vector contact

Primary Manufacturers of Pesticides BASFGermany Bayer ( includes Agrevo, Aventis, Wellcome ) Germany CheminovaDenmark DowUSA FMCUSA MakteshimIsrael SumitomoJapan Syngenta ( includes ICI, Novartis, Zeneca ) Switzerland Innumerable generic producers Argentina, China, India, Hungary, Italy, S Korea etc.

Insecticides for Vector Control (VC) approved by WHOPES Classactive ingredientGlobal use* for VCEPA status Organochlorines DDT, dieldrin Restricted by UNEP- Organophosphates FenitrothionWidespread R, S- FenthionWidespread L, Sphase-out malathionWidespread L, R, S(+) naled-+ Pirimiphos-methylWidespread L, R, S- temephosWidespread L(+) carbamatesbendiocarbWidespread R- propoxurWidespread, R, S- pyrethroidsnatural pyrethrinsConsumer/Domestic+ syntheticsnon-RLimited+ R non-αWidespread R, S+ R α-cyanoDominant R, S-/+ IGRsJH mimicsWidespread+ chitin inhibitorLimited- *L, larvicide; R, residual; S, space-spray

Novel insecticides Benzoylureas, e.g. novaluron (Makteshim) Neonicotinoids, e.g. imidacloprid (Bayer) Phenylpyrazoles, e.g. fipronil (BASF) Spinosins, e.g. spinosad (Dow)

Pesticide formulations EC, emulsifiable concentrate SC, suspension concentrate CS, capsule suspension EW, emulsion in water WG, wettable grain WP, wettable powder aerosol

product$/galRate*$/acreCost ratio Synergized Permethrin2.0<1 Malathion 96% tech Naled (Dibrom™ 14) ~1 Fenthion (Baytex™ LC) x Synergised Resmethrin (Scourge™ 18-54) x Adulticide Cost Comparison *highest label rate: 10 mph

Mosquito Repellents provide only transient personal protection inconveniently  DMP (USDA/CMAVE)  Deet (USDA/CMAVE)  Ethyl hexanediol  Indalone  Di-n-propylisocinchoronate  Bicycloheptene dicarboximide  Tetrahydro furaldehyde  IR3535 (Bayrepel)  SS220 (USDA/CAIBL)  skin-so-soft™ (Avon)  citronella & many others of dubious value

from ITNs (Insecticide-Treated Nets) to LLINs (Long-Lasting Insecticidal Nets) Olyset™ − Sumitomo Permanet™ − Vestergaard-Frandsen

Fifth update on Long Lasting Insecticidal Nets Current Status And Programmatic Issues: Geneva, 5/01/2004 PermaNet 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 following conclusions and recommendations: “PermaNet 2.0 is a long lasting insecticidal mosquito net where the insecticide (deltamethrin 55 mg a.i./m 2 ) 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:  retain/improve/acquire/invent safe & fast-acting chemicals for:  better personal protection from mosquitoes & other biting arthropods  more effective community-wide vector control programs  improved targetting of vectors (enhanced formulations & equipment)  overcoming vector resistance problems with new actives  foster newly productive and growing collaborations, involving industry, academia & government agencies involving industry, academia & government agencies  deliver new products for vector control potentially benefitting mankind generally as well as particular interest groups (military, industry, mosquito control workers)

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 Public Health Pesticides  European Commission – Biocides Directive  FQPA objective: EPA to consider unique benefits of public health pesticides  Definition of public health pesticide: any minor use pesticide used predominantly in public health programs for vector control or other recognized health protection uses

Public Health Pesticides -- Unreasonable Adverse Effects EPA must consider the risks and benefits of public health pesticides separate from risks and benefits of other pesticides Risks of vector pesticides

Public Health Pesticides FQPA considerations  Expedited registration of PHPs  Data requirements commensurate with PH needs  Waiver of fees  Views of DHHS when canceling PHPs  $12 million for DHHS testing of PHPs  EPA/DA/DHHS to develop program to control 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