Pesticide Resistance in Bed Bugs Everywhere!!!!!
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2/24/2018 Pesticide Resistance in Bed bugs were virtually eradicated from the U.S. in Bed Bugs the post WWII era due to DDT and other powerful Shujuan (Lucy) Li insecticides. University of Arizona Alvaro Romero New Mexico State University 2 By the 1960s, bed bugs had developed resistance Public housing Apartments to DDT, methoxychlor and analogues, BHC, Schools dieldrin and analogues , and pyrethrins ( Busvine 1958, Hospitals Nursing homes Cwilich & Mer 1957, Mallis and Miller 1964 ) . Homes Transportation Child care Medical facilities Hotels & motels Health care facilities Airports Movie theaters Department stores Products, vendors, or commercial services mentioned or pictured in this seminar are for Everywhere!!!!! illustrative purposes only and are not meant to be endorsements. 3 4 University of Arizona; Arizona Pest Management Center 1 2/24/2018 Possible reasons for treatment failure? Missed some Clutter Reintroduction Have you seen these after treatments? 5 6 Dose - response assays for field - collected strains Bed bugs survived direct insecticide sprays 99 deltamethrin 90 Ft. Dix F1 50 ) e l a c 10 s t CIN1 i b o 1.0 r p ( y t i l a t r 99 - cyhalothrin o m e 90 g a t n Resistance ratio (RR) at least 6,000 !!! e c Ft. Dix r 50 e P 10 CIN1 Suspend® ( Deltamethrin ) 1.0 10 -7 10 -6 10 -5 10 -4 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 10 4 Treatment (mg active ingredient/cm 2 ) Products, vendors, or commercial services mentioned or pictured in this seminar are for illustrative purposes only and are not meant Romero et al. (2007) J. Med. Entomol . to be endorsements. University of Arizona; Arizona Pest Management Center 2 2/24/2018 Pesticide Resistance • Describes the decreased susceptibility of a pest population to a pesticide that was previously effective at controlling the pest. • Occurs when a population of insects builds up a tolerance to a specific chemical, or group of chemicals with the same Mode of Action, or the mechanism by which the chemical causes death in the pest. • Pests evolve pesticide resistance via natural selection: the most resistant individuals survive and pass on their genetic traits to their offspring. 9 https:// en.wikipedia.org /wiki/ Pesticide_resistance 10 Reports of insecticide resistance in “modern” bed bugs DENMARK • Pyrethroids • Carbamates UK • Pyrethroids • Carbamates Resistance Mechanisms in GERMANY JAPAN Pyrethroids Pyrethroids FRANCE Bed Bugs Pyrethroids USA THAILAND • Pyrethroids C. lectularius ISRAEL • Pyrethroids • Organophosphates Pyrethroids • Neonicotinoids • DDT • Carbamates • Organophosphates KENYA C. hemipterus Pyrethroids • Pyrethroids C. lectularius SRI LANKA MALAYSIA • DDT C. hemipterus DDT • Carbamates TANZANIA • Pyrethroids Pyrethroids • Organophosphates C. hemipterus Pyrethroids • DDT • Carbamates C. lectularius and C. hemipterus • Organophosphates AUSTRALIA C. lectularius • Pyrethroids • Carbamates • DDT C. hemipterus • Pyrethroids Dang et al. 2017 12 University of Arizona; Arizona Pest Management Center 3 2/24/2018 Four Types of Resistance Penetration Resistance 1) Penetration – resistant insects may absorb the • Resistant bed bugs may absorb the toxin toxin slower than susceptible insects. slower than susceptible insects. 2) Target - site – the target site where the toxin usually • Reduced cuticular penetration – thickening or acts in the insect has been genetically modified to remodeling of the cuticle may contribute to reduce the product’s effects. decreased 3) Metabolic – resistant insects may naturally detoxify insecticide or destroy the toxin faster than susceptible insects, penetration. or quickly rid their bodies of the toxic molecules. 4) Behavioral – resistant insects may detect or recognize a danger and avoid the toxin. Photography by Tim Flach , Getty Images. Insecticide Resistance ActionInsecticide Committee Resistance Action Com http :// www.irac - online.org /about/resistance/mechanisms/ 13 PENETRATION RESISTANCE Target - site Resistance • Reduced insecticide toxicity through cuticle ( Koganemaru et al. 2013) • Thickening of cuticle (Lilly et al. 2016) • The target site where the toxin usually acts in • Upregulation of cuticular protein genes associated with insecticide the insect has been genetically modified to resistance ( Bai et al. 2011, Mamidala et al. 2012, Koganemaru et al . 2013, Zhu et al. 2013) reduce the product’s effects. • Commonly used insecticides target an ion channel and cause nerves to fire continuously, paralyzing and quickly killing the insects - resistant bed bugs may carry a mutation in the ion channel that prevents the pesticide from binding. University of Arizona; Arizona Pest Management Center 4 2/24/2018 TARGET - SITE INSENSITIVITY 1. VGSC : Pyrethroids , DDT “Knockdown resistance ( Kdr - type)” C. lectularius : - V419L / L925I (USA , Europe, Asia, Australia) - I936F (Australia) C. hemipterus - M918I / L1014F (Australia, India, Thailand, Malaysia, Kenya) 2. AChEs : OPs, carbamates “Altered AChEs ” - (CAChE1, CAChE2 ) Binding site 3. GABA receptors: Cyclodienes (e.g. dieldrin ), Fipronil “ Insensitive GABA receptors or Rdl - mutation ” 4. nAChRs : Neonicotinoids ? “Altered nAChRs ” V oltage - gated sodium channel (VGSC), acetylcholinesterase ( AChE ), organophosphate (OP ), gamma - aminobutyric acid (GABA), GABA - gated chlorine channel (GABA receptors), nicotinic acetylcholine receptors ( nAChRs ) Zhu et al. 2010, Durand et al. 2012, Yoon et al. 2008, Seong et al. 2010, Palenchar et al. 2015, Dang et al. 2015 and 2017, Romero and Anderson 2016 Metabolic Resistance METABOLIC RESISTANCE • Metabolic enzymes (namely p450s, esterases , and GSTs), as well as ABC transporters) are involved. Detoxifying enzymes • A broad spectrum of activity against different insecticide classes. Binding site Glutathione S - transferases ( GSTs), ATP - binding cassette (ABC) transporters University of Arizona; Arizona Pest Management Center 5 2/24/2018 Physiological Resistance • P450s Overexpression of genes • M ultiple mechanisms may contribute to pyrethroid Increased enzymatic activity resistance simultaneously in a single bed bug Inhibition by chemicals (synergists) population ( Adelman et al. 2011, Bai et al. 2011, Mamidala et al. • Esterases Overexpression of genes 2012, Zhu et al. 2013 ). Increased enzymatic activity Inhibition by chemicals (synergists) • P enetration resistance ( cuticular proteins), target • GST O verexpression of genes site insensitivity ( kdr - type), metabolic resistance Increased enzymatic activity (metabolic detoxifying enzymes P450s and • ABC Transporters Overexpression of genes esterases , ABC transporters)( Yoon et al. 2008, Zhu et al. Increased efficiency of toxin removal 2010, Adelman et al. 2011, Koganemaru et al. 2013, Mamidala et al. 2011 and 2012 ) . Adelman et al. 2011, Zhu et al. 2010 and 2013, Romero et al. 2009, Hardstone et al. 2015. Mamidala et al. 2012. Behavioral Resistance • Resistant insects may detect or recognize a danger and avoid the toxin. Detoxifying enzymes • Stimulus - dependent behaviors (e.g. irritability and repellency). – Excito - repellency in bed bugs ( Romero et al. 2009 ) – Potential behavioral resistance Target site insensitivity • Understand bed bugs’ unique behavior. Adelman et al. (2011) Mamidala et al. (2012) Zhu et al. (2013) University of Arizona; Arizona Pest Management Center 6 2/24/2018 Multiple resistance, and cross resistance? How can we use information on insecticide resistance for resistance management? • Target - site insensitivity - Monitor resistance • Metabolic resistance - Development of chemicals that inhibit detoxifying enzymes associated with resistance (synergists). • P enetration resistance - Development of insecticides and formulations to enhance insecticide penetration through the cuticle. Factors Affecting Bed Bug Control Integrated approaches for management of • The extent of the infestation. pesticide resistance • H ow well the area is prepared (hiding places • Integrated Pest Management (IPM) approach is the removed, bed isolated, laundering of linens, most likely strategy to successfully eliminate bed bugs. etc. ). • Integrated approaches for management of • The quality and coverage of the pesticide potentially resistant bed bugs. application. • Choose most appropriate treatment options based • The targeting of all life stages. on: – Level of infestation • Whether or not the bed bug population has – Level of clutter developed resistance either to the specific – Square footage pesticide or to the class of pesticides. – Customer needs – Structure types 27 28 University of Arizona; Arizona Pest Management Center 7 2/24/2018 Non - chemical m ethods Chemical Methods Becoming the primary methods used • > 300 EPA registered products. in combination with chemical • Seven chemical classes of pesticides: methods. • Pyrethrins – Heat (>122 ° F) • Pyrethroids e.g. Dryer, steam, heat container • Neonicotinoids – Cold • Desiccants ( DE, Cimexa , Boric acid) • Biochemicals ( Cold pressed neem oil ) e.g. Freezer, liquid CO 2 – Vacuuming • Pyrroles ( chlorfenapyr ) • Insect growth regulators – Isolation e.g. Encasement, bag infested items • Dichlorvos (known as DDVP, an organophosphate) as a pest strip. 29 30 G r o u p 1 5 : I n h i b i to r s o f c h i ti n b i o s y n th e s i s , ty p e 0 ( O n l y m a j o r r e p r e s e n ta ti v e s o f t h e g r o u p a r e s h o w n ) G r o u p 1 : A c e ty l c h o l i n e s te r a s e (A C h E) i n h i b i to r s (O n l y ma j o r r e p r e se n t a t i ve s o f t h e g ro u p s a r e sh o w n ) Mo d e o f A c ti o n C l a s s i fi c a ti o n F l u f e n o xu ro n N o va l u ro n T ri f l u mu ro n A ce p h a t e Me t h a mid o p h o s A ld i ca rb O xa myl • Resistance to pyrethroid products is D i f l u b e n zu ro n L u f e n u ro n T e f l u b e n zu ro n 15 Be n zo yl u re a s F e n i t ro t h i o n Me t h i o ca rb G r o u p 1 6 : I n h i b i to r s o f G r o u p 1 7 : Mo u l ti n g G r o u p 1 8 : Ec d y s o n e r e c e p to r a g o n i s ts C a rb a ryl T h io d i ca rb C h l o rp yri f o s Pr o f e n o f o s c h i ti n b i o s y n th e s i s , d i s r u p to r s , D i p te r a n ty p e 1 very high.