Viruses vector control proposal: genus Aedes emphasis

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w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Review

article

Viruses

vector

control

proposal:

genus

Aedes

emphasis

Nelson

Nogueira

Reis

a

_,

_Alcino

_Lázaro

_da

_Silva

b

_,

_Elma

_Pereira

_Guedes

_Reis

c

_,

Flávia

Chaves

e

Silva

d

_,

_Igor

_Guedes

_Nogueira

_Reis

b,∗

a_Cirurgia_Vascular,_Belo_Horizonte,_MG,_Brazil

b_Universidade_Federal_de_Minas_Gerais,_Belo_Horizonte,_MG,_Brazil c_Centro_de_{Especialidades}_Médicas,_Belo_Horizonte,_MG,_Brazil

d_Faculdade_de_Ciências_Médicas_de_Minas_Gerais,_Belo_Horizonte,_MG,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received13November2016 Accepted29March2017 Availableonline31May2017

Keywords:

Dengue Vectorcontrol Aedes Arbovirus

Sterileinsecttechnique

a

b

s

t

r

a

c

t

Thedenguefeverisamajorpublichealthproblemintheworld.InBrazil,in2015,therewere 1,534,932cases,being20,320casesofsevereform,and811deathsrelatedtothisdisease. ThedistributionofAedesaegypti,thevector,isextensive.Recently,ZikaandChikungunya viruseshadarisen,sharingthesamevectorasdengueandbecameahugepublichealth issue.Withoutspeciﬁctreatment,itisurgentlyrequiredasaneffectivevectorcontrol.This articleisfocusedonreviewingvectorcontrolstrategies,theireffectiveness,viabilityand economicalimpact.Amongall,theSterileInsectTechniqueishighlightedasthebestoption tobeadoptedinBrazil,onceitislargelyeffectivelyusedintheUSAandMexicoforplagues relatedtoagribusiness.

Introduction

Denguefeverisamajorpublichealthproblemintheworld. TheWorldHealthOrganization(WHO)estimatesthat2/5of theworld’spopulationareatriskofhavingthedisease.1_It_is

themostcommondiseasecausedbyanarbovirus.2_The

dis-tributionofAedesaegypti,thevector,iswidespread,alongwith the simultaneouscirculationoffour serotypes ofthe virus (DENV1,DENV2,DENV3,andDENV4).1,3

Associatedwiththis problem,once theyhavethe same vector, Zika and Chikungunya are on the rise. Since2007,

∗ _{Corresponding}_author.

E-mailaddress:[email protected](I.G.Reis).

55 countries from America,Asia,Africa,and Oceania have detectedlocaltransmissionofZykavirus.However,theﬁrst outbreakoccurred in2015affectingalmost1.5million peo-ple in Brazil,with 80% asymptomatic cases. Sincethen, it hasbeenreportedin31countriesandAmericanterritories. Recently,asevereassociationbetweenZykavirusand micro-cephalia, retina lesions,and Guillian-Barrè syndrome have beenreported.4_The_recent_outbreaks_in_the_South_America,

CentralAmerica,andtheCaribbeansrepresentthearbovirus mostsevere episodeintheEast hemisphereon thelast 20 years.

http://dx.doi.org/10.1016/j.bjid.2017.03.020

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Chikungunyaemergedin2013,andleavesatrailofjoint symptoms.Notably,therearenospeciﬁctreatmentsforthese arboviruses.Inthisseverescenario,effectivevectorcontrolis crucial,speciallyA.aegyptiandAedesalbopictus,highlyinvasive species.5

In 2015, between January and November, 1.5 million DenguecaseswasidentifiedinBrazil,accordingtothe Min-istry of Health. In the same period, 17,146 Chikungunya suspectcaseswasidentified,6726beingconfirmedlater. Fur-thermore,Zykawasdetectedin18Brazilianstates,with739 suspectedcasesofmicrocephalytill21stofNovember,2015.6

In2016,1,399,480probableDenguecaseswereregistered aroundthecountry,between3rdofJanuaryand9thofJuly. Additional499,317casesweredroppedlater.RegardingZyka, 14,739wereregisteredasprobable,6903beingconﬁrmedlater byclinicalandepidemiologicalcriteriaorlaboratorytesting. InrelationtoChikungunya,itwas169,656probablecases.7

Economicimpact

TherealeconomicimpactofDengueisnotwelldocumented. ItisestimatedasanaverageperpatientofUS541dollarsand 1394dollars,respectively,foroutpatientandinpatient treat-ment.Themeandiseasedurationis11.9daysforoutpatients and11daysforinpatients.Amonginpatients,studentslost5.6 schooldaysandadults9.9workingdaysduetothiscondition. Thisdisease imposessubstantialcostseitheronthehealth sectorandgeneraleconomy.8

Thetotalestimatedcost was468million dollarsa year, inastudyperformedbetween2009and2013.Adjustingfor theunreportedcases,thecostjumpsto1212milliondollarsa year.9

The incidence, mortality, and morbidity of Dengue are underestimated. “Global Burden of Diseases Study, 2013” reportestimatedanaverageof9221deaths,causedbythis arbovirus,ayear,between1990and2013,being8277in1990 andpeaking11,302in2010.Itresultedinatotalof576,900 yearsoflifelostbyprematuredeathduetodenguefeverin 2013alone.Theincidenceconsiderablyraisedbetween1990 and2013, withthenumber ofcasesdoubling each decade. Consideringacute,mildandsevere cases,andpost-dengue chronicfatiguetherewillbeabout566,000livedyears with incapacity.Consideringfatalandnon-fataloutcomestogether, denguewasresponsiblefor1.14millionyearslostdueto inca-pacity,in2013.Itisbelievedthatthesenumberswereeven higher.2

In Brazil,the incidencein 2014 was 555,462 cases. The potentially severe clinical presentation accounted for 8975 casesand453deaths.In2015,therewere1,534,932cases,being 20,320severeand811deaths.2,10_If_laboratory_testing_were

rou-tinelyperformedonthesuspectcases,therewouldcertainly beevenmorediagnosedpatients.11

Regarding Zyka and Chikungunya, the studies on inci-dence,mortality,morbidity,andsequelaeratesofmid-and long-termare atearlystages.Inmicrocephalycasesdueto Zika,itisestimatedthatthesocialandeconomicalcostswill behugeandlonglasting.

The A. aegypti control and dengue prevention in São Paulo,Brazil,in2005,had anestimatedcostof1.99dollars perperson.Itwas considered:humanresources, uniforms,

ﬁeld material, individual protection material, pulverizing equipments,strategicsupply(insecticideandlarvicide),and vehicles.Itshouldbeaddedtothecostsoflaboratorytesting, educationalinformation,andpressmaterial.12 _According_to

theBrazilianMinistryofHealth,2010–2014, thefederal gov-ernmentspentaroundR$4.2billioninpreventivemeasures and Denguetreatment.Duringthatperiod,theexpenditure withthediseaseraised48%–fromR$613.4millionin2010to R$911.8millionin2014.13

TheDenguevectorandotherviruses

TheDenguevectorinBrazil,inurbanareasistheA.aegypti.14

ItisalsotheYellowFever,theZikavirus,andtheChikungunya vector. It prefersplaces with higherhuman concentration. SpeciesfromAfrica,belongtothephylum Arthropoda,class

Insecta,orderDiptera,familyCulicidae,genusAedes.The repro-duction anddispersion stagesoccur whenthe mosquitois adult.Duringthenuptialﬂight,thewingedadult,femaleand malemateonce.Asingleinseminationisenoughtofertilizeall theeggs.Theycantravelupto300m,andthepregnantfemale canﬂyupto3km.Theyfeedonplantsyrup,butthefemale needbloodproteintomaturetheireggs.15_Other_species_of_the

AedesgenushavebeendetectedinBrazil.16

Vectorcontrolmethods

TheAedesmosquitoisacrescentpublichealthconcern,and itscontroloreradicationisurgent.Theavailableorin devel-opmentcontrolmethodscanbedividedintoﬁvecategories:1 –environmentalbreedingsitescontrol;2–mechanicaltraps; 3–insectfertilityreductiontechnique;4–insecticides;and5 –transgenicinsect.17

Reductionofvectorbreedingsitesintheenvironment

Itisthecontrolofthevectorbreedingsitesinstandingwater. Permanent actionsdecrease breeding focus.Education and population’sparticipationarenecessary.Itisrecommended continuingpreventivemeasuresandvisitstoallriskspotsin ordertoﬁghtthevectorinearlystages.1

Mechanicaltraps

Therearedifferenttypesoftraps,whichimprisontheinsects, theeggs,andthelarvae.

Insectfertilityreductiontechniques

Therearetwobiologicalstrategiesofvectorcontrol:Wolbachia

relatedtechniqueandsterileinsectproductionbyradiation technique.

Ontheﬁrststrategy,itwasproposedtheinfectionofAedes

mosquitoes with Wolbachia endosymbiotic, which inhibits the viralreplicationand dissemination.Onthe14thdayof infection,theWolbachiacompletelyblockstheDengue trans-missioninatleast37.5%.Theseresultshighlightthepotential usefulnessofWolbachiabasedstrategiestoprotectthe popu-lationfromDenguefever.18

Onthesecondstrategy,themalesproducedinlaboratory areexposedtolowradiationandsterilized,whilekeepingthe copulationcapacity.Theinsectmadewithimpairedfertilityis releasedintotheenvironmenttomatewithwildinsectsand

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producesterileeggs,eliminatingthenthenextgeneration.In astudy,thematingcapabilitieswerecompared,i.e. insemina-tionability,sterilizingability,andmatingcompetitivenessof irradiatedmale(35Gy)andtheWolbachiabasedstrategy,with malesofdifferentages.Therewasnosigniﬁcantdifference ontheinseminationabilitybetweenirradiatedandinfected males.19

Chemicalproductstoeliminatetheinsectsorlarvae

Consistsontheinsecticideuse,withdifferentpesticide appli-cationmethods,forwingedvectorstageelimination.Inorder topreventstings,itisusedasrepellents.

Geneticengineering

Itisbasedontheproductionoftransgenicinsects,whichcarry adominantlethalallelecapableofkillingsubsequentAedes generations.20_This_strategy_was_defended_by_a_{joint-venture}

formedbyOxitecandMoscamed.TheOxitecisasubsidiary companyofIntrexon,biotechnologymultinationallistedon thestockmarketinNewYork.MoscamedisaBrazilian non-profitinstitution.Thepartnershiphasamodificationinsect factory.MosquitoesdesignatedOX513Aaremalesand have receivedtwogenes.Thefirstoneisanactivationsystembuilt fromasyntheticDNAoffusedEscherichiacoliandherpesvirus. Thesecond isa marine coralgene from Discosoma, which worksasafluorescentmarkersothatthemosquitoeshave dif-ferentluminosityincomparisontowildones,makingpossible todetectitspresencebyspeciallightexposure.Thefirstgene hastheobjectiveofshorteningtheinsect’slifeandleadtothat speciesterminationinaregion.Thisoccursasthemodified malesmatewithwildfemalesoftheenvironment,producing descendentsthatwillnotsurvivetilladultstageduetothe lethalgene.21

Discussion

Dengue, Zika and Chikungunya are relevant public health issues.Consideringthemorbimortalityrate,thecostsandthe social-economicimpacts,thecontrolandextinctionofthese diseaseswouldbringimmeasurablegainsforthenation.

Therearethreemainoptionstosolvetheproblemscaused bytheseviruses:eliminatethevirus,eliminatethevectors, orimmunizepeople.Theﬁrstoptionisnotfeasibleasﬁrst approach.

Immunizing the population using an effective vaccine withoutadverseeffectswouldbeagreatintervention.Atthe moment,Denguevaccineisonﬁeldtests,butthereisno vac-cineforZikaorChikungunyaonthehorizon.

Eliminatetheseviruses’vectorswouldalsosolvethe prob-lem,andthereareoptionsinthislineofaction.Thereduction of breeding sites in the environment, with elimination of thestandingwaterreservoirsandlarvicideuse,demand per-manentactions. Inasimilar way,the use ofinsecticide to controlthe adultmosquito. Educationand population par-ticipationare necessary.1 _In_a_tropical _country,_the _climate

andtherain conducivetoproliferation ofinsectsare a dif-ﬁcultobstacle.Thislineofactionhasbeenthebackboneof theBrazilianGovernmentDengueandotherarboviruses con-trolstrategies,withinternationalorganizationssupport,such

asWHO.Nonetheless,Denguefeverstillhasfrequentintense outbreaks. Recently,aBrazilianMinister ofHealthcameto publictosaythatthecurrentmethodsusedforvector con-trolhavebeenineffective.Inaddition,thereisthearousalof ChikungunyaandZika.

Thetechniquesofinsect’snextgenerationelimination con-sistontheinductionofsterileeggsproduction,oryoungsick insects withshorterlifecycle. These are attractiveoptions because theywould ultimately eliminate the vectors, irre-spectiveofeducationalmeasures,climate,anddoesnotuse pesticides.

Regardingtheuseoftransgenicinsecttechnique,in2012 anattemptwasmadeinJuazeiroandJacobinacities,stateof Bahia,Brazil,byreleasingthoseinsectsinthesuburbs.An80% reductionontheA.aegypti’slarvaepopulationwasreported, together with 95% reduction of adult winged mosquitoes. Theseresultsweredescribedinanindependentreview pub-lished on “PLoS NeglectedTropical Diseases”, inJuly 2015. OtherindependentstudiesontheefficacyoftheOX513Atobe conductedbyProfessorMargarethCapurro,UniversityofSao Paulo,couldnotbeconcludedduetobudgetcuts.However, preliminarydatasuggestedthemodifiedinsect’sefficacy.The testinJacobina,Bahiashoweda79%reductionoftheinsect population.Despitethesuccessnewsspreadingbythemedia, thetestdidnotleavegoodimpressionamonglocals,andthere wereimportantdemonstrationsagainstitduetostrikingraise inDenguefevercasesinthecity.Eventaking intoaccount thatthemodifiedinsectswerenotreleasedinthewholeurban area,itwasexpectedareductionofclinicalcases.Theissue waslargelyexploredatBBCnews.21

TheCNTBio,organoftheScience,Technologyand Innova-tionMinistry,releasedthecommercialuseofthetransgenic mosquito inspite ofconcerns expressedby civil organiza-tionsand thenewsofJacobina.SinceApril2015,Piracicaba city,SaoPaulo,wasthefirsttoadoptthetransgenicsaspart oftheDenguecontrolprogram.AsofMarch2015,thePublic Ministryrecommendedthe suspensionofmosquitorelease atthecity,undertheargumentthattheefficacyhadnotbeen provedandalludedtotheJacobinaepisode.Thedecisionwas revised onemonth laterand the mosquitoes were release. Itisestimatedthat23millionmosquitoeshadalreadybeen releasedinCecapandEldoradosuburbs.ThePiracicabapress informedthatitwastooearlytoevaluatetheresultsbecause therewasnobaselineforcomparison.Localdatarevealedthat 60%ofcapturedlarvaehadinheritedthemodifiedgene. How-ever,statistics showedthattherewere934Denguecasesin 2014,whiletherewasalready3668confirmedcasestill7thof December,2015.21

In2016,Piracicabaregistered142confirmedDenguecases and714notificationstill19thofFebruary,accordingtolocal Health Secretary.Also,therewere eightsuspectedcasesof Chikungunya.ThenumberconfirmedcasesofDenguewould be238%higherthan2015,ifcomparedtothedatapublished bythegovernmentatthebeginningof2014.Thenotification rateinearly2016wasalso99%higherthan2015.22

Regardingsterileeggsproductiontechnique,therearetwo maintechniques:Wolbachiabasedtechniqueandtheradiation sterilizedinsects.Theproducedinsectwithimpaired fertil-ityisreleasedontheenvironmenttomatewildinsectsand generatesterileeggs,eliminatingthenextgeneration.

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Ontheﬁrststrategy,itwasproposedtheinfectionofAedes

mosquitoes with Wolbachia endosymbiotic, which inhibits theviralreplication anddissemination.On the14thdayof infection,theWolbachiacompletelyblockstheDengue trans-missioninatleast37.5%.Theseresultshighlightthepotential usefulnessofWolbachiabasedstrategiestoprotectthe popu-lationfromDenguefever.18

Onthesecondstrategy,themalesproducedinlaboratory areexposedtolowradiationandsterilized,howeverkeeping thecopulationcapacity.Theinsectmadewithimpaired fertil-ityisreleasedintotheenvironmenttomatewithwildinsects andproducesterileeggs,eliminatingthenthenext genera-tion.Inastudy,thematingcapabilitieswere compared,i.e. inseminationability,sterilizing ability,andmating compet-itivenessofirradiatedmales35Gy andtheWolbachiabased strategy,withmalesofdifferentages.Therewasnosigniﬁcant differenceontheinseminationabilitybetweenirradiatedand infectedmales.19

Thesterileinsecttechnique(SIT)wasdesignedandcreated bythe American Entomologist E.F.Knipling as an alterna-tiveforvectorcontroloreveneradicationofthescrewworm ﬂy,Cochliomyiahominivorax, whichusedtoplaguethe cattle farms inthe USA, affectingthe leatherindustry. Theﬁnal resultwasafantasticsuccess.Theygotridofthebug. After-wards,theprojectexpandedtothesouth,involvingMexico, CentralAmerica,andColombia.Thislastcountry,considered theplagueborder,hasanalertsystem:whenevertheinsect reappearscomingfromSouthAmerica,newreleaseofsterile insectsshouldbeimplementedinordertocontrolit.23

The eradication cronology of the screwworm ﬂy in the Americas,usingSIT,isshownontheadaptedmap(Fig.1).

Theeconomicimpactwassigniﬁcantwhilecontrollingthis leatherplagueusingSIT.Beforeeradication,therewasahigh costtofarmers,whohadtospendontrainedcavalryfor peri-odicherdinspection,facilities,annuallossof10%ofthecattle herd(Texas),woundtreatment,pesticideuse,leather’s dam-ageanddepreciation.In1957,beforeeradication,theberne plaguewasresponsibleforalivestockindustrylossofU$20 millionayear,ontheSoutheast.24_On_the_same_way,_in_1960,

the cattlelosswas estimatedinmorethan U$100million annually.Aneconomicstudy,in1972,estimatedthatthe rein-fectionontheSouthwouldcosttothelivestockindustryabout U$372million.19

Thecostoferadicationprograms, in1976,was approxi-matelyU$15million.ConsideringthepotentiallossesofU$ 372million,therewasasigniﬁcanteconomicreturn.Also,it wasestimatedthattheeconomicbeneﬁtforthecattlefarmers asresultofplaguecontrol,between1962and1976,washigher thanU$1billion.19

TheSITusesionizingradiationtoinducerandom chromos-somicrearrangement,leadingtosterilemales.Itwastheﬁrst sterile-malesystemdeveloped.Thecurrentlymostemployed methodforinsectandmitesterilizationisthroughionizing radiation,derivedfromCo60_and_Cs137_{radioisotopes,} acceler-ator(operatesunder10MeV)generatedelectrons,andX-ray generatedbyelectron beamwith energyunder5MeV. The neutronsaremoreeffectivethanX-rayandgammaradiation forinsectsterilization. However,neutroncaneasily induce radioactivityand,duetoimmobilityanddifﬁcultavailability ofnuclear reactors (source ofneutrons), its use would not

be feasible in mostof the SIT projects. According to Food andAgricultureOrganizationoftheUnitedNations(FAO),one sterileinsectisdeﬁnedasoneinsectsubmittedtoaproper treatmentthatmakesitunabletoproduceviableoffspring.

TheconceptofPlagueIntegratedManagement(PIM)gained further popularity after the 70s, when the pesticide use suffered restrictions. At the International Plant Protection Convention(IPPC)wasestablishedthattheSITisabiological controlstrategy,beingincorporatedtoeradicationprograms orcontroloverlargeareas,whoseplannedactionshavetobe implementedbyamanagementcoordinationprogram,acting regionally,beyondthelimitsofruralorurbanpropriety.

WiththeSITdevelopment,therewasalsothe ampliﬁca-tionanddevelopmentofnewscienceareassuchas:biology and nutritionofinsects,insectmassproduction,molecular biology,insectbehavior,andcontroloverlargeareasmodels.25

Regarding screwworm control, in the 40s, monthsafter weeklyreleaseofSITscrewwormsontheCuracaoIsland,the plaguewaseradicated.Today,lotsofcountrieshavenational SITprogramswithbioindustriesforC.capitatacreation(USA, Mexico,Guatemala,Argentina,Chile,Peru,Portugal,Tunisia, Thailand,andSouthAfrica),somespeciesofgenusAnastrepha

(Mexicoand USA)and Bactrocera (USA, Japan, Malaysia)for controland/oreradication.Theuseofthistechnique expan-sion have provedsuccess inprotecting fruit-growing areas againstMediterraneanﬂyinfestation.23

Despiteoriginallyproposedtoeradicatelivestockand agri-culture plagues, the technique awaken the possibility of controlling human diseases’ vectors due to its undeniable success.1_If_it_shows_efﬁcacy_on_controlling_human_diseases’

vectors, there would translate in exceptional gains. Some researchershavepublishedthetheoreticalbasisfortheSIT useonthecombatagainstAedes.

TheSIThasbeenusedinlotsofprogramswithsuccess againstdifferentagriculturalplaguesaswellasinsectsof med-icalimportancesuchasTse-Tsemosquitoes.PhaseIstudies haveshownitspotentialincontrollingthemosquito popula-tion.Thesterilemaleshavetomeetastandardizedquality control established by the International Agency ofAtomic Energy,inwhichtheinsectshavetobecapableofflying,attract females,mate,andtransferringsemendespitebeinginfertile. Bellini et al. conducted apilot experiment usingSIT in fiveclinicaltrialstodevelopamethodologytosuppressthe populationsofA.albopictus,inthreesmallcitiesinnorthItaly, between2005and2009.Createdmaleinsects,sexedbya sie-vingtechniquethatallowsrecoveryofabout26–29%ofmales, wereexposedtogammaradiationandimmediatelyreleased in the environment. The results showed that sterile male releasedatarateof896–1590insects/hainducedasignificant sterilelevelonthewildpopulationofinsects.Theyhave esti-matedthattheobjectiveofkeeping81%ofsterileeggsleads toinsectsuppression.Immigrationofpregnantfemaleswas notthemainconcernoverthesmallvillages,wherethetests werecarriedout.23

TheSIThasbeenstudiedontheA.albopictuscontrol.This vector has global expansion, and the absence of vaccines againstthemajorityofarbovirusestransmittedbythese vec-torshasstimulatedthedevelopmentofcontrolstrategieswith SITinordertocontroldiseasetransmissionbycontrolling nat-uralvectors.

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Control and Eradication of Screwworm fly larvae in the United

States of America and Mexico

1957 - 1958: Florida, 14 million sterile larvae/week

Belize: incidence reduction Guatemala: incidence reduction 1958 - 1960: Florida, 50 to 75 million sterile larvae/week

May/1962: Texas, 22 million sterile larvae/week

October/1962: Texas/New Mexico, 75 million sterile larvae/week No cases in Oklahoma, Arkansas and Louisiana

1965: California, implemented program

Mexico: 1972, 205.5 million sterile larvae/week

1981: Mexico, 400 to 500 million sterile larvae/week

1967 to 1981: Texas, 155 million sterile larvae/week; 300 in 1978: 150 in 1979; eradication in 1981

1982: Mexico, implemented program

1983: Mexico, implemented program

1984: Mexico, implemented program 1976, 10 to 200 million larvae/week 1978 to 1979, 300 million sterile larvae/week 1964: Arizona, implemented program

Fig.1–MapadaptedfromJamesE.Novy.26

Proposalofvectorcontrolbysterileinsecttechnique

Denguefever endemicsituation hastobefacedalong with its expensive preventivecontrol strategies and therapeutic demand.Inaddition,thecurrentlyusedmethodshaveproved ineffective.Therefore,SITwouldtheoricallybethebestoption. Itisurgenttheuseofaneffectivemethod,speciallywiththe ZikaandChikungunyavirusontherise,whosestratospheric costshavenotyetbeenestimated.SIThastheadvantageof beingamethodthatdoesnotpollutetheenvironment,leads toeradication,anddoesnotdependonsanitaryeducationof thepopulation.Itiseffectivebyitself.

Itisnecessarytoattractacademiczeal,andtheenthusiasm ofpoliticiansandadministrativeauthorities,notwithstanding thistechniquehasno“lobby”andwouldnotgenerateproﬁt unlike pesticideand medicines.Itis theonlymethod that hasprovedefﬁcaciousinlargescalevectorcontrolofother insectspeciesandhasalreadypilotstudieswithpromising resultswiththeAedesgenus.WhenplanningtheuseofSIT, itisnecessarytounderstandAedes’reproductionbehavioron theenvironment:

a) Maleagglomeration; b) Sexualpheromonerelease;

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c) Copulationcall; d) Femaleapproximation;

e) Copulationbeginning (thefemale canaccept ornotthe male);

f) Copulationending; g) Durationofcopulation;

h) Incasespermathecaisnotﬁlled,thefemalecanseekfor othermales.

Aftercopulation,thefemalesbeginthesearchforan ovipo-sition site.19 _The_SIT _{implementation} _depends,_exclusively,

ontheacademicenthusiasmdefendedbyspecialists.Atthe moment,itisnotsupportedbyanyprivatecompanyonthe stockmarket,andhasnopoliticalinﬂuencetosupportit.

BrazilalreadyhassomeexperiencewithSITuse.A biofac-tory,sterileinsectproducer, namedMoscamed wasbuiltin Juazeiro,Bahia,in2005.Itismainlyfocusedonplague con-trol(C.capitata) intheagribusiness.Itslocationisstrategic onceSanFrancisco valleyisresponsibleformorethan95% mangoandgrapesexportationofthecountry.Inaddition,this otherfruitﬂies(AnastrephaobliqueandA.fraterculus)presentin theregionareconsideredplagueswithquaternaryimportance insomecountrieslikeUSA,Japan,Europe,andAsia. There-fore,itisnecessitytomaintainalowprevalenceoffruitﬂies’ populationontheregion,i.e.Fly/Trap/Dayratelowerthan1.0 (FTD<1.0).16

In September 2015, the Agriculture, Livestock and Sup-plyMinistrylaunchedtheFlyFruitNationalCombatProgram aimingtoinstallingandmaintainingriskmitigationsystems, certiﬁcationanderadicationprograms.Inthiscase,the pro-gramaimstoimplementactionstoeradicateCeratitiscapitata

andAnastrephafraterculusinfruitproductionandexportation zones,lookingforwardtoprovidinghealthyfruitsand ensur-ingquaternarysafetytotheimporters.

TheSITisstillanunderexploredstrategyoptioninBrazil. However,thesuccessofthistechniqueallovertheworld sti-mulatestheincreaseofofﬁcialmanagementanderadication programsinagroecosystemsandrural/urbanareas.

Theorically,aprojectofthisscaleaimingtoeradicateAedes

from our environment, would have to meet the following requirements:

- Logic,scienceandpracticewell-foundedproject;

- Sponsorshipofastrongpoliticalandadministrativegroup; - Viabilityofmanufacturingthesterilemosquito;

- Viabilityinkeepingthesterilevectoralive,forasufﬁcient periodtillreleasingitontheenvironment;

- Sterilevector’sabilitytocopulatewiththewildinsects; - Sterileeggsasaresultofthereproductionprocess; - Createmethodologyforevaluatingtheresults;

- Discover the needed frequency and duration of insect release intotheenvironmenttocontrolorextinguishthe wildvectors;

- Planpreparationofnewreleaseofthesterilemosquitoesif thevectorreappearsaftersometime;

- Wholeoperationcostanalysis.

In addition to the above items, it is highly needed to convince the relevant authority. A task force has to be builtbyBrazilianandinternationalspecialistswithproved

experienceontheissue,tostudy,plan,andmaketheproject viablefollowedbyapilotimplementation.After demonstra-tionofviability,theprojectwouldthenbeexpandedtotherest ofthecountry.

Conclusion

Dengueremainsamajorpublichealthproblemintheworld. TheWHOestimatesthat2.5billionpeoplewereaffectedin 2013.Dengueistheworld’smorefrequentarbovirus.InBrazil, theincidencein2014wasof555,462cases.Associatedwith thisproblem,oncetheysharethesamevector,thereisZika and Chikungunya on the rise.The potentially severe clini-calpresentationoccurredin8975caseswith453deaths.In 2015,therewere1,534,932cases,20,320ofwhomweresevere with811deaths.Therealeconomicimpactofthediseaseis poorlydocumented,anditisestimatedanaverage541dollars and1394dollarsperpatient,respectively,foroutpatientand inpatienttreatment.Thetotalestimatedcostwas468million dollarsayear,inastudyconductedbetween2009and2013. Adjustingtheunreportedresults,thecostjumpsto1212 mil-liondollarsayear.TherehasbeenanefforttowardDengueand arbovirusescontrol,howevermoreintenseoutbreakshappen frequently.Recently,theBrazilianMinisterofHealthcameto publicsayingthatthemethodscurrentlyusedforvector con-trolhaveprovedineffective.Inthiscontext,aﬁrmactionto resolvetheproblemiswarrantedandvectorcontrolthrough SITisundoubtedlythemosteffectivestrategy,irrespectiveof thepopulation’ssanitaryeducation.

Conﬂicts

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interest

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