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MethodsMethods forfor vectorvector controlcontrol

Michele Michele MaroliMaroli

IstitutoIstituto SuperioreSuperiore didi SanitSanitàà, Rome, Italy , Rome, Italy MIPI Department MIPI Department

VectorVector--Borne Diseases and International HealthBorne Diseases and International Health

michele.maroli@iss.itmichele.maroli@iss.it

Session 1. Methods

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ToolsTools forfor LeishmaniaLeishmania vectorvector controlcontrol

SandflySandfly breedingbreeding--sites are sites are generally difficult to find, and generally difficult to find, and therefore control measures therefore control measures oriented specifically against oriented specifically against immature stages are not immature stages are not feasiblefeasible

At present, there are few At present, there are few effective methods other than effective methods other than chemical control chemical control against adult against adult sandfliessandflies

SandfliesSandflies are are haematophagoushaematophagouspests, so their control may be pests, so their control may be required even where they are required even where they are not active as disease vectorsnot active as disease vectors

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Control measures aimed at reducing Control measures aimed at reducing sandflysandflypopulations and hostpopulations and host--vector contactvector contact

1. Insecticide residual spraying (IRS) in houses and animal shelters

2. Insecticide treated nets for human use (ITNs)

3. Repellents applied on people’s skin exposed to sandfly bites

4. Topical application of insecticides on dogs for prevention of canine leishmaniasis

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IRS implementationIRS implementation

The effectiveness of IRS The effectiveness of IRS may depend on the may depend on the degree to which degree to which sandfliessandflieshave adapted to manhave adapted to man--made environmentsmade environments

Thus IRS will be much Thus IRS will be much more effective in urban more effective in urban situations, where every situations, where every house and animal shelter is house and animal shelter is treated, than in rural areas, treated, than in rural areas, where relatively few, widely where relatively few, widely dispersed dwellings are dispersed dwellings are sprayedsprayed

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Prerequisites for IRS implementationPrerequisites for IRS implementation

IRS campaign depends IRS campaign depends also on the availability of also on the availability of a suitable public health a suitable public health infrastructure, including infrastructure, including adequate supplies of adequate supplies of insecticide, spraying insecticide, spraying equipment and trained equipment and trained personnelpersonnel

Moreover, such Moreover, such personnel should be personnel should be trained not only in trained not only in insecticide application, insecticide application, but also in safety but also in safety procedures as well as procedures as well as monitoring techniquesmonitoring techniques

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PostPost--interventionintervention [[periodicallyperiodically]]PrePre--interventionintervention

Monitoring techniques for IRS implementationMonitoring techniques for IRS implementation

2

5

10

20

3040506070

80

90

95

98

3

4

5

6

7

-210

-110 1

110

210

310

TEMPO (min)

% M

OR

TALI

TA'

PR

OB

ITS

PAPA-RMPAPA-ROPERNI-VE

Insecticide base-line susceptibility

Vector density Evaluation of IRS residualeffect on the treated surfaces

Vector density

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MonitoringMonitoring the the residualresidual effecteffect byby test test conescones

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InsecticideInsecticide EfficacyEfficacy or or durationduration CountryCountry YearYear

DDTDDT 9 9 monthsmonths IndiaIndia 19961996

MalathionMalathion 88--9 9 monthsmonths IndiaIndia 19851985

PermethrinPermethrin 50% 50% reductionreduction EgyptEgypt 19931993

DeltamethrinDeltamethrinNotNot significativesignificativeSignificativeSignificative

ColombiaColombiaBrazilBrazil

1995199519911991

LambdaLambda--cyhalothrincyhalothrin

90% 90% reductionreduction6 6 monthsmonthsOnlyOnly 3 3 monthsmonths

BrazilBrazilPerPerùùVenezuelaVenezuela

199719972000200020012001

ExamplesExamples ofof IRS IRS fieldfield interventionsinterventions

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Malaria and Malaria and sandflysandfly controlcontrolThere are several examples of There are several examples of sandflysandfly populations being populations being affected by IRS directed against other pest speciesaffected by IRS directed against other pest species

The malaria control in Italy based on the use of DDT, The malaria control in Italy based on the use of DDT, reduced significantly the reduced significantly the LeishmaniaLeishmania transmission.transmission.The same occurred in India, Iran, Syria, and Greece.The same occurred in India, Iran, Syria, and Greece.

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Nowadays IRS campaignNowadays IRS campaign[[ZaimZaim M. & M. & JambulingamJambulingam P. (2007) GLOBAL INSECTICIDE USE FOR VECTORP. (2007) GLOBAL INSECTICIDE USE FOR VECTOR--BORNE BORNE DISEASE CONTROLDISEASE CONTROL WHO/CDS/NTD/WHOPES/GCDPP]WHO/CDS/NTD/WHOPES/GCDPP]

Countries reporting the insecticide use for Countries reporting the insecticide use for leishmaniasisleishmaniasisvector control [indoor residual spraying]vector control [indoor residual spraying]

-- 2 from Americas 2 from Americas (Brazil and Paraguay)(Brazil and Paraguay)-- 3 from the Mediterranean Region 3 from the Mediterranean Region ((Morocco,Syria,IranMorocco,Syria,Iran))

Insecticides most extensively used, by class (2003Insecticides most extensively used, by class (2003--05)05)

-- OrganophosphatesOrganophosphates, , ChlorpyrifosChlorpyrifos--methyl; methyl; -- CarbamatesCarbamates, , PropoxurPropoxur; ; -- PyrethroidsPyrethroids, Alpha, Alpha--cypermethrincypermethrin, , CypermethrinCypermethrin, ,

DeltamethrinDeltamethrin, Lambda, Lambda--cyhalothrincyhalothrin..

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NeedsNeeds of of periodicalperiodicalinterventionsinterventions

SkilledSkilled personelpersonel and and suitablesuitableequipmentequipment

LimitationLimitation toto treattreat allall sandflysandflyrestingresting sitessites

CostCost/benefit/benefit

RiskRisk ofof the the appearanceappearance ofofinsecticideinsecticide resistanceresistance

Environmental and practical restrictions for IRS IRS

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Susceptibility of sandflies to insecticides

SandfliesSandflies remain susceptible to remain susceptible to all the major insecticidal groups all the major insecticidal groups and there is no pressing need to and there is no pressing need to develop new compounds develop new compounds specifically for specifically for sandflysandfly controlcontrol

To date most records of resistance refer to DDT in only three spTo date most records of resistance refer to DDT in only three specieseciesP. P. papatasipapatasi, , P. P. argentipesargentipesS. S. shortishorti

in one country (India), although there are reports of increased in one country (India), although there are reports of increased tolerance to tolerance to this compound in several countriesthis compound in several countries

SandfliesSandflies have been shown to possess have been shown to possess detoxification mechanisms that could confer detoxification mechanisms that could confer protection on other groups and insecticide protection on other groups and insecticide resistance may arise in other populations, as a resistance may arise in other populations, as a result of result of leishmaniasisleishmaniasis control measures or control measures or indirect exposure to compounds used to control indirect exposure to compounds used to control malaria or denguemalaria or dengue

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Insecticide treated nets (Insecticide treated nets (ITNsITNs))

Insecticide treated Insecticide treated nets (nets (ITNsITNs) have ) have proven efficacy in proven efficacy in protecting humans protecting humans against arthropod against arthropod vectors of malaria, vectors of malaria, lymphatic lymphatic filariasisfilariasis, , ChagasChagas disease and disease and leishmaniasisleishmaniasis

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ITNsITNs useuse and and LeishmaniasisLeishmaniasis

ITNsITNs are easy to use and are easy to use and require less technical and require less technical and capital resources to capital resources to implement, compared to implement, compared to other vector control other vector control methodsmethods

They are costThey are cost--effective, effective, which has led to their which has led to their extensive implementation extensive implementation by countries on a large by countries on a large scalescale

The use of The use of ITNsITNs may may represent the most represent the most sustainable method of sustainable method of reducing reducing intradomiciliaryintradomiciliarytransmission of transmission of LeishmaniaLeishmania

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AdvantageAdvantage of of ITNsITNs useuse

An advantage of An advantage of ITNsITNsuse is that members of use is that members of affected communities can affected communities can treat the nets treat the nets themselves, whether themselves, whether these are manufactured these are manufactured locally or supplied by locally or supplied by health authoritieshealth authorities

ITNsITNs currently currently represent a key represent a key malaria control malaria control strategy, however strategy, however low insecticide relow insecticide re--treatment rates treatment rates remain problematicremain problematic

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ITNsITNs rere--impregnationimpregnation & & LLINsLLINs

During recent years, longDuring recent years, long--lasting lasting insecticideinsecticide--treated nets (LLINs) have been treated nets (LLINs) have been developed to overcome the problems of:developed to overcome the problems of:

low relow re--treatment rates, treatment rates,

washing, washing,

and erratic dose of the insecticideand erratic dose of the insecticide

Two methods are used for producing Two methods are used for producing LLINsLLINs::

incorporation of insecticide into incorporation of insecticide into fibersfibers, and , and surface treatment of net surface treatment of net fibersfibers or finished netsor finished nets

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Commercially produced Commercially produced LLINsLLINs ((bednetbednet))

OlysetOlyset®®a.ia.i. = . = 2% permethrin 2% permethrin incorporated within incorporated within

fibersfibers

PermaNetPermaNet®® 2.02.0a.ia.i. = . = deltamethrindeltamethrinThe target dosage is 55 The target dosage is 55

mg/mmg/m²²..

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SyntheticSynthetic pyrethroidspyrethroids

Pyrethroids used for the treatment of the nets combine the properties of low to moderate mammalian toxicity, low volatility and high insecticidal activity

Are fast actinginsecticides and show irritant propertiesagainst sandflies

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Effect of pirethroids on poisoned sandflies

AntiAnti--feedingfeeding = = femalefemale sandfliessandflies unableunable totofeedfeed on the on the hosthost

Knock downKnock down = = sandfliessandflies fall to the ground fall to the ground

unable to moveunable to moveThese These sandfliessandflies could regain movement in 1 hcould regain movement in 1 h

ToxicToxic = = sandfliessandflies die within 24 hdie within 24 h

FunctionalFunctional = = sandfliessandflies disabled beyond the disabled beyond the point of survivalpoint of survival

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Functional effect Functional effect [[similar to toxic effectsimilar to toxic effect]]

It is probable that this It is probable that this phenomenon occurs also in phenomenon occurs also in the field and that mutilated the field and that mutilated flies are unlikely to survive flies are unlikely to survive

SandfliesSandflies exposed to exposed to pyrethroidspyrethroids lose some lose some legs before dyinglegs before dying

Surviving Surviving sandfliessandfliesable to fly with several able to fly with several lost legs, sometimes up lost legs, sometimes up to 4, are also commonly to 4, are also commonly observedobserved

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Alive showing leg losses Alive showing leg losses [No. of legs][No. of legs]

TestTest ITNsITNsCodeCode

No.No. DeadDead AliveAlive

[1] [1] [2][2] [3] [3] [4] [4]

11 901901--00 5050 1313 3737 66 1010 99 77

22 901901--11 5050 99 4141 66 1212 1010 55

33 901901--22 5151 99 4242 77 88 1313 22

44 901901--33 5151 77 4444 1010 99 1111 00

55 901901--44 5050 66 4444 1111 88 99 00

66 901901--55 5252 55 4545 1010 99 99 00

77 901901--1010 5050 33 4747 1818 33 22 00

Alive Alive P. P. papatasipapatasi 24 h post24 h post--exposure showing leg lossesexposure showing leg losses

Standard WHO cones with a 3 min exposure time to Standard WHO cones with a 3 min exposure time to ITNsITNs

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CountryCountry AuthorsAuthors PyrethroidPyrethroid usedused ImpactImpact DurationDuration

SandflySandfly densitydensity CLCL

SignificantSignificant

--

????

--

--

--

High High reductionreduction

3 3 monthsmonths

6 6 monthsmonths

6 6 monthsmonths

33--4 4 monthsmonths

7 7 weeksweeks

12 months12 months

AfghanistanAfghanistan ReyburnReyburn et alet al, 2000, 2000 PermethrinPermethrin (0.5 g/m(0.5 g/m22)) --

ColombiaColombia Alexander Alexander et alet al, , 19951995

DeltamethrinDeltamethrin L. L. youngiyoungi ((100.0)100.0)

IranIran Nadim Nadim et alet al, 1995, 1995 DeltamethrinDeltamethrin 25 mg/m25 mg/m22 P. sergentiP. sergenti

KenyaKenya BasimikeBasimike & & MutingaMutinga, , 19951995

PermethrinPermethrin 0.5 g /m20.5 g /m2 P. martiniP. martini ((88.8)88.8)

SudanSudan ElnaiemElnaiem et alet al, 1999a, 1999a PermethrinPermethrin 0.5 g /m0.5 g /m22 P. P. papatasipapatasi ((signicantsignicant))

VenezuelaVenezuela FeliciangeliFeliciangeli etet alal, , 19951995

DeltamethrinDeltamethrin 60 mg/m60 mg/m2 2 L. L. ovallesiovallesi ((notnotsignificantsignificant))

KrogerKroger etet alal., 2002., 2002 LambdacyhalothrinLambdacyhalothrin 12.5 12.5 mg/mmg/m22

LutzomyiaLutzomyia spsp

Encouraging results on use of Encouraging results on use of ITNsITNs against against sandfliessandflies have been obtained from several field have been obtained from several field interventionintervention

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CommunityCommunity--based trialsbased trials

The efficacy of The efficacy of ITNsITNs against against leishmaniasisleishmaniasis has been has been demonstrated by few communitydemonstrated by few community--based trials focused on based trials focused on Old World Old World sandflysandfly species, species,

principally principally P. P. sergentisergenti, , peridomesticperidomestic/urban foci/urban foci

AfghanistanAfghanistanReyburnReyburn et al (2000). et al (2000). Trans R Soc Trans R Soc TropTrop Med Med HygHyg.. 2000 2000 JulJul--Aug;94(4): 361Aug;94(4): 361--366.366.

IranIranNadimNadim et al (1995) WHO/LEISH/95.37.et al (1995) WHO/LEISH/95.37.

TurkeyTurkeyAltenAlten et al (2003) J. Vector Ecol. 28, 53et al (2003) J. Vector Ecol. 28, 53--6464..

SyriaSyriaTayehTayeh et al (1997). WHO/LEISH/97.41.et al (1997). WHO/LEISH/97.41.JaloukJalouk et al (2007).et al (2007). Trans Roy Trans Roy SocSoc TropTrop MedMed HygHyg, 101: , 101: 360360--367. 367.

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0

1

2

3

4

5

pre-intervention post-intervention

ACL

rate

(%)

0

1

2

3

4

5

pre-intervention post-interventionAC

L ra

te (%

)

A B

ITNsITNs to prevent ACL in Aleppo governorate, Syria (to prevent ACL in Aleppo governorate, Syria (JaloukJalouket al., 2007)et al., 2007)

Active ACL lesions rates recorded before and after intervention Active ACL lesions rates recorded before and after intervention in treated in treated (A)(A) and control villages and control villages (B).(B).

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Ongoing communityOngoing community--based trials aimed based trials aimed to asses the to asses the effectiveneseffectivenes of of LLINsLLINs in the in the prevention of prevention of visceral visceral leishmniasisleishmniasis (VL)(VL)

MSF and VL control in MSF and VL control in EastEast--AfricaAfrica

KALANET EU project in KALANET EU project in L. L. donovanidonovani endemic areas of endemic areas of the the Bihar regionBihar region

Session 5. Control and update on interventionsSession 5. Control and update on interventions

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Chemical repellentsChemical repellents

The use of insect repellents or The use of insect repellents or protective clothing may be the protective clothing may be the only prophylactic measures in only prophylactic measures in areas where areas where LeishmaniaLeishmaniatransmission is extratransmission is extra--domiciliarydomiciliary

They should be They should be considered for use considered for use also by people who also by people who are only temporarily are only temporarily at risk of at risk of LeishmaniaLeishmaniainfection, such as infection, such as tourists, soldiers tourists, soldiers ectect..

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Commercial repellentsCommercial repellents

Among the synthetic repellents, Among the synthetic repellents, the gold standard is the gold standard is DEETDEET, which , which is highly effective against is highly effective against haematophagoushaematophagous insects and in insects and in use for more than 50 years. use for more than 50 years.

Its efficacy has been also proven Its efficacy has been also proven against against LeishmaniaLeishmania vectorsvectors

Recently, the efficacy of a Recently, the efficacy of a new new piperidinepiperidine compound compound [KBR 3023][KBR 3023] has been has been demonstrated also against demonstrated also against phlebotominephlebotomine vectorsvectors

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Laboratory tests on human volunteers showed Laboratory tests on human volunteers showed 100% protection (100% protection (untilluntill the 7th hour) by 20% the 7th hour) by 20% KBR 3025KBR 3025 commercial formulation against the commercial formulation against the

bite of bite of P. P. papatasipapatasi and P. and P. perniciosusperniciosus

0

10

20

30

40

50

60

70

80

90

100

O I II III IV V VI VII VIII IX

% p

rote

cti

on

0,8% 0,2% 0,02% PicaridinaNeemNeem--oiloil

KBR 3025KBR 3025

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Preventative measures for dogsPreventative measures for dogs

Although certain wild Although certain wild animal species may be animal species may be involved in the involved in the epidemiology of ZVL, epidemiology of ZVL, domestic dogs appear to domestic dogs appear to be the principal reservoir be the principal reservoir host of host of L. L. infantuminfantumthroughout the worldthroughout the world

Much of the focus on Much of the focus on control of ZVL is control of ZVL is currently placed on currently placed on these animals and these animals and preventing preventing sandflysandfly bites bites is a priority to protect is a priority to protect dogs from dogs from leishmaniasisleishmaniasis

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Researches have been carried out on chemical compounds to be Researches have been carried out on chemical compounds to be used on dogs as an effective measure in controlling used on dogs as an effective measure in controlling CanLCanL

In particular, the impact of mass use of In particular, the impact of mass use of

Deltamethrin 4% [impregnated dog collars] Permethrin 50% - Imidacloprid 10% [spot-on topical application]Permethrin 2% - Pyriproxyfen 0.02% [spray application]Permetrin 65% [spot-on topical application]

have been evaluated in controlling have been evaluated in controlling CanLCanL

PyrethroidsPyrethroids usedused asas biocidesbiocides againstagainst ectoparassitesectoparassites

Topical application Protector band

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[Irritancy effect ]anti-feeding

[>90%][>90%]

Protective

for dog

Toxic

for sandflies

AntiAnti--feedingfeeding and and insecticidalinsecticidal effecteffect byby contactcontact

Knock-downLeg losses (alive flies)

Mortality [>25%<90%]

100% blood fed

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healthyhealthy infectedinfected

AntiAnti--feedingfeeding effecteffect >90%>90%

IndividualIndividual protectionprotection

Mortality=Mortality= 100% 100% bloodblood fedfed

Mass Mass protectionprotection

AntiAnti--feedingfeeding + + insecticidalinsecticidal effectseffects

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SpeciesSpecies ActiveActive ingredientsingredients (%) (%) AuthorsAuthors

P. P. perniciosusperniciosus -- PermethrinPermethrin (2)(2)+Pyriproxyfen+Pyriproxyfen (0,02)(0,02) AsherAsher etet al 1998; al 1998; MolinaMolina etet al al 2001; 2001; MercierMercier etet al 2003al 2003

-- PermethrinPermethrin (65)(65) MolinaMolina etet al 2001; al 2001; ReithingerReithingeretet al 2001al 2001

-- PermethrinPermethrin (50)(50)+Imidacloprid+Imidacloprid (10) (10) Mirò Mirò etet al 2005al 2005

-- DeltamethrinDeltamethrin (4)(4)+Trifenilphosphate+Trifenilphosphate KillickKillick--KendrickKendrick etet al, 1997; al, 1997; LucientesLucientes etet al 1999; al 1999;

L. L. longipalpislongipalpis -- PermethrinPermethrin (50)(50)+Imidacloprid+Imidacloprid (10)(10) MenckeMencke etet al 2005al 2005

-- DeltamethrinDeltamethrin (4)(4)+Trifenilphosphate+Trifenilphosphate David David etet al 2001al 2001

L. intermediaL. intermedia -- PermethrinPermethrin (65)(65) ReithingerReithinger etet al 2001al 2001

L. L. migoneimigonei -- DeltamethrinDeltamethrin (4)(4)+Trifenilphosphate+Trifenilphosphate David David etet al 2001al 2001

P. P. papatasipapatasi -- DeltamethrinDeltamethrin (4)(4)+Trifenilphosphate+Trifenilphosphate MenckeMencke etet al 2003al 2003

The antiThe anti--feeding and insecticidal effect have feeding and insecticidal effect have been demonstrated experimentally for a limited been demonstrated experimentally for a limited

number of number of LeishmaniaLeishmania vectorsvectors

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MeasuresMeasures CountryCountryReferenceReference

No. of No. of dogsdogs(control)(control)

InterventionInterventionperiodperiod

% of % of reductionreductionCanLCanL-- VLVL

209 209 (1)(1) 204 204 (2)(2) + (218)+ (218) 89 89 (1)(1) and 93 and 93 (2)(2) CanLCanL

ExpotExpot BrasilBrasil-- GiffoniGiffoni etet al 2002al 2002 150 + (146)150 + (146) 4 4 monthsmonths 50 50 CanLCanL

50 50 (3)(3)--8686(4)(4) CanLCanL52 52 CanLCanL

54 54 CanLCanL -- 43 VL43 VL

49 49 CanLCanL50 50 CanLCanL

AdvantixAdvantix ItalyItaly-- Otranto Otranto etet al 2007al 2007

354 + (371)354 + (371)49 + (150)49 + (150)

466 + (354)466 + (354)

1246 + (1267)1246 + (1267)136 + (97)136 + (97)

8 8 monthsmonths

2 2 seasonsseasons1 season1 season

6 6 monthsmonths

1 1 yearyear5 5 monthsmonths

ScaliborScalibor ItalyItaly-- MaroliMaroli etet al 2001al 2001-- MaroliMaroli etet al 2002al 2002IranIran-- MazloumiMazloumi GavganiGavgani etet al 2002al 2002BrasilBrasil-- OliveiraOliveira--LimaLima etet al 2002al 2002-- ReithingerReithinger etet al 2004al 2004

The impact The impact ofof preventativepreventative measuresmeasures on on CanLCanL and VL and VL incidenceincidence

(1)(1) Treatment Treatment eacheach 4 4 weeksweeks; ;

(2)(2) Treatment Treatment eacheach 2 2 weeksweeks;;

(3)(3) First First sandflysandfly season; season;

(4)(4) SecondSecond sandflysandfly seasonseason

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PerspectivesPerspectives

ITNsITNs [[LLINsLLINs] may offer the best solution ] may offer the best solution in rural areas where transmission is in rural areas where transmission is largely largely intradomiciliaryintradomiciliary

LargeLarge--scale interventions based on IRS scale interventions based on IRS are no longer sustainable in most situations are no longer sustainable in most situations

In rural areas where dwellings are more In rural areas where dwellings are more dispersed and surrounded by large, dispersed and surrounded by large, untargeted "reservoir" populations of untargeted "reservoir" populations of sandfliessandflies, IRS of houses may be both , IRS of houses may be both unpractical for logistic reasons and unpractical for logistic reasons and ineffectiveineffective

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ConclusionsConclusions

More focalised measures are required More focalised measures are required which may require increased community which may require increased community participation and education in preventative participation and education in preventative measures against measures against leishmaniasisleishmaniasis

Improved information on aspects such as,Improved information on aspects such as,

biting behaviour and biting behaviour and resting/breeding sitesresting/breeding sites

would make delivery of existing compounds would make delivery of existing compounds more efficient, resulting in lowered costs of more efficient, resulting in lowered costs of interventions, higher efficacy and fewer interventions, higher efficacy and fewer detrimental effects to the environmentdetrimental effects to the environment

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ThankThank youyou forforyouryour attentionattention