PHJ_18

PublicHealthBayer Environmental Science Journal No.18 November 2006

INSECTICIDE RESISTANCEResistance against insecticides is an increasing challenge wherever diseases are transmitted by arthropod vectors. Many factors need to be considered to successfullyimplement effective long-term resistancemanagement.

PUBLIC HEALTH JOURNAL 18/20062

C O N T E N T

5

Editorial

Column: Christian Verschueren

Why effective insecticide resistancemanagement is important

8Insecticide resistance in public health pests

A challenge for effective vector control

C O V E R S T O R Y

24

Combatting resistance to insecticides in malaria control

Gains made in India

R E S I S T A N C E M A N A G E M E N T

Important aspectsto be considered in arthropod pestmanagement.

4

30

Insecticide resistancemanagement in a multi-resistant malaria vectorscenario

A Mexican trialshows sustainability

16Pyrethroid resistance in malaria vectors

Operational implications in Africa

by Ralf Nauen

by Pierre F. Guillet

by A.D. Rodriguez, R.P. Penilla, M.H. Rodriguez, J. Hemingway

by A.P. Dash, K. Raghavendra,M.K.K. Pillai


C O N T E N T

Notes

CD-ROM

V E C T O R C O N T R O L

50

Ethiopia: Support from UNICEF in the fight against malaria

Focus on distributing insecticide-treated nets

52Non-governmental organizations

Their help is increasingly important

38Malaria control on Bioko Island, Equatorial Guinea

Surpassing original targets

5863

Cover photo: Corbis

45

Chikungunya outbreaks in IndianOcean islands

Mosquito-borne viral disease

N G O

54

NGO Profile: PSI

Success with measurable health impactInterview with Desmond Chavasse on page 56

by Michael B. Nathan

57Aid project in the Ssese Islands

Mosquito nets for orphans


K E Y F A C T S

Nerve transmission

Abbreviations: AChE = Acetylcholinesterase Ach = Acetylcholine ChAT = C

Fenthion

Bendiocarb

Organophosphates&

Carbamates

O

O

O

NH

O

OOPPSS

OOMMeeOOMMee

SS

Nerve transmission

AChE

MACE

MACE = Modified Acetylcholinesterase kdr = knock-down re

Biochemical target sites


Choline Acetyl-Transferase vg-Na+ channel = voltage-gated sodium channel

Pyrethroids&DDT

Deltamethrin

OOOO

BrBr

BrBr

CCNNOO

+a+

CCll CCll

CCllCCllCCll

vg-Na+channel

DDTkdr

esistance

of synthetic insecticides

ONLY FOUR different chemical classes of syntheticinsecticides are used to treat adult mosquitoes:organochlorines, organophosphates, carbamates andpyrethroids. These insecticides act on two differenttarget sites with three modes of action: organophos-phates and carbamates induce phosphorylation andcarbamylation. Both inhibit acetylcholinesterase, anenzyme of crucial importance in terminating nervepulses. Synthetic pyrethroids and DDT are modulatorsof voltage-gated sodium channels and in most caseswith fast knock-down properties.

Available as poster on theenclosed Public Health CD-ROM


E D I T O R I A L

Insecticide resistance is an overall issue concerning notonly pests in agriculture, but also disease transmittingvectors and other insects important in public health. Theseinclude flies, cockroaches, fleas, bedbugs, Chagas bugs,sandflies – and especially mosquitoes. The problem isparticularly severe in vector control because although the

agricultural industry has put new insecticides on the market, no new active ingredientclasses are suitable for targeting adult mosquitoes.

This means we have to live with the tools we have and to use them responsibly andcarefully. Many of the articles in this issue of the Public Health Journal No. 18describe strategies for managing malaria vector control in the face of growinginsecticide resistance. The reports come from Africa, Mexico, India and other regionswhere the burden of malaria and other insect-borne diseases is still a major healthproblem and a cause of poverty. The articles by various experts in the field emphasizethe importance of resistance monitoring, rotation or mosaic spraying schemes todelay or avoid resistance development.

One cornerstone is the introduction of bendiocarb for indoor residual spraying incases where pyrethroid and DDT resistances are already presenting operationalchallenges. Insecticide Resistance Management (IRM) has become an important partof the strategy of Bayer Environmental Science. We are pursuing this with the supportof many institutions such as national health authorities, academia and the WHO.

Besides our main theme of Insecticide Resistance Management we also focus onother themes in this edition – such as the recent chikungunya outbreaks. We havealso started a new feature series where we highlight the important contribution ofnon-profit organizations (NGOs) in efforts to combat public health issues.

We wish you pleasant reading.

Pascal Housset

Dear Readers,

PASCAL HOUSSET Head of

Bayer Environmental Science

C O L U M N

or over half a century the responsible plantscience industry has strived to develop products

to meet the increasing global demands forimproved public health and the availability of foodand fiber. A key challenge for the industry has thusbeen to expand the toolbox of available products bymaintaining a steady flow of new, ever-more effec-tive insecticides with novel modes of action thatalso meet the increasingly stringent regulatory stan-dards for human and environmental safety.

It has proved equally challenging to protect andmaximize the benefits of developing new insecti-cides by maintaining the effective life of these prod-ucts in the field. This is because with their abundantnumbers and generally short life-cycles, pestinsects under continuous selection pressure candevelop resistance to the insecticides used againstthem. By 2005, the number of species of insectsthat had developed resistance to one or more groupsof insecticides was estimated to be well over 500.More recently, a number of pest species of publichealth importance have evolved resistance, asinsecticide use in these sectors has expanded.Moreover, a number of cases of insecticide resist-ance are currently critical with some key specieshaving few or no available effective classes ofinsecticide available. Given the inherent ability of

Why effective insecticide resistancemanagement is important

Dr Christian Verschueren is the Director General of CropLife International*. Inthe following article he explains how the effective management of invertebratepest populations important in public health, veterinary, agricultural and horti-cultural issues depends on a variety of inputs. One major area is the use ofefficacious synthetic insecticides according to the principles of IntegratedPest and Vector Management.

insect populations to evolve resistance, it is imper-ative to develop and implement effective insecticideresistance management (IRM) strategies at an earlystage in the commercial life of an insecticidalproduct, so that resistance is prevented or delayed.Similar strategies may be employed to solveexisting resistance problems, although it isacknowledged that it is much easier to proactivelyprevent the development of resistance than it is tosolve resistance problems once they have devel-oped. Effective IRM is vital and one of the mostchallenging issues in modern applied entomology.This is illustrated by the fact thatinsecticide resistance issues arecentral to man’s efforts tocontrol major vector-bornediseases and improve agricul-tural production.

The socio-economic burdenassociated with tropical diseasessuch as malaria, dengue, filariasisand trypanosomiasis is a seriousimpediment to development inmany tropical countries,and most of thesediseases are not

Dr Christian Verschueren

F


* CropLife International is a global federation representing the plant scienceindustry and a network of regional and national associations in 91 countries.www.croplife.org

5


C O L U M N

only major health concerns but also a major causeof poverty. It is estimated that malaria alone hasreduced the gross national product of the Africancontinent by more than 20% over the past 15 years.Vector-borne diseases account for a very significantpart of total morbidity due to infectious diseases,and occur not only in the tropics but also in manytemperate countries. Recent estimates indicate that,annually, there are 300-500 million clinical cases ofmalaria, leading to more than one million deaths,mostly children.

In high-transmission areas (which include mostparts of Africa) malaria incidence cannot bereduced if, in parallel with early diagnosis andtreatment, transmission is not controlled throughvery effective vector-control and/or personal-protection interventions. Accordingly, insecticidesremain the most important element of integratedapproaches to vector control. Although publichealth accounts for only a very small fraction ofoverall insecticide quantities applied, many vectorspecies of public health importance have alreadydeveloped resistance to one or more insecticides.

While the use of IRM strategies employing a num-ber of compounds with different modes of action isideal, the control of adult mosquitoes dependsentirely on insecticides with just two target sites inthe insect nervous system (see diagram on coverflap). The loss of useful compounds and the devel-opment of widespread resistance to existingcompounds highlight the urgent need for a newmosquito adulticide.

New technologies such as insecticide-treatedbed nets (ITNs) and insecticide-treated materials(ITMs) are now highly promoted and used to

protect particularly children and pregnantwomen. However, ITNs still remain highlydependent on a single class of insecticides: thesynthetic pyrethroids.

It is also important to understand that almost allpublic health insecticide classes are also used inagriculture. When vectors breed within or close toagricultural crops, they can be exposed to thesame or similar insecticidal compounds anddevelop resistance. This phenomenon is of partic-ular relevance for malaria vectors. Such consider-ations underline the importance of resistanceexperts in both sectors working together tomanage resistance.

At one time it was believed that the industrycould always invent ways out of resistance prob-lems by developing new insecticides with novelmodes of action which would be unaffected bypre-existing resistance mechanisms. Such anapproach assumed that an endless supply of suchnew compounds was possible, and that it wasacceptable to use new insecticides indiscriminatelyuntil they failed. Modern, more enlightenedapproaches acknowledge that it is hugely expen-sive, very time-consuming and not at all easy todevelop new insecticides. Estimates from CropLifeAmerica and the European Crop ProtectionAssociation (ECPA) in 2003 suggest that the costof developing a new active ingredient is US$ 185million. Registered compounds should therefore beregarded as valuable resources, and protected fromresistance developing to them.

An essential feature of modern, successful IRMstrategies is the availability of a toolbox of insecti-cidal compounds with a broad range of modes ofaction. Experience has shown that all effectiveinsecticide resistance management strategies workby reducing the selection for resistance from anyone type of insecticide or mode of action. This canbe achieved by various means including the use ofsequences, alternations, rotations, mixtures ormosaics of insecticides.

The major manufacturers of insecticides areall committed to good product stewardship to

The massive efforts currently deve-loped to control malaria, especially inAfrica, may be jeopardized by thewidespread development of pyrethroidresistance due to the permanent expo-sure of adult mosquitoes to this class ofinsecticides.

“

”

Website (see page 29). IRAC International is com-prised of key technical personnel from the agro-chemical companies affiliated with CropLifethrough membership in the relevant NationalAssociations (ECPA, CropLife America, etc).Current member companies are BASF, BayerCropScience, Dow AgroSciences, DuPont, FMC,Sumitomo and Syngenta. The InternationalCommittee supports resistance managementproject teams and also provides a central coordina-tion role to regional, country and technical groupsaround the world.

More recently, much attention has been focused onthe need for effective vector control, highlighted bythe development of widespread resistance to thekey insecticide classes used for vector control. Totackle this problem WHO, the Innovative VectorControl Consortium (IVCC) funded by the Bill &Melinda Gates Foundation and IRAC are joiningforces. IRAC has responded recently by forming aspecialist Public Health Team to work with thesebodies and to provide the technical inputs neces-sary to help combat insecticide resistance in keyvector species. One of the IRAC Public Healthteam’s first actions has been to develop a manualon the ‘Prevention and Management of InsecticideResistance in Vectors and Pests of Public HealthImportance’.

Clearly, the manufacturers of insecticides put greatefforts into sustaining the effectiveness of theirproducts and avoiding resistance problems. Asindicated earlier, this is done not only as a part ofresponsible product stewardship, but also becausesusceptibility to particular modes of action is valu-able, and once lost they may be hard or impossibleto recover. Strict adherence to IRM guidelines andapplication requirements, consultation with localIRM experts and integration of good integratedcrop and pest management systems will helppreserve susceptibility.


C O L U M N

sustain and prolong the effective commercial life oftheir products. The development and implementa-tion of successful IRM strategies form a key part ofthis effort. The knowledge gained from researchstudies on resistance helps to sustain valuableeffective products in the market place. Dependingon the individual resistance management issuesconcerned, companies may collaborate to harmo-nize the IRM requirements for compounds from asingle mode of action group, even though they aredeveloped and marketed by different companies.This is vital if growers and pest control profession-als are to understand the IRM strategies they arerequired to implement at a practical level.

At an all industry level, the Insecticide ResistanceAction Committee (IRAC) is a Specialist TechnicalGroup under the umbrella of CropLife Inter-national. IRAC is also recognized by The Food andAgriculture Organization (FAO) and the WorldHealth Organization (WHO) of the United Nationsas an advisory body on matters pertaining to resist-ance to insecticides.

The group’s activities are coordinated by theIRAC International Committee, and Country orRegional Committees with the information dissem-inated through conferences, meetings, workshops,publications, educational materials and the IRAC

7

This column is an excerpt from a longerarticle by Dr Christian Verschueren. You can find the whole article on theenclosed Public Health CD-ROM.

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A challenge for

INSECT-BORNE DISEASES are a problem worldwide, made worse by increasing resistance of the vectors to insecticides. To control chagas disease in Bolivia, malaria in Africa or sandflies in the Middle East, whichtransmit leishmaniasis, it is essential that resistance management strategies are implemented.

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C O V E R S T O R Y

PUBLIC HEALTH JOURNAL 18/2006 9

Insecticide resistance in public health pests

effective vector control

How resistance emerges,

what mechanisms are

involved, what is done to

monitor resistance and

what are possible options

to manage insecticide

resistance. These are

essential aspects in dealing

with disease-transmitting

insect pests in Public

Health.


C O V E R S T O R Y

WHO, regulatory bodies and thepublic sector) as an issue that needsa proactive approach. In this direc-tion the Insecticide ResistanceAction Committee (IRAC) coordi-nates a private sector response toeither preventing or at least delayingthe development of insecticideresistance. IRAC not only facilitatescommunication and education on allaspects of insecticide resistance, but

also promotes the development of resistancemanagement guidelines (see page 29: IRAC).

How resistant populations develop

Frequent applications of the same insecticide willselect for those individuals in a population that areable to survive recommended levels of thecompounds due to a stable genetic change. If onedoes not switch between different modes of action(or chemical classes) in application regimes, thenumber of less susceptible individuals willincrease. Over a certain period of time (it maytake months or even years) such one-sided insec-ticide administration will result in a resistantpopulation. This is even more likely if combinedwith high reproductive potentials and short lifecycles producing several generations per season.

Complicated by cross-resistance

In most cases a resistant pest population usuallyalso shows resistance to other compounds withinthe same chemistry class, e.g. resistance againstone pyrethroid usually results in resistanceagainst the whole group of pyrethroids. This isknown as cross-resistance. Sometimes, depend-ing on the nature of the resistance mechanism,cross-resistance may even arise between chemicalclasses, e.g. organophosphates and carbamates(see Fig. 2 page 14: Major biochemical mecha-nisms of resistance).

n public health many diseases aretransmitted by arthropod vectors,

e.g. mosquitoes (malaria, denguefever, yellow fever, encephalitis,filariasis, West Nile fever and chikun-gunya), ticks (e.g. Lyme disease) andsandflies (leishmaniasis). It has beendemonstrated in the past that the useof insecticides can dramatically reducethe risk of insect-borne diseases. Thisis well documented by the WHO andin numerous scientific investigations and reports,particularly concerning the most widespread andimportant disease, malaria.

Serious threat of insecticide resistance

Since the introduction of synthetic insecticides tocontrol arthropod pests the selection pressure onpopulations has increased drastically, with manyspecies developing mechanisms to withstandinsecticide treatments. There is little doubt that

insecticide resistance has evolved to all classes ofinsecticides and is counteracting the control ofmany invertebrate pests of agricultural impor-tance, disease vectors and other insects importantin public health. The list of public health pestsresistant to insecticides has been growing fordecades and includes disease vectors such asmany known mosquito species, fleas and ticks, aswell as cockroaches, bedbugs, houseflies andmore recently also Chagas bugs and sandflies.

Insecticide resistance is viewed as an extremelyserious threat in crop protection and vector con-trol, and is considered by many parties (industry,

I

Insecticide resistance is defined as a heritablechange in the sensitivity of a pest populationthat is reflected in the repeated failure of aproduct to achieve the expected level of controlwhen used according to the label recommen-dation for that disease vector species.

The author:

Dr RALF NAUEN Chairman IRAC PublicHealth Working Group,

Bayer CropScience


C O V E R S T O R Y

Furthermore, resistance development due toselection pressure in disease vectors is complicatedby an additional (sometimes neglected) aspect:frequent application of similar synthetic insecti-cides to control important agricultural pests mayindirectly affect the susceptibility of insectsimportant in public health.

Surveillance is essential

Once insecticide resistance is established in apopulation it can profoundly affect public healthby the possible reemergence of vector-bornediseases. When resistance is monitored insuspected cases it is often too late. Focusing onsurveillance wherever possible is essential inorder to react proactively as soon as a regionalpopulation seems to be changing its susceptibilitytowards synthetic insecticides. For this purposethe WHO has published numerous monographson methods to ensure the surveillance of resist-ance development to many different insecticides,e.g. by diagnostic dose bioassays for mosquitoes(see list of monographs on www.who.int). A diag-nostic dose tested in insecticide-coated glass vials

usually provides 100% mortality of a susceptiblepopulation within one hour. In contrast, resistantpopulations survive such doses, at least to acertain extent.

Insecticide classes are limited

Another major aspect in terms of selectionpressure on important public health insect speciesis the fact that only a limited number of insecti-cide classes are available. Only four differentchemical classes of synthetic insecticides are (orhave been) used to treat adult mosquitoes, i.e.organochlorines, organophosphates, carbamatesand pyrethroids. Even the original compound(permethrin) of the synthetic pyrethroids has beenavailable for more than 30 years (see Fig. 1 below).

It is important to note that these four chemicalclasses address only three different modes ofaction. Therefore, there is much less target-sitediversity for the control of public health pests (seediagram on cover flap) than in the agriculturalsector. In principle, all insecticidal classes havetheir biochemical target sites in the insect’s

Only a limited number of insecticide classesare available for adultmosquito control. Nonew malaria mosquitoadulticide has beenapproved by the WHO in the last 15 years.

Insectides for mosquito control

Years WHO approved insecticides

1940-45

1946-50

1951-55

1956-60

1961-65

1966-70

1971-75

1976-80

1981-85

1986-90

1991-95

1996-00

2001-05

DDT

Lindane

Malathion

Fenitrothion Propoxur

Chlorpyrifos-methyl

Pirimiphos-methyl Bendiocarb Permethrin

Cypermethrin

Alpha-cypermethrin Cyfluthrin

Lambda-cyhalothrin Deltamethrin Bifenthrin

Etofenprox

OrganochlorinesOrganophosphates

CarbamatesPyrethroids

Fig. 1


C O V E R S T O R Y

central nervous system, i.e. cholinergic nervetransmission, which is one of the reasons why theyact quite rapidly.

Pyrethroids have excellent properties

Insecticide classes used to control adult mosqui-toes as malaria vectors have to meet specificrequirements, i.e. excellent contact action, a rapidknock-down effect and selective toxicology. Thisis why the pyrethroids in particular were most suc-cessfully used in mosquito control over the lastdecades, with economic values of ca. 60% and80% in residual use and space spray, respectively.Due to their excellent properties they account for100% of global bednet treatments. Adding up allthese numbers one could easily imagine that thepyrethroid selection pressure on many pests ofimportance in public health is considerable,particularly on malaria vectors. The risk of resist-ance development to pyrethroid insecticides inmosquitoes is therefore quite high.

Mechanisms of resistance

Extensively studied in the past, resistancemechanisms in mosquitoes can be divided intotwo groups, metabolic (degradation of the activeingredient by detoxification enzymes) and target-site resistance (mutations in the target proteins).Both mechanisms can be quite specific, althoughthere is a tendency for metabolic mechanisms tobe more versatile with regard to cross resistancebetween chemical classes. A compilation of themajor mechanisms of resistance and theirrespective importance for the different chemicalclasses used in malaria vector control is given inFigure 2 (see page 14: Major biochemical mech-anisms of resistance).

Resistance to pyrethroids andorganochlorines

Mosquitoes’ resistance to pyrethroids and DDT iseither conferred by a mutation in the voltage-gated sodium channel (kdr) or by elevated levelsof microsomal monooxygenases. Severalmonooxygenase genes have been associated withpyrethroid resistance, particularly relating topermethrin. DDT resistance is also specificallyconferred by the so-called DDT-dehydrochlori-nase, a glutathione S-transferase. In addition, rdl(resistance to dieldrin, a mutation in the GABA-gated chloride channel) results in resistance toorganochlorines other than DDT. In contrast topest insects of agricultural importance, esteraseshave not yet been shown to play a major role inconferring pyrethroid resistance in mosquitoes.

Resistance to organophosphates and carbamates

In contrast to pyrethroids, over-expression ofesterases by gene amplification providesconsiderable organophosphate (and to a certainextent carbamate) resistance in mosquitoes. Thishas been reported as an evolutionary response toselection by organophosphates and carbamates.A second mechanism of importance is MACE.Both organophosphates and carbamates are

Behavioral resistanceInsecticide resistance in mosquitoes isnot always based on biochemical mech-anisms such as metabolic detoxificationor target-site mutations, but may also beconferred by behavioral changes inresponse to prolonged sprayingprograms. Behavioral resistance doesnot have the same importance asphysiological resistance, but can beconsidered a contributing factor, leadingto the avoidance of lethal doses of aninsecticide. A behavioral response iseither dependent or independent on astimulus. If mosquitoes avoid a treatedplace due to sensing the insecticide it isconsidered to be a behavioral changedependent on a stimulus, whereas theselective occupation of an untreatedarea can be considered a stimulusindependent response.


C O V E R S T O R Y

affected by this target-site mutation in acetyl-cholinesterase. Monooxygenases only play aminor role in organophosphate and – if any – incarbamate resistance.

Monooxygenase-based cross resistance to carba-mates has been described as unusual inmosquitoes. It was only reported for propoxur asa notable exception, whereas bendiocarb againstthe very same mosquito strains gives excellentcontrol at diagnostic doses. This is likely to bedue to the structural uniqueness of bendiocarb,which carries a bis-methylated methylenedioxy-motif possibly resilient to attack by insectcytochrome P-450 enzymes. In other words,although these carbamates share the same modeof action as organophosphates they are struc-turally different and may select for differentmechanisms of resistance.

Resistance management a challenge

The management of insecticide resistance, ormore precisely, the management of arthropod pestsusceptibility is crucial. It should be considered asone of the most challenging issues in modernapplied entomology. The effective management ofmalaria vectors by only a limited number of insec-ticide chemical classes is a challenge in itself. Asbriefly outlined here, the chemical options for aresistance management strategy in adult mosqui-toes are limited. Currently there are only fourchemical classes of insecticides addressing justtwo different insect target sites!

Larvicides provide new options

Mosquito larvae carry the same resistance genesas adults. Therefore, they are also resistant to thesame compounds, although the extent of theresistance might differ between adults and larvae.However, there are also various new classes oflarvicides for controlling immature insect popula-tions (see page 45: Chikungunya). One class,called insect growth regulators (IGRs) has variousbiological modes of action. So far IGRs areusually detoxified by metabolic enzymes such as

ENCEPHALITIS transmittingmosquitoes often breed in ricefields – use of agriculturalinsecticides can trigger thedevelopment of resistance invector control.

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C O V E R S T O R Y

Fig. 2: The metabolic detoxification enzymes described to confer insecticide resistance inmosquitoes are: esterases, monooxygenases and glutathione S-transferases (in blue). Two majortarget-site mechanisms are relevant today: kdr (knock-down resistance), a mutation in thevoltage-gated sodium channel (in pink), and MACE (modified acetylcholinesterase) (in green).The respective importance of each resistance mechanism is indicated by the size of the circle.

Pyrethroids

DDT

Carbamates

Organophosphates

Metabolic

Esterases Monooxygenases GSH S-Transferases

Target-site

kdr MACE

microsomal monooxygenases. No cases of target-site resistance have yet been described for anyIGR. Biologicals such as bacterial endotoxins arealso an option. Resistance to Bacillus sphaericustoxin has been described in field populations andlaboratory selected strains of different species ofmosquitoes. This resistance is due to the toxinfailing to bind to the specific mid-gut receptors,which is caused by several mutations in the bind-ing protein. Usually, no cross-resistance toBacillus thuringiensis (BTI) is seen, because thetoxins of these bacteria bind to different mid-gutreceptor proteins.

Rotation recommended

Most recommendable is the rotational use ofchemicals with different modes of action, rather

than alternating members of one chemical class ordifferent chemical classes addressing the sametarget site. Possible implications of resistancemechanisms on such strategies can be worked outfrom Figure 2. For example, the presence of kdrresistance renders DDT and pyrethroids lesseffective, whereas carbamates such as bendiocarbor organophosphates such as fenthion can still beused. If the MACE mechanism is not a problem,one may even think about the rotational use ofcarbamates and organophosphates. This mightincrease the chances of regaining pyrethroidsusceptibility. However, this should be carefullymonitored.

Furthermore, it seems much more likely to selectfor cross-resistance to organophosphates than topyrethroids when using carbamates in alternation

Major biochemical mechanisms of resistance


C O V E R S T O R Y

Effective long-term resistance management isnecessary, but many factors need to be consid-ered to successfully implement strategies. Thisis not only achieved by the availability ofinsecticides but is also driven by other factors,e.g. training courses and educational materialon disease prevention, or by vector control per-sonnel in general educating managementprinciples, to ensure proper implementationand surveillance. Of course, new active ingre-dients with new modes of action would bemost welcome in order to diversify the vectorcontrol toolbox and extend the life cycle of allavailable insecticides, thus lowering the risk ofreemerging vector-borne diseases.

CONCLUSION

Article on the enclosed Public Health CD-ROM

with pyrethroids, particularly due to possibleselection for MACE-based resistance. Inconclusion, both organophosphates and carba-mates, particularly bendiocarb are useful asrotational partners in resistance managementstrategies in order to sustain pyrethroid suscepti-bility in mosquitoes.

1st International Workshopon Resistance ManagementSouth Africa, 29-30 June 2004

A meeting on malaria vector resistance wasorganized in South Africa by the MedicalResearch Council. The objectives of the meet-ing were to review the current situation ofresistance in Southern Africa, mechanismsinvolved and practical implications for vectorcontrol in the region. This meeting was spon-sored by Bayer Environmental Science.

About 40 people participated from 9 coun-tries, including South Africa, Swaziland andMozambique, and managers of 5 MalariaControl Programs, representatives of WHO

(HQ & AFRO) and scientists involved invector resistance (UK, Mexico). Detailedquestions for further research were addressed.

Some recommendations made during themeeting:

• WHO to coordinate the development ofguidelines for resistance management withspecial reference to Southern Africa, and withthe target audience being program managers.• Industry to develop new formulations (OPs,carbamates, pyrethroids), which would last for12 months on all surfaces, including mud andcement.• Pesticide industry to contribute to resistancemonitoring within the framework of productstewardship (modalities to be further discussed).

The document regarding“Recommended actions to supportresearch and control strategies”can be found on the enclosedPublic Health CD-ROM



Pyrethroid resistance in malaria vectors

Operational implications in AfricaWidespread insecticide resistance in African malaria vectors raises concernsabout chemical-based vector control interventions. WHO expert Dr Pierre F.Guillet outlines the challenges malaria vector control programs now face. Inparticular, to ensure that a chosen insecticide provides the expected efficacyfor the calculated duration, as well as how to use insecticides in a way thatminimizes development of resistance.

page 18: kdr mutations). Metabolic resistance hasalso been reported from Kenya, Cameroon andsuspected in Nigeria. But due to problems associ-ated with the complexity and reliability ofbiochemical assays, especially for oxidases, meta-bolic resistance in An. gambiae has most likely

been under-reported. Oxidase-based resistance has been found inanother major vector, An. funestusin South Africa as well as inMozambique.

Carbosulfan (carbamate) resistancewas recently reported from WestAfrica in Côte d’Ivoire. It has beenattributed to modified acethyl-cholinesterase (AChE), a majorgene conferring resistance to carba-mate and organophosphate insecti-cides (see page 8: Coverstory).Data from preliminary surveys

done in West Africa showed the presence of theAChE mutation at a low frequency in Benin but ata relatively high frequency (around 50%) inBurkina Faso, Côte d’Ivoire and Sierra Leone. Itis also suspected in Ghana. There is no knownevidence of any recent tests made withorganophosphate insecticides.

Testing the impact of resistance

Resistance can be interpretated in different ways,either biologically (e.g. the presence of a

yrethroid resistance in African malaria vectorswas first detected in Côte d’Ivoire in a major

vector species, Anopheles gambiae. At that time,the use of pyrethroid treated nets or any other vec-tor control intervention in this area was almostnon-existent. It was suggested that resistancecame from using these insecticidesin agriculture and/or households.This met with skepticism and thepotential implications of such resist-ance were grossly underestimated, ifnot ignored. In 1998, a quick surveywas carried out in six countries ofWest, Central and Southern Africa.It confirmed the presence of strongresistance to permethrin and DDT inthree West African countries, resist-ance to DDT in one Central Africancountry and susceptibility to bothpermethrin and DDT in oneSouthern African country. Recentdata gathered through the African Network forVector Resistance (ANVR) showed thatpyrethroid and DDT resistance is not onlywidespread over West and Central Africa, but alsopresent in Eastern Africa, involving differentresistance mechanisms.

Common resistance mechanisms

Knock-down resistance (kdr) is the most frequent-ly found mutation in African malaria vectorsbelonging to the An. gambiae complex (see box

P

The author:

DR PIERRE F. GUILLET WHO, Vector Control &

Prevention, Global MalariaProgramme


INCIDENCES of malaria attacks were reduced by 50% in children protectedby permethrin treated nets compared to unprotected children.

resistance gene) or operationally (failure of avector control intervention). The presence ofresistance does not necessarily imply that anintervention has lost its efficacy or effectiveness.The overall public health impact of any insecti-cide is not just related to its efficacy but also toadditional interacting factors, which result in adramatic reduction of target insects acting asvectors and in transmission. Monitoring insecti-cide resistance is an essential part of anychemical-based vector control intervention. Onceresistance has been found and the mechanismidentified, it is essential to understand its potentialimpact on efficacy and eventually on the effec-tiveness of insecticide-based vector controlinterventions. A number of steps and complexinvestigations should be carried out in laboratory,then small-scale field experiments, followed byvillage-scale trials.

Laboratory and small-scale fieldexperiments

Mortality and blood feeding inhibition induced bypyrethroid treated nets are only moderatelyreduced by the kdr mutation as observed in a num-ber of laboratory investigations. It has been shownthat kdr resistant mosquitoes landing on treatednetting can stay 10 to 20 times longer than sus-ceptible ones, since mutation dramatically reducesthe knock-down effect of pyrethroids as well astheir irritant effect on mosquitoes. As a conse-quence, female mosquitoes can stay longer on thetreated netting and finally pick up enough insecti-cide to inhibit blood feeding and to be killed.

Laboratory and experimental hut studies with car-bamate resistant An. gambiae have shown thatcarbosulfan treated nets in experimental huts

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(free-flying mosquitoes) are highly effectivedespite a high level of resistance. On the contrary,mortality was dramatically reduced when resistantmosquitoes were exposed to treated surfaces. It ispossible that the limited impact of kdr on the effi-cacy of pyrethroid treated nets might also apply toother resistance mechanisms and insecticides. Thisneeds to be investigated further.

Village-scale trials

Laboratory and experimental hut investigationsprovide valuable information on the impact ofresistance on vector behavior and survival.However, they do not provide evidence about thepossible impact under real life situations, so anecessary further step is large-scale field trials.Such trials are difficult, long and expensive,therefore evidence on the impact of resistance oninsecticide-treated net (ITN) efficacy has beenlimited so far.

In a first trial in an area of Côte d’Ivoire with avery high frequency of the kdr mutation (over85%), the use of permethrin treated nets reducedthe incidence of malaria attacks (morbidity) inprotected children by 50% compared to unprotect-ed children. However, treated nets made no

Knock-down resistance (kdr) mutations occur insodium channels, the target site for DDT andpyrethroids (see diagram on cover flap). A quicksurvey in Côte d’Ivoire and Burkina Faso showedthat the kdr mutation was widespread and com-monly occurring at high to very high levels.Interestingly, the mutation was found only in oneparticular form of An.gambiae, the savannah (S)form, but absent from another closely relatedform, Mopti (M). A similar situation has beenfound in Nigeria. Later on, the kdr mutation wasdetected in the M form in Benin and BurkinaFaso. Between 1999 and 2003, a rapid increase in

kdr mutations

detectable impact on the vector population, e.g.reducing densities and/or infectivity. The conclu-sion was that permethrin treated nets do providegood personal protection against malaria vectorseven in areas with a high level of pyrethroidresistance. The lack of entomological impactcould be attributed to kdr resistance and/or the useof permethrin, which tends to repel rather thankill mosquitoes.

Confirming the results

A larger-scale field trial involving eight pairedvillages was carried out in an area of high kdrfrequency (over 95%) in northern Côte d’Ivoire toassess the efficacy of lambda-cyhalothrin (treatednets versus no net). The protective efficacy oftreated nets for children under the age of 5 was56%, equivalent to what is seen in a similarsavannah area with susceptible vectors. But hereITNs had a dramatic impact on An. funestus popu-lations, interrupting transmission by this species.In addition to being fully susceptible topyrethroids, this species is very sensitive to indoorresidual spraying (IRS) and ITNs because of itslower sensitivity to the excito-repellent effect ofDDT and pyrethroids compared to An. gambiae.ITNs also made a significant impact on An. gambiae

the kdr frequency was observed in Côte d’Ivoire,starting from the Atlantic coast and rapidly mov-ing northward in savannah areas. A different kdrmutation was found in An. gambiae from EastAfrica. This East Africa mutation (kdrE) induces alower level of pyrethroid resistance than the WestAfrica mutation (kdrW) but a higher level of DDTresistance. It was discovered later that the twomutations were overlapping in large parts ofAfrica. In Libreville, Gabon, the two mutationswere found at a frequency of 100% (37% kdrW,63% kdrE). Almost 50% of mosquitoes carriedboth mutations. kdrW was also found far to theeast, in Uganda, where both mutations were alsofound in a single mosquito.



populations, dramatically reducing but not inter-rupting malaria transmission.

These trials confirmed the results from laboratoryand experimental hut investigations that kdr resist-ance has marginal impact on the protective efficacyof pyrethroid treated nets. Therefore, this resistanceshould not be seen as an immediate obstacle todeploying and scaling up ITN interventions.

Evidence on the impact of metabolic resistance islimited. In a preliminary trial ITN efficacy wassignificantly reduced in an area with oxidase-based resistance in Cameroon. It is worth notingthan the same metabolic resistance in An. funestusin Southern Africa has a dramatic impact onreducing the efficacy of IRS programs usingpyrethroids, forcing malaria control programs torevert to DDT spraying, or to using costly alterna-tives. It is interesting to note that in an area withkdr resistance (Burkina Faso) a newly developedpermethrin impregnated film tested in experimen-tal huts was much less effective with resistantmosquitoes than with sensitive ones for bothmortality and blood feeding inhibition.

Does vector control select for insecticideresistance?

The answer is undoubtedly yes. Most long-termchemical-based vector control programs, includ-ing malaria, have faced resistance problems.However, resistance prospects depend on verycomplex factors and differ from one program tothe other depending on the insecticide used, vector

behavior (especially in avoiding the insecticide),bio-ecology, population dynamics and the lifestage targeted (larvae or adults). DDT, for exam-ple, has been used against malaria vectors formore than 50 consecutive years in a number ofeco-epidemiologic settings without facing signifi-cant resistance problems.

Although DDT resistance is widespread, aftermore than 50 years of use, e.g. in South Africa,major vectors never developed resistance, or onlyat low levels. This is due to the impact of the treat-ment on vector population dynamics and the factthat the product exerts only a limited selectionpressure on the vector. For example, it targets onlyendophilic females and is strongly excito-repel-lent, meaning it diverts vectors to animals morethan killing them or selecting resistance. In con-trast, today kdr frequencies are more than 80%over very wide areas where no serious or sustainedvector control program has been implemented.This is because selective pressure by DDT and bypyrethroids has been high due to contamination oflarval breeding sites by agricultural insecticides,which also explains why AChE has been selectedto a high frequency in addition to kdr. If we havemore and better information on target site muta-tion resistance this is only because the tools formonitoring this resistance are much better thanthose for monitoring metabolic resistance.

The impact of resistance also depends on the typeof intervention and which specific physiologicalvector stage is targeted. Both DDT and pyre-throids act on the same target-site (see diagram on

ANOPHELES STEPHENSI CULEX QUINQUEFASCIATUS

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cover flap) and have a similar impact on vectorbehavior. Whether sprayed on walls or nets, theseproducts target only female mosquitoes (the onlyones biting humans) and within females, theendophilic (resting indoors) and endophagic (feed-ing on humans indoor) ones. With ITNs, the pri-mary target is a hungry host-seeking mosquito.The search for a blood meal is a vital process: if afemale mosquito is unable to take a blood mealduring the night following egg laying her survivalchances are significantly reduced. This means ahost-seeking female mosquito will tend to be verypersistent, flying on and around an ITN desperate-ly trying to get a blood meal. In doing so, she willeasily pick up a lethal dose of insecticide. ITNs aretherefore a trap with the most attractive bait formajor malaria vectors.

Avoidance behavior

Conversely, the primary targets for IRS are fedfemale mosquitoes looking for a resting site aftera blood meal. They tend to avoid treated surfacesif the insecticide has any irritant effect, such asDDT and some pyrethroids. Unless they are fully

susceptible and can be killed even after very briefexposure, mosquitoes will tend to leave the treatedhouses and eventually survive. This behavioralavoidance of insecticide has long been identifiedas having important implications in IRS interven-tions based on DDT or pyrethroid spraying. Inaddition, because of the excito-repellent effect ofthese insecticides, an important fraction of the tar-get mosquitoes deterred or repelled outside areforced to feed on cattle or other domestic animals.As a result, the selective pressure exerted by theseinsecticides on adult malaria vector populations islimited and in some circumstances might not beenough to induce resistance development.However, once resistance has developed, theinsecticide may still protect human populations,for example by diverting vectors to rest outsideand feed on domestic animals.

Know the vector biology

In contrast, selective pressure is relatively highwith larvicides since all individuals in the treatedarea are exposed and larvae cannot avoid theinsecticide. The importance of vector ecology in

VILLAGE-SCALE studies are needed toassess the impact ofresistance on vectorbehavior and survival inreal life situations.

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insecticide resistance selection is exemplified byAn. gambiae and An. funestus, two major malariavectors in Africa. In West Africa, the S form ofAn. gambiae larvae preferentially breed in rainpuddles, possibly located near crop fields (e.g. cot-ton) that are repeatedly sprayed with insecticides.As a result, these breeding sites are often contam-inated by agricultural insecticides. Larvae of theM form breed in more permanent waterways or inrice fields where relatively little insecticides aresprayed. Significantly, widespread and high levelDDT and pyrethroid resistance has been found inthe S but not the M form. An. funestus breeds inpermanent water bodies shaded by vegetation, alsousually not exposed to agricultural insecticides.Until now An. funestus has remained fully suscep-tible in most parts of Africa, including the WestAfrica cotton belt. The link between larval ecology,agriculture and vector resistance has also beenparticularly obvious in Mexico and Turkey.

Will the use of ITNs select for pyrethroidresistance?

Again, the overall answer is likely yes, with somenuances. Two studies carried out in experimentalhuts in an area with high pyrethroid resistance inCôte d’Ivoire showed selection of resistance toalpha-cypermethrin and etofenprox. Two otherstudies carried out in the same area and an areawith lower resistance (Benin) showed that resist-ance is unlikely to be selected by permethrin,especially if resistance is still at an early stage ofdevelopment. As long as the kdr mutation is absentor present at low frequencies, it seems unlikelythat ITNs will either select or dramatically accel-erate the development of this resistance. Little canbe said at this stage concerning other resistancemechanisms, especially detoxification.

Is resistance management with ITNs feasible?

Although kdr resistance does not appear as animmediate obstacle to large-scale deployment ofITNs, pyrethroid resistance in malaria vectorsremains a major concern globally. As long asinsecticides play a key role in malaria transmissioncontrol there is a need to choose interventions thatare effective despite resistance. A number of tac-tics have been proposed, the most common beingthe use of mixtures or mosaic treatments or rota-tion of unrelated insecticides over time.

Can non-pyrethroid insecticides be used on nets?

Nets treated with organophosphate (pirimiphos-methyl) or carbamate (carbosulfan) insecticidesare very effective in killing vector mosquitoes,including the nuisance mosquito Culex quinque-fasciatus. However, since organophosphates donot prevent blood-feeding, nets treated with theseinsecticides do not provide any personal protec-tion against malaria vectors, in contrast to carbo-sulfan (and of course pyrethroids). In addition,these two insecticides do not last long enough onnets (especially the very volatile organophos-phates) for practical application, unless residual



activity can be increased in the future usinglonger-lasting formulations. In addition, the useof carbamate alone tended to actively selectresistance mediated by modified acethyl-cholinesterases. The same would likely occurwith organophosphates. Another limitation to theuse of non-pyrethroids on nets is the human safe-ty issue. OPs and particularly carbamate insecti-cides can potentially cause greater harm to ITNusers than pyrethroids, both during treatment andnet use. It is therefore desirable to find solutionsthat take advantage of non-pyrethroids, while

overcoming their limitations. This has beenaddressed by combining pyrethroids and non-pyrethroids on a single net.

Combining insecticides on one net

Combinations can be either a mosaic or insecticidemixture. The concept of combining insecticides onnets was introduced to restore efficacy againstresistant mosquitoes, while preventing furtherdevelopment of resistance. Combination of apyrethroid (bifentrin) on the lower part of the net

Pyrethroid insecticides have been used for severalyears for the treatment of bednets to protect againstmalaria-carrying mosquitoes. The effectiveness ofsuch bednets in reducing morbidity and mortalityfrom malaria has been documented elsewhere(WHO, 2000). The WHO Roll Back Malaria(RBM) project has made insecticide-treated bed-nets one of the cornerstones of the effort to reducemalaria, setting the goal in October 1999 of ensur-ing coverage of 60 million African families withinsecticide-treated mosquito nets over a five-yearperiod. The present consensus is that pyrethroids –at the levels currently employed – are generally oflow risk to human health, both for operators andfor users of treated bednets.

The WHO Pesticide Evaluation Scheme(WHOPES) currently recommends a number ofinsecticides, all pyrethroids, for the treatment ofbednets (Najera & Zaim, 2002). A review of thesafety of pyrethroid-treated bednets has been pub-lished (Zaim et al., 2000), and in a detailed riskassessment on the use of deltamethrin on bednets,Barlow; Sullivan & Lines (2001) support thesafety-in-use of this particular insecticide.

Need for a generic risk assessment model

However, detailed assessments of the otherWHOPES-approved compounds have yet to bepublished.

Because of the development of insect resistance tothe commonly used pyrethroids, there is now aneed to consider the use of alternative insecticideclasses for vector control in the treatment of bed-nets. Alternatives under consideration includeorganophosphates and carbamates, which differfrom the pyrethroids in their mode of action andare inherently more acutely toxic and less stable.Thus there is an urgent need for safety assessmentof such treatments before they are used in the field.There is also a need to assess the risks from thevarious methods of bednet treatment that may beused, including the types of insecticide formula-tion used and the newer, more persistent insecti-cide treatments. A generic risk assessment modelis therefore needed, based on typical scenarios forthe preparation and use of insecticide-treated bed-nets and on average or “worst case” values forenvironmental and human parameters, which areapplicable to any insecticide.

W H O P E S

Quoted from paragraph 2.1 in: “A generic risk assessment model for insecticide treatment of mosquitonets and their subsequent use“ (WHO/CDS/WHOPES/GCDPP/2004.6) You can find the whole article at: www.who.int/whopes/guidelines/en/



Scaling up vector control interventions inAfrica, either ITNs or IRS, will require signif-icant strengthening of resistance monitoring,e.g. through the African Network for VectorResistance (ANVR). The choice of insecti-cides will have to rely on detailed mapping of

resistance, identification of resistancemechanisms and an under-standing of potential opera-tional implications of resist-

ance. It will also require adop-tion of pragmatic resistance man-

agement tactics supported by astrong component of operationalresearch. This should be directlylinked to operations to assess localfield situations in real time and

guide programs in their efforts to sustaineffective vector control programs.

CONCLUSION

This article is an excerptfrom a longer contributionby Dr Pierre F. Guillet. You can find the completearticle including the references on theenclosed Public HealthCD-ROM.

and a carbamate (carbosulfan) on the upper partand the roof (mosaic treatment) fully restored netefficacy against resistant An. gambiae (kdr andmodified acethylcholinesterase) as well as multi-resistant Culex quinquefasciatus. Experimentalhut investigations with various insecticide combi-nations and locations showed that the full benefitof insecticide combination is obtained by treatingthe roof with a non-pyrethroid and the four sideswith a pyrethroid insecticide. Combinations canalso use a mixture of two insecticides, and mighthave a practical interest for treating mosquito nets,especially if there is a synergy between the prod-ucts used. Pyrethroids and organophosphateseffectively have a synergic effect when used as amixture on nets, which raised interesting prospectsfor ITNs. Unfortunately, it appeared that the syn-ergistic effect does not occur with pyrethroidresistant mosquitoes in the laboratory, nor in thefield. Interestingly, it seems that neither the mix-ture nor the mosaic treatment using a carbamateand a pyrethroid selected for both modified AChEand kdr, while the non-selection of kdr bypyrethroid alone was again confirmed.

Recent investigations on thebehavior of vector mosquitoesflying around a net have con-firmed the important role of theroof in the insecticidal action ofITNs. Since mosquitoes come incontact with several parts of atreated net while trying to seek outa blood meal, the mosaic treatmentcan be seen as equivalent to a mix-ture, except that mosquitoes areexposed to 2 different chemicals inturn (mosaic) instead of simultaneous-ly (mixtures). A big advantage of themosaic approach is that each insecti-cide can be used at the full opera-tional dose without seriousfinancial and safety implica-tions. A potential limitationof a mixture, in addition tosafety considerations, is therate of decay of the two

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products: if this is not identical at some time pointduring the net's usable life, treatment no longerrepresents a mixture.

Industry is currently addressing the challenge ofadapting the long-lasting treatment technologiesto the use of non-pyrethroid insecticides. Thiswould require an available insecticide with therequired efficacy and safety to treat the wholenet, which is not yet the case, as well as strictcontrol over users. However, rotation of insecti-cides is almost unfeasible with ITNs. LNs usual-ly last for 3 to 5 years, which does not fit with thetime-scale for a rotation approach usuallyplanned on a shorter basis.

nsecticide resistance is an important issue inmalaria control, with some vectors already

multi-resistant. Agricultural usage ofinsecticides has also increased theselection pressure on disease vectorsthat rest and breed on the crops. Theuse of insecticides is currently themajor method of prevention and con-trol of many vector-borne diseases.Dengue control, for example, relies on

I



A large-scale field trial in Mexico evaluated resistance management strategiesfor dealing with, delaying or even stopping insecticide resistance selection.Biological and biochemical assays showed that high level resistancedevelopment was reduced and kept at low levels by using rotation or mosaicschemes rather than single insecticide regimes.

the use of larvicides, such as organophosphates,or space sprays. Although alternatives such as

bio-insecticides and insect growthregulators (IGR) are available, theirhigher costs often prevent their use indeveloping countries. Since only afew new molecules for vector controlare being developed, new approachesto retain efficacy of currently avail-able public health insecticides are

The authors:

DR A. D. RODRIGUEZ, DR R. P. PENILLA,

DR M. H. RODRIGUEZ Centro de Investigaciónde Paludismo, Mexico

PROF J. HEMINGWAYLiverpool School of

Tropical Medicine, UK

Insecticide resistance management in a multi-resistant malaria vector scenario

A Mexican trial showssustainability

clearly needed. Resistance management strategiesare an option that could delay or in the most favor-able scenario, stop resistance development whilemaintaining disease control.

To establish whether predicted methods ofresistance management would work under opera-tional conditions, the IRAC public health groupsponsored an ambitious resistant managementprogram against Anopheles albimanus, the multi-resistant New World malaria vector (see boxpage 29: IRAC).

Designing operational conditions

In the coastal plain of Chiapas, Mexico, a large-scale field trial was undertaken from 1996-2002to evaluate rotations and mosaics of insecticides



MAP OF THE STUDY AREA indicating the groups of villages and the treatments.

MOS = mosaic application, PYR = single use of a pyrethroid, DDT = single use of DDT, ROT = annual rotation of insecticides.

(see map above). The site was chosen because ofthe history of insecticide use in Mexico. Extensiveagricultural and public health insecticide use dur-ing the 1960’s and 1970’s selected multiple insec-ticide resistance mechanisms in An. albimanus,the main coastal malaria vector. Subsequentchanges in land use, the reduction in cotton farm-ing and the success of malaria control activitiesconsequently decreased insecticide use. Thisresulted in a well-documented regression towardsinsecticide susceptibility in An. albimanus to allinsecticides except DDT – as measured by diag-nostic WHO mortality tests (see table page 26:Experimental design). DDT resistance was main-tained by continued use of this insecticide formalaria control activities in Mexico.

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Twenty-four villages were selected and groupedinto sets of three villages, which were randomlyassigned to one of four treatment regimes (see mappage 25).

All insecticides involved in the study were appliedas part of normal anti-malarial activities threetimes per year, with the exception of DDT, whichwas sprayed twice per year. Insecticides weresprayed with a Hudson X-Pert® sprayer with

nozzle No. 8002. Wall bioassays to monitor resid-ual efficacy of insecticides were conducted oneday and then every month, after spraying. Goodkilling effect of mosquitoes was achieved with allproducts at the applied dosages (pirimiphos-methyl)at 2 g a.i./m2, deltamethrin at 0.025 g a.i./m2, ben-diocarb at 0.4 g a.i./m2 and DDT at 2 g a.i./m2), withmosquito mortalities averaging around 75% fourmonths after insecticide application.

EXPERIMENTAL DESIGNFour treatment regimes wereassigned to the selectedvillages:

PYR = pyrethroid (deltamethrin)

OP = organophosphate (pirimiphos-methyl)

CAR = carbamate (bendiocarb)

Singleinsecticide

Traditional

Rotation

Mosaic

Unrelatedinsecticides

Two unrelatedinsecticides

Year 1 Year 2 Year 3 Year 4 Year 5 Year 6

SingleinsecticideTraditional

A: OP B: PYR

DDT

PYR PYR PYR PYR PYR PYR

OP CAR OPPYR PYR PYR

AA

A

BBA

BA B

AA

A

BBA

BA B

AA

A

BBA

BA B

AA

A

BBA

BA B

AA

A

BBA

BA B

AA

A

BBA

BA B

DDT DDT DDT DDT DDT

Insecticide

DDTMalathionFenitrothionFenthionChlorphoximPropoxurDeltamethrinCypermethrinBendiocarbPirimiphos-methyl

Concentration (%)

4512.540.10.0250.10.14

1982

38844497988964

1983

399357

100999557828799

1990

479999

100

86

1997

4010010099

10010099

100100100

Mortality (%)

Mortality of Anopheles albimanus

MORTALITY of Anopheles albimanus from the Chiapas coastal plain to WHO diagnosticadult doses of different insecticides during the early 1980’s and late 1990’s.



Field-caught mosquitoes in the lab

The frequency of all resistance mechanisms wasmonitored before and during the interventionperiod by biochemical assays, along with WHOdiagnostic bioassays using insecticide impregnat-ed papers. Field samples of mosquitoes werecollected on a regular basis approximately threemonths after each spray round and the F1 genera-tion reared from the field-caught mosquitoes wereused for all assays. When few mosquitoes wereavailable, priority was given to biochemicalassays since this method was the most sensitivefor detection of small changes in resistance.Biochemical assay results were compared withthe susceptible An. albimanus Panama strain.Logistic regression analyses were used to deter-mine the effect of the different treatment regimeson the frequency of different resistance mecha-nisms. Pyrethroid treatment and pre-spray wereset as reference variables in the analysis. Since nochanges were observed in DDT resistance levels

A NUMBER OFVILLAGES wereselected for a large-scale field trial.

under any treatment scheme during the wholestudy period, data from DDT treated villages wereexcluded from the analyses.

It had been anticipated that DDT resistanceshould have declined over time when the DDTselection pressure was relaxed. It did not. Thereare two possible reasons for this. Either the DDTstill on the walls (given the longevity of the activeagent) was sufficient to maintain positive selec-tion – or perhaps more likely the resistance hadbeen selected so long ago and then maintainedthat any negative selection associated with DDTresistance genes had been counterbalanced byother genetic changes, thus removing the negativefitness costs of the resistance genes.

Rotation or mosaic schemes moreeffective?

Bioassays showed that continuous use of apyrethroid gradually increased pyrethroid

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resistance in the mosquito field population overthe first four years: resistance then remainedstable for the next two years. In the rotation andmosaic schemes, pyrethroid and organophosphateresistance were selected at low levels andremained stable. No carbamate resistance wasobserved in the rotation scheme.

The biochemical assays (see box below) showedthat although enzyme activity patterns varied, thechances of high level resistance developmentusing a rotation or a mosaic regime were signifi-cantly lower than the rate at which resistance wasselected using a pyrethroid alone.

Delaying resistance selection

Both the rotation and mosaic strategies performedwell operationally and were accepted by the local

Organophosphate and carbamate resistance inAnopheles is often due to a change in theinsecticide's target site, acetylcholinesterase(AChE). Odds ratios for individuals withaltered AChE above the normal insecticidesusceptible range were significantly higherfor the rotation and mosaic treatmentscompared to the single pyrethroid treatmentduring most of the study period, and after theapplication of both organophosphate andcarbamate in the rotation system.

Altered AChE was the main mechanism con-ferring resistance against organophosphatesand carbamates in Mexico and resistanceincreased slightly due to this mechanism withboth the rotation and mosaic regime.

Esterase-based organophosphate andpyrethroid resistance is also common in mos-quitoes. Odds ratio for individuals withesterase levels (measured with the substrateρNPA) above the normal susceptible range

Resistance biochemistryindicated that the rotational regime kept thatmechanism at or below “acceptable” levels,as compared to the single use of a pyrethroid.This suggests that esterases play an impor-tant role in conferring pyrethroid resistancein An. albimanus.

Odds ratios for individuals with esterase levelsusing α-naphthyl acetate as a substrate wereabove the normal susceptible range for boththe rotation and mosaic regimes, hence theyselected for individuals with this type ofresistance mechanism.

The odds ratios for individuals withcytochrome P450s above the normal susceptiblerange also indicated that by the fourth year ofusing the pyrethroid or the rotation, a signifi-cantly higher frequency of individuals withthis resistance mechanism were selected.There was no evidence of selection of a glu-tathione transferase-based mechanism by anyof the four treatments.

population. Hence, rotations or mosaics should beimplemented as part of normal malaria controloperations, to reduce the likelihood of resistancedevelopment. Even in areas where resistance isalready present these strategies may still workwell and delay high level resistance selection.

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IRAC is an inter-company group formed in1984 to provide insecticide and acaricideresistance management strategies to helpreduce the development of resistance in insectand mite pests.

The key to managing resistance is to reduceselection pressure caused by the over-use ormisuse of an insecticide, because this couldresult in the selection of resistant forms of thepest and the consequent evolution of popula-tions that are resistant to that insecticide.

IRAC believes that Resistance Managementshould be an integral part of Integrated PestManagement and provides for sustainableagriculture and improved public health.

Insecticide ResistanceAction Committee

New public health insecticides have beenbrought to market at a slower rate than insecti-cide resistance has developed, and regulatoryissues have further reduced the available insec-ticide choice. Better resistance managementof current and new public health insecticides,to delay or even stop resistance selection, isneeded if vector control is to be sustainable inthe long-term.

CONCLUSION

Article (with plots of odds ratios) onthe enclosed Public Health CD-ROM

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IRAC is acting as a Specialist Technical Group ofCropLife.

www.irac-online.org

The format of the rotation scheme should takeinto account the previous history of insecticideresistance or insecticide use.

Where resistance management is undertakenresistance levels should be monitored regularly. Inthe course of this trial the biochemical assays,although variable, were more reliable andpractical than the bioassays. More insects couldbe processed compared to the WHO method and agreater amount of information was generated permosquito when sample numbers were low.

WAITING FOR the house to besprayed after movinggoods and furnitureoutside.

30

R E S I S T A N C E M A N A G E M E N TR E S I S T A N C E M A N A G E M E N T

Combatting resistance to insecticides in malaria control

Gains made in India Eradication programs in the 1950s dramatically reduced malaria cases in India.This remarkable success was possible using DDT. Then in the 1970s malariaresurged in India, largely due to the development of insecticide resistance inmalaria vectors. But with continued application of well-targeted insecticidesIndia succeeded in reducing the disease burden again and maintaining thisover the last 25 years. Now managing the spread of resistance is of primaryimportance for sustaining insecticide-based vector control.

significant breakthrough in the 20th centuryhas been the spectacular success in control-

ling human malaria and an ever-lengthening list ofvector-borne diseases through a well-structuredvector control program coupled with curative

A treatment. The discovery of the insecticidalproperties of DDT during the Second World Warfacilitated the development of successful vectorcontrol programs worldwide. A classical examplehas been the success story of malaria control in

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RURAL AREAS face differentproblems in terms of vectorecology and the logistics ofimplementing control programs.

India solely relying on DDT. The launching of theNational Malaria Eradication Program in the1950s indeed dramatically reduced the abysmalfigure of 75 million malaria cases per year to aremarkable low of 49 thousand cases by the year1962, with no recorded deaths. This was evidentlypossible with the use of DDT, which could effec-tively control the malaria vectors due to its broad-spectrum toxicity coupled with excito-repellency.However, this success could not be sustained forlong and India witnessed malaria resurgence inthe 1970s. The situation was further aggravatedby the emergence and re-emergence of manyother vector-borne diseases.

Setback in malaria control

The Modified Plan of Operations (MPO)launched in 1977, continued to deploy powerfulwell-targeted insecticides along with other tools.This strategy brought down the disease burden in

India to a stable level of two million reportedcases of malaria per annum by 1980 and has keptthis under control for the last two and a halfdecades. This remarkable achievement has beenrecognized as yet another successful story, a dis-tinction the National Vector Borne DiseaseControl Program (NVBDCP) of India shares withBrazil, Eritrea and Vietnam.

The severe setback inmalaria control witnessedin India during the 1970swas largely due to thedevelopment of resistanceto insecticides by malariavectors. It is a recognizedfact that mosquitoes havethe innate ability tomutate and outwit anyingenious insecticidedeveloped to decimate them. Indeed, it will be aHerculean task for the national program not onlyto achieve further reduction in malaria but also tosustain the gains achieved so far. This necessarilywarrants a paradigm shift in the operation ofinsecticide-based vector control strategies so as toprolong their useful life. This indeed, is the needof the hour mainly due to the lack of globallyavailable new insecticides for vector control.

Insecticides effective in vector control

Insecticides are effectively used in diverse ways totarget vectors and produce optimum control basedon the insects’ behavioral traits. Indoor residualspraying (IRS) using wettable powder (WP)formulations are targeted against adult mosqui-toes, while emulsifiable concentrates (EC) areused for larval control. In addition, fogging orspace sprays (ULV or thermal) are deployed dur-ing epidemics. Also insecticide impregnated bednets, including long-lasting insecticidal nets

The authors:

DR A.P. DASH, DR K. RAGHAVENDRA

National Institute of Malaria Research (Indian Council of Medical Research)

DR M.K.K. PILLAI Former Head,

Department of Zoology,University of Delhi



(hexachlorocyclohexane, another insecticide in thegroup of organochlorines) was used at 2 g/sqm forthree rounds per year. Setbacks in the eradicationprogram began in 1966 due to cross resistance toDDT and HCH first reported in the early 1960s.

This situation led to the more logical option ofintroducing malathion in the states of Gujarat andMaharashtra in 1969 to combat DDT-HCH-resist-ant An. culicifacies. Within four years of its intro-duction the first reports of resistance to malathionin An. culicifacies came from these states.Simultaneously, India was witnessing a severeresurgence of malaria in many parts of the coun-try. This became full-blown by 1976, when 6.47million cases were reported, the largest numberever since the introduction of DDT. Thus, it wasnecessary to explore new strategies and thenational program looked to introduce newinsecticide molecules to contain the tripleresistant An. culicifacies.

Synthetic pyrethroids showed promise with theirremarkable insecticidal activity and low mam-malian toxicity. The National Institute of MalariaResearch (NIMR, formerly known as MalariaResearch Centre) has the distinction of evaluatingthe field efficacy of deltamethrin (syntheticpyrethroid) for the first time in India. By the mid-1990s this insecticide had been introduced intothe national program. During the last two decades,besides deltamethrin, other structurally relatedand equally effective pyrethroids, such ascyfluthrin, lambda-cyhalothrin and alpha-cyper-methrin, were field evaluated and regularly usedfor IRS. At the same time suitable formulations ofthese pyrethroid insecticides were made availablefor impregnating mosquito nets. This interventionis part of vector control at community levels inareas with increased risk of malaria. The nationalprogram has also accepted in principle the intro-duction of LNs. A tablet formulation for convert-ing nets into LNs is available and under field trialswith NIMR 1. These efforts would facilitate large-scale use of LNs especially in areas where theoperation of IRS is not feasible.

(LNs), have recently been introduced as an effec-tive tool to control malaria.

Organochlorine insecticide DDT was initiallyintroduced in 1944 on an experimental basis in theallied forces camps on the Assam-Burma frontduring the Second World War and subsequently incivilian areas in Orissa and Karnataka states. Inthe 1950s, the National Malaria EradicationProgram (NMEP) was launched relying on thestandard protocol of deploying DDT in indoorresidual spraying at 1 g/sqm for two rounds peryear. Wherever DDT was found ineffective HCH

Historic events

• DDT introduced in 1944 on the Assam-Burma front during the Second World War.

• The National Malaria Eradication Program(NMEP) launched in the 1950s was based solely on DDT spraying.

• Use of DDT dramatically reduced the malaria burden up to the mid-1960s.

• Setbacks began in 1966 due to vectors developing resistance to DDT and HCH.

• Malathion introduced in 1969 to combat DDT-HCH-resistant mosquitoes.

• First reports of resistance to malathion in 1973 – malaria resurgence peaks in 1976.

• Modified Plan of Operations (MPO) launched in 1977 deploying well-targeted insecticides and other tools.

• Pyrethroids (first deltamethrin, then others)introduced into the national program in themid-1990s.

• During the last two decades pyrethroid formulations developed for impregnating mosquito nets.

• HCH withdrawn from the national program in 1997 due to health concerns.

• Deltamethrin resistance first detected in 2002, followed by low level resistance to other synthetic pyrethroids.


Fifty-eight of the 450 anopheline speciesreported so far in the world are recorded inIndia. Of these, only ten species of Anophelesare known to be vectors of malaria, althoughsix of them are considered to be primaryvectors having distinct geographical distribu-tion, with diverse ecological niches and trans-mission dynamics (see table below).

With the exception of An. stephensi, othervectors are species complexes comprisingsibling species or isomorphic species differ-ing in vectorial competence, insecticidalsusceptibility, ecological traits and behavior.Proper understanding of these factors hasbecome imperative to elucidate theirtransmission dynamics and initiate innovativecontrol strategies.

The primary vector, An. culicifacies withwide-spread distribution, efficiently transmitsboth Plasmodium vivax and P. falciparummalaria. It breeds prolifically duringmonsoons and often causes sporadic localizedepidemics in different parts of the country.Indeed 60 to 70% of malaria incidence inIndia is transmitted by An. culicifacies and anequivalent proportion of the annual budget formalaria control in India is spent on controllingthis species.

An. stephensi is an urban malaria vector andaccounts for about 12% of malaria cases annu-ally. This species, which perennially transmits

MALARIA VECTORS IN INDIA

malaria, is an important vector in arid zones ofRajasthan. In this region this species has aunique characteristic of breeding proficientlyin underground water tanks (Tankas) prevalentin villages and urban areas. Furthermore, insome of these arid areas increasedprecipitation facilitates prolific breeding ofAn. culicifacies which can often lead to local-ized outbreaks of malaria.

An. fluviatilis inhabiting hilly regions of thecountry contributes to about 15% of casesannually, while the other three species,An. minimus and An. dirus confined to north-eastern regions and An. sundaicus in Andamanand Nicobar Islands, together contribute toabout 8-9% of cases.

Species

An. culicifaciesAn. stephensiAn. fluviatilisAn. minimusAn. dirusAn. sundaicusAn. annularis*An. philippinensis*An. jeyporiensis*An. varuna*

Prevalence

Rural plains and peri-urban areasMainly urban areas Hills and foothillsNorth eastern statesNorth eastern statesAdaman and Nicobar IslandsEastern region North eastern statesEastern region Eastern region and sporadic in southern region

Primary vectors * Secondary vectors/local importance

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In a national program for larval control, organo-phosphate insecticides temephos, fenthion andpirimiphos-methyl are used. Bacterial endotoxinformulations from Bacillus thuringiensisisraelensis H-14 are also used selectively inbreeding habitats.

Status of insecticide resistance in malariavectors

Malaria control in India currently only usesorganochlorine, organophosphates and syntheticpyrethroids. Carbamate insecticides used else-

where are yet to be introduced into the Indiananti-malaria program.

DDT resistance was first reported inAn. culicifacies in 1958 in Gujarat and

later from various other states.Development of resistance in this impor-

tant vector species necessitated withdrawalof DDT from many parts of the country (see

table on page 36: Insecticide resistance inAn. culicifacies). HCH introduced in 1958, regis-tered the first case of resistance in 1962 and soonresistance became widespread in many states. Thevector achieved the unique distinction of doubleresistance to DDT and HCH in 233 districts in 16states and in two union territories. Owing tohuman health concerns HCH was subsequentlywithdrawn from the program in 1997. DDT isdesignated as an “exempted” insecticide for use inpublic health sprays within the mandated quantityof production of 10,000 MT for exclusive use tocontain kala-azar and malaria in certain areas.

Malathion resistance in An. culicifacies was firstreported from Gujarat in 1973 and later becamewidespread throughout the country. The resistanceproblem was aggravated when An. culicifaciesacquired triple resistance to DDT, HCH andmalathion in 182 districts in 13 states and in1 union territory. In certain areas it was also foundthat agricultural use of malathion induced resist-ance in An. culicifacies in the states of AndhraPradesh, Madhya Pradesh and Maharashtra wheremalathion was never used in public health.

Geographical distribution of insecticide resistance in An. culicifacies

Quadruple resistance to DDT, dieldrin, malathion and deltamethrin

Triple resistance to DDT, dieldrin and malathion

Double resistance to DDT and dieldrin

Resistance to DDT

Reports not available

35


Synthetic pyrethroids were introduced tocounteract triple resistance in An. culicifacies inmany states by 1990. However, contrary to expec-tations An. culicifacies exhibited deltamethrinresistance in Surat and Rameshwaram by 2002.Recent monitoring in different states has revealedlow levels of resistance to different pyrethroids inMaharashtra, Gujarat, Madhya Pradesh,Karnataka and Tamil Nadu. This indeed indicatesthe possibility of resistance to syntheticpyrethroids becoming widespread in the nearfuture and might result in a setback in sustainingmalaria control in India. Moreover, extensive useof synthetic pyrethroids in agriculture and thepractice of enhanced use of pyrethroid impregnatedbed nets will accelerate the selection of resistanceto pyrethroids in An. culicifacies, putting insecti-cide-based vector control at a turning point.

Increasing mosquito vector tolerance

An. stephensi, though a vector of urban malaria,also prevails in peri-urban areas. In urban areasonly larvicides are used and this vector has notdeveloped resistance to any insecticide or bacterialpesticides (Bti) used in larval control. However,adults have shown resistance to DDT alone, toDDT and HCH, and to DDT, HCH and malathion,mainly in peri-urban areas (see table on page 36:Insecticide resistance inAn. stephensi). A slightincrease in tolerance tosynthetic pyrethroids wasalso reported from peri-urban areas and wherethis is additionally sub-jected to selection pressurefrom IRS used againstAn. culicifacies.

An. fluviatilis is responsi-ble for transmission ofabout 15% of new malariacases annually in hilly andfoot hill regions of Orissa,Madhya Pradesh, Uttar-anchal and Chhattisgarh.

This species was found mostly susceptible toDDT except for a few stray reports of resistancefrom some states. This species was found to beresistant to DDT in two districts of Orissa and onedistrict each in Uttar Pradesh and Uttaranchal. A1997 survey showed DDT resistance in 11 dis-tricts in 4 states. But it was susceptible tomalathion and deltamethrin. It is worth mention-ing that in Koraput (Orissa) the species was foundto be susceptible to DDT.

An. minimus and An. dirus are the main vectors ofthe north-eastern states of India. Both species arereported to be susceptible to DDT. An. sundaicus,the exclusive vector of Andamans and NicobarIslands, is also reported to be susceptible to DDT.

Management of resistance essential

The insecticide resistance problem is of seriousconcern in India with regard to An. culicifacies,which is responsible for more than 60-70% of themalaria burden in this country, with intermittentoutbreaks/epidemics. It is apparent from recentsurveys that this species has acquired resistance toDDT and malathion and is at the threshold ofdeveloping widespread resistance to the wholespectrum of synthetic pyrethroids currently in usefor malaria control. Thus An. culicifacies, an

omnipresent vector in mostparts of India, is currentlysubjected to intense selec-tion pressure from varioussynthetic pyrethroids usedin public health for IRSand impregnated bed nets,in addition to intenseselection pressure from theextensive deployment ofsynthetic pyrethroids inagriculture. Hence, vectorcontrol solely based onsynthetic pyrethroids maynot be promising in thenear future. The problem iscompounded by the factthat no newer, saferP

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insecticides are available for use in public healthnow or in the near future.

This scenario evidently requires an immediateconsideration of managing the existing and futurespread of resistance as a primary solution to sus-taining insecticide-based vector control. Existingpractices of substitution with more effectiveinsecticides on an ad hoc basis to counteractresistance has always failed, since resistance is anatural evolutionary outcome from environmentalstress caused by continued pesticide onslaught.Therefore, to sustain insecticide-based vectorcontrol and to mitigate resistance, the primary aimshould be to delay the onset of resistance to pesti-cides and thereby increase their useful life. This ispossible by drastically altering operational strate-gies in vector control programs, based on a betterunderstanding of the chemical traits of theinsecticides, their modes of action and theirvulnerability to detoxifications rendering themineffective. Vector control has to focus onselecting the right insecticide in resistant areas toprevent or slow down development and geograph-ical spread of resistance.

Rotation strategies sustain susceptability

The many strategies suggested for the manage-ment of resistance include a time bound rotationof chemically unrelated insecticides differing inmode of action and susceptibility to differentenzymatic detoxification. WHO recommends apreplanned time bound rotation to effectivelycheck the onset of resistance and sustain vectorcontrol with relative ease. This essentiallyrequires a minimum of two, but preferably threeinsecticides to be rotated in tandem. One suchsuccessful campaign has been the OnchocerciasisControl Program (OCP) in West Africa involvingrotation of temephos, phoxim and Bti (H14).

Other success stories in malaria control include acampaign against malaria vectors in Mexico usingan organophsophate compound, a synthetic pyre-throid and a carbamate, and in South Africa usingsynthetic pyrethroids, carbamate and DDT. Thecarbamate bendiocarb field trials in rotation withDDT and synthetic pyrethroids in Mexico andSouth Africa demonstrated a reversion to DDT andpyrethroid susceptibility in malaria vectors. InIndia, carbamates can be profitably used in resist-ance management of malaria vectors, especiallyAn. culicifacies. Bendiocarb insecticide has thedesirable residual efficacy and no long-term per-sistence in the environment as documented by

Type of resistance

DDTDouble* Triple**

Insecticide resistance in An. stephensi

Number of states

763

Number of districts

34278

Type of resistance

DDTDouble* Triple** Quadruple***

Insecticide resistance in An. culicifacies

Number of states

1816132

Number of districts

2862331822

* Double resistance to DDT and dieldrin ** Triple resistance to DDT, dieldrin and malathion

*** Quadruple resistance to DDT, dieldrin, malathion and deltamethrin.



Insecticide resistance is a serious problem inIndia. Malaria eradication programs mustimmediately consider managing the spread ofresistance in order to sustain insecticide-basedvector control. A rotational approach to man-aging insecticide resistance could open up newperspectives in vector control scenarios inglobal malaria control. It is needless to empha-size that concerted efforts of governmental,non-governmental and private sectors in thisnew endeavor could lead to achieving the finalgoal of a malaria-free society.

CONCLUSION


WHO.2 In addition, this insecticide is not used inagriculture, an added advantage to vector controlprograms by avoiding the selection of resistancein disease vectors as non-target species of agricul-tural sprays.

India at cross roads

Since the rapid development of resistance to syn-thetic pyrethroids is looming on the horizon,malaria control in India is at cross roads. Thenational program needs to seriously focus itsattention on preventing or minimizing the devel-opment of pyrethroid resistance in An. culicifaciesby resorting to a judicious and prudent strategy ofinsecticide rotation. At present, the national pro-gram has no alternative insecticide for effectivevector control or for management of resistance.However, possibilities include selective use of anyof the effective organophosphate or carbamatecompounds. Bendiocarb3, evaluated by NIMRand other institutions in India, was found to beeffective against An. culicifacies. It is an idealinsecticide to be used against vectors in multipleresistant areas in rotation with the program’sexisting insecticides, wherever needed, in order tosustain and effectively control malaria in the yearsto come in a cost-effective manner and retain thegains achieved so far in malaria control.

NO ALTERNATIVE insecticides are availablefor effective vector control in India, so existingcompounds will have to be used selectivelyand in rotation.

1 See page 59: Vector management in India

2 Pesticides and their application – For the control of vectorsand pests of public health importance.WHO/CDS/NTD/WHOPES/GCDPP/2006.1. Sixth Edition.

3 See page 59: Vector management in India

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SURPASSING ORIGINAL TARGETS

Malaria control on Bioko Island, Equatorial Guinea

WINDOWTRAPSconfirm theeffectivenessof the spraying program.P

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The main strategy of the Bioko IslandMalaria Control Project is indoorresidual spraying with the goal ofreducing the incidence of malaria andassociated mortality by substantiallyreducing malaria transmission. Earlyemergence of knock-down resistance(kdr) to pyrethroids and DDT requiredswitching to a carbamate. Preliminaryresults indicate a rapid and consider-able impact with significant benefitsparticularly for the poor.

rior to the Bioko Island Malaria ControlProject (BIMCP) malaria incidence was

extremely high on Bioko Island, with reportedPlasmodium falciparum parasite infection rates ofover 50% among children aged 2 to 9 years. Theprincipal vectors in Equatorial Guinea areAn. gambiae and An. funestus, and malaria trans-mission was year-round.

The BIMCP started in 2003 with financial supportfrom Marathon Oil Corporation, its partners andthe Government of Equatorial Guinea. Departingfrom many other country strategies based mainlyon personal protection using long-lastinginsecticidal nets (LNs), the BIMCP relies onindoor residual spraying (IRS) as the principalcontrol strategy.

This is because the main objective of the BIMCPis not just to significantly reduce morbidity andmortality due to malaria (the objectives of RollBack Malaria), but to achieve a substantial reduc-tion or virtual elimination of malaria transmissionon Bioko Island within five years. The main bene-ficiaries are children under 15 years of age andpregnant women, although all Biokans benefitdirectly from reduced transmission.

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Unique partnership

The US$ 12 million, 5-year commitment is aunique, voluntary, multi-stakeholder partnershipbetween:

• The corporate sector (Marathon Oil and its partners).

• The Government of Equatorial Guinea.• Civil society organizations (Medical Care

Development International/MCDI) who serves as the lead implementing organization.

• One World Development Group (OWDG).• Research institutes (the South African Medical

Research Council/MRC and the Harvard Schoolof Public Health).

• The community of Bioko Island.

Based on best practice

The BIMCP strategy was originally designed by ateam from the Harvard University School ofPublic Health in consultation with the SouthAfrican MRC, working with the Ministry ofHealth of Equatorial Guinea and the HealthService Department of Marathon Oil. It was basedon international evidence of best practice to reducemalaria transmission, including extensive and

highly successful previous experiences using IRSas a principal component of integrated malariacontrol initiatives. Particular attention was paid tothe important role of IRS in eradication effortsduring the 1950s and 60s. Also its effectiveness inmalaria control initiatives in other high transmis-sion areas (e.g. the humid coastal area of Tanga,the Pare-Tayeta region in Tanzania and the humidarea of Nyanza in Kenya) was noted, in addition tothe long-standing and highly successful use of IRSin Southern Africa.

Setting up the project

Launching of the BIMCP was greatly helped bythe logistic and administrative capacities ofMarathon Oil operating on Bioko Island, and theirstrong working relations with the Government. Atotal of 80 national spraymen and supervisorswere trained and capacity building mechanismswere established. Bioko was divided into sprayingareas by administrative district and satelliteimagery helped establish the boundaries. Anannual implementation plan was developed inconsultation with the Ministry of Health.

A specially chosen Information, Education andCommunication (IEC) advance team notified

bReduce transmission through indoor residual spraying (IRS) of all residential structures on the island.

b Improve malaria diagnosis through a combination of enhanced microscopy and the introduction of rapid diagnostic tests (RDTs) at health centers without laboratories.

b Improve case management through the introduction of artemisinin-based combination therapy (ACT), given a reported 56% failure rate for chloroquine.

b Implement intermittent preventive therapy (IPT) during pregnancy. bDisseminate comprehensive information, education and communications (IEC)

to support both IRS and case management. bEstablish state-of-the-art monitoring and evaluation system. bSecure early and concerted investment in capacity-building and the full integration

of BIMCP activities into the national Malaria Control Program as a necessary condition for sustainability.

Principal BIMCP goals

104,000

102,000

100,000

98,000

96,000

94,000

92,000

90,000

88,000

86,000Round 1 Round 2 Round 3

2004Deltamethrin

2005Bendiocarb

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96,353

92,440

103,099

2005Bendiocarb



communities throughout the island about impend-ing spraying activity, meeting with communityleaders to mobilize community support. Sincesprayteams visit almost all households on Bioko,this contact also provides an important vehicle forspreading and reinforcing educational messages.For example, information on how to prevent expo-sure to insecticide, how to maximize the usefullife of the residual spray, and where to seek helpin case of fever and suspected malaria. The spray-men also obtain informed consent from house-holds to have their homes sprayed and recordimportant data on spray coverage.

Baseline data

An IRS spray database is used to track and regu-late insecticide usage by spray point, spraymanand date. It records the number of rooms sprayedand surface area covered, and allows for detailedanalysis of insecticide usage. This is comparedwith records on the number of insecticide sachetsdistributed by the central or provincial store per

day. Excessive (or sub-optimal) usage is quicklyspotted so follow-up inspection and remedialaction can be taken.

96 window traps were also installed in 16 sentinelsites located around the Island. Daily mosquitocatches from these traps are counted and analyzedfor malaria infectivity by species. A baseline sur-vey of 575 households living in the environs ofthese same sentinel sites was completed inFebruary 2004. This included data on all-causeinfant and child mortality (under 5 years, datafrom 1,137 mothers); parasitemia and anemiaanalyzed in blood smears from 2,440 childrenunder 15 years of age; IRS and insecticide-treatednet coverage; self-reported morbidity requiring orundergoing anti-malarial treatment and preven-tion. Subsequent household surveys have beenconducted annually. These surveys provide statisti-cally significant comparisons between sentinelsites each year, as well as comparisons betweenyears at the same site.

IN 2005the total number ofstructures treatedwith bendiocarb(two rounds) wassignificantly higherthan with delta-methrin in 2004.

Indoor residual spraying



GRAPH adapted from data produced by Medical Research Council, Durban, South Africa.

The baseline data indicated that one-fourth of thetotal trapped mosquitoes were malaria vectors. Inaddition, overall human infection withPlasmodium falciparum was about 45% withrural prevalence being somewhat higher thanurban prevalence. Three-quarters of children aged1-14 were anemic, with a significantly higher rateamong children suffering from malaria. Thebaseline mortality for children under 5 years wasestimated as 169 per thousand births.

Life saving results

The 2004 IRS program was originally based on asingle spray round using a long-lasting WP for-mulation of deltamethrin (K-Othrine® WP). Theimpact of the BIMCP on malaria transmissionwas based on the mosquito capture data from the96 window traps. After the first round of sprayingthe average number of infected mosquitoes wasreduced by 80%. The percentage of children onBioko Island with malaria parasites in their bloodwas reduced by 30% (see box: Significant impactof IRS on malaria).

By reducing the need to spend money on malariatreatment the BIMCP benefited all households,but in particular those who can least afford treat-ment. Analysis of malaria treatment costs beforeand after the first round of spraying revealed thatIRS resulted in savings equaling about 8% of thepoorest households’ total annual income and 3%of the wealthiest. Malaria control can clearly beviewed as an important component of nationalpoverty alleviation in highly endemic countries.

Insecticide resistance necessitated alternatives

The window trap samples are also analyzed forthe presence of the pyrethroid knock-downresistance genotype. The knock-down resistancegenotype was first reported in malaria vectorscollected on Bioko in 2002. After the first sprayround in 2004 knock-down resistance was foundto have emerged rapidly in the mosquito popula-tion of An. gambiae. On the contrary the sprayingeffect on An. funestus was drastic (see chartabove). Since knock-down resistance genes also

Impact on malaria vector count island-wide

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An. funestusAn. gambiae

Average number An. gambiae and An. funestus per trap per 100 nights (December 2003 – August 2005)



confer resistance to DDT, this compelled theBIMCP team to recommend a switch fromdeltamethrin to a WP formulation of bendiocarb(FICAM® WP), a carbamate insecticide. However,carbamates have an expected shorter residual lifethan pyrethroids, meaning the switch wouldrequire twice-yearly spraying, effectively doublingannual operating costs.

Marathon Oil and its partners supported thisswitch and agreed to absorb the higher costs asso-ciated with the enhanced spraying campaign andmore expensive bendiocarb product. Two roundsof spraying with bendiocarb were conducted in2005 (see chart page 41: Indoor residual spray-ing), and the project initiated its fourth round ofspraying with the product in February 2006.Rotation of insecticides back to pyrethroids is alsobeing considered for future years.

4:1 benefit to cost ratio

Total BIMCP expenditures in the 1st year of oper-ations were roughly US$ 2.3 million, includingtraining, equipment, etc., that will be used overthe lifespan of the project. Estimated savings intreatment costs for averted malaria cases resultingfrom the first spraying round in 2004 were US$10.8 million. This represents a minimum benefitto cost ratio of 4:1 for the first year of the project– in other words US$ 4 in benefits for each US$ 1invested by Marathon and the Government ofEquatorial Guinea.

In the short-term IRS is clearly a more expensivemalaria control intervention than LNs. But theability to achieve high coverage within a fairlyshort time, considerably reducing malaria trans-mission and hence the burden of malaria, makes ita relatively cost-effective alternative.

Moreover, the savings in avoided treatment costsare also expected to have an important welfare-enhancing effect on the population. It shouldrelease more of their income for other essentialbasic needs, goods and services. In turn, it ishoped this will eventually lead to improvementsin housing and environmental conditions, which

will help ensure that transmission does notrebound and that the incidence of malaria remainslow to non-existent.

Lessons learned

• IRS is very effective in reducing malaria trans-mission and associated parasitemia prevalence onBioko Island, even after just one round of spraying.• IRS also has a significant impact on reducinganemia and the reported incidence of clinicalmalaria infection.

Although detailed analyses of the impactof IRS are still underway, preliminaryresults are highly encouraging and fullyconsistent with expectations. The follow-ing data reflect the results obtained afterthe 1st sprayround of only usingpyrethroids in 2004.

• The total number of infective An. gam-biae and An. funestus caught in windowtraps was reduced to 24% and 8%,respectively, of pre-spray levels.• Within 4 months the total number ofAn. gambiae in the window trapsincreased very rapidly giving a clearindication of resistance against thepyrethroid used.• Parasitemia prevalence among under15 year olds was reduced from 46% in2004 to 31% in 2005.• Anemia among under 15 year olds wasreduced by 10%, from 76% in 2004 to66% in 2005.• The self-reported probability of clinicalmalaria decreased by 67% between 2004and 2005.• Registered malaria cases among oilworkers decreased by 65% between2004 and 2005.

Significant impact ofIRS on malaria



• The Bioko experience confirms that IRS is acost-effective strategy for malaria transmissionreduction in high transmission, hyper-endemicisland contexts.• The benefit of IRS has an appreciable impacton poverty alleviation.• The impact of IRS on transmission reductionenhances the likelihood of sustainability of otherintegrated malaria control initiatives.• The BIMCP contract between Marathon Oiland the Government of Equatorial Guinea providesa framework for co-financing malaria control. • The unique multi-stakeholder partnership hasgreatly enhanced opportunities for achievingrapid and substantial success. Partnerships similarto the BIMCP offer international corporations aviable model for engaging in population-basedhealth activities that are outside their line of busi-ness. The model shows how corporate sociallyresponsible investments can maximize the posi-tive impact on the people of the country or regionswhere they are working.• The BIMCP has direct benefits for MarathonOil and its corporate partners (healthier work-force), which will enable it to continue to expandits activities on Bioko and improve work condi-tions for its employees.

Results after just two years indicate that theBIMCP is having a rapid and substantialimpact on reducing transmission as well as theincidence of malaria on Bioko Island. This hasattracted considerable international donorattention, encouraging further funding by theGlobal Fund to fight AIDS, Tuberculosis andMalaria to extend the BIMCP to the Island ofAnnobon and mainland Equatorial Guinea(starting in 2006). The newly launched USPresidential Malaria Initiative has also award-ed a grant to MCDI to reinforce the capacity ofthe Ministry of Health and Social Welfare ofEquatorial Guinea, particularly in the area ofdeveloping health information systems. Whencombined with the BIMCP resources, this willgreatly enhance the potential for substantiallyreducing malaria transmission and associatedmalaria morbidity and mortality throughoutEquatorial Guinea.

CONCLUSION

This article is based on contributions by Dr Luis Benavente and Dr Christopher Schwabe (MCDI), andDr Adel Chaouch (Marathon). Youcan find the article as well as thescientific report (and references) onthe enclosed Public Health CD-ROM.

WITH THE HELP ofhandheld wireless devicessurveyors collect familymedical data.

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As has been shown the use of IRS is an adequateand cost-effective tool to impact malaria.Nevertheless, it will fail when resistance occurs,such as pyrethroid / DDT kdr type. The rotationaluse of a non cross resistant chemical class (here acarbamate – bendiocarb) makes continuation ofintervention possible. Because of the economicalimpact, a switch back to a pyrethroid (for example,when the resistance level has gone down) has tobe an integral part of the plan.

45


Chikungunya outbreaks in Indian Ocean islands

Mosquito-borne viral diseaseChikungunya means “stooped walk” in Swahili, describing how someonesuffering from the disease moves. Like dengue fever, chikungunya is a viraldisease transmitted by mosquitoes. In 2005 and 2006 an epidemic of chikun-gunya spread among the islands of the South-West Indian Ocean, affectingthe Comoros, Mayotte, La Réunion, Mauritius, Seychelles and Madagascar.

dengue-like syndrome, with suddenonset of fever and joint pains, particu-larly affecting the hands, wrists,ankles and feet. Severe chills, leu-copenia and a maculopapular rash arealso common, but the infection canalso be symptomless.

The virus was first isolated in 1953from a patient in Tanzania (the formerTanganyika), East Africa. It is anAlphavirus belonging to the familyTogaviridae with a geographic distri-bution that includes sub-Saharan

a Réunion appears to have beenthe most seriously affected; the

number of cases is estimated to havesurpassed 260,000 – approximatelyone-third of the total population. Thegreat majority of these occurred in thefirst few months of 2006. However, bymid-2006, the cooler, drier australwinter season, the incidence rate haddeclined to very low levels.

Long recognized as a self-limiting,often debilitating but rarely fatal ill-ness, chikungunya manifests as a

The author:

DR MICHAEL B.NATHAN

Vector Ecology &Management,

Department of Controlof Neglected Tropical

Diseases, WHO

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SYMPTOMS appear 4 to 7days after being bitten by aninfected mosquito. High feveris accompanied by variousflu-like symptoms, backacheand pains in the muscles,joints or bones. The pain canbe so severe that patients areunable to walk.

THE CHIKUNGUNYAVIRUS is mainly transmitted by Aedesaegypti.

Africa, South-East Asia and the Indian sub-conti-nent. It is transmitted by mosquitoes, evidenceindicating the involvement of Aedes species,including Ae. furcifer and Ae. africanus inAfrica, and Ae. aegypti and Ae. albopictus inAsia. The virus has been isolated from non-human primates in Africa but in Asia the zoonoticstatus is not well understood.

Extension of geographical distribution

Several key features of the recent epidemic havebrought unprecedented attention to this arboviraldisease. With the exception of the Seychelles,where serological evidence of chikungunya viruswas previously reported1, the first is that theIndian Ocean event represents an extension of thegeographical distribution of chikungunya virus.Indeed, not only was this essentially a “virginsoil” outbreak, but the public health services ofthe region had very limited prior experience with

the prevention and control of arboviruses, theexception being a major outbreak of dengue feverin the Seychelles in 1977, and a subsequent butsmall outbreak in La Réunion in 2004. Ae. albopic-tus was the probable vector on those occasions.

Another striking feature was the explosive natureof the epidemic, especially in La Réunion, wherethere was an estimated peak incidence of morethan 40,000 cases in the first week of February2006. This is clearly indicative of a highlyefficient vector population. Though relativelyclose to continental Africa, the main Africanvectors of chikungunya are either absent or rare inthe cluster of Indian Ocean islands. In MauritiusAe. aegypti is reportedly no longer present and inLa Réunion, if it persists, it is only as isolatedsylvatic populations. Its disappearance from theseislands has been attributed to the anopheline-targeted malaria eradication campaigns of the1960s and 1970s. Ae. aegypti has never beenfound in the Seychelles. By contrast, Ae. albopic-tus is widespread in these and neighbouringislands (in Madagascar it is confined to the littoralzone along the east coast) and is considered tohave been the main and possibly the only vector.Before the rapid spread of this species to conti-nental Africa, Europe and the Americas during thelast three to four decades, the islands of the South-West Indian Ocean represented the westernmostlimit of its distribution which otherwise was

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confined to South-East Asia and some islands ofthe Western Pacific.

Competitive mosquito species

On the Indian Ocean islands Ae. albopictus typi-cally breeds in shady and confined rain-filled nat-ural habitats such as plant axils, bamboo nodesand rock holes, and in artificial container habitatssuch as abandoned tyres (see photo above),saucers under potted plants, and discarded foodcontainers. It is an aggressive and largely outdoor,day-biting species. The fact that the domestic formof Ae. aegypti has been unable to re-colonize theabundant artificial container habitats typical of thisspecies, may be due to factors related to inter-specific competition from a long-establishedAe. albopictus population.

Suffering a range of symptoms

From the perspective of clinical presentation,which was well-documented in La Réunion, theseverity of illness was particularly noteworthy.

RAIN-FILLED containerssuch as abandoned tyresprovide ideal breedinggrounds for Ae. aegyptiand Ae. albopictusmosquitoes. These tyresmust be removed,destroyed or treated with insecticide.

Neurological signs and fulminant hepatitis werereported among a number of patients with con-firmed chikungunya infection. Moreover, amongdeath certificates issued during the first sixmonths of 2006, 240 made mention of chikun-gunya. However, it is to be noted that morbidityrates due to chronic diseases are high in LaRéunion and the majority of registered deaths wereamong the elderly. This suggests that the infectionmay have been a contributory factor leading tothose deaths but that other underlying health condi-tions were the primary causes of mortality.

Higher virus amplification

Genetic studies during the epidemic linked thechikungunya virus to a strain from East Africa2.The researchers were also able to show how subtlechanges in non-structural proteins occurred duringthe course of the epidemic. They hypothesized thatthese changes may have led to higher virus ampli-fication in the mosquito host, which in turn mayhave contributed to the explosive increase in trans-mission during the 2006 rainy season.

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An increase in outbreaks

Lastly, the epidemic yet again serves to illustratehow interconnected the world has become.Arbovirus epidemics such as this one cannot beseen as isolated events, even when they occur inareas of relative geographical isolation.Conversely, geographically isolated islands areclearly not without risk for the introduction ofnew viruses and vectors. There are cultural andtrade links between some of the islands and main-land Africa, from where the virus may have beenintroduced on this occasion. There are also strongnational, cultural and tourist links between theislands and mainland Europe as well as to theIndian sub-continent.

La Réunion and Mayotte are overseas depart-ments of France, while the Comoros andMadagascar are former French colonies.Mauritius and Seychelles were British before theygained independence. These links resulted in anestimated 1.5 million people travelling betweenthe islands and mainland Europe in 2004, mostlyby air3. Not surprisingly, in 2005-2006 thechikungunya virus has been repeatedly importedto Europe, including more than 300 confirmedcases in metropolitan France alone (beyond main-land Europe, cases were also imported to theisland of Martinique in the Caribbean, to Canada,India and Hong Kong, among other places).

RECENT OUTBREAKS of chikungunya have been reported from the areas circled in red. See also page 59, Latest outbreaks: Mosquito-borne diseases spreading.



Since last year cases of the mosquito-borneviral disease chikungunya increased dramati-cally in regions around the Indian Ocean. Themain outbreak control activity is mosquitocontrol. In the case of epidemics IntegratedVector Management’s first task is to reduce themosquito population as rapidly as possible tostop transmission. The long-term goal is tomaintain the vector population at a low levelwith targeted monitoring systems and focuseduse of vector control measures.

CONCLUSION


With the chikungunya outbreak repre-senting a major public health concern,Bayer Environmental Science coordi-nated with the local health authorities,the French Ministry of Health (LaRéunion), the WHO and others in theirintervention strategy to fight thefurther spread of the virus. The mosteffective and rapid way to control dis-ease transmission is by reducing themosquito population. Insecticides candramatically reduce the risk of insect-borne diseases. Following an emergency visit after thefirst awareness of the disease out-break, Bayer Environmental Sciencesent a team of technical experts to bothMauritius and La Réunion at the endof March 2006 to advise the Ministryof Health, intervention teams and localauthorities and decision makers in“best practice” issues. This includedadditional training to ensure theappropriate products (such as Aqua K-Othrine®) were used correctlyaccording to label instructions andwithout risk for humans and the envi-ronment. Appropriate insecticides arebest applied in intervals shorter thanthe incubation period of the pathogenin the vector, to prevent spreading ofthe disease to other regions.


Joining forces

In Europe this has raised public health concernsabout the risk of local transmission in areas whereAe. albopictus has become established and wheremeteorological conditions are seasonably favor-able, e.g. on the south-east coast of France.Additionally, there are close cultural ties betweenMauritius and India, where chikungunya has alsospread this year. However, it is not clear whetherthere are any epidemiological links between thetwo events.

Protective measures

As with dengue, there is no public health vaccine,nor specific treatment for chikungunya. Measuresto control the vector(s) and individual protectionagainst mosquito bites are the only options avail-able for prevention and control. These includechemical methods and, more importantly in thecase of Ae. albopictus, the elimination or manage-ment of larval habitats that are close to humanhabitation. Effective implementation of thesesource reduction measures requires strong socialmobilization and communication actions. Withthe continuing risk of seasonal transmission ofchikungunya and of outbreaks of dengue and pos-sibly other arboviruses, efforts are progressingamong the islands of the sub-region to strengthentheir disease surveillance network and vector con-trol capabilities.

1 Calisher et al. 1981, Bull. WHO, 59: 619-6222 Schuffenecker et al. PLoS Medicine, 2006, 3: 2633 Eurostat

49

Latest outbreaks of Chikungunya see notes onpage 59.



Ethiopia: Support from UNICEF in the fight against malaria

SOME 200 CHILDREN sawnets being treated at each siteevery day.

Focus on distributing insecticide-treated netsUNICEF is one of the founding members of the Roll Back Malaria (RBM)partnership initiative and as such supports health authorities in malariaaffected countries. Programs running in Ethiopia provide an example of howthis support works in practice and which preferences play a role in thetreatment of nets.

UNICEF sees the focus of its work in the fightagainst malaria in Ethiopia as supporting thegovernment in various aspects of malaria control,prevention and treatment. This ranges from the useof insecticide-treated nets (ITNs) to case manage-ment, involving diagnosis and treatment of malaria.The recently introduced rapid diagnostic tests,which like pregnancy tests can be used at home,represent a big shift in case management. UNICEFalso works in social communication at the commu-nity level – training, discussion groups, distributionand treatment of nets.

Distributing 2 million ITNs

Programs focusing on the use of insecticide-treatednets for personal protection have proved highlysuccessful. For example, in 2005 the Ethiopiangovernment purchased 1.2 million nets and afurther 1.8 million through UNICEF, including1 million K-O TAB® 1-2-3 kits. This made itpossible to distribute twomillion insecticide-treatednets throughout hundreds ofemergency prone districtsbefore the malaria season inSeptember. In many cases,these nets were treated in frontof the recipients, an importanttool for health education. Inaddition, UNICEF consult-ants helped with distributionplans, micro-planning, training

for net treatment, monitoring and evaluation. A listwas developed of all villages most prone to malaria,and the consultants worked out the number of netsneeded for maximum coverage – two nets perhousehold. In some villages the number of treatednets has now reached 80%.

Different treatment methods used

The regional health authorities decided how totreat the nets, choosing between three mainmethods. The first method was based on masstreatment – 4 thousand nets were treated in oneplace by 30 trained people. This process lasted3-4 weeks and then the nets were distributed viahealth centers. However, this chosen method onlyinvolved a small proportion of the total nets.

With the second method 325 emergency villageswere chosen as a priority and it was decided to addthe nets to existing distribution programs such as

medicines. The nets weretreated in front of the recipi-ents. Women and children(particularly under 5) are thekey targets here. This isimportant for health educa-tion, since the recipients, i.e.mothers and older children,



then go and put the nets up in their huts. Around200 children per day at each site saw the netsbeing treated.

The so-called intermediate method involved somenets at health centers. These nets were treated asthey were distributed to ensure 100% treatment.This strategy was based on the general observationthat in Ethiopia it is more difficult to get people tore-treat their old nets than elsewhere.

Before the malaria season

K-O TAB® 1-2-3 played an important role in thetreatment of nets, particularly in regions with abetter capacity to treat nets. These treatment kitswere also chosen because it was faster to treat anddistribute such ITNs than to obtain pre-treated nets– ahead of the malaria season.

The use of a binder in the K-O TAB® 1-2-3 formu-lation means the insecticide remains active for up to20 washes. This is a key point in a continent whereas many as 120 million untreated nets already existand where many people do not treat their netsregularly. Although not WHOPES approved(expected December 2006), studies on the washresistance of such treated nets have been encourag-ing. These results certainly were an important factorin the Ethiopian government’s choice.

With children being one of the main groupsaffected by malaria, and as a member of theRBM partnership, UNICEF is closely involvedin programs to combat this disease. InEthiopia, where many people do not re-treattheir old nets, UNICEF focuses on regionaltreatment programs to convert mosquito netsinto long lasting insecticide-treated nets (LNs).This proved to be faster than obtainingpre-treated nets in order to provide as muchpersonal protection as possible before themalaria season.

CONCLUSION


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MASS DIPPING OF NETS,drying and packing.

THE MAIN MISSIONSof NGOs are addressingimportant public healthissues helping disadvan-taged populationsaccess health care andputting an end to localand global poverty.


N G O

Their help is increasingly importantIndependent of governments, NGOs today make an invaluable contribution tointernational development. They typically focus on social, human rights,welfare, relief, health and environmental issues, and generally depend ondonations and voluntary service. The following is a brief introduction to NGOsin general and marks the beginning of a series of specific portraits.

Non-governmental organizations

he World Bank defines NGOs as “privateorganizations that pursue activities to relieve

suffering, promote the interests of the poor, protectthe environment, provide basic social services, orundertake community development”. However,the term NGO is very broad and covers manydifferent types of associations, including privatevoluntary organizations (PVOs), community-based organizations (CBOs, also known as grass-roots organizations) and charities.

Two centuries of development

Voluntary associations of citizens have existedthroughout history, but NGOs as known todaydeveloped over the last two centuries. One of the

first was the International Committee of the RedCross, established in 1863. The term “non-govern-mental organization” was introduced with thefounding of the United Nations in 1945, and todaymany international NGOs act as consultants forvarious UN agencies.

There are now thousands of NGOs of every sizeand form throughout the world: in 1995 a UNreport estimated nearly 29,000 internationalNGOs, most created in the previous 30 years, andeven more national ones (e.g. about 2 million inthe US and 65,000 in Russia). Current estimates ofnational NGOs in developing countries liebetween 6,000 and 30,000.

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Funding large budgets

In 1992 international NGOs channeled over US$ 7.6 billion of aid to developing countries.Today this sum is considerably more. Majorsources of NGO funding include the sale of goodsand services, private donations, and grants frominternational institutions or national governments.Although “NGO” implies independence fromgovernments, some NGOs depend heavily onthem for their funding. For example, about aquarter of the income of the famine relieforganization Oxfam is usually funded by theBritish government and the EU, and MédecinsSans Frontières receives almost 50 percent of itsincome from government sources.

NGOs’ strengths, roles and missions

The specific strengths of NGOs lie in their stronggrassroots links, field-based expertise, ability toinnovate and adapt, application-orientedapproaches, hands-on methods and tools, long-term commitment, and finally their cost-effective-ness. They also play an important role inemploying people in developing countries, wherelocal expertise is often undervalued.

NGOs focus on humanitarian issues, develop-mental aid and sustainable development. Indeed,the vital role played by NGOs in sustainabledevelopment was recognized in Agenda 21 of theRio de Janeiro Convention in 1992. Some NGOsact primarily as lobbyists, raising awareness,acceptance and knowledge, while others mainlyconduct programs and activities – although theseactivities often overlap.

Development NGOs notice immediate needs andrespond to them, delivering services directly tothose affected. They are actively involved in fooddistribution, disaster relief, homeless/refugeeshelter, vaccination programs, family planning,pre- and post-natal care, and ultimately buildingup self-reliant, sustainable local action. Their mainmission is putting an end to local/global poverty,

helping disadvantaged populations access healthcare and addressing important public health issues.

Focusing on specific NGOs

In this, and future editions of Public HealthJournal we will be presenting short profiles ofNGOs and non-profit organizations involved inissues relevant to the topics and fields addressedby Bayer Environmental Science. We are startingthis series on the next page with a brief look atPopulation Services International (PSI).

MANY NGOs are actively involved in fooddistribution, disaster relief and refugee shelter,delivering services directly to those affected.

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NGO Profile: PSI

Success with measurable health impact PSI is one of the leading non-profit organizations in the world. This is effecti-vely highlighted by its activities and successful projects in 70 countries,focusing on major health concerns such as HIV/AIDS, malaria, nutrientdeficiencies, safe water and family planning. The following article provides abrief introduction to PSI.

program offices worldwide. Here, PSI activelysupports Ministries of Health in 70 developingcountries, offering a wide range of health productsand services, and is involved in 30 malaria coun-try programs. PSI delivers products and servicesto improve health and save lives in populationsvulnerable to malaria, HIV/AIDS, contaminatedwater and other major public health concernsworldwide.

Founded in 1970, PSI initially worked in familyplanning (hence the name Population ServicesInternational) in Bangladesh, Kenya, India,Pakistan and Sri Lanka. In 1980, PSI launchedoral rehydration salts in Bangladesh and in 1988

hereas business operations measure theirsuccess in financial assets, PSI measures its

success in impact on health, disease and death. In2004, PSI calculated that its programs directlyprevented 650,000 HIV infections, 6.1 millionunintended pregnancies, 11.5 million bouts ofmalaria and a variety of other global healthproblems.

Global engagement to save lives

Population Services International (PSI) is a non-profit organization based in Washington D.C. Butwith only 151 US staff, its global engagement isreflected by the 7,000 local PSI staff working at its

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CURRENTLY providinginsecticide treated mosquitonets (ITNs) to 28 countries inAfrica, Asia and SouthAmerica, PSI is one of thelargest distributors of ITNs inthe world. Last year PSIdelivered over 10 millioninsecticide treatment kits forconverting nets in the fieldinto ITNs (and LNs), makingthem one of Bayer’s primarycustomers for K-O TAB®

and K-O TAB® 1-2-3.

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started its first HIV/AIDS prevention project in theDemocratic Republic of Congo (DRC). PSI turnedto the problems of malaria and safe water systemsin the mid-1990s, pioneering one of the world’sfirst insecticide treated mosquito net (ITN) pro-jects in the Central African Republic in 1995.

PSI’s mission is “to promote health products andother types of healthy behavior that enable low-income and other vulnerable people to leadhealthier lives.” In particular, this involvesnumerous programs for targeting heavilysubsidized prevention and treatment productsdirectly to risk groups.

Malaria control means prevention andtreatment

PSI’s numerous activities and global engagementin public health are exemplified by its contribu-tions to combating malaria in many developingcountries. PSI tailors its malaria control programsto fit the needs of each country, their Ministry ofHealth and the local RBM partnership. PSIprograms focus on delivering insecticide treatedmosquito nets (ITNs) and long lasting insecticidalnets (LNs) to malaria risk groups – especiallypregnant women and children under five – as wellas marketing a pre-packaged therapy (PPT) fortreating malaria. Targeting of highly subsidized, oreven free, malaria prevention and treatmentproducts directly to the most vulnerable groups iscombined in parallel with stimulating thecommercial sector.

Segmented delivery

Such segmented delivery (based on populationvariables such as risk, access, socio-economicstatus, etc.) not only increases the availability ofeffective and affordable malaria products to all,but also maximizes efficient and sustained productdelivery. When suitably managed, it can operatesmoothly in parallel within the same country. Twoexamples of such programs are Smartnet inTanzania and the Malawi ITN delivery model (seeissue No. 17 of Public Health Journal).

The non-profit organization PSI carefullycalculates its contribution to improving healthand saving lives worldwide. Its combinedproduct delivery strategies not only deliverprevention and treatment products and servic-es to people most at risk, but also stimulateefficient and sustained product supplies.

The recently launched PSI link to malariaprovides a range of downloadable sources of malaria information (www.psi.org/malaria/malaria-downloads.html). The paperon The Costs and Effects of the Malawi ITNModel (http://www.malariajournal.com/con-tent/pdf/1475-2875-4-22.pdf) provides de-tailed figures for economically evaluating thecost-effectiveness of ITN programs.

www.psi.org

CONCLUSION


Today, PSI manages ITN projects in 28 countriesin Africa, Asia and South America. In 2005 alone,PSI delivered more than 3.5 million malaria treat-ment kits, 8.5 million insecticide treated mosquitonets (50% LNs) and over 10 million insecticidetreatment kits, making it one of the largestdistributors of ITNs in the world and an importantactor in the global Roll Back Malaria (RBM)partnership.

Donors provide vital support

As a non-profit organization PSI depends uponfinancial donations to support its, often highlysubsidized, projects worldwide. Major PSI donorsinclude US, UK, German and Dutch govern-ments, the Global Fund to fight Aids, TB andMalaria (GFATM), UNICEF, the Bill and MelindaGates Foundation and other private foundations.


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In malaria control – one size does not fit all

Interview with Desmond Chavasse, Global Director of Malaria Control

Based in Nairobi, Kenya, Dr. Chavasse is responsible forPSI’s malaria control programs in 30 countries in Africa, Asiaand Latin America. He has 19 years experience in the controlof vector borne diseases, particularly malaria and the analysisof ITN delivery models in the field.

Why did PSI decide to add malaria to its activitiesand how important is that area to PSI?

Currently malaria control represents the fastestgrowing program area for PSI and is one of our coreactivities. We added malaria control to our activitiesbecause of the severity of the disease in the coun-tries in which we have programs and because wehave a comparative advantage in supportingMinistries of Health in the delivery of effectivemalaria prevention and treatment products accom-panied by behavior change communications.

What are the reasons for PSI focusing on ITNs inits malaria control programs?

Distribution of ITNs and LNs is an important partof PSI’s malaria control activities because ourprograms are able to leverage a broad range ofpublic, private and NGO delivery channels appro-priate for maximizing access to malaria vulnera-ble groups. PSI now focuses equally on increasingaccess to effective malaria treatment, particularlythe new artemisinin-based combination therapies(ACTs), through delivery of prepackaged drugsin combination with provider training and com-munications campaigns to improve treatmentseeking behavior.

Is there a best model to get ITN/LNs to the peoplewho need them?

The quick answer is no – one size does NOT fitall. The opportunities and constraints to deliver-

ing ITNs across malaria affected countries varyimmensely and this demands tailored approachesto delivery in line with national guidelines deter-mined by Ministries of Health. Depending on thecontext, delivering nets free of charge as part ofvaccination campaigns, sustained supply of netsor vouchers through antenatal clinics, distributionthrough NGO networks and supply through com-mercial channels all have a role and PSI practicesall of them as the situation demands. You willnever hear me describe PSI’s approach to ITNdelivery as “social marketing”. We simply useour comparative advantage in procurement, dis-tribution, marketing and communications tomaximize access to vulnerable groups underprevailing local conditions.

What was the basic rationale behind your deci-sion to go ahead with the long lasting re-treat-ment, K-O TAB® 1-2-3, in Tanzania and Kenya?

The decision was easy. There is no other productcurrently on the market which is able to increasethe effective life of a traditionally treated mosquitonet. While the effective life of K-O TAB® 1-2-3under field conditions has yet to be determined,there is already sufficient evidence to indicate thatit will last longer than traditional treatments.Therefore, the bundling of traditional nets with K-O TAB® 1-2-3 will provide significantlygreater health impact than untreated nets bundledwith traditional treatment kits when LNs cannotbe considered. Furthermore, campaign treatmentof nets in the field with K-O TAB® 1-2-3 can con-vert a crop of traditional nets to longer lastinginsecticidal nets.

PSI has reached an agreement with Bayer Environmental Science to implement several millionunits of K-O TAB® 1-2-3 in Tanzania.

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lisabeth Friedrich makes it clear that her workis no more than “a drop in the ocean.” But in

the villages on the Island of Bugala, as well as onthe small neighboring islands this aid can savelives and improve chances for the future.

The high number of orphans can be explained bythe fact that many parents die not only frommalaria, but above all from AIDS. HIV-infectedparents often move back to the island with theirchildren. When the parents die the childrenremain there alone and urgently need help.

Since 1999 this sprightly senior citizen has metthe call from the episcopal house Masaka(Uganda) through theSenior Citizen ExpertService. In the meantime,with support from friends,projects include renovatingthe outpatient station aswell as building a primaryschool and orphanage. Arainwater storage systemwas installed for the dry

With no publicity, limited resources, but considerable personal engagement,private initiatives are making a vital contribution to development aid. Anexample is an aid action for orphans in the Ssese Islands on Lake Victoria inAfrica (Uganda) coordinated by a German midwife.

season. A larger outpatients station with a labora-tory is currently being built – although the projectkeeps being delayed due to a shortage of money.

In her arduous travels over the island ElisabethFriedrich searches for orphans living in huts in thescattered villages. Included in the aid provided areschool exercise books and rolls of material forschool uniforms, which are sewn by women’sgroups – but above all mosquito nets to protect thechildren particularly at risk (up to the age of five)from malaria. Nets together with treatment kits(K-O TAB®) are provided by Bayer Environ-mental Science and its local partner QualityChemicals. They are distributed locally by

Elisabeth Friedrich throughthe women’s groups.Elisabeth Friedrich: “Werely on such help!”

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Mosquitonets fororphans

Aid project in the SseseIslands

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Asia: Countriesvow to step upmalaria fight

Facing a resurgence of malaria inmuch of southern and southeast-ern Asia, health ministers from11 countries in the regionpledged after meeting inBangladesh in August to bolsterthe fight against the disease. Theministers from such countries asIndia, Sri Lanka and Thailandsaid they would boost spendingto prevent malaria and set a goalof giving 80% of householdsaccess to pesticide-treated mos-quito nets by 2010.

Quoted from UN Wire Newsletter

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Erratum

In our previous issue of Public Health Journal No. 17 wementioned on page 23 that for nets which incorporateinsecticides into the extruded fibers the label recommen-dation is to heat up the net to enhance faster migration.Sumitomo brought to our attention that this recommenda-tion does not exist for the Olyset label and it is definitelynot a recommendation of Sumitomo.

RBM Partners in Dakar: Countries identify resource requirementsRBM Partners worked with fif-teen countries in Dakar between7-15 September 2006 to identi-fy the resource requirementsthat would enable sustainableimpact – and reduction in deathsfrom malaria by 2010/15. TheWorld Bank held an intensivefive-day Regional Workshop at

which partners developed thenecessary strategies to addressgaps – financial and program-matic – so as to provide harmo-nized support to country pro-grams and to attract additionalresources from major donors. Inpreparation for the Workshop,National Malaria Control

Managers undertook a procure-ment and supply chain manage-ment workshop and a detailedand comprehensive review oftheir country plans, sharingexperiences and challenges toscaling-up malaria control.

Quoted from RBM Newsletter

Malaria commitment: ClintonGlobal Initiative annual meeting RBM Partnership presented itscommitment to heads of state,CEOs, religious leaders, philan-thropists, NGOs and foundationheads at this years annual meet-ing of the Clinton GlobalInitiative (CGI) in New York,20-22 September 2006. Thecommitment seeks to strengthenthe capacity of 30 countries tofoster a community-drivenresponse to malaria, and toincrease access to and use ofcurrent malaria interventions.First Lady Laura Bush backed

the malaria fight by announcinga US Malaria Summit, billed forDecember 2006.

Quoted from RBM Newsletter

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PUBLIC HEALTH JOURNAL18/2006 59

India: Vectormanagement As part of vector controlprograms in areas with increasedrisk of malaria, the NationalInstitute of Malaria Research(NIMR) is conducting field trialson suitable formulations forconverting nets into LNs using K-O TAB® 1-2-3 from BayerEnvironmental Science (see page32). In addition, bendiocarb WP80% (Ficam) has recently beenregistered in India and will beintroduced in malaria controlprograms for rotational use inresistance management – pend-ing a TAC implementation deci-sion (see page 37).

On 15 September in Washington,the World Health Organizationlaunched a Position Statementon the use of Indoor ResidualSpraying (IRS) stressing that itmust be considered a primaryintervention against malaria,

WHO: IRS as primary intervention against malaria

Latest outbreaks: Mosquito-bornediseases spreading Recent outbreaks of mosquito-borne diseases across India havecaused many deaths and over-whelmed hospitals and clinics.With 71 deaths in the southernstate of Kerala in September2006, severe outbreaks ofchikungunya reported fromsouthern India and Pakistan sug-gest that it is rapidly movingnorth. The Indian Governmenttook political steps and measuresfor Integrated Vector Manage-ment, including the use of spacesprays to stop the outbreak.Health Ministers of boarderstates attended a meeting atBangalore from 18-20 July,where they requested Rs 800million from the central

Government for chickungunyacontrol. They also recommendedestablishing chickungunya refer-ral laboratories in each affectedstate. The Joint Director ofHealth from Karnataka State hadalready issued a circular to allDistrict Malaria Officers inMarch 2006 on how to tackleoutbreaks of chikungunya.

Experts assume that chikungun-ya is not a “new” disease, butthat in the past many cases werethought to be dengue fever.However, dengue fever itself isalso causing grave concern, withalmost 600 cases and over 93deaths reported in India over sixweeks in August/September. On

October 5, the Guardian newspa-per reported that three membersof the prime minister's familywere taken to hospital sufferingfrom high fever symptomatic ofdengue. Scenes of panic in Delhiearlier that week were due todoctors turning away patientssuspected of having denguefever because of a lack of bloodsupplies for transfusions.

These mosquito-borne diseasesare also on the increase in Asia.There have been more than 160deaths from dengue fever in thePhilippines this year, andIndonesia has recently reportedan outbreak of chickungunya(see article on page 45).

Sources: WHO, UN Wire Newsletter, the Guardian

together with insecticide treatednets, and artemisinin-based com-bination therapies (ACTs).WHO commits to work moreclosely with countries to expandand improve IRS interventions.Quoted from RBM website

to stop malaria claiming the lives of millions. Wehave the tools, there is increased funding – now wemust act.”

Focus on women and children

The RBM partners were also challenged to look atmalaria from a gender perspective. “It is criticalthat women at every level come together to createawareness of the magnitude of the problem andhighlight the inequalities that impact women, asprimary health care givers and sufferers of malar-ia. The integration of a gender perspective foreffective malaria control is crucial,” said Chaka-Chaka, UNICEF Ambassador for malaria. And

according to Dr Awa Marie Coll-Seck,Executive Secretary of the Roll BackMalaria Partnership: “The gender per-spective on malaria research and allareas of malaria control implementationhas been neglected in the current globalresponse to the disease mainly becausethere is little understanding of thegender aspect of malaria.”

Taking the actions forward

With a sense of urgency the RBMpartners committed themselves, to takeforward the actions agreed at theYaoundé RBM Partners Forum, includ-ing the following priority actions, andto implementing the RBM GlobalStrategic Plan 2005-2015, holding eachother accountable to its resource needs,targets and timelines:

PUBLIC HEALTH 18/200660

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NICEF Ambassador Yvonne Chaka Chaka,Assistant Director General of the World

Health Organization (WHO) Dr. Anarfi Asamoah-Baah, and AIDS activist Milly Katana were amongthose who urged the assembled Ministers, repre-sentatives of lead UN agencies, non-governmentalorganizations, the private sector, communities andkey malaria stakeholders to use the currentmomentum to combine forces and acceleratescale-up of malaria control.

“Today there is global recognition that this diseasecan and must be tackled as a matter of urgency,”stated Mr Olanguena Awono, the host Minister ofHealth. “All of us have the collective responsibility

Yaoundé: Call to action on Malaria

The Roll Back Malaria (RBM) Partners’ Forum V held 18-19 November 2005 in Yaoundé,Cameroon, aimed to refocus global efforts to fight malaria and overcome the barriers that arehindering progress. The key recommendations of the meeting were synthesized in theYaoundé Call to Action, a commitment by all partners and stakeholders to ensure coordina-ted, harmonized and intensified activities over the next ten years.

WOMEN AND CHILDREN bear the greatest burden of malaria asprimary health care givers and sufferers of the disease.

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www.rollbackmalaria.org/forumV/

Considering the magnitude of the disease, inparticular its devastating impact on young chil-dren and pregnant women, and its economicconsequences in Africa.Acknowledging that the implementation ofeffective interventions has enabled some coun-tries to reduce the illness and death caused bymalaria, we note with concern that the targetsof the Abuja Declaration on Roll Back Malariain Africa of April 2000 have not been achieved.Recognizing that these successes can bereplicated provided sustained funding is avail-able and is complemented by national leader-ship and mobilization of adequate humanresources at all levels of the health system.Alarmed that current levels of global spend-ing on malaria control are only 20% of the esti-mated US$ 3 billion needed annually, anddeeply concerned about the lack of long-termpredictability of funding that is provided.Acknowledging that adequate investment in,and incentives for, research and developmentare required to ensure new and effective medi-

Key recommendations

cines, diagnostics, vaccines, vector controltools and strengthened health systems. Building on all previous commitments andtargets to roll back malaria, and recognizingthat increased global attention to developmentand poverty reduction as expressed in theMillennium Development Goals, has createdan unprecedented opportunity for rolling backmalaria. Aware that the effects of malaria reach farbeyond health and that the response requiresthe involvement of society as a whole. Emphasizing the importance of nationalleadership for a single coordinating authority, asingle national plan and a single monitoring andevaluation framework. Our duty is to the people and communitiesthat suffer most from malaria, but whose voic-es are all too often not heard. High-level com-mitment and action is needed by all partnersled by the principle of local ownership of thechallenges and solutions for reducing thedevastating impact of malaria.

Under the banner “United against malaria to save lives and reduce poverty”, theparticipants of the RBM meeting expressed their commitment to work together to rapidlyscale-up action against malaria. These are their key recommendations:

• National governments should continue to devel-op national plans for scaled-up action, linked tohealth and development plans, through participa-tory mechanisms, establish broad based nationalcoordinating mechanisms and scale-up programs.

• In supporting national governments all otherRBM partners, consistent with principles agreed inParis in March 2005 (Paris Declaration on AIDEffectiveness), should base their overall supporton countries’ national strategies and implement,where feasible, common arrangements at countrylevel for planning, funding, disbursement, moni-

toring, evaluating and reporting to government onactivities, progress and impact.

• To rapidly establish monitoring mechanisms toensure mutual accountability to these commit-ments, and joint review of progress towards them.

The RBM partners who met in Yaoundé invited allthose who share their commitment to engage inthis Call to Action.

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Malaria (bad air), or “intermittentfever” had long been a concern ofnaval and army doctors becauseof its devastating effects on thoseinvolved in campaigns or explo-rations abroad and Europeancolonialism. The Frenchman

History: Discovering the malaria parasite

Charles Louis Alphonse Laveran

Sources

The Fever Trail: In search of the cure for malaria by Mark HonigsbaumMosquito: The Story of Man’s Deadliest Foe by Andrew Spielman,

Michael D’AntonioDictionary of the History of Science, Macmillan Press Ltd.http://nobelprize.org/medicine/laureates/1907/laveran-bio.html

Plaguing mankind since prehistoric times, there had longbeen those who argued that the “ague” was caused by“pestiliferous miasmas” from swamps. Acquiring the namemalaria in the 18th century, the disease was common inAncient Asia, the Near East and early Europe – Romansoldiers even died of malaria in Scotland. But although con-tinuing to be a major problem in warmer climates, it hadvirtually disappeared from Europe by 1880, the year CharlesLouis Alphonse Laveran discovered the malaria parasite.

professor at the École de Val-de-Grâce, a position Laveran laterheld twice.

Seen through a microscope

However, it was during theperiod between these twoappointments, when posted toAlgeria (1878-83) that hedecided to study malaria. Thanksto the discovery of the micro-scope he managed to observe themalaria parasite in the blood ofmalaria patients. In 1882 hevisited Rome to confirm that theblood parasites he had observedin Algeria were present in malariapatients from Campagna, Italy.He concluded that these proto-zoa were the cause of malaria.Although initially met byskepticism, his results weresubsequently confirmed byscientists from many countries.

He continued his research intodisease-causing protozoa and in1907 was awarded the NobelPrize in medicine for his work.His interest in malaria continuedand he was the first to suggestthat the malaria parasite mustexist outside the human body.

Linking mosquitoes withmalaria

The life cycle of the parasite wasdetermined by Camillo Golgi,and the mosquito’s role in itstransmission by Ronald Ross,Patrick Manson, Amico Bignamiand others. Laveran was closelyinvolved in investigating rela-tionships between Anophelesand malaria. Armed with thisinformation, he could then focuson campaigns to combat thisendemic disease, particularly inswamps in Corsica and Algeria.

SKETCH of an infected Anophelesmosquito by Ronald Ross, 1902.

Charles Louis Alphonse Laveran(1845-1922) came from a med-ical military background and washimself an army physician. Bornin Paris, he went to Algeria withhis family when he was veryyoung. He returned to Francewhen his father was appointed


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AFRICA MALARIA DAY / REPORT 2006www.rbm.who.int/amd2006/index.html

Bill & Melinda Gates Foundationwww.gatesfoundation.org

Centers for Disease Control and Preventionwww.cdc.gov/malaria

CORE (NGOs)www.coregroup.org

CropLife Internationalwww.croplife.org

DFID Department for International Development (UK)www.dfid.gov.uk

Insecticide Resistance Action Committee (IRAC) www.irac-online.org

International Federation of Red Cross and Red CrescentSocietieswww.ifrc.org

Liverpool School of Tropical Medicinewww.liv.ac.uk/lstm

London School of Hygiene and Tropical Medicine (LSHTM)www.lshtm.ac.uk

Malaria Research Council (MRC) South Africawww.malaria.org.za

National Institute of Malaria Research (ICMR) Delhiwww.mrcindia.org

NetMarkwww.netmarkafrica.org

PMI (President’s Malaria Initiative)www.fightingmalaria.gov

PSI (Population Services International)www.psi.org

The Global Fund to fight AIDS, tuberculosis and malariawww.theglobalfund.org

The United Nations Foundationwww.unfoundation.org

The World Bankwww.worldbank.org/malaria

UNICEFwww.unicef.org

United Nations Development Programmewww.undp.org

USAIDwww.usaid.gov

WORLD MALARIA REPORT 2005www.rbm.who.int/wmr2005/

WHO / Global Malaria Programme (GMP)www.who.int/malaria/

WHO / WHOPESwww.who.int/whopes/

Link ListWith reference to the topics in this issue of Public Health Journalwe include a summary of the main Internet links, where you canfind further information, the latest reports and statements.


Business Manager Vector ControlDr Gerhard Hesseemail: [email protected]

Australia / PacificJustin McBeathemail: [email protected]

CARTSEEMuge Yagciogluemail: [email protected]

IndiaDr Anil Makkapatiemail: [email protected]

Latin AmericaClaudio Teixeiraemail: [email protected]

MENAPAshraf Sheblemail: [email protected]

Southeast AsiaJason Nashemail: [email protected]

Dr Nai Pin Leeemail: [email protected]

Sub-Saharan AfricaMark Edwardesemail: [email protected]

FOR INFORMATION PLEASE CONTACT

Events2nd International Workshop on Resistance Management22 - 24 November 2006, Durban, South Africa

5th European Congress onTropical Medicine andInternational Health 24 - 28 May 2007, Amsterdam, Netherlandswww.trop-amsterdam2007.com

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RESISTANCE is not only an issue concerning mosquitoes and Chagas bugs asvectors of important tropical diseases, but also a problem affecting a whole range of publichealth pests. In various countries the control of cockroaches and houseflies, as carriers ofvarious disease causing bacteria, fungi, etc., has become very difficult due to rapidlyspreading resistance. Even decades ago head lice and bedbugs were among the first peststo develop resistance.

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