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Impact of pesticide resistance and network for global pesticide resistance management based on a regional structure

F. Thullner

The author's address is Am Forsthaus 17, D-65510 Wallrabenstein, Germany.
Dedication.
This article is dedicated to Dr David Kemp, Senior Principal Research Scientist, Commonwealth Scientific and Industrial Research Organization (CSIRO), who is a well-known specialist for tick and fly control and resistance and taught the author in pesticide resistance management.

INCIDENCE DE LA RÉSISTANCE AUX PESTICIDES ET RÉSEAU POUR LA GESTION MONDIALE DE LA RÉSISTANCE AUX PESTICIDES BASÉ SUR UNE STRUCTURE RÉGIONALE

Les problèmes de résistance aux pesticides affectent une vaste gamme d'activités dans le domaine de l'agriculture et de la santé publique. Néanmoins, cette question n'occupe pas une place suffisante dans les campagnes de lutte et d'éradication, notamment en ce qui concerne les effets sur des organismes non visés. Cet article présente des exemples dans le domaine de la santé animale qui montrent la complexité de cette question, les interactions possibles provenant de l'utilisation de pesticides et le développement de la résistance qui en résulte. Les liens indissociables qui existent entre la résistance et les résidus, ainsi que l'incidence sur le commerce international dans le nouveau contexte du commerce agricole, compte tenu de l'Accord sanitaire et phytosanitaire (SPS) de l'Organisation mondiale du commerce (OMC), montrent qu'il est urgent de mettre en place une gestion mondiale de la résistance aux pesticides afin de garantir des pesticides efficaces à faibles résidus. Un réseau de gestion de la résistance requiert tant la participation de toutes les parties concernées que celle des laboratoires régionaux de référence. Pour maîtriser la résistance aux pesticides et lutter de façon durable contre elle, il est essentiel que le problème soit traité par l'homologation de pesticides efficaces, la disponibilité et le respect de directives pour l'utilisation des pesticides et les moyens adéquats permettant le suivi et le diagnostic de la situation au niveau du terrain.

EFECTOS DE LA RESISTENCIA A LOS PLAGUICIDAS Y RED PARA LA PREVENCION MUNDIAL DE LA RESISTENCIA A LOS PLAGUICIDAS BASADA EN UNA ESTRUCTURA REGIONAL

Los problemas de la resistencia a los plaguicidas afectan a una amplia variedad de actividades de la agricultura y la salud pública.
No obstante, la cuestión de la resistencia no recibe suficiente atención en las campañas de lucha y erradicación, sobre todo en relación con los efectos indirectos. El presente artículo presenta ejemplos relativos a la sanidad animal para ilustrar la complejidad del problema y las posibles interacciones derivadas de la utilización de plaguicidas, así como la consiguiente aparición de resistencia. Las complejas conexiones entre resistencia y residuos y los efectos en el comercio internacional en las nuevas condiciones del comercio agropecuario, basadas en el Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias de la Organización Mundial del Comercio, ponen de manifiesto la urgente necesidad de establecer un sistema de prevención mundial de la resistencia a los plaguicidas, con objeto de mantener plaguicidas eficaces y con escasos residuos. Para una red de prevención de la resistencia se requiere la participación de todas las partes interesadas, así como de laboratorios de referencia regionales.
Para establecer un mecanismo sostenible de prevención y control de la resistencia a los plaguicidas es imprescindible que se aborde el problema por medio de un registro efectivo de estas sustancias, la disponibilidad y el cumplimiento de directrices sobre su utilización y el empleo de medios adecuados para supervisar y diagnosticar la situación sobre el terreno.

Pesticide resistance is a common and overlapping problem between the fields of agriculture, veterinary medicine and public health. Nevertheless, resistance, especially concerning non-target effects, is not adequately considered in control and eradication campaigns. Examples from the field of animal health illustrate the complexity involved and possible interactions owing to pesticide use and consequent resistance development. The inextricable linkage between resistance and residues and its impact on international trade emphasize the urgency for establishing global pesticide resistance management (PRM) practices in order to preserve efficient, low-residue pesticides. This is particularly so in the new agricultural trade environment, based on the World Trade Organization's (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures (SPS). A network for PRM requires the participation of all parties involved and regional reference laboratories. A cornerstone for sustainable PRM is the consideration of the resistance issue in pesticide registration requirements, covering proper pesticide use, resistance diagnosis and monitoring and preventive measures.

PESTICIDE RESISTANCE - AN OVERLAPPING ISSUE

During the last four decades resistance to pesticides has been, and remains, the most important technical problem facing vector and pest control programmes in the fields of agriculture, veterinary medicine and public health (Shidrawi, 1990). Because pesticides are used in crop production, animal health and public health, the problem of resistance consequently needs to be addressed not only within each of these separate fields (e.g. non-target effects of insect control on tick control and vice versa in animal health) but also as a common and overlapping problem between them (Fig. 1).

Strange as it may seem, intensive efforts to control pests on crops by insecticides have in a number of cases diminished humans' ability to control adequately insect vectors of human disease in the same environment. The ready availability of pesticides, often accompanied by inadequate controls, has led to excesses in their use. Pesticide abuse has not only complicated agricultural pest control by the selection of resistant strains of pests and the suppression of beneficial insects but, in some cases, has also profoundly altered the susceptibility levels of vectors of human disease (Roush and Tabashnik, 1990). It is suspected, however, that the same negative interaction is having an impact on certain pests in the field of livestock production. Despite these interdependent relations, there is a tendency to tackle pesticide resistance as an isolated entity within each of the different fields. There is no common international agreement on pesticide resistance, with the exception of the International Code of Conduct on the Distribution and Use of Pesticides, Article 3.10 (FAO, 1990). A concerted approach, supported by a normative/legal backup of countermeasures to pesticide resistance is imperative for long-term preventive and curative resistance management. There is an urgent need to conserve, through coordinated PRM, efficient low-residue pesticides. This is because efficient non-banned pesticides are a limited, non-renewable resource and the hitherto neglected pesticide resistance/pesticide residue link is having an increasing impact on international trade.
In the highly interrelated, interdependent world of modern technology and trade, the challenge of protecting crops and livestock from insects, diseases, weeds and other pests without hazard to people, animals or their environment requires the combined and sustained efforts of scientists, technicians and administrators; producers, processors and distributors; industry and government; and of nations working together to establish and administer sound, acceptable standards of food safety and environmental quality (FAO, 1985).

RESISTANCE AND PESTICIDE USE IN ANIMAL HEALTH

Within the field of animal health, acaricides, insecticides and endectocides are widely used for parasite control. Although efforts to establish integrated pest management (IPM) are increasing, control and eradication campaigns still depend largely or totally on pesticides, and can therefore be jeopardized by pesticide resistance (Fig. 2). The screwworm eradication programme in the Americas and in North Africa was based on the sterile insect technique combined with the use of organophosphate (OP), the latter acting as a curative for treatment of infested wounds and as a prophylactic to prevent infestation.

To assure the success of any control programme, resistance testing is necessary before deciding which pesticide should be used and resistance monitoring needs to be continued during the campaign. The frequency of resistance monitoring activities will depend on the parasite's generation interval, for example, in a tick control programme, monitoring intervals for Boophilus spp. must be shorter than those for Amblyomma variegatum, which even under the most suitable conditions completes only one generation per year. Another factor contributing to resistance development is the rate of reproduction of the pest. The fact that tsetse fly control programmes, despite intensive insecticide use, so far do not suffer from resistance problems can most likely be attributed to the pest's low reproductive rate. Surveillance should focus on both target and non-target species in order to assess the overall risk, for example the effects of insecticides used in fly control programmes on ticks and vice versa.
Resistance to synthetic pyrethroids (SP) in tick and horn fly populations in the same environment has already caused severe control problems: SP resistance in ticks can in most cases be overcome by using amitraz, which is not effective for horn fly control. On the other hand, organophosphates are being increasingly used for horn fly control (Kunz, 1995), but meet with widespread resistance from ticks.
The diagnosis of resistance to flumethrin in Boophilus microplus as a non-target species within the Caribbean Amblyomma Programme (CAP) has emphasized the need for reliable resistance testing and monitoring in target and non-target species wherever pesticides are used on a large scale. This resistance was diagnosed at the FAO World Acaricide Resistance Reference Centre (WARRC) which collaborates with the CAP. WARRC has also encouraged the consideration of non-target effects on ticks of insecticides used in tsetse fly control programmes because of their dual application. However, the lower concentrations and less frequent treatments that are adequate for tsetse control may lead to resistance in ticks. This example again emphasizes the need for strategies to be designed for the whole pest complex and not just for a single species (Forrester, 1990).
Intensive use of endectocides, for example in southern Brazil, primarily aiming at myiasis and helminth control, is also suspected to contribute to resistance development in the target parasites themselves as well as in other ectoparasites. Severe tick resistance problems affecting the common acaricides, both organophosphates and synthetic pyrethroids, are also contributing to increased endectocide use. Although amitraz resistance is less common, many farmers prefer endectocides in order to control concurrent pests such as endoparasites and Dermatobia hominis. Another important factor making intensive endectocide use possible is the generic competition: cheaper products are increasingly appealing to cost-conscious users.

 

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Pesticide resistance - an overlapping issue
Résistance aux pesticides - une question qui en recouvre d'autres
Resistencia a los plaguicidas: problemas superpuestos

 

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Pesticides in animal health
Les pesticides et la santé des animaux
Los plaguicidas en la sanidad animal

In other regions suffering from severe resistance problems in cattle tick control, the use of amitraz has more than tripled, not only because of its efficacy against SP-resistant ticks, but also because it is a low-residue acaricide. In the event of the development and spread of amitraz resistance, tick control would collapse. The alternatives such as the tick vaccine and development inhibitor (fluazuron) require different control strategies which are not immediately applicable. Also, the vaccine developed for the control of the single host tick Boophilus microplus is recommended as part of a tick control strategy which includes chemical usage in an integrated control programme. The development inhibitor has caused international trade problems owing to residues.

Pesticide use for the control of Varroa jacobsoni in bees may not include non-target effects but the spread of the parasite and the increase of resistance is alarming.
However, the urgent need for resistance countermeasures is more than obvious. In addition to reliable resistance testing and monitoring these should also include investigation into resistance mechanisms and development in order to be in a position to carry out resistance risk analysis in the future.
Parasite control in the field of animal health and its complex implications underline the necessity for interaction between all parties involved. Joint approaches and concerted actions are needed to conserve efficient, low-residue pesticides before the situation changes from alarming to critical. FAO, in collaboration with the Animal Health Industry's recently established Ectoparasite Resistance Working Group (ERWG [AH]) and the affiliated Insecticide Resistance Committee (IRAC) maintains a key role in the initiation and coordination of PRM.

IMPACT OF PESTICIDE RESISTANCE

Pesticide resistance triggers a chain reaction which, through deteriorated efficacy, leads to a higher amount of residues and finally becomes an obstacle to international trade (Fig. 3).

When resistance starts to build up, the user often tries to overcome the unsatisfactory performance by increasing the dose of the pesticide or the frequency of applications. This type of irrational countermeasure, in addition to possible environmental contamination, contributes to the increase of pesticide residues in food, agricultural commodities and animal feed. The problems of resistance and residues are inextricably linked (Kunz and Kemp, 1994), the latter belonging to the most important non-tariff trade barriers when levels exceed the maximum residue level (MRL) allowed by the importing country or, more important, when the importing country has no defined MRL, which means that any detectable amount of the pesticide can lead to import restrictions. This is the case when the particular pesticide is not registered in the importing country, such as the SP flumethrin which is widely used on cattle for tick and fly control in tropical regions but is not registered in the United States. As a matter of fact, a country or region that has severe problems of resistance to a certain pest and does not have the necessary resources and infrastructure for applying PRM will use cheaper pesticides. Consequently, because of the resistance, it will be forced to use the newer and often more expensive pesticides, which are not yet registered in other countries because they do not have the same problem. Unfortunately, these countries are often attractive importing countries, such as the United States or countries of the European Union (EU).
Even though the linkage between resistance and residues seems obvious, international organizations with a normative mandate still concentrate on the residue and environmental contamination problem but do not tackle the resistance problem with the same effort. The Codex Alimentarius Commission (CAC) has set more than 3 200 MRLs for pesticides, assisted by the Codex Committee on Pesticide Residues (CCPR), the Codex Committee on Residues of Veterinary Drugs in Foods (CCRVDF) and the Joint FAO/WHO Meeting on Pesticide Residues (JMPR). The latter comprises the WHO Expert Group on Pesticide Residues and the FAO Panel of Experts on Pesticide Residues in Food and the Environment. FAO and the United Nations Environment Programme (UNEP) are working on the production of an international legally binding instrument for the application of the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade.
However, although important and valuable efforts have been made, the only document of a normative character dealing with the problem of pesticide resistance is the International Code of Conduct on the Distribution and Use of Pesticides, Article 3. 3.10, where "it is recognized that the development of resistance of pests to pesticides can be a major problem. Therefore, governments, industry, national institutions, international organizations and public sector groups should collaborate in developing strategies which will prolong the useful life of valuable pesticides and reduce the adverse effects of the development of resistant species" (FAO, 1990). The need for a joint approach to address this issue is underlined by the alarming increase of pesticide resistance problems which make it more difficult to protect low-residue pesticides and by the lack of awareness that such pesticides are essential components of modern approaches to IPM and to sustainable agriculture and pest control in human and animal health.

 

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Impact of pesticide resistance
Effets de la résistance aux pesticides
Efectos de la resistencia a los plaguicidas

 

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Network for pesticide resistance management
Réseau pour la gestion de la résistance aux pesticides
Red para la prevención de la resistencia a los plaguicidas

Pesticide resistance/residue complex in the context of the World Trade Organization's (WTO) Sanitary and Phytosanitary (SPS) agreement

The WTO's SPS Agreement is the most influential instrument concerning the current international agricultural trade environment (Thiermann, 1996). This agreement advocates SPS measures of concern to the application of food safety and animal and plant health regulations. It encourages member countries to "harmonize" national SPS measures with existing international standards, guidelines and recommendations. The standards set by the Codex Alimentarius Commission (CAC) and the International Office of Epizootics (OIE) are generally recognized as the most important. The SPS Agreement explicitly permits governments to choose higher standards where there is scientific justification to do so or as a consequence of consistent risk decisions based on an appropriate risk assessment (WTO, 1995). One government can challenge another country's food safety or animal and plant health requirements on the grounds that they are not justified by scientific evidence. An example is the anticipated United States challenge to the EU's ban on hormone-treated beef. In this WTO challenge, the United States has gained the support of Australia, New Zealand and Latin American countries. Another asset of the changing pattern of trade, as influenced through the SPS Agreement, is the recognition of pest- and disease-free zones (regionalization) which may not correspond to political boundaries for trade purposes.

As a result of these changes in trade barriers, many countries will use SPS conditions, with or without the legal backing to control imports. Therefore, in the short term, until the WTO's SPS principles are fully implemented, there will be an increase of certain unjustified "trade irritants" (Thiermann, 1996). These may quite feasibly include the issues of pesticide residues and the occurrence of resistance itself. The negative impact of pesticide residues on trade will become even more important in the future and it is highly likely that importing countries will use pesticide residues and violations of the MRL to a much higher extent in order to restrict imports. Developing countries with severe resistance problems do not have the credible infrastructure necessary for the reliable surveillance and monitoring of the associated problems of pesticide residues and resistance, and hence are not able to apply IPM and reduce the amount of pesticide used. Consequently, they have to continue using large quantities of any available pesticide, including banned chemicals and new drugs not yet approved by several attractive importing countries, thus adversely affecting their opportunities to exploit external markets.


CONSIDERATION OF PESTICIDE RESISTANCE IN REGISTRATION REQUIREMENTS

Items for discussion for an amended version of FAO Guidelines for the Registration and Control of Pesticides

INTRODUCTION
To ensure the extended effective life of new and existing pesticides, among other things, a reliable setup is required:

  • for identifying the development and emergence of pesticide resistance;
  • for monitoring the development and emergence of pesticide resistance; and
  • for applying countermeasures.

1. LABORATORY
The laboratory carrying out or responsible for resistance testing should be acknowledged by the regional or national authority concerned. The same laboratory should also be responsible for resistance monitoring.

2. METHODOLOGY
A standard methodology for resistance diagnosis should be defined and agreed on by all parties involved so that they are in a position to identify resistance of the respective pest(s) to the candidate pesticide. This should, in particular, include a definition of the susceptible reference and how to apply it. The maintenance of a susceptible reference strain is most likely to be required.

3. CROSS-RESISTANCE
The risk of cross-resistance needs to be covered within the context of efficacy testing. This requires the nomination and maintenance of resistant reference strains.

4. SURVEILLANCE
A scheme for monitoring resistance development after registration should be defined. In particular, the participation and financial contribution of the parties involved (see point 6) needs to be defined.

5. EXTENSION WORK
Regular information (including field days, farm visits, videos, etc.) on adequate pesticide use and risks concerning resistance development and economic consequences should be provided. Participation of the parties named under point 6 needs to be defined.

6. PARTICIPATION/FINANCIAL CONTRIBUTION OF PRODUCERS, INDUSTRY, GOVERNMENT, REGIONAL AUTHORITY AND INTERNATIONAL ORGANIZATIONS
Support of some of the above-mentioned parties may be critical for the effective implementation of any pesticide resistance strategy. Therefore, their participation should be defined in a feasible way.


ESTABLISHING A NETWORK FOR PESTICIDE RESISTANCE MANAGEMENT

PRM requires the collaboration and sustained efforts of international organizations, industry, investigating institutions, government and users at the international, regional, national and local levels (Fig. 4) in line with FAO's Code of Conduct.

At the international level

Future PRM activities demand adequate input and support from FAO and WHO, these being the relevant international organizations with the appropriate normative mandate. They therefore play a key role in backing up resistance countermeasures and avoidance tactics through the setting of standards, guidelines and recommendations in close collaboration with relevant research institutes and IRAC experts. IRAC is recognized as an advisory body by FAO and WHO.

A cornerstone for sustainable and coordinated PRM is the introduction of pesticide resistance and related issues into the already existing guidelines for pesticide registration. It is therefore suggested that these guidelines should be amended jointly by FAO and WHO in consultation with the pharmaceutical industry. They should address proper pesticide use, resistance diagnosis and monitoring and, to some extent, research into resistance avoidance (see Box). Pesticide producers who contribute to better pesticide use as defined in the new guidelines (Box, points 5 and 6) should be given improved trade selling opportunities under the umbrella of FAO and WHO (e.g. special approval stamp, recommendations to national and regional authorities and farmers' associations). Traders of generic products are likely to be excluded from this procedure if it is obvious that they cannot provide the necessary high standard of technical and commercial support for the product. This will provide the incentive for the R&D-based companies to continue to contribute to PRM through after-sales responsibility for their own products. Industry's support is critical for the effective implementation of any PRM strategy (Forrester, 1990).

At the regional and national level

At the regional level, standardized methods for resistance testing and monitoring consistent with the guidelines need to be introduced into pesticide registration requirements. In the long term, the legal support of measures to counter resistance is an essential component of PRM. Regional reference laboratories need to be established and accredited by the regional trade organization. These should then establish and coordinate a network of national and local laboratories in cooperation with the regional commercial sector and farmers' associations. The ability of the regional reference laboratory to perform its central role will depend on its recognition by the regional trade organization.

International organizations should encourage this procedure, which is in accordance with the concept of harmonization and regionalization, and corresponds to the WTO's SPS Agreement. However, both the private and public sectors have much to accomplish if proper PRM and IPM are to be achieved, preferably prompted by common long-term goals and not by an immediate protection crisis (Leonhard and Perrin, 1994). This is complicated by the paradox that, once resistance has formed, the frequencies are so high that most of the best options to manage it are no longer as effective. Evolution seems not to work with a crisis mentality; we can rest reasonably assured that pest populations are preparing their solutions to our pesticides while we dither over what to do next (Roush, 1993). Notwithstanding, this article is intended to encourage policy-makers to take the first steps in forming the framework of concerted and comprehensive action for the establishment of sustainable PRM.

Bibliography

FAO. 1985. Guidelines for the Registration and Control of Pesticides. Rome.
FAO. 1990. International Code of Conduct on the Distribution and Use of Pesticides (Amended version). Rome.
Forrester, N.W. 1990. Designing, implementing and servicing an insecticide resistance management strategy. Pestic. Sci., 28: 167-179.
Kunz, S.E. 1995. Development of resistance and its management in U.S. hornfly (Haematobia irritans) populations. Paper presented at the International Seminar on Animal Parisitology, 11-13 October, Acapulco, Mexico.
Kunz, S.E. & Kemp, D.H. 1994. Insecticides and acaricides: resistance and environmental impact. Rev. sci. tech. Off. int. Epiz., 13: 1249-1286.
Leonhard, P.K. & Perrin, R.M. 1994. Resistance management - making it happen. In British Crop Protection Council, ed. Proc. Brighton Crop Protection Conference, Pest and Diseases, 21-24 November, p. 969-974.
Roush, R.T. 1993. Occurrence, genetics and management of insecticide resistance. Parasitol. Today, 9: 174-179.
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Shidrawi, G.R. 1990. A WHO global programme for monitoring vector resistance to pesticides. Bull. World Health Org., 68: 403-408.
Thiermann, A. 1996. Impact of the sanitary measures of the World Trade Organization on animal production and trade in the Americas. Paper presented at the Expert Consultation on Non-tariff Trade Barriers, 26-28 August, San José, Costa Rica.
WTO. 1995. Trading into the future. Geneva. 

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