MONITORING AND SURVEILLANCE

3. MONITORING AND SURVEILLANCE

3.1. Antimicrobial resistance

The development of harmonised antimicrobial resistance and surveillance programmes in animals and animal derived food was one of the first tasks in the development of an antibiotic policy to provide information for risk assessment and evaluate the effect of an antibiotic policy (WHO, 2000). A review of the national monitoring programmes (Gnanou and Sanders, 2000) described as state of the art, was the basis for an analysis of the needs to improve the European system. Recommendations established by the members of a European concerted action (Wray and Gnanou, 2000) suggested developing a monitoring programme of veterinary pathogens, zoonotic bacteria, and indicator bacteria (Caprioli et al., 2000). Almost all of these recommendations were rediscussed by an international expert group and proposed by OIE at the international level (Franklin et al., 2001). Monitoring the antimicrobial resistance of zoonotic bac- teria will be requested in the future zoonosis directive (Common Position [EC] N⬚13/2003) and will be a part of surveillance networks implemented in the European Union for communicable diseases (Common Decision of 17 July 2003). In the meantime, several European countries have improved the existing system.

Antibiotic Use in Animals 655 For example, the monitoring programme of antimicrobial resistance of veteri-

nary pathogens has been extended from cattle (Martel et al., 1995) to other major species (pig and poultry) in France (Jouy et al., 2002). Several countries such as France (Sanders et al., 2002), Germany (Guerra et al., 2003), Spain (Brinas et al., 2003; Moreno et al., 2000; Teshager et al., 2000) and the United Kingdom (Goodyear, 2002) have implemented monitoring programmes of antimicrobial resistance for E. coli and Enterococcus faecium collected in faeces or the caecal content of slaughtered animals based on the same epidemiological approach permitting international comparisons (Bywater et al., 2003). For salmonella, the cooperation between national scientific teams from the veteri- nary and human sectors has permitted comparisons between isolates from differ- ent origins and was the basis for molecular epidemiological studies (Baggesen et al., 2000; Threlfall et al., 2003). These studies made it possible to distinguish different ways of dissemination according to serotypes and to analyse the complexity of animal and human relationships.

In 2003, a concerted action ARBAO II began to provide an external quality assurance system for antibiotyping and a web resource to collect national data about antimicrobial resistance in parallel with the global salmonella survey supported by WHO (http://www.vetinst.dk). This concerted action is an impor- tant step in the process of standardisation and harmonisation of bacterial antimicrobial susceptibility testing methods in the veterinary field. The inter- laboratory study, based on proficiency testing of selected bacterial species (Salmonella, E. coli, Streptococcus, Staphylococcus, Pasteurella, Mannheimia, Campylobacter) will contribute to the comparison among the national surveil- lance programmes as recommended by OIE (White et al., 2001).

3.2. Antibiotic use

The use of antibiotics as feed additives depends on the type of production of the herds and is based on zootechnical choices made by the producer. In the European Union, antibiotics used as veterinary drugs are the only prescribed medicines. To be used in food producing animals, antibiotics should first be listed in directive 2377/90 which defines the list of products with maximum residue limits after risk assessment by the Committee of Veterinary Medicinal Products of the EMEA. The prescription of antibiotics is under the responsi- bility of veterinarians. Depending on the country, the drug is delivered by a pharmacist and/or a veterinarian. In several countries, drugs listed in animal health programmes established by veterinarians and approved by authorities can also be sold by producer organisations after authorisation by authorities and under veterinarian control.

656 Pascal Sanders The monitoring of antimicrobial usage in food animals for the protection of

human health was recommended by the scientific community and international bodies (Nicholls et al., 2001). To develop effective antibiotic policies and follow their effect, it is necessary to know which drugs are administered to food producing animals and to determine, why, when, and how they are used. However, no study of drug consumption fails to come up against complex problems associated with data acquisition and processing (Chauvin et al., 2001; Grave et al., 1999b). Information about drug usage should directly be collected from pharmaceutical companies. This approach was been imple- mented by several countries, mainly Nordic countries (Aarestrup, 1999; Grave, 1999b; Wierup, 2001b) where veterinary drug regulations allow them to col- lect sales. The United Kingdom (VMD, 2003) and the Netherlands (Anonymous, 2002b) also collect this data and France has begun recently. The total consumption or sales can be expressed in terms of active substance weight, in kilograms or tons at national level. This methodology is limited by the fact that many veterinary drugs are approved and sold for different animal species. A single active substance may consequently be used in several species. Only new products (approved for one species) or products specifically designed for one animal type (e.g., fish, poultry) or usage (intra-mammary treatment) can be directly compared with the potential consumer population or usage. Moreover, it is difficult to accurately determine the population at risk, even though some statistics exist. A more detailed analysis, relating consump- tion to the metabolic body weight of consumers (animals or humans) could be carried out. These calculations could be based on approximation both of the consumer population and of the average body weight. This approach is also limited by the rapid growth of food producing animals with large differences in body weights and growth rates between species (Chauvin et al., 2001). Another approach is to define a defined daily dose (DDD) as in human medi- cine. This approach was used to study the drug usage for mastitis in cattle in Sweden and Norway (Grave et al., 1999a). The main problem encountered when using the DDD in veterinary medicine is due to dosage variations between different animal species. Besides, few DDD have been defined to date in veterinary medicine (Grave et al., 1999b).

Another approach is to study drug consumption at the population level. Epidemiological studies in herds made it possible to collect information about drug usage in herds under investigation and analyse trends in antibiotic resis- tance in bacterial populations. The effect of different antibiotic use and man- agement systems can also be investigated. This epidemiological approach is very effective but has a high cost and is labour intensive. The relationship between antibiotic exposure and antibiotic resistance in bacteria should also be investigated by collecting information about animal treatment at the time of sampling for the monitoring of antimicrobial resistance in intestinal flora.

Antibiotic Use in Animals 657 If the registration of treatment in the flock is effective, this approach provides

data to investigate the link between drug use and resistance. On the basis of their experience, the Danish have developed a new surveillance system, called VetStat, which provides detailed data on the consumption pattern of all pre- scription medicines at herd level according to species, age, group, and diag- nostic group (Stege et al., 2003). It is based on the registration of drug usage at farm level identified in a national database where the number of animals regis- tered by species and age group is recorded. The veterinary prescriber must provide information about the identity and quantity of medicine prescribed, the target animals, age group, and the disease. The drug usage is described by the disease, the ATC classification system and the defined animal daily dosage (ADD) which is a technical unit describing mean daily maintenance dosage defined for each package species age group. Standardised animal body weights by species and age group are used to allow the calculation of the mean percentage of animals treated per day within the period of interest. Data may

be grouped according to herd identity, period, species, age group, veterinarian, practice, ATC-Code, disease groups, or geographic region. Farm level statis- tics are directly available via the Internet to the farmers, veterinarians, and the veterinary authority as a tool for comparing drug usage between herds and at national level. An important application will be pharmaco-epidemiological research combining data concerning medication and vaccine strategies with antimicrobial resistance.

In human medicine, the variation of the antibiotic dosage regimen prescribed and the level of exposure of the treated subject has been identified as major fac- tors for the selection of antibiotic resistant strains (Guillemot et al., 1998; Gyssens, 2001). Collecting information about the variability of the dosage regi- men prescribed and the dosage regimen really applied on the animals should be

a way of investigating risk factors related to veterinary practice. These data could be collected at the level of veterinarians by way of postal survey (Chauvin et al., 2002). This approach makes it possible to describe the pre- scription patterns in different pathologies. Large variations in the duration of treatment have been recorded (Chauvin et al., 2002a).

Analysing drug consumption requires developing new information tools in many countries to collect robust information about drug prescription at the herd level. An international agreement concerning the handling of topics, such as dosage regimen variations (daily dose, length of treatment), differentiation between short- and long-acting formulations, drug potency, liability of dosage, and other variations in the therapeutic course should be sought. Common def- initions should be reached to obtain comparable figures for international research (Chauvin et al., 2001). These tools are now in development in few European countries but need to be discussed and compared to select the best tools according to the epidemiological objectives (Chauvin et al., 2002b).

658 Pascal Sanders