sou · GLB3132d1 · 1998-01-01 00:00:00 — A further increase was expected but, as shown, did not take place. This might be explained by the improved health situation in piglets which presumably has been accompanied by a similar decrease in the usage of this particular combination of drugs. Resistance to streptomycin and tetracycline is still high, but compared to results from other countries (e.g. , 1991; and Moisan, 1994) the overall figures indicate a favourable situation. Antibiotic resistance in porcine % COLI strains isolated in during different time periods (%). (From Franklin unpublished data and Franklin, 1984; , 1996) 4ABELL 8 !NTIBIOTIKARESISTENS HOS E. coli FR¥N SVIN ISOLERADE I 3VERIGE UNDER OLIKA TIDSPERIODER &R¥N &RANKLIN OPUBLICERADE DATA OCH &RANKLIN .O OF ISOLATES INVESTIGATED 1Breakpoint = value above which the isolate has been classified as resistant; 2 Denotes the trimethoprim concentration; 3 Denotes number of investigated isolates; 4 ND= not "RYTPUNKT V¤RDE ¶VER VILKEN ISOLATET BETECKNATS SOM RESISTENT !VSER KONCENTRATION TROMETOPRIM N ANTAL UNDERS¶KTA ISOLAT .$ EJ UNDERS¶KT Proportion of 3TAPHYLOCOCCUS AUREUS (isolated from clinical mastitis in dairy cows in during different years) with resistance to different antibacterials (Data from Franklin and , 1983; and Franklin, 1987; , 1996) 4ABELL 8) !NDEL AV S.aureus ISOLERADE FR¥N KLINISK MASTIT HOS N¶T I 3VERIGE UNDER OLIKA ¥R VILKA UPPVISAR RESISTENS MOT VISSA ANTIBAKTERIELLA MEDEL $ATA FR¥N &RANKLIN AND (ORN AF 2ANTZTIEN 2OBERTSSON AND &RANKLIN 9EAR .O OF ISOLATES INVESTIGATED 1Breakpoint = value above which the isolate has been classified as resistant; 2 Resistant isolates determined on the basis of b-lactamase production; 3 ND = not determined "RYTPUNKT V¤RDE ¶VER VILKET ISOLATEN BED¶MTS SOM RESISTENTA 2ESITENS BEST¤MD SOM PRODUKTION AV b LAKTAMAS .$ EJ UNDERS¶KT Among the udder pathogens causing bovine mastitis, 3 AUREUS is the most important causative agent. It gives rise not only to severe acute inflammation but also to chronic subclinical conditions. In , about of clinical mastitic cases are caused by this species. Besides 3 AUREUS, a number of other staphylococcal species are associated with bovine mastitis. About 5 to of the 3 AUREUS isolates from clinical cases of mastitis are resistant to penicillin due to penicillinase production (Table 2.XI). Penicillin resistance is more common in coagulase-negative staphylococci (about , L. , personal communication2) 3ERPULINA HYODYSENTERIAE is the causative agent of swine dysentery. Minimum inhibitory concentrations () for 67 Swedish strains were determined for seven antibiotics. The strains were isolated from herds with and without dysentery problems in the period 1988 to 1990 (, 1991). The distribution of values are shown in Table 2.XII. The values of tylosin and virginiamycin indicate that these drugs would no longer be effective for treatment of swine dysentery. 2 , Laboratory Veterinary Officer, , (), Antibacterial sensitivity of 67 isolates of 3ERPULINA HYODYSENTERIAE from Swedish pigs (Data from , 1991) 4ABELL 8)) +¤NSLIGHET F¶R ANTIBAKTERIELLA MEDEL HOS ISOLAT AV Serpulina hyodysenteriae FR¥N SVENSKA GRISAR $ATA FR¥N 'UNNARSSON ET AL -)# OF DIFFERENT ANTIBACTERIAL SUBSTANCES uG ML Surveys for antimicrobial resistance in commensals, i.e. non-pathogenic bacteria, have only recently been initiated in . Preliminary results from these studies are given below. In a study on poultry bacteria, enterococci and % COLI were isolated on selective media from neck skin and hindgut samples representing 52 poultry flocks slaughtered in 9 different slaughterhouses (Greko, 1996). A total of 207 isolates of %NTEROCOCCUS spp. and 194 isolates of % COLI were investigated for values for a range of antibacterials. Results from this study are shown in table 2.XIII and 2.XIV. The figures show an overall low level of resistance for both enterococci and % COLI. The one exception is the prevalence of resistance against tetracyclines in enterococci. Tetracyclines are not frequently used in Swedish poultry production, and corresponding figures for other bacteria isolated from chickens (#AMPYLOBACTER JEJUNI, % COLI) do not indicate a high exposure to this drug. Table 2.XIII Resistance in %NTEROCOCCUS spp. isolated from chicken (neck- skin and faecal samples). of isolates = 194 4ABELL 8))) 2ESISTENS HOS Enterococcus SPP ISOLERADE FR¥N KYCKLING FECES PROV !NTAL ISOLAT 0ROPORTION OF ISOLATES RESISTANT 1Breakpoint = value above which the isolate has been classified as resistant "RYTPUNKT V¤RDE ¶VER VILKET ISOLATEN BED¶MTS SOM RESISTENTA Resistance in % COLI isolated from chicken (neck-skin and faecal samples). of isolates = 194 4ABELL 8)6 2ESISTENS HOS E.coli ISOLERADE FR¥N KYCKLING FECES PROV !NTAL ISOLAT 0ROPORTION OF ISOLATES RESISTANT 1Breakpoint = value above which the isolate has been classified as resistant; 2One isolate, also resistant to enrofloxacin (MIC=1µg/ml) "RYTPUNKT V¤RDE ¶VER VILKET ISOLATEN BED¶MTS SOM RESISTENTA %TT ISOLAT ¤VEN RESISTENT MOT ENROFLOXACIN The antibacterial resistance of enterococci and % COLI isolated from piglets has recently been investigated in a cohort study (Greko, 1997; , 1997). Briefly, in a study aiming to investigate the possible occurrence of resistance to zinc oxide among commensal % COLI of piglets in , a total of 300 faecal samples were examined. The samples were collected 2-3 weeks after weaning from piglets in a total of 30 herds; 10 herds were using olaquindox as medicated feed (160 ppm), 10 herds were using zinc oxide (2500 ppm) and 10 herds used no medication. No isolates of coliforms with resistance to zinc oxide were found (, 1997). All samples were also cultured on selective media containing 50µg/ml of vancomycin. No vancomycin-resistant enterococci were found. From non-antibiotic containing media, enterococci and coliforms were selected at random from each sample for further investigation. shows the results of determinations of minimum inhibitory concentration () of different antibiotics for %NTEROCOCCUS spp. and table 2.XVI the corresponding results for % COLI. Taken together, the figures are comparatively favourable. The number of isolates investigated from each group is too small to validate any conclusions with regard to differences between groups. Some conflicting observations on differences between groups can be made. For enterococci, the figures on resistance to neomycin and streptomycin in the non-medicated group seem higher than those from the other groups. On the other hand, such differences cannot be observed for % COLI. Similar observations can be made for % COLI and tetracycline resistance. Resistance to macrolides in enterococci seem to be more frequently of constitutive type in non-medicated groups. A lower prevalence of resistance to chloramphenicol in % COLI from the non- medicated group is not reflected in the figures for enterococci. Resistance to different antibacterials in %NTEROCOCCUS spp. isolated from weaned pigs in herds using different regimes 4ABELL 86 2ESISTENS MOT OLIKA ANTIBACTERIELLA MEDEL HOS Enterococcus SPP ISOLERADE FR¥N AVVANDA GRISAR I BES¤TTNINGAR MED OLIKA REGIM 1Breakpoint = value above which the isolate has been classified as resistant; 2 n= number "RYTPUNKT V¤RDE ¶VER VILKET ISOLATEN BED¶MTS SOM RESISTENTA N ANTAL UNDERS¶KTA ISOLAT Table 2.XVI Resistance to different antibacterials in % COLI isolated from weaned pigs in herds using different regimes 4ABELL 86) 2ESISTENS MOT OLIKA ANTIBAKTERIELLA MEDEL HOS E. coli ISOLERADE FR¥N AVVANDA GRISAR I BES¤TTNINGAR MED OLIKA REGIM 1Breakpoint = value above which the isolate has been classified as resistant; 2 n= number "RYTPUNKT V¤RDE ¶VER VILKET ISOLATEN BED¶MTS SOM RESISTENTA N ANTAL UNDERS¶KTA ISOLAT 2.7.4Some comments on the resistance figures As shown above, available data indicate that antibacterial resistance is comparatively low in most bacteria from Swedish food producing animals. For most substances this reflects the consumption figures. However, other factors than antimicrobial usage may also contribute to resistance to certain substances at a high level (see chapter 4). Continuous monitoring for antimicrobial resistance is necessary for detecting trends in resistance development. It is important to remeber, though, that resistance data only shows the phenotypic expression of resistance traits. Thus, further research on the genes behind the resistance is also necessary. Antibacterial substances are valuable therapeutic tools in both veterinary and human medicine. Their use both as therapeuticals and as feed additives have contributed to the development of the contemporary animal industry. In , all antimicrobial substances used in animals are classified as pharmaceutical specialities and are only available on veterinary prescription. The ban on antimicrobial feed additives in 1986 was associated with animal health problems in certain production systems. These health problems have to a large extent been overcome, and todays total consumption of antibacterials in veterinary medicine is considerably lower () than what was used before the ban. The lower consumption is reflected in a comparatively favourable resistance situation in most animal bacteria. The Swedish experience shows that changes in production systems are necessary in order to adjust to animal production without antimicrobial feed additives, but also that such adjustments are possible and might pay off in a better situation regarding antibacterial resistance among zoonotic and animal bacteria. "EHAR - 3CRIMSHAW . 3 'UZMAN - ! AND 'ORDON * % , 1968. field study in Guatemalan villages, 1959-1964. An epidemiological appraisal of its wisdom and errors. !RCHIVES OF %NVIRONMENTAL (EALTH 814-827. "ERDTSSON % , 1996. Campylobacter in broiler chickens- The mode of spread in chicken flocks with special reference to food hygiene. (Thesis). "J¶RNEROT , , 1996. förbjöd antibiotika i tillväxtstimulerande syfte 1986 - vad hände med förbrukningen? +UNGLIGA 3KOGS OCH ,ANTBRUKSAKADEMIENS 4IDSKRIFT 57-68. "J¶RNEROT , &RANKLIN ! AND 4YSEN % , 1996. Usage of antibacterial and antiparasitic drugs in animals in between 1988 and 1993. 6ETERINARY RECORD 282-286. #OLEGRAVE 4 AND 7ESLEY 4 1995. 4HE FEED ADDITIVES MARKET PERFORMANCE ENHANCEMENT AND DISEASE CONTROL 32 Animal Pharm Reports. %LWINGER + %NGSTR¶M " "ERNDTSON % &OSSUM / AND 7ALDENSTEDT , , 1996. Effect of growth promoters and coccidiostats on performance and growth of #LOSTRIDIUM PERFRINGENS in the caeca of broilers. )N PROCEEDINGS OF 88 7ORLD S 0OULTRY #ONGRESS 2-5 September, %LWINGER + %NGSTR¶M " &OSSUM / (3 AND 4EGL¶F " , 1994. Effect of coccidiostats on necrotic enteritis and performance in broiler chickens. 3WEDISH *OURNAL OF !GRIULTURAL 2ESEARCH 39-44. %LWINGER + 3CHNEITZ # "ERNDTSON % &OSSUM / 4EGL¶F " AND %NGSR¶M " , 1992. Factors affecting the incidence of necrotic enteritis, caecal carriage of #LOSTRIDIUM PERFRINGENS and bird performance in broiler chickens. %LWINGER + AND 4EGL¶F " , 1991. Performance of broiler chickens as influenced by a dietary enzyme complex with and without antibiotic supplementation. !RCHIV FUR 'EFLUGELKUNDE %NDTZ ( 0 2UIIS ' * +LINGEREN " *ANSEN 7 ( 2EYDEN 4 AND -OUTON 2 0 , 1991. Quinolone resistance in campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. *OURNAL OF !NTIMICROBIAL #HEMOTHERAPY 199-208. &IEMS , / "OUCQUE # 6 AND #OTTYN " ' , 1995. Effect of feed antibiotics on animal performances, meat quality and health in ruminants, and on aspects of environmental pollution. )N PROCEEDINGS OF 3CIENTIFIC CONFERENCE ON GROWTH PROMOTION IN MEAT PRODUCTION REPORT AND CONCLUSIONS -1, . Antimicrobial drug resistance in porcine enterotoxigenic Escherichia coli of O- group 149 and non-enterotoxigenic Escherichia coli. 6ETERINARY -ICROBIOLOGY 467-475. Antibiotikaresistens hos salmonellastammar isolerade på SVA 1992-1994, rapport till . AND 2EHBINDER 6 , 1994. Antibiotic resistance i Salmonella isolated from animal sources in . )N PROCEEDINGS OF !NTIMICROBIALS IN ANIMAL INTENSIVE PRODUCTION October 25-27, 1994, Ploufragran. AND (ORN AF 2ANTZTIEN - , 1983. Antimicrobial drug sensitivity of Staphylococcus aureus strains isolated from bovine milk. .ORDISK 6ETERIN¤RMEDICIN 447-454. AND 7IERUP - , 1987. Antibiotikaresistens hos salmonellastammar isolerade från nötkreatur , Rapport till Lantbruksstyrelsen. '# , 1996. Inventering av resistens mot antibakteriella medel hos enterokocker från kyckling (rapport). '# , 1997. Sensitivity to antibacterials in % COLI and enterococci isolated from piglets in (in manuscript). (ORN AF 2ANTZIEN - ,ANDEN ! AND 2ANTZIEN - ( A , 1991. Resistensundersökning av svenska isolat av Treponema hyodysenteriae. 3VENSK 6ETERIN¤RTIDNING 349-352. 'UZMAN - ! 3 AND -ONROE 2 * , 1958. Growth and development of Central I. Growth responses of rural Guatemalan school children to daily administration of penicillin and aureomycin. !MERICAN *OURNAL OF #LINICAL .UTRITION 430- '¶RANSSON , ,ANGE 3 AND ,ONNROTH ) , 1995. Post weaning diarrhoea: focus on diet. 0IG .EWS AND )NFORMATION 89N-91N. '¶RANSSON , -ARTINSSON + ,ANGE 3 AND ,¶NNROTH ) , 1993. Feed-induced lectins in piglets. *OURNAL OF 6ETERINARY -EDICINE " 478-484. Zinkoxid tilsat foderet til forebyggelse af % COLI-betinget fravenningsdiarre. (YOLOGISK 4IDSKRIFT 42-43. Djurhälsomässiga behobet av fodermedelsantibiotika i smågrisproducerande besättningar. 3VENSK 6ETERIN¤RTIDNING 57-65. Profylaktiska effekter av zinkoxid eller olaquindox mot avvänjningsdiarré hos svin. 3VENSK 6ETERIN¤RTIDNING 217-222. *OHNSON * AND 2EID 7 - , 1970. Anticoccidial drugs: lesions scoring techniques in battery and floor-pen experiments with chickens. %XPERIMENTAL 0ARSITOLOGY 30-36. *ONSON ' AND *ACOBSSON , 1973. Foderantibiotikas inverkan på kalvdödlighet. 3VENSK 6ETERIN¤RTIDNING 17-22. ,"3, 1977. Utredning avseende utnyttjandet av specialämnen såsom antibiotika/kemoterapeutika, vilka i tillväxtbefrämjande syfte inblandas i foder. -AC$OUGALL , , 1957. The effect of aureomycin on undernourished african children. 4HE *OURNAL OF 4ROPICAL 0EDIATRICS 74-81. -ACKAY ) & 3 0ATRICK 3 * 3TAFFORD $ AND #LEVELAND & 3 , 1956. The influence of vitamin B12 and aureomycin upon the growth of protein deficient children. *OURNAL OF .UTRITION -, &RANKLIN ! (ORN AF 2ANTZIEN - AND 7ALLGREN 0 , 1996. values of faecal isolates of % COLI isolates from piglets in . )N PROCEEDINGS OF TH )063 #ONGRESS 7-10, 1996, , . -, (. 7ALLGREN 0 AND &RANKLIN ! Sensitivity to olaquindox and zinc oxide in coliform bacteria from weaned piglets. submitted to the 15th (1998). -ORVAN ( AND -OISAN * # , 1994. Sensibilite des salmonelles aux antibiotiques en elevage industriel. )N PROCEEDINGS OF !NTIMICROBIALS IN ANIMAL INTENSIVE PRODUCTION ISPAIA- Zoopole, October 25-27, 1994, Ploufragran. .ILSSON , , 1996. Mastiter - infektionspanorama och antibiotikaresistens (att publiceras). .ILSSON , AND '# , 1997. Survey of the use of antimicrobial drugs in veterinary medicine with special emphasis on mastitis treatment. )N PROCEEDINGS OF .ORDIC 3EMINAR 2EGARDING THE &UTURE 5SE OF !NTIBIOTICS IN -ASTITIS 4HERAPY .-3- January 21-22, . /DENSVIK + , 1997. Sammanställning över foderläkemedel 1995 och 1996. 3VENSK 6ETERIN¤RTIDNING 386-389. 0OHL 0 6ERLINDEN - ,INTERMANS 0 6AN 2OBAEYS ' AND 3TOCKMANS ' , 1991. Antibiogrammes des enterobacteries pathogenes pour les animaux delevage et les pigeons, isolees en de 1986 a 1990. !NNALES DE MEDICINE VETERINAIRE 101-108. 0OULSEN ( $ , 1995. Zinc oxide for weaning piglets. !CTA !GRICULTUAE 3CANDINAVICA 3ECTION ! !NIMAL HEALTH 3CINECE 159-167. 2OBERTSSON * AND &RANKLIN ! Antibiotikaresistens hos bakterier från akuta mastiter på kor. 3VENSK VETERIN¤RTIDNING 115-120. 2OBERTSSON * AND ,UNDEHEIM . Prohibited use of antibiotics as a feed additive for growth promotion - effect on piglet health and production parameters. )N PROCEEDINGS OFTH )063 #ONGRESS 26-30, . 2OBINSON 0 , 1952. Controlled trial of aureomycin in premature twins and triplets. 4HE ,ANCET I 52. 2UTQVIST , # , 1970. Antibiotic resistance of bacteria. 3VENSK 6ETERIN¤RTIDNING 307-308. 3MITH ( 7 AND 4UCKER * & , 1978. The effect of antimicrobial feed additives on the colonization of the alimentary tract of chickens by 3ALMONELLA TYPHIMURIUM. *OURNAL OF (YGIENE 217- 3MITH 7 ( AND 4UCKER * & , 1980. Further observations on the effect of feeding diets containing avoparcin, bacitracin and sodium arsenilate on the colonization of the alimentary tract of poultry by salmonella organisms. *OURNAL OF (YGIENE 137-150. 3NELLING # % , 1952. The value of aureomycin in prevention of cross infection in the hospital for sick children. #ANADIAN -EDICAL !SSOCOATION *OURNAL 6-7. 3TOKESTAD % , 2 AND *UKES 4 ( , 1949. Further observations on the animal protein factor. 0ROCEEDINGS OF THE 3OCIETY OF "IOLOGICAL AND %XPERIMENTAL -EDICINE 523-528. 3TOKESTAD % , 2 AND *UKES 4 ( , 1950. The multiple nature of the animal protein factor. *OURNAL OF "IOLOGICAL #HEMISTRY 647-654. 363, 1990. Riktlinjer för antibiotikainblandning i foder till svin. 3VENSK 6ETERIN¤RTIDNING 407- 413. 4AYLOR # % , 1967. Synergism between infections and malnutrition (editorial). !RCHIVES OF %NVIRONMENTAL (EALTH 650. 7IERUP - , 1989. Antibiotikaförbrukning hos djur i . 3VENSK 6ETERIN¤RTIDNING 299-311. 7IERUP - , 1996. förbjöd antibiotika i tillväxtbefrämjande syfte 1986 - vad hände med djurhälsan och hur löstes problemen? +UNGLIGA 3KOGS OCH ,ANTBRUKSAKADEMIENS 4IDSKRIFT 7IERUP - # , 7OLD 4ROELL - AND !GEN¤S ) , 1987. Animal consumption of antibiotic and chemotherapeutic drugs in during 1980, 1982 and 1984. 6ETERINARY RESEARCH COMMUNICATIONS 397-405. 7IERUP - ,ARSSON + (OLTENIUS 0 *ACOBSSON 3 / AND -ANSSON ) , 1975. foderantibiotika på antibiotikaresistens, överförbar antibiotikaresistens, morbiditet och tillväxt hos mellankalv. .ORDISK 6ETERIN¤RMEDICIN 253-265. 3Mode of action and effects of antibacterial feed additives The mode of action of antibacterial feed additives () has been the subject of numerous scientific reports. However, most of these deal with effects, rather than modes of action. The exact mechanisms regulating the growth promoting effect of is not precisely known (for a review see Thomke and Elwinger, 1997c). Rosen (1995) has compiled responses in poultry and pigs associated with dietary supplements of (table 3.I). This table illustrates the diversity of the responses to . will alter the intestinal bacterial flora and reduce the number of sensitive microorganisms. Most in use within the EU have effects on gram-positive bacteria. An early and fundamental finding was that young germ-free chickens, that grew approximately faster than conventionally- reared chickens, did not respond to dietary inclusion of (and Park, 1959; Eyssen and De Somer, 1967). Inoculation of germ-free chickens with %NTEROCOCCUS FAECALIS - a common inhabitant of the intestinal tract - lowered growth performance significantly. Dietary inclusion of , however, restored growth performance of inoculated birds (and , 1959; Eyssen and De Somer, 1967). Some other micro-organisms that have been associated with growth suppression are: %NTEROCOCCUS FAECIUM (Coates, 1980; Fuller, 1994) and #LOSTRIDIUM PERFRINGENS (and , 1959; Stutz ET AL , 1983a; Stutz ET AL , 1983b). The mechanism for the proposed growth suppressing effect has not been clarified. In animals given , reduced weight of the intestine, thinning of the intestinal wall and shortening of the gut has been recorded (Jukes ET AL , 1956; Stutz ET AL , 1983b). These results suggest a lowered number of mucosal cells which, in turn, possibly also reflect the mucosal cell turn-over rate. Research has shown a similar lowered mucosal cell turn-over rate as well as a thinner intestinal wall in germ-free chickens, as compared to conventionally reared chickens (Coates, 1980). This indicates that the dietary inclusion of will alter these intestinal characteristics towards the properties seen in germ free animals. Mode of action and effects Some physiological, nutritional and metabolic effects ascribed to (modified from Rosen, 1995) 4ABELL ) .¥GRA FYSIOLOGISKA NUTRITIONELLA OCH METABOLISKA EFFEKTER SOM TILLSKRIVITS !&4 MODIFIERAT FR¥N 2OSEN a denotes a reduction; denotes an increase; denotes no change It seems likely that the change of the intestinal flora and the subsequent changes in the intestine, including a slower intestinal passage rate, associated with usage are linked to the many reported effects on nutrient breakdown, nutrient losses and nutrient absorption. Examples are the lowered breakdown of easily fermentable nutrients and the restriction in breakdown of essential amino acids, leading to a general nutrient saving effect. Mode of action and effects 3.1.2Suggested main mode of action As are antibacterial substances, it is likely that their growth promoting effect is associated with their inhibitory effect on intestinal microbes. As discussed above, at dosages permitted for growth promotion, will alter the intestinal microbial flora. Increased understanding of the complex relationships between the immune system and other functions of the body offer possibilities to better understand the mode of action of . Infections and growth rate It is well established that growth rate and feed efficiency are reduced as a sequel to infection. This is why for example specific pathogen free (SPF) animals grow faster than animals in a conventional environment. Similarly animals reared in carefully cleaned and disinfected units grow faster than animals reared under a lower level of sanitary conditions. It has been shown that absence of disease increases the capacity of pigs to grow (, 1959; Caldwell ET AL , 1961). In Danish SPF systems, feed conversion is lower and growth rate higher than for conventionally reared pigs (Jorgensen, 1987). Similar observations have been reported in Swedish studies by (1993a) (Figure 3.I). Chickens housed in clean, disinfected quarters also grow faster and more efficiently than chickens housed in less sanitary conditions, even in the absence of any clinical signs of infectious diseases (Roura ET AL , 1992). Immune responses and growth rate An infectious challenge is a common form of stress encountered by growing animals. Infectious challenges may, or may not, result in clinical diseases, depending on the pathogenicity of the challenging microorganism and the immunocompetence of the animal. A stress response is indicated by decreased growth rates and quantitative changes in nutritional requirements (cit. from Klasing ET AL , 1987). In humans, reduced food intake is considered to play a major role in infection-induced weight loss (Grunfeld ET AL , 1996). This has also been shown in animals. Studying chickens, Klasing and co- workers (1987), found a growth depressive effect associated with an immune response. This effect was correlated to the immunogenic strength of the agent tested, the duration and the intensity of the immune response. The response to combinations of immunogens was additive. The dominating factor in the reduction of the animals weight gain was shown to be a decrease in feed intake, while the remainder was the effect of less efficient routes in the intermediary metabolism (Klasing ET AL , 1987). Roura and co-workers (Roura ET AL , 1992) showed the influence of the animal environment on weight gain and feed efficiency in chickens (see table 3. IIb.). Mode of action and effects with a low or high level of chronic immune system activation revealed lower feed intake, reduced body weight gain, lower daily protein accretion and more feed required per kg weight gain in pigs with a high level of chronic immune system activation (see table 3.IIa. )(Stahly, 1996). Responses of pigs with a low or high level of antigen exposure to dietary antibacterial agents (carbadox). Adopted from Stahly (1996)