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, 1993,12 (3), 909-922
Successful therapeutic regimens for treating Brucella melitensis and Brucella abortus infections in cows
A.I. RADWAN *, S.I. BEKAIRI *, A.M. AL-BOKMY *, P.V.S. PRASAD *, O.M. MOHAMED ** and S.T. HUSSAIN **
Summary: Three therapeutic regimens were evaluated in 121 cows naturally infected with Brucella melitensis or Brucella abortus, using a combination of long-acting Oxytetracycline (LA-OTC), streptomycin (ST) and OTCintramammary infusion (IMI). Cessation of shedding of b r u c e l l a in udder secretions and absence of Brucella in selected tissues were considered criteria for successful treatment. Regimen A (tested on 35 cows) consisted of LA-OTC 25 mg/kg administered intramuscularly (i.m.) every 3 days for 42 days, ST 25 mg/kg i.m. daily for 8 days, and OTC-IMI 20 ml/teat daily for 4 days. Regimen B (tested on 53 cows) was similar to regimen A, except that ST was administered every 2 days for 16 days and OTC-IMI every 2 days for 8 days. Both regimens were equally effective in eliminating Brucella organisms from all cows involved in the tests and no relapses were recorded. However, regimen C, which was similar to regimen A, except that ST was administered every 3 days for 24 days and OTC-IMI every 3 days for 12 days, resulted in the elimination of Brucella organisms from only 30 (91%) of 33 cows. Before commencement of the therapeutic regimens, B. melitensis biovar 1 or 2 had been repeatedly isolated from udder secretions of 103 cows and B. abortus biovar 1 from mammary secretions of 18 cows. KEYWORDS: Antibiotics - Brucella abortus - Brucella melitensis - Cattle Oxytetracycline - Streptomycin - Therapy.
INTRODUCTION Several c h e m o t h e r a p e u t i c agents have b e e n employed in recent decades for the treatment of Brucella abortus infection in cows; however, n o n e of these has been entirely successful. N u m e r o u s chemical agents, general antimicrobials (phenols or dyes), trace elements, minerals and mixtures of vitamins (A and E ) have b e e n tried unsuccessfully. F u r t h e r m o r e , a t t e m p t s using antibiotics such as penicillin or sulfonamides failed to cause cessation of the shedding of B. abortus from the mammary secretions of infected cows, or caused only temporary cessation (7,11,37).
* Animal Production and Health Section, National Agriculture and Water Research Centre, Ministry of Agriculture and Water, P.O. Box 17285, Riyadh 11484, Saudi Arabia. ** National Agriculture Development Co., P.O. Box 2557, Riyadh 11461, Saudi Arabia.
injections of L A .m. daily for 6 weeks) combined with ST (1 g i.25.500 or 1. .p. alone or in combination with ST. effective and least expensive means of achieving complete elimination of B.m. daily for 1 week) resulted in cessation of shedding of B. singly or in combination. In addition.m. route.] or i. serious local reactions were reported in cows. such therapeutic regimens have been applied in infected herds to prevent abortions and reduce the spread of brucellosis. abortus in 10 (71. Consequently.O T C (20 mg/kg i. Radwan and colleagues (35) evaluated six different long-term treatment regimens on 480 sheep and goats naturally infected with B. every 2 days for 4 weeks combined with ST 20 mg/kg i.000 mg O T C daily for 6 weeks. However. In addition. In a n o t h e r study. has resulted in the reduction of abortions in infected herds or individual cows (20.O T C 25 mg/kg i. However. 6 sheep were Brucella-iiee. every 3 days for 2 weeks) alone was successful in curing 3 (21%) of 14 cows. the majority of the treated sheep developed subcutaneous sterile abscesses in the flank at the site of repeated i. when L A . then 20 days later with 1. With regard to brucellosis in sheep. 52%.) inoculations with O T C (12.p. melitensis or B. inoculation of L A . in order to make treatment of Briicella-infected cows with superior genes a viable alternative to slaughter. In view of the encouraging results in cows (24. abortus from naturallyinfected cows. at necropsy (34). ST and OTC intramammary infusion (IMI) in eliminating B. Only one sheep was found to be bacteriologically positive at slaughter. Furthermore. due to repeated intraperitoneal (i. Furthermore. every 3 days for 6 weeks. Radwan and colleagues (34) conducted a long-term treatment trial using a variety of doses of O T C .4 g t o g e t h e r with i m m u n e serum for 3 days.p.p. melitensis. inoculation with OTC.m.000 mg LA-OTC i.910 The use of broad-spectrum antibiotics such as aureomycin. With the development of Oxytetracycline (OTC) and long-acting (LA)-OTC. 46 days after infection (30). on 118 sheep naturally infected with B. tetracyclines and streptomycin (ST). increasing the percentage of Brucella-tree sheep to 82%.24. terramycin. Moreover.21). abortus were injected daily for 6 days with 1 g Chlortetracycline. these regimens have failed to result in complete cure. the cost of therapy.O T C combined with ST. Recently. treatment with OTC (250 mg i. In one of these studies. practical. when 8 infected Najdi sheep were inoculated with 1.13. In this trial. 9 sheep experimentally infected with B. groups of infected Najdi sheep were injected with 250. melitensis in the 80 sheep and goats treated (35).O T C was combined with ST (20 mg/kg intravenously [i. melitensis. the use of these agents alone or in combination with ST has succeeded in eliminating the symptoms of this disease and reducing the shedding of brucellae by infected cows. In this trial. 69% and 100% of the sheep were found to be Brucella-îre-c at the end of the trial. daily for 1 week) 14 (67%) of 21 cows w e r e successfully treated (25).V.4%) of 14 cows (24). the presence of antibiotic residues in milk and the failure to cure udder infections in many cases have led to the general conclusion that such treatment is unsuitable for the control of bovine brucellosis.] every 3 days for 2 weeks) combined with ST (20 mg/kg i. using high doses of L A .m.O T C (20 mg/kg intramuscularly [i. the present study was undertaken to evaluate the efficacy of three long-term therapeutic regimens using a combination of LA-OTC. by the i.25) and the successful results in sheep and goats (35). the regimens previously tried involved small doses and few injections of the antibiotics used. In the respective groups. The aim of the study was to obtain a therapeutic regimen which is effective. safe. However. daily for 3 weeks) showed a synergistic effect.m. without side-effects and relatively inexpensive. One of these regimens ( L A . every 2 days for 2 weeks) proved to be the most practical.29).m.p.
number of previous pregnancies. abortus was small. All cows in the study were isolated from other animals. B. approximately four years prior to this study. all n o n . 89 cows were found not to be pregnant (having already aborted or calved 4-8 months before t r e a t m e n t ) and 32 cows were in various stages of pregnancy. each containing l g or 4 g. These two herds originally tested seronegative on arrival in Saudi A r a b i a . Three months later. The reason for the division into three treatment schedules was to choose the most practical and effective regimen. melitensis. a total of 3 calves (1 from a cow in each treatment group) were sacrificed. dissolved (just before use) in 3 ml or 12 ml sterile distilled water. B. This herd contained few seropositive cows on arrival in Saudi A r a b i a .O T C is a long-acting antibiotic. in contrast to ST and OTC-IMI which are not. respectively . eight years prior to the present study. melitensis (biovars 1 and 2) which had been introduced to the two farms 8-12 m o n t h s before bovine brucellosis occurred in the two cattle herds (unpublished findings).O T C injectable solution (from F i a n c e ) containing 200 mg O T C base p e r millilitre . In two herds. date of recent pregnancy and n u m b e r of previous abortions due to Brucella. The cows originated from three large commercial dairy herds raised in the central and eastern provinces of Saudi Arabia. The three herds were composed of highly valuable breeding cows originally imported from the United States of America (USA) and Europe. T h e animals belonged to two breeds (108 Holstein x Friesian and 13 Jersey). Non-treated cows were not included as controls. E g y p t ) supplied in vials. One m o n t h after t r e a t m e n t . as several previous studies have indicated that Brucella infections persist in cattle and s p o n t a n e o u s recovery is uncommon (10. T h e cows contracted brucellosis from sheep and goats infected with B.p r e g n a n t cows were artificially inseminated. Herd records indicated that none of the cows had been vaccinated during calfhood.28). these were placed in g r o u p B together with 35 cows with B. immediately after birth.L A . In the third herd. without regard to age. which gave positive results for brucellosis after serological and bacteriological tests. and selected tissue samples were cultured.911 MATERIALS AND METHODS Animals A total of 121 cows were selected.ST sulphate (from Giza. particularly because L A . Milking was ceased in lactating cows. Shortly before initiation of the present treatment regimens. The 121 cows were divided into three treatment groups (A.22. and selected tissues were collected for bacteriological examination. abortus biovar 1 was isolated from the mammary secretions of 18 cows. These animals were selected to provide a m o r e conclusive evaluation than that obtained in previous studies. Since the number of available cows infected with B. Therapeutic agents The pharmaceutical products used in this study were as follows: . The cows were aged 3-10 years and weighed between 450 kg and 750 kg. B and C). melitensis was isolated from udder secretions of 103 cows (biovar 1 from 97 cows and biovar 2 from 6 cows). In addition. a total of 12 pregnant cows (4 from each t r e a t m e n t group) were sacrificed.
and bacteriologically-positive cows were serologically tested again immediately before initiation of the present treatment regimens and at monthly intervals after completion of treatment (for 4 months in 12 sacrificed cows and for 16 months in the remaining 109 cows). liver. T h e rose bengal test antigen was obtained from the Central Veterinary Laboratory. Immediately before initiation of the therapeutic regimens. United Kingdom. 5 mg Prednisolone and 10 ml special excipient. and sections of udder.O T C and ST were injected i. Following the three serological examinations.m. each containing 200 mg OTC hydrochloride. liver and spleen. samples of stomach contents. thigh and shoulder muscles. Therapeutic regimens The treatment regimens of the three groups of infected cows are shown in Table I. In addition. Iowa.OTC-IMI (from Athens. Animals testing positive to the rose bengal test were retested by the standard US plate agglutination procedure for the determination of Brucella antibody titres (3). Bacteriological examination T h e m e d i u m for Brucella culture was p r e p a r e d as described previously (35).912 . every month after completion of treatment until calving and again every 2 weeks after calving for 6 m o n t h s . lung and spleen of foetuses from the sacrificed animals were cultured. precrural. Furthermore. USA. Aliquots from each udder secretion sample were spread with sterile cotton swabs on 2-4 freshly prepared plates of culture medium. at a dosage of 20-30 ml per site. The date of previous abortions in relation to the initiation of treatment was not recorded on the farms involved. sera from the selected 121 serologically. animals were initially screened for the presence of Brucella agglutinins by the rose bengal test (3). milk samples from all seropositive cows were subjected to bacteriological examination for identification of Brucella shedders. T h e isolated 2 . Separate 30 ml samples of udder secretions from each quarter were also cultured every week during treatment. brain. A t each examination. udder secretion. New Haw. sera from all calves born from treated cows were examined immediately after birth. The standard Brucella plate antigen (made of B. mesenteric. ovary.O T C at the c o m m e n c e m e n t of therapy. uterus. prescapular. The plates were incubated at 37°C for 7 days in the presence and absence of 10% C 0 a t m o s p h e r e . iliac. popliteal and head lymph nodes. 100 mg neomycin sulphate. abortus strain 1119-3) was obtained from the United States Department of Agriculture in Ames. Weybridge. In addition. from the 12 pregnant sacrificed cows (4 cows from each treatment group which were slaughtered at 4 months post-treatment) the following tissue specimens were aseptically collected for bacteriological examination: supramammary. In addition. cultures of udder secretions were m a d e from the selected 121 positive cows to confirm shedding of Brucella organisms. mediastinal. The L A . 100 mg oleandomycin p h o s p h a t e . in the cervical. Similar selected tissue specimens were cultured from 3 sacrificed newborn calves (1 from a cow in each treatment group). Agglutination at 1:100 or greater was considered positive. Serological testing All animals were subjected to three successive serological examinations at monthly intervals. Both ST and OTC-IMI were administered with L A . Each tissue specimen was individually homogenised in a tissue grinder and aliquots were spread with sterile cotton swabs on several (4-8) freshly prepared plates of culture medium. Greece) in 10 ml syringes.
abortus from naturally-infected cows Regimen FA v 3 No.of Periodicity treated Therapeutic agents cows Route Dosage E ™° Y ^¿J. melitensis cows naturally infected with B. 25mg/kg i.m.m. i.m. 25mg/kg IMI 20 ml/teat 3 3 27/29(91%) i. abortus long-acting Oxytetracycline injectable solution (from France) 200 mg/ml streptomycin sulphate (from Egypt) Oxytetracycline intramammary infusion (from Greece) 913 . 25mg/kg &OTC-IMlig) IMI 20 ml/teat 25mg/kg 2 2 3 4/4 4 e C 3 33W LA-OTC( ) STW &OTC-IMl(s) i.: IMI: a) b) c) d) e) f) g) intramuscular (injection) intramammary infusion number of sacrificed cows from which selected tissues were cultured for Brucella number of cows from which mammary secretions were repeatedly cultured for Brucella cows naturally infected with B.m.TABLE I Efficacy of three treatment regimens in eliminating Brucella melitensis or B.m. 25 mg/kg IMI 20 ml/teat 1 e B 8 14 49/49(100%) 35(c) ST(f) 18( ) 14 8 4 3/4 d LA-OTC( ) i.m. 1 4 8 4/4 31/31 (100%) 3 14 A 35(c) LA-OTC( ) ST( ) & OTC-IMI(g) f 25mg/kg i. No of Success/treated Tissuesa)Udder secretions < > b e i.m.
in addition to routine bacteriological examination for listeriosis. In addition. On the whole. no systemic reactions were observed in any of the treated cows during the treatment period. the cows had b e e n living in an infected environment for periods of between 1 and 8 years. When Brucella organisms could no longer be recovered from udder secretions nor from any of the selected tissue specimens collected at necropsy. The biotyping of the identified isolates was performed at the Central Veterinary Laboratory. B and C experienced n o r m a l calving within 4 m o n t h s following completion of the treatment. the treated cows expelled placenta from the womb without requiring any special manual manipulation. The abortion rate in the three herds ranged between 5% and 1 5 % and the infertility r a t e was approximately 1 5 % . 94% b e c a m e p r e g n a n t and experienced n o r m a l calving. salmonellosis. particularly in the thigh muscles. No abortions were observed a m o n g the treated cows. biochemically and serologically (3). F u r t h e r m o r e . However. B and C. there were no cases of metritis or mastitis in the treated cows. T h e s e slight local reactions disappeared within 36 hours. Side-effects of the therapeutic agents In 8 cows. and the average cost of the therapeutic agents alone used (regimen A. microscopically. In this study. Cost of therapeutic agents and animals The weight of the treated cows ranged between 450 kg and 750 kg. aborted foetuses from the three cattle herds involved were cultured for Brucella isolation. mycoplasmosis and mycotic abortion. in the breeding season following treatment. . the respective cow was considered to be cured (successful t r e a t m e n t ) . there were unusually high rates of metritis. C o n t i n u e d or r e s u m e d shedding of Brucella organisms in udder secretions or the isolation of Brucella organisms from any of the tissue specimens obtained at necropsy were considered as conclusive evidence of treatment failure. Before t r e a t m e n t . or the use of c h e m o t h e r a p e u t i c measures. Weybridge. Of the cows treated with regimens A. Furthermore. there was very light swelling and signs of painful sensations at the site of r e p e a t e d L A . B or C) in treating a cow weighing 600 kg was US$186 (SR700). and milk production was within the normal range for uninfected animals of the same breed.O T C and ST. the 32 cows which were in various stages of pregnancy at the time of initiation of the therapeutic regimens A. United Kingdom. the cows were living in an uninfected environment.O T C injections. retained placenta and mastitis. Moreover. with milk production reduced by 10-15%. Meat inspection of the twelve cows which were slaughtered (4 months post-treatment) revealed complete absence of any detectable abnormalities in the muscles at the site of intramuscular inoculations of L A .914 Brucella cultures were identified morphologically. New Haw. RESULTS Breeding performance A comparison was made between breeding performance in the three herds prior to identification of the infected cows and that in the treated animals in the breeding season following treatment.
melitensis) were treated with regimen C. T h e efficacy of the t h r e e t r e a t m e n t regimens applied in eliminating B. melitensis and 18 infected with B. All selected tissue specimens from the 3 newborn calves (1 calf from a cow in each treatment group) were found to be free from Brucella organisms. In addition. In regimen A. including the cost of air freight to Saudi Arabia. Bacteriological findings In the present study. The average number of Brucella colonies recovered per plate from the udder secretion samples of these 2 cows prior to treatment was approximately 30 times higher than the number recovered following treatment.600 each. B or C). When 53 cows (of which 35 were naturally infected with B. melitensis biovar 1 was isolated from the repeated udder secretion samples from only 2 of 29 cows. at a cost of US$3. However. the selected tissue specimens from 4 sacrificed cows (at 4 months posttreatment) and all repeated udder secretion samples from the remaining 31 cows (for 16 months post-treatment) were all found to be free from Brucella organisms. melitensis or B. abortus w e r e isolated. in the 3 cows of regimen C where t r e a t m e n t failed. However. t h r e e and four dilutions in 4 2 % .915 The treated cows were imported a few years previously as pregnant heifers. Serological findings Among the treated animals. In addition. . The Brucella agglutinin titres w e r e also c o m p a r e d with results o b t a i n e d p r e treatment and 16 months post-treatment in the remaining 109 treated cows. T h e remaining 8 slaughtered cows did not show any decrease in titre over the same period. There was a decrease of two. melitensis or B. when these 2 Brucella-shedding cows were re-treated with regimen B. abortus) were treated with regimen B. 4 3 % and 10% of the treated cows respectively. shedding of Brucella organisms in mammary secretions had ceased when these secretions were cultured (1 week after initiation of the antibiotherapy) and did not recommence. Salmonella. In all successfully treated cows in the present study (118 cows treated with regimen A. when 33 cows (naturally infected with B. which ranged between 2 and 8 colonies per plate. there was a decrease of only one dilution in the US plate agglutination test (from 400 to 200) from the beginning of t r e a t m e n t until 4 months post-treatment in 4 of 12 slaughtered cows. no Listeria. abortus from 121 naturally-infected cows is shown in Table I. udder tissue and supramammary lymph nodes of only 1 of 4 sacrificed cows (at 4 months post-treatment). only 5% of the 109 cows became seronegative 16 months posttreatment. all selected tissue samples from 4 slaughtered cows and the repeated udder secretion samples were found to be Brucella-free. or after calving in the other 2 cows (these animals were then re-treated with regimen B). they ceased shedding Brucella. only B. B. However. Mycoplasma or pathogenic fungi were isolated from the aborted foetuses examined in the three herds. B. melitensis biovar 2 was isolated (1-5 colonies per plate) from mammary secretions. while all calves born from treated cows were seronegative for brucellosis. the amount of shedding declined after the initiation of treatment and remained low until 4 months post-treatment in 1 slaughtered cow.
particularly in lymph nodes. practical and safe antibiotherapy would be of e n o r m o u s benefit to producers in these countries as an alternative to slaughter of infected animals of high value.19.5. 35. namely: the Netherlands. In addition. B. An eradication campaign through slaughter and compensation is not within the economic scope of developing countries.23. abortus.4. metritis. On arrival in Saudi Arabia. one worker assessed the average cost of an infected cow at approximately US$3. not just for abortion or stillbirth. for economic reasons this method cannot be applied in all cases. two of the cattle herds contracted B. melitensis biovars 1. Such infection was directly responsible for the high rate of abortions. T h e following explanations were given for the previous t r e a t m e n t failures and difficulties: a) Brucella organisms are known to survive within phagocytic cells of the reticuloendothelial system.16. cattle with superior genetic potential have become increasingly valuable. camels and dairy cattle. infertility. goats. melitensis accounted for 92% of human cases and B.6. however. retained placenta and mastitis with reduced milk production.31. Germany and France. These cattle were originally imported as p r e g n a n t heifers from the USA and some E u r o p e a n countries. liver.34. abortus for 8%. 2 and 3 were responsible for all infections in sheep. Brucellosis has been reported and confirmed in both livestock and humans in Saudi Arabia. abortus infection. especially where it is difficult to change agricultural customs or social habits.32. However. it is recognised that the economic consequences of infection are e n c o u n t e r e d principally during initial infection and become less prominent in further pregnancies. bone marrow.22.214.171.124). the . suis was not found in animals or humans (1. loss of milk production. Moreover. T h e infected vaccinated animals continue to present a serious public health risk. melitensis infection from sheep and goats raised on the same farms. and the reduced h u m a n productivity resulting from a spread of infection (38). but from the subsequent problems or irregular breeding.33. leading to serious consequences for cattle performance and cattle handlers. On the other hand. In a campaign against brucellosis. commercial dairy production was introduced to Saudi Arabia through the importation of valuable and highly productive exotic cattle at a very high cost. Slaughter of infected animals with superior genetic potential has serious economic and genetic consequences (24). Transmission of this infection to cattle p r o d u c e d an infection similar to that p r o d u c e d by B. none has been fully successful. with the development and widespread use of techniques such as artificial insemination and embryo transfer. B. the cattle were raised in large n u m b e r s u n d e r intensive management systems and sometimes together with small ruminants. mass vaccination of infected herds protects only uninfected animals without altering the course of infection. it is impossible to apply only one method which would suit every country. Consequently.916 DISCUSSION In order to increase milk production. In the present study. while B. except cows in one dairy herd which had B. abortus. spleen. Although this has been the goal of several workers. Livestock producers in Saudi Arabia and in many other developing countries cannot afford the traditional "test and slaughter" approach used in developed countries. A n effective. The "test and slaughter" m e t h o d combined with calfhood vaccination no doubt contributes to considerable reduction in the number of infected herds. in B.
O T C or ST was used alone.11. early studies (20. The L A .24. However. However. i) Presence of antibiotic residues in milk and m e a t of t r e a t e d animals. f) Use of only one antibiotic (20. were less effective in eliminating Brucella organisms in infected cows. The present study aimed to overcome the above problems and involved work under particularly difficult conditions with regard to the level of infection among the cows used.917 mammary glands. relapses after antimicrobial t r e a t m e n t w e r e also explained by the intracellular location of brucellae (9. the O T C base was used because it is capable of penetrating intracellularly and inhibits bacterial protein synthesis at the level of the ribosomes. L A . abortus. c o m p l e m e n t and antibiotics.34).13. melitensis (35). For this reason.O T C combined with ST was used for the t r e a t m e n t of cows naturally infected with B. h) Failure to cure udder infections in many cases (24.5-1. reproductive organs and tissues with a weak blood supply. before initiation of the present treatment regimens. milking was stopped in lactating cows and udders were completely evacuated before each injection.O T C and ST proved very effective in curing sheep and goats naturally infected with B. Consequently.I M I and ST. despite the use of a combination of L A . F u r t h e r m o r e .29). Consequently. because it is known to inhibit p r o t e i n synthesis of G r a m .24).) inoculation of L A . b) Incorrect choice of antibiotics (7. O T C proved to be effectively bactericidal when combined with 10 µg/ml of ST (15.25.29). 25. ST was also used. and are therefore p r o t e c t e d from antibodies.26). p e r m i t t e d growth or was bacteriostatic for brucellae within tissue cells. O T C .25.m. abortus within bovine cells cultured in vitro.24.25. when administered every 3 days in regimen C. e) Use of the intraperitoneal route for administration of antibiotics created serious reactions in some cases (17.O T C variant was selected to save time and effort and to provide long-lasting O T C concentration in blood plasma.26. Since successful therapy in human beings appears to depend on the permeability of cell walls to drugs (24). and the possible harmful effect on consumers (27). a combination of L A . T h e ability of Brucella organisms to survive intracellularly can result in long-term chronic infection. OTC-IMI was used locally in combination with systemic (i.O T C and ST.25. In addition.0 µg/ml.37). Furthermore. several authors failed to cure udder infections in many cases (24. 34. 36).n e g a t i v e bacteria. For these reasons. However. ST acts synergistically with O T C to inhibit growth of B.24.26). melitensis or B.25) on the treatment of bovine brucellosis indicated poor success rates when L A .26. c) Insufficient doses of effective antibiotics (12. which were all serologically and (particularly) bacteriologically positive.25.25.O T C and ST. g) High cost of antibiotherapy (24. In addition.12. This may be due to the'fact that both ST and OTC-IMI are . in order to decrease the n u m b e r of Brucella organisms in u d d e r tissues and secretions.26). This c o m b i n a t i o n p r o v e d to be highly effective in eliminating Brucella organisms from all infected cows in regimens A and B. the following points were taken into account when attempting to obtain more successful results. in infected cows. d) Insufficient duration of treatment (8. as one injection gave an effective concentration of 0. O T C at 0.6 ug/ml for three days (26).34).13.21.24.
In the present study. relapses did not occur in any of the 88 cows treated with regimen A or B (provided that the treatment protocol is strictly observed). Also. In Saudi Arabia. Other investigators. this treatment would probably be limited to valuable breeding animals. consequently.O T C did not result in harmful systemic effects or any obvious lasting local reactions at the site of inoculation. the treated cows were originally imported as pregnant heifers at an average cost of US$3. only a small n u m b e r of Brucella colonies were recovered from large tissue samples. the cost of supplies and intervention should be considered.34). inoculation of L A . The cost of antibiotics used was calculated according to sale prices in the Saudi market at the time of the experiment (US$1 = SR3. at the present time.13.12. the majority (approximately 90%) of the cows treated were monitored bacteriologically for 16 months post-treatment in order to detect possible relapses. However.600. in other situations. Relapses have also been reported in cows (14. T h e results obtained were in agreement with findings on successful treatment of brucellosis in sheep and goats when monitored for 8 months post-treatment (35). The present results of serological examinations were of some use in evaluating the effectiveness of the treatment regimens. including the cost of air freight. B or C for treating a cow of an average weight of 600 kg was US$186 (SR700). because all serological and bacteriological examinations were performed free of charge at Government institutions. practical.75). further research may yield a regimen . all t r e a t e d cows were dried before initiation of treatment. reported that serological findings were not useful in evaluating the effectiveness of treatment regimens (24. In humans. The doses and duration of application of selected antibiotics in the present study indicate that the long-term therapy and the drug combinations used yielded better results than several other regimens (8. without side-effects and relatively inexpensive in causing cessation of the symptoms of brucellosis and eliminating Brucella organisms from infected cows.25. However. due to the development of several serious local reactions at the site of injection. relapses occurred in only 3 of 33 cows treated with regimen C. i.I M I alone would be effective for the treatement of lactating cows due to the continuous flushing of OTC by milking. T h e average cost of the antibiotics used in regimen A. This did not include the cost of e q u i p m e n t or interventions. a small number of relapses do occur. when treatment protocols were strictly observed. Consequently. In the present study. However. although O T C has been considered the most effective antibiotic for treatment of brucellosis. it seems unlikely that O T C . However.m. In the present trial.26. and the protection of Brucella organisms in the presence of milk. inoculation of OTC was not safe.25). In the present study.918 not long-acting antibiotics. In conclusion.24. Even in relapsed cows (3 animals in regimen C). Previous studies in cows and sheep (17.p. 34) concluded that i.24. which is considered economically feasible in Saudi Arabia. However. there was no risk of harmful effects on h u m a n beings from antibiotic residues in the milk from these cows during and after treatment. however. as animals were only monitored for 16 months post-treatment. regimens A and B proved to be effective. and t h e r e was no nontreated control group for comparison.29). the residues of antibiotics in milk and meat of treated animals should be investigated to determine accurately when milk and/or meat can be safely consumed following completion of the treatment regimens. the results were not conclusive. The cost of successful treatment of a cow represents approximately 5% of the original price of the animal.
pratiquée un jour sur deux pendant huit jours.A. pratiquée également tous les trois jours pendant 12 jours.V. O. melitensis ont été régulièrement isolés dans les sécrétions mammaires de 103 vaches et le biotype 1 de B. ACKNOWLEDGEMENTS The a u t h o r s wish to express their sincere t h a n k s to M. * * * DES PROTOCOLES THÉRAPEUTIQUES EFFICACES POUR LE TRAITEMENT DE L'INFECTION PAR BRUCELLA MELITENSIS ET BRUCELLA ABORTUS CHEZ LES VACHES.M.S. for their s u p p o r t and c o . . sauf pour la ST qui était administrée un jour sur deux pendant 16 jours et pour l'OTC-IMI.) quotidiennement pendant huit jours et en une OTC-IMI quotidienne de 20 ml par trayon pendant quatre jours. Prasad. The authors also acknowledge the technical assistance of A . Mukayel and A . Bin Salamah. Résumé : Trois protocoles thérapeutiques ont été évalués chez 121 vaches atteintes d'une infection naturelle par Brucella melitensis ou Brucella abortus. Le protocole A (appliqué à 35 vaches) consistait en une administration intramusculaire (i. Mohamed et S. D i r e c t o r General of the Saudi National Agriculture and Water Research Centre and National Director of Project 016/UTFN/SAU/FAO. hormis pour la ST qui était administrée tous les trois jours pendant 24 jours et l'OTC-IMI. Furthermore. Radwan.) de 25 mg/kg de LA-OTC tous les trois jours pendant 42 jours. Le protocole B (appliqué à 53 vaches) était similaire au précédent. de 25 mg/kg de ST (i.M. it is concluded that the failure of a small number of cows to respond to regimen C cannot be accounted for by t h e d e v e l o p m e n t of resistance by Brucella.I. Hussain. Bekairi. .I.m. Les deux modes de traitement se sont révélés aussi efficaces l'un que l'autre pour l'élimination totale des brucelles des vaches objet de l'expérimentation et aucune récidive n'a été constatée. Deux critères ont été jugés déterminants pour conclure au succès du traitement : l'arrêt de l'excrétion de brucelles dans les sécrétions mammaires et l'absence de brucelles dans des tissus spécifiques. similaire au protocole A.m. Thanks are also extended to the owners and veterinary staff of the three dairy farms involved. A. combinant à la fois l'Oxytétracycline à action prolongée (long-acting Oxytetracycline : LA-OTC). Al-Taher. for his encouragement and co-operation. Avant l'application de ces trois protocoles thérapeutiques. P. Al-Bokmy. Quant au protocole C. T h e t r e a t m e n t of seropositive animals should be performed together with vaccination of all seronegative animals in the same herd to achieve effective control and minimise public health risks.919 which could b e used for the t r e a t m e n t of all infected animals in a h e r d and for prophylaxis of those animals recently exposed to Brucella infection. les bio types 1 ou 2 de B.T. la streptomycine (ST) et l'infusion intramammaire d'OTC (OTC-intramammary infusion : OTC-IMI).o p e r a t i o n in t h e i m p l e m e n t a t i o n of the p r e s e n t treatment regimens. S. il n'a permis l'élimination des brucelles que sur 30 (91 %) des 33 vaches traitées. abortus dans celles de 18 vaches.S.
El protocolo A.. * PROTOCOLOS TERAPÉUTICOS EFICACES PARA EL TRATAMIENTO DE LA INFECCIÓN POR BRUCELLA MELITENSIS Y BRUCELLA ABORTUS EN VACAS. que se experimentó en 53 vacas.Streptomycine .Brucella abortus .Thérapie. similar al protocolo A salvo en que la ST se administraba cada tres días durante 24 días y la OTC-IMI también cada tres días durante 12 días.351-357.920 MOTS-CLÉS : Antibiotiques .Techniques for the brucellosis laboratory.H.Estreptomicina . . & V E R G E R J . M .Bovins .G. era similar al anterior excepto en cuanto a la ST.m. El protocolo B. que fue experimentado en 35 vacas.) de 25 mg/kg de LA-OTC cada tres días durante 42 días. M . a partir de una combinación de oxitetraciclina de acción prolongada (long-acting Oxytetracycline: LA-OTC). Institut National de la Recherche Agronomique. estreptomicina (ST) e infusión intramamaria de OTC (OTC-intramammary infusion: OTC-IMI).Bovinos . Por último. (1988).V. .M. Ann. .Brucellosis in children.Oxitetraciclina .S.. 3. . O. Prasad.25-27. (1984). (1986). Resumen: Se evaluaron tres protocolos terapéuticos en 121 vacas infectadas por vía natural por Brucella melitensis o Brucella abortus. Hussain. P.m.Y.A. 2. el protocolo C. es decir. Soc.G.I.D. C . S.M E Z A I N I S. Saudi biol.. 7. Bekairi. PALABRAS CLAVE: Antibióticos . REFERENCES 1.Brucella melitensis . & HARLAND P. . los biotipos 1 o 2 de B. Paris. 6. Para considerar el tratamiento exitoso se tuvieron en cuenta dos criterios: el cese de la excreción de brucelas en las secreciones mamarias y la ausencia de brucelas en tejidos específicos. & CHOU N. abortus en las secreciones mamarias de 18 vacas. consistía en la administración intramuscular (i.Terapéutica.Oxytétracycline . .. HAWARI A.R. JONES L . CHEN M . A L . que se administró cada dos días durante 16 días. Radwan. A.Brucella abortus . . Antes de aplicar estos tres protocolos terapéuticos. y ala OTC-IMI. WANG C F . Mohamed y S. de 25 mg/kg de ST (i. sólo permitió eliminación de brucelas en 30 de las 33 vacas tratadas. que se administró cada dos días durante ocho días. melitensis fueron regularmente aislados en las secreciones mamarias de 103 vacas y el biotipo 1 de B. un 91%.) diarios durante ocho días y en una OTC-IMI diaria de 20 ml por pezón durante 4 días. CHANG S.T. ALTON G. AL-MARSHEDY A.M. 190 pp.I. Uno y otro tratamiento se mostraron equivalentemente eficaces para la eliminación total de las brucelas en las vacas tratadas y no se constató ninguna recidiva. Saudi Med..S.Brucella melitensis . SINOUSSI Y .E. A N G U S R. Al-Bokmy. Proc.A study on brucellosis among animals of some farms and rural areas of Saudi Arabia.
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