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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.
In one of these studies.V.p. daily for 1 week) resulted in cessation of shedding of B. serious local reactions were reported in cows.) inoculations with O T C (12. In a n o t h e r study. at necropsy (34). In the respective groups.4 g t o g e t h e r with i m m u n e serum for 3 days.29).p. inoculation of L A . due to repeated intraperitoneal (i.m. injections of L A . the majority of the treated sheep developed subcutaneous sterile abscesses in the flank at the site of repeated i.m. 6 sheep were Brucella-iiee. practical. abortus from naturallyinfected cows.m.O T C 25 mg/kg i. 9 sheep experimentally infected with B. alone or in combination with ST. tetracyclines and streptomycin (ST). abortus in 10 (71. without side-effects and relatively inexpensive.13. route. melitensis in the 80 sheep and goats treated (35). Furthermore. in order to make treatment of Briicella-infected cows with superior genes a viable alternative to slaughter. every 3 days for 6 weeks.m. inoculation with OTC. when L A . 52%. However. melitensis or B. groups of infected Najdi sheep were injected with 250.24.p. With the development of Oxytetracycline (OTC) and long-acting (LA)-OTC. treatment with OTC (250 mg i. has resulted in the reduction of abortions in infected herds or individual cows (20. these regimens have failed to result in complete cure.] or i.O T C combined with ST.p. then 20 days later with 1. In this trial. every 3 days for 2 weeks) alone was successful in curing 3 (21%) of 14 cows. However. ST and OTC intramammary infusion (IMI) in eliminating B.21). The aim of the study was to obtain a therapeutic regimen which is effective. daily for 3 weeks) showed a synergistic effect. . With regard to brucellosis in sheep. In addition. the present study was undertaken to evaluate the efficacy of three long-term therapeutic regimens using a combination of LA-OTC. effective and least expensive means of achieving complete elimination of B. daily for 6 weeks) combined with ST (1 g i. terramycin.m. safe. Moreover.25. Consequently. such therapeutic regimens have been applied in infected herds to prevent abortions and reduce the spread of brucellosis.500 or 1. increasing the percentage of Brucella-tree sheep to 82%. 69% and 100% of the sheep were found to be Brucella-îre-c at the end of the trial. when 8 infected Najdi sheep were inoculated with 1. Furthermore. the cost of therapy.] every 3 days for 2 weeks) combined with ST (20 mg/kg i. 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. Radwan and colleagues (35) evaluated six different long-term treatment regimens on 480 sheep and goats naturally infected with B. However. on 118 sheep naturally infected with B. Recently.25) and the successful results in sheep and goats (35). melitensis.O T C (20 mg/kg intramuscularly [i. 46 days after infection (30). Radwan and colleagues (34) conducted a long-term treatment trial using a variety of doses of O T C . every 2 days for 4 weeks combined with ST 20 mg/kg i. daily for 1 week) 14 (67%) of 21 cows w e r e successfully treated (25).4%) of 14 cows (24).m. 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. abortus were injected daily for 6 days with 1 g Chlortetracycline.O T C (20 mg/kg i.p. In addition. the regimens previously tried involved small doses and few injections of the antibiotics used.O T C was combined with ST (20 mg/kg intravenously [i. One of these regimens ( L A . singly or in combination.m. by the i. using high doses of L A . In view of the encouraging results in cows (24.000 mg O T C daily for 6 weeks. every 2 days for 2 weeks) proved to be the most practical. Only one sheep was found to be bacteriologically positive at slaughter. In this trial.910 The use of broad-spectrum antibiotics such as aureomycin.000 mg LA-OTC i. melitensis.
This herd contained few seropositive cows on arrival in Saudi A r a b i a . respectively . The three herds were composed of highly valuable breeding cows originally imported from the United States of America (USA) and Europe. and selected tissues were collected for bacteriological examination. in contrast to ST and OTC-IMI which are not.ST sulphate (from Giza. melitensis. a total of 12 pregnant cows (4 from each t r e a t m e n t group) were sacrificed. number of previous pregnancies. The 121 cows were divided into three treatment groups (A. eight years prior to the present study. Therapeutic agents The pharmaceutical products used in this study were as follows: . each containing l g or 4 g.O T C is a long-acting antibiotic. particularly because L A . B.L A . 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. abortus biovar 1 was isolated from the mammary secretions of 18 cows. and selected tissue samples were cultured. T h e animals belonged to two breeds (108 Holstein x Friesian and 13 Jersey). approximately four years prior to this study. Herd records indicated that none of the cows had been vaccinated during calfhood. without regard to age.22. B and C).28). In addition.O T C injectable solution (from F i a n c e ) containing 200 mg O T C base p e r millilitre . The reason for the division into three treatment schedules was to choose the most practical and effective regimen. Milking was ceased in lactating cows. These animals were selected to provide a m o r e conclusive evaluation than that obtained in previous studies. 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. Non-treated cows were not included as controls.p r e g n a n t cows were artificially inseminated. melitensis was isolated from udder secretions of 103 cows (biovar 1 from 97 cows and biovar 2 from 6 cows). In two herds. which gave positive results for brucellosis after serological and bacteriological tests. date of recent pregnancy and n u m b e r of previous abortions due to Brucella. abortus was small.911 MATERIALS AND METHODS Animals A total of 121 cows were selected. The cows were aged 3-10 years and weighed between 450 kg and 750 kg. dissolved (just before use) in 3 ml or 12 ml sterile distilled water. a total of 3 calves (1 from a cow in each treatment group) were sacrificed. immediately after birth. all n o n . The cows originated from three large commercial dairy herds raised in the central and eastern provinces of Saudi Arabia. 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). T h e cows contracted brucellosis from sheep and goats infected with B. One m o n t h after t r e a t m e n t . B. E g y p t ) supplied in vials. In the third herd. Shortly before initiation of the present treatment regimens. these were placed in g r o u p B together with 35 cows with B. All cows in the study were isolated from other animals. These two herds originally tested seronegative on arrival in Saudi A r a b i a . Three months later. Since the number of available cows infected with B.
and sections of udder. liver and spleen. The standard Brucella plate antigen (made of B. milk samples from all seropositive cows were subjected to bacteriological examination for identification of Brucella shedders. precrural. abortus strain 1119-3) was obtained from the United States Department of Agriculture in Ames. samples of stomach contents. iliac. animals were initially screened for the presence of Brucella agglutinins by the rose bengal test (3). Greece) in 10 ml syringes. brain. lung and spleen of foetuses from the sacrificed animals were cultured. Furthermore. USA. 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).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). udder secretion. Similar selected tissue specimens were cultured from 3 sacrificed newborn calves (1 from a cow in each treatment group).O T C and ST were injected i. 5 mg Prednisolone and 10 ml special excipient. New Haw. Therapeutic regimens The treatment regimens of the three groups of infected cows are shown in Table I. Both ST and OTC-IMI were administered with L A . popliteal and head lymph nodes. Serological testing All animals were subjected to three successive serological examinations at monthly intervals. Aliquots from each udder secretion sample were spread with sterile cotton swabs on 2-4 freshly prepared plates of culture medium. The date of previous abortions in relation to the initiation of treatment was not recorded on the farms involved. 100 mg oleandomycin p h o s p h a t e .OTC-IMI (from Athens. Following the three serological examinations. each containing 200 mg OTC hydrochloride. In addition. mediastinal. A t each examination. T h e rose bengal test antigen was obtained from the Central Veterinary Laboratory. sera from all calves born from treated cows were examined immediately after birth. 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 . uterus. ovary.O T C at the c o m m e n c e m e n t of therapy. Iowa. every month after completion of treatment until calving and again every 2 weeks after calving for 6 m o n t h s . in the cervical. prescapular. 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. Weybridge. sera from the selected 121 serologically. at a dosage of 20-30 ml per site. thigh and shoulder muscles. Separate 30 ml samples of udder secretions from each quarter were also cultured every week during treatment. 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. T h e isolated 2 . Agglutination at 1:100 or greater was considered positive. Immediately before initiation of the therapeutic regimens. The L A . 100 mg neomycin sulphate.912 .m. liver. mesenteric. 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). cultures of udder secretions were m a d e from the selected 121 positive cows to confirm shedding of Brucella organisms. United Kingdom.
m.m. abortus from naturally-infected cows Regimen FA v 3 No.TABLE I Efficacy of three treatment regimens in eliminating Brucella melitensis or B. i.m. 25mg/kg i.of Periodicity treated Therapeutic agents cows Route Dosage E ™° Y ^¿J. melitensis cows naturally infected with B.m. abortus long-acting Oxytetracycline injectable solution (from France) 200 mg/ml streptomycin sulphate (from Egypt) Oxytetracycline intramammary infusion (from Greece) 913 . 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. No of Success/treated Tissuesa)Udder secretions < > b e 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. 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. 25mg/kg IMI 20 ml/teat 3 3 27/29(91%) i.
Cost of therapeutic agents and animals The weight of the treated cows ranged between 450 kg and 750 kg. the cows were living in an uninfected environment. 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 . the treated cows expelled placenta from the womb without requiring any special manual manipulation. 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. F u r t h e r m o r e . New Haw. Weybridge. B and C. the respective cow was considered to be cured (successful t r e a t m e n t ) .O T C and ST. The abortion rate in the three herds ranged between 5% and 1 5 % and the infertility r a t e was approximately 1 5 % . . 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. retained placenta and mastitis. The biotyping of the identified isolates was performed at the Central Veterinary Laboratory. No abortions were observed a m o n g the treated cows. Of the cows treated with regimens A. In addition. there was very light swelling and signs of painful sensations at the site of r e p e a t e d L A . 94% b e c a m e p r e g n a n t and experienced n o r m a l calving.914 Brucella cultures were identified morphologically. B and C experienced n o r m a l calving within 4 m o n t h s following completion of the treatment. there were no cases of metritis or mastitis in the treated cows. salmonellosis. in the breeding season following treatment. Before t r e a t m e n t . there were unusually high rates of metritis. the cows had b e e n living in an infected environment for periods of between 1 and 8 years. Furthermore. In this study. aborted foetuses from the three cattle herds involved were cultured for Brucella isolation. biochemically and serologically (3). with milk production reduced by 10-15%. Moreover. no systemic reactions were observed in any of the treated cows during the treatment period. However. particularly in the thigh muscles. On the whole.O T C injections. T h e s e slight local reactions disappeared within 36 hours. Side-effects of the therapeutic agents In 8 cows. When Brucella organisms could no longer be recovered from udder secretions nor from any of the selected tissue specimens collected at necropsy. United Kingdom. the 32 cows which were in various stages of pregnancy at the time of initiation of the therapeutic regimens A. B or C) in treating a cow weighing 600 kg was US$186 (SR700). microscopically. in addition to routine bacteriological examination for listeriosis. mycoplasmosis and mycotic abortion. and milk production was within the normal range for uninfected animals of the same breed. and the average cost of the therapeutic agents alone used (regimen A. or the use of c h e m o t h e r a p e u t i c measures.
abortus) were treated with regimen B. or after calving in the other 2 cows (these animals were then re-treated with regimen B). Salmonella.915 The treated cows were imported a few years previously as pregnant heifers. only 5% of the 109 cows became seronegative 16 months posttreatment. only B. melitensis) were treated with regimen C. melitensis biovar 1 was isolated from the repeated udder secretion samples from only 2 of 29 cows. However. 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. 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. B. However. while all calves born from treated cows were seronegative for brucellosis. when these 2 Brucella-shedding cows were re-treated with regimen B. at a cost of US$3. In addition.600 each. 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. the amount of shedding declined after the initiation of treatment and remained low until 4 months post-treatment in 1 slaughtered cow. T h e remaining 8 slaughtered cows did not show any decrease in titre over the same period. all selected tissue samples from 4 slaughtered cows and the repeated udder secretion samples were found to be Brucella-free. udder tissue and supramammary lymph nodes of only 1 of 4 sacrificed cows (at 4 months post-treatment). In regimen A. abortus w e r e isolated. . There was a decrease of two. melitensis and 18 infected with B. when 33 cows (naturally infected with B. no Listeria. t h r e e and four dilutions in 4 2 % . 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. When 53 cows (of which 35 were naturally infected with B. in the 3 cows of regimen C where t r e a t m e n t failed. 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. However. they ceased shedding Brucella. which ranged between 2 and 8 colonies per plate. including the cost of air freight to Saudi Arabia. 4 3 % and 10% of the treated cows respectively. melitensis biovar 2 was isolated (1-5 colonies per plate) from mammary secretions. B. 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. abortus from 121 naturally-infected cows is shown in Table I. 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. Bacteriological findings In the present study. In all successfully treated cows in the present study (118 cows treated with regimen A. melitensis or B. In addition. melitensis or B. B or C). Mycoplasma or pathogenic fungi were isolated from the aborted foetuses examined in the three herds. Serological findings Among the treated animals.
two of the cattle herds contracted B. Moreover. 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. spleen. In the present study. it is impossible to apply only one method which would suit every country. metritis. in B.19. Livestock producers in Saudi Arabia and in many other developing countries cannot afford the traditional "test and slaughter" approach used in developed countries. mass vaccination of infected herds protects only uninfected animals without altering the course of infection. except cows in one dairy herd which had B.39).31. melitensis infection from sheep and goats raised on the same farms. In addition. the . 35. camels and dairy cattle. Brucellosis has been reported and confirmed in both livestock and humans in Saudi Arabia. loss of milk production. An eradication campaign through slaughter and compensation is not within the economic scope of developing countries.16. 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. melitensis biovars 1. leading to serious consequences for cattle performance and cattle handlers.18. 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. T h e infected vaccinated animals continue to present a serious public health risk. B.200. abortus for 8%. B. commercial dairy production was introduced to Saudi Arabia through the importation of valuable and highly productive exotic cattle at a very high cost. melitensis accounted for 92% of human cases and B. infertility. liver. 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. Consequently. however. 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. especially where it is difficult to change agricultural customs or social habits. none has been fully successful. namely: the Netherlands. but from the subsequent problems or irregular breeding. A n effective. abortus infection. retained placenta and mastitis with reduced milk production. On the other hand. cattle with superior genetic potential have become increasingly valuable. 2 and 3 were responsible for all infections in sheep. Slaughter of infected animals with superior genetic potential has serious economic and genetic consequences (24).33. In a campaign against brucellosis. 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.4. On arrival in Saudi Arabia.23. However. not just for abortion or stillbirth. for economic reasons this method cannot be applied in all cases.2. abortus.916 DISCUSSION In order to increase milk production. and the reduced h u m a n productivity resulting from a spread of infection (38). goats. abortus. 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. Germany and France. Such infection was directly responsible for the high rate of abortions. Although this has been the goal of several workers. one worker assessed the average cost of an infected cow at approximately US$3. suis was not found in animals or humans (1.6. while B. with the development and widespread use of techniques such as artificial insemination and embryo transfer. particularly in lymph nodes.5. bone marrow.32.34.
In addition. For this reason.24).25. melitensis or B. ST acts synergistically with O T C to inhibit growth of B.21.26). In addition. 34. as one injection gave an effective concentration of 0. reproductive organs and tissues with a weak blood supply. Consequently. several authors failed to cure udder infections in many cases (24. c o m p l e m e n t and antibiotics. were less effective in eliminating Brucella organisms in infected cows.25.) inoculation of L A .25.25. The L A . 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. because it is known to inhibit p r o t e i n synthesis of G r a m . early studies (20. abortus.24. Furthermore. Consequently. However.I M I and ST. abortus within bovine cells cultured in vitro. O T C . p e r m i t t e d growth or was bacteriostatic for brucellae within tissue cells. OTC-IMI was used locally in combination with systemic (i. h) Failure to cure udder infections in many cases (24. L A .26).25. f) Use of only one antibiotic (20. 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. c) Insufficient doses of effective antibiotics (12.25. when administered every 3 days in regimen C. d) Insufficient duration of treatment (8. However.11.O T C variant was selected to save time and effort and to provide long-lasting O T C concentration in blood plasma. O T C at 0.6 ug/ml for three days (26).24.n e g a t i v e bacteria. 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. F u r t h e r m o r e . e) Use of the intraperitoneal route for administration of antibiotics created serious reactions in some cases (17.12. b) Incorrect choice of antibiotics (7. i) Presence of antibiotic residues in milk and m e a t of t r e a t e d animals.37). a combination of L A .0 µg/ml. before initiation of the present treatment regimens.O T C and ST. O T C proved to be effectively bactericidal when combined with 10 µg/ml of ST (15.26). in infected cows.13. melitensis (35).34). relapses after antimicrobial t r e a t m e n t w e r e also explained by the intracellular location of brucellae (9.29).O T C or ST was used alone.26. despite the use of a combination of L A .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. 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.25) on the treatment of bovine brucellosis indicated poor success rates when L A . Since successful therapy in human beings appears to depend on the permeability of cell walls to drugs (24). 36).m. the following points were taken into account when attempting to obtain more successful results. ST was also used.13.O T C and ST proved very effective in curing sheep and goats naturally infected with B. and are therefore p r o t e c t e d from antibodies.24. 25. milking was stopped in lactating cows and udders were completely evacuated before each injection. g) High cost of antibiotherapy (24. However. which were all serologically and (particularly) bacteriologically positive. For these reasons. and the possible harmful effect on consumers (27).O T C and ST.26.5-1.34).24.917 mammary glands. T h e ability of Brucella organisms to survive intracellularly can result in long-term chronic infection.29).
all t r e a t e d cows were dried before initiation of treatment.24. when treatment protocols were strictly observed. inoculation of OTC was not safe. as animals were only monitored for 16 months post-treatment. The present results of serological examinations were of some use in evaluating the effectiveness of the treatment regimens.p. relapses occurred in only 3 of 33 cows treated with regimen C. the treated cows were originally imported as pregnant heifers at an average cost of US$3.25). In the present study. In the present trial.600. due to the development of several serious local reactions at the site of injection. Previous studies in cows and sheep (17. This did not include the cost of e q u i p m e n t or interventions. In the present study. although O T C has been considered the most effective antibiotic for treatment of brucellosis.918 not long-acting antibiotics. and t h e r e was no nontreated control group for comparison.24. Even in relapsed cows (3 animals in regimen C). at the present time.25. a small number of relapses do occur. However. regimens A and B proved to be effective. consequently.I M I alone would be effective for the treatement of lactating cows due to the continuous flushing of OTC by milking.29). the cost of supplies and intervention should be considered. inoculation of L A . Relapses have also been reported in cows (14. However. the majority (approximately 90%) of the cows treated were monitored bacteriologically for 16 months post-treatment in order to detect possible relapses. However. however. which is considered economically feasible in Saudi Arabia. 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. Also. However. However. without side-effects and relatively inexpensive in causing cessation of the symptoms of brucellosis and eliminating Brucella organisms from infected cows. only a small n u m b e r of Brucella colonies were recovered from large tissue samples. because all serological and bacteriological examinations were performed free of charge at Government institutions. The cost of successful treatment of a cow represents approximately 5% of the original price of the animal. Consequently. 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). 34) concluded that i. this treatment would probably be limited to valuable breeding animals.75). reported that serological findings were not useful in evaluating the effectiveness of treatment regimens (24.34). and the protection of Brucella organisms in the presence of milk. including the cost of air freight. Other investigators. In the present study. further research may yield a regimen .O T C did not result in harmful systemic effects or any obvious lasting local reactions at the site of inoculation. in other situations. relapses did not occur in any of the 88 cows treated with regimen A or B (provided that the treatment protocol is strictly observed).26. i.13. The cost of antibiotics used was calculated according to sale prices in the Saudi market at the time of the experiment (US$1 = SR3. B or C for treating a cow of an average weight of 600 kg was US$186 (SR700).m. 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.12. T h e average cost of the antibiotics used in regimen A. the results were not conclusive. 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. In conclusion. In humans. it seems unlikely that O T C . practical. In Saudi Arabia.
Hussain. Thanks are also extended to the owners and veterinary staff of the three dairy farms involved. sauf pour la ST qui était administrée un jour sur deux pendant 16 jours et pour l'OTC-IMI. Résumé : Trois protocoles thérapeutiques ont été évalués chez 121 vaches atteintes d'une infection naturelle par Brucella melitensis ou Brucella abortus.I. .M. Avant l'application de ces trois protocoles thérapeutiques.S. similaire au protocole A. les bio types 1 ou 2 de B. Mukayel and A .) de 25 mg/kg de LA-OTC tous les trois jours pendant 42 jours. Prasad.m.I. Bin Salamah. de 25 mg/kg de ST (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. for his encouragement and co-operation. Quant au protocole C. .A. melitensis ont été régulièrement isolés dans les sécrétions mammaires de 103 vaches et le biotype 1 de B. 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.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.) quotidiennement pendant huit jours et en une OTC-IMI quotidienne de 20 ml par trayon pendant quatre jours.V. 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. la streptomycine (ST) et l'infusion intramammaire d'OTC (OTC-intramammary infusion : OTC-IMI). hormis pour la ST qui était administrée tous les trois jours pendant 24 jours et l'OTC-IMI. Le protocole B (appliqué à 53 vaches) était similaire au précédent. P.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. * * * DES PROTOCOLES THÉRAPEUTIQUES EFFICACES POUR LE TRAITEMENT DE L'INFECTION PAR BRUCELLA MELITENSIS ET BRUCELLA ABORTUS CHEZ LES VACHES. A. il n'a permis l'élimination des brucelles que sur 30 (91 %) des 33 vaches traitées. The authors also acknowledge the technical assistance of A . Al-Taher. 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. Bekairi. for their s u p p o r t and c o . Furthermore.M. O. pratiquée également tous les trois jours pendant 12 jours. Al-Bokmy. 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.T. Radwan. Le protocole A (appliqué à 35 vaches) consistait en une administration intramusculaire (i. S. Mohamed et S. ACKNOWLEDGEMENTS The a u t h o r s wish to express their sincere t h a n k s to M.S. abortus dans celles de 18 vaches. pratiquée un jour sur deux pendant huit jours. combinant à la fois l'Oxytétracycline à action prolongée (long-acting Oxytetracycline : LA-OTC).
Prasad..R. sólo permitió eliminación de brucelas en 30 de las 33 vacas tratadas. y ala OTC-IMI. el protocolo C. * PROTOCOLOS TERAPÉUTICOS EFICACES PARA EL TRATAMIENTO DE LA INFECCIÓN POR BRUCELLA MELITENSIS Y BRUCELLA ABORTUS EN VACAS. Proc.Y. Al-Bokmy. que se administró cada dos días durante ocho días.Brucella melitensis . 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. O. Por último. & HARLAND P. melitensis fueron regularmente aislados en las secreciones mamarias de 103 vacas y el biotipo 1 de B.. (1986). SINOUSSI Y . 3. PALABRAS CLAVE: Antibióticos .351-357. Resumen: Se evaluaron tres protocolos terapéuticos en 121 vacas infectadas por vía natural por Brucella melitensis o Brucella abortus. abortus en las secreciones mamarias de 18 vacas. Hussain. estreptomicina (ST) e infusión intramamaria de OTC (OTC-intramammary infusion: OTC-IMI). A. El protocolo B. JONES L .Thérapie.Brucellosis in children. CHANG S. Ann. S. ALTON G. Paris. que se administró cada dos días durante 16 días. (1984). CHEN M . . M . HAWARI A. un 91%. de 25 mg/kg de ST (i.M E Z A I N I S. Bekairi. . (1988). a partir de una combinación de oxitetraciclina de acción prolongada (long-acting Oxytetracycline: LA-OTC).Brucella abortus . WANG C F . . Institut National de la Recherche Agronomique.V.M.E.T.Streptomycine .25-27.Estreptomicina .m.I. que se experimentó en 53 vacas. .. 7.D. que fue experimentado en 35 vacas. Soc.I. consistía en la administración intramuscular (i. 190 pp.) diarios durante ocho días y en una OTC-IMI diaria de 20 ml por pezón durante 4 días. A L .H.G. .. Mohamed y S.A.) de 25 mg/kg de LA-OTC cada tres días durante 42 días. 2.Oxitetraciclina .m. M . 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. El protocolo A. es decir.G. & V E R G E R J . Radwan. . AL-MARSHEDY A. .Terapéutica.Oxytétracycline .920 MOTS-CLÉS : Antibiotiques .A study on brucellosis among animals of some farms and rural areas of Saudi Arabia. Saudi biol.M. era similar al anterior excepto en cuanto a la ST. los biotipos 1 o 2 de B.Bovinos .Brucella melitensis . Saudi Med.Techniques for the brucellosis laboratory.S.Brucella abortus . REFERENCES 1.S.. C . P. 6.Bovins . 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. A N G U S R. Antes de aplicar estos tres protocolos terapéuticos.
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