Volume 16
THE CANADIAN VETERINARY JOURNAL LA REVUE VETERINAIRE CANADIENNE August-aout 1975
No. 8
A CLINICAL EVALUATION OF ANTIMICROBIAL AGENTS AND TEMPORARY STARVATION IN THE TREATMENT OF ACUTE UNDIFFERENTIATED DIARRHEA IN NEWBORN CALVES 0. M. Radostits, C. S. Rhodes, M. E. Mitchell, T. P. Spotswood and M. S. Wenkoff* INTRODUCTION
NEONATAL DIARRHEA is a major cause of economic loss in raising calves (23). The morbidity in some herds may reach 75% and the mortality rate can vary from 10 to 25% of all calves born (12, 30). In Western Canada the mortality rate of affected calves which
of fluids and electrolytes (3, 4, 9, 32). At least two aspects of treatment of calves with diarrhea for which there is little or no information available are 1) the rationale for the use of antimicrobial agents orally and parenterally and 2) the rationale for starvation from milk or continued feeding of milk during the diarrheic period. Veterinarians have usually assumed that diarrheic calves have an infectious enteritis and the potential to develop bacteremia and/or septicemia and thus the widespread use of calf scour preparations containing antimicrobial agents for oral administration. But what is the evidence that the calf affected with acute neonatal diarrhea needs an antibiotic orally? Is it not possible that the antibiotic might alter the intestinal microflora and actually make things worse? There may be some justification for the parenteral use of antibiotics to combat the effects of bacteremia and to prevent localization in meninges, joints and eyes. One recent report by Boyd et al (2) showed that severely affected calves which were unable to stand had a leucocytosis suggestive of an infectious process. Whether or not calves with diarrhea should be starved from milk or be fed continuously (in the case of beef calves, taken off the cow or left with the cow) has been controversial. Blaxter (1) has shown that the digestibility of nutrients in diarrheic calves is reduced considerably and used the term "physiological starvation" to describe the negative nutrient balance which existed in the calves. Continued feeding of milk to diarrheic calves could aggravate the diarrhea by providing excessive substrate to the intestinal microflora and therefore they should be starved until they return to normal. Conversely it might be argued that diarrheic calves should be fed some milk (even though a reduced amount) because they are use
are
treated for diarrhea in veterinary clinics varies from 30 to 50% (0. M. Radostits, unpublished information). Even with the considerable effort which veterinarians put into the treatment of "scouring calves", the overall survival rate of calves submitted to large animal clinics is only about 70% and there is general agreement that of the calves which are discharged from the clinic alive a further 10 to 15% relapse and die on the farm. Both the treatment and control of neonatal diarrhea in calves are difficult, frustrating, and unrewarding because often the cause of the diarrhea cannot be determined quickly and accurately. The causes of acute neonatal diarrhea in calves include enteropathogenic Escherichia coli and Salmonellae (7, 11, 27), Reo and Corona-like viruses (10, 20), Chlamydia sp. (6), possibly the viruses of infectious bovine rhinotracheitis and bovine virus diarrhea (16, 21, 25, 33), adenovirus (18) and nutritional causes such as milk replacers containing heat denatured whey proteins (28). There are probably other causes which have not yet been determined. The biochemical events which occur in newborn calves affected with acute diarrhea are known and considerable progress has been made in the last ten years in treating the physiological effects of the disease through the *Department of Veterinary Clinical Studies, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO.
)19
CAN. VET. JOUR., vol. 16, no. 8, August, 1975
CANADIN VETINARY JOURNAL
TABLE I CONDITIONS AND DESIGN OF TREATMENTS USED IN TREATING CALVES WITH
Feeding regime
DIARRHEA
Milk-starved for 24 hours and given oral electrolytes during period of starvation
Antibacterial Ampicillin orally No. 1 (45)a Nifuraldezone No. 3 (44) orally and chloramphenicol parenterally No antibacterial No. 5 (48) "No. of calves in each treatment group.
in a state of negative nutrient balance and starvation. The objectives of this clinical trial were to compare the survival rates of calves affected with acute undifferentiated neonatal diarrhea and treated with two different antimicrobial treatments and no antimicrobial agents. Also, the effect of continued feeding of cows' whole milk to diarrheic calves was compared with starvation for a 24 hour period.
Cows' whole milk given when willing to suck from nipple bottle No. 2 (38) No. 4 (45)
No. 6 (34)
TABLE II ORAL ELECTROLYTE FORMULA Sodium chloride Potassium chloride Sodium bicarbonate Potassium phosphate
117.0 g 150.0 g 168. 0 g
(K2HPO4)
135.0 g Total 570. 0 g For 1000 ml of solution add 5.7 g of powder to which may also be added 50 g of glucose. For 4000 ml of solution add 23 g of powder to which may be added 200 g of glucose. The above final solution is offered to calves by nipple bottle or given by stomach tube at a rate of 150 ml per kg body weight per 24 hours in three divided doses.
MATERIALS AND METHODS During April and May of 1973 (for a 60 day period) each calf which was admitted to the large animal clinic of the Western College of Veterinary Medicine for the treatment of acute neonatal diarrhea was assigned to one of six different randomized treatment groups. Each calf was examined clinically on admission, placed in an individual pen and fluid travenously. Nifuraldezone was administered therapy begun and continued as necessary. at the dose rate of 2 gm initially, followed by The fluids and electrolytes used consisted of 1 gm every 12 hours for up to six treatments. equal mixtures of isotonic saline (0.85%) and Chloramphenicol was given at a dose rate of isotonic sodium bicarbonate (1.3%). Rehydra- 20 mgm per kg body weight every 12 hours tion therapy at 100 ml per kg body weight for a total of six treatments. No antimicrobial usually required from four to six hours and therapy was given to calves in Groups 5 and 6. maintenance therapy at 150 ml per kg body Calv'es in Groups 1, 3 and 5 were starved weight was continued for 20 hours or more from milk for the first 24 hours but did receive (3) using indwelling intravenous catheters fluids and oral electrolytes orally during this (34). period (Table II). Following starvation, The experimental design of the clinical trial were fed milk by stomach tube if they calves were is shown in Table I. Calves in Groups 1 and 2 unwilling to drink voluntarily. Cows' whole received ampicillin1 orally at approximately milk was obtained daily from the University 400 mg per 34 kg body weight every 12 hours of Saskatchewan dairy herd and fed in nippled for up to five days. Groups 3 and 4 received bottles at the rate of 8% body weight equivanifuraldezone2 orally and chloramphenicol3 in- lent divided into two feedings. When the calves appeared clinically normal, 1Penbritin, Ayerst Laboratories, Montreal, Quedrank voluntarily and had passed formed feces, bec. 2Entefur, Eaton Laboratories, Norwich, New they were discharged and considered a surYork. vival statistic. No follow-up information was 3Veticol, Clark-Cote, Calgary, Alberta. obtained after discharge from the clinic. 220
NEONATAL DIARRHEA
TABLE III PERCENTAGE SURVIVAL RATE OF CALVES IN EACH GROUP (a) Includes all calves regardless of length of hospital stay. (b) Includes only calves hospitalized for three or more days. Feeding regime
Antibacterial
Ampicillin orally Nifuraldezone orally and chloramphenicol parenterally No antibacterial
Milk-starved for 24 hours and given oral electrolytes during period of starvation
Cows' whole milk given when willing to suck from nipple bottle
a
b
a
b
73 70
60 53
63 84
50 90
60
61
76
60
RESULTS A total of 254 calves were included in the
trial. The survival rates were analyzed statistically: 1) for all calves regardless of the length of hospitalization and 2) for only those calves which were hospitalized for three days or more. When all calves were considered (Table III) the survival rates in Groups 1, 4 and 6 were greater than in Groups 2, 3 and 5, but the differences were not significant (P < .05). Of the calves which were hospitalized for three days or more (Table III) the survival rate was highest in Group 4 (nitrofuraldezone orally, chloramphenicol parenterally and continued milk feeding) but not significantly (P < .05) higher than the survival rates in the other groups. The degree of clinical dehydration of the calves on admission to the clinic is shown in Table IV. Calves affected with mild dehydration (4 to 6% of total body weight) were able to stand, those affected with moderate dehydration (6 to 8% of total body weight) were unable to stand without assistance and were in sternal recumbency, while those with severe dehydration (8 to 10% of total body weight) were in lateral recumbency and usually comatose. The duration of diarrhea in days prior to admission to the clinic is shown in Table V. Length of hospitalization in days is shown in Table VI. The pathological findings of calves which died are shown in Table VII. The professional and technical man hours which were necessary to conduct the trial were enormous. The trial extended over a 60 day period and required one veterinarian and two 221
TABLE IV CLINICAL EVALUATION OF DEHYDRATION OF CALVES ON ADMISSION
Degree of dehydration Mild 4-6% of body weight Moderate 6-8% of body weight Severe 8-10%
No. of calves
Percent
70
28
76
31
of body weight
101
41
TABLE V DURATION OF DIARRHEA BEFORE CALVES ADMITTED TO THE CLINIC
No. of days Less than one 1 2
3 4 More than four
No. of calves
Percent
52 62 33 29 15 36
23 27 15 13 7 16
TABLE VI NUMBER OF DAYS CALvEs HOSPITALIZED DURING TREATMENT FOR DIARRHEA
No. of days 1 2 3
4-5 6-7 More than seven
No. of calves
Percent
94 67 41 24 15 13
37 26 16 9 6 5
CANADUIN VETERINARY JOURNAL
TABLE VII FREQUENCY OF LESIONS FOUND AT NECROPSY OF 75 CALVES WHICH DIED Lesion or pathological diagnosis Enteritis Salmonellosis Bronchopneumonia Arthritis Pulmonary edema Peritonitis Omphaphlebitis Serouis atrophy
Lesion or pathological diagnosis Nephritis Abomasitis Intestinal obstruction Meningitis Hydronephrosis Cystitis Aspiration pneumonia Hepatic degeneration
No. 48 28 16 11 9 7 7 5
animal technicians on a full-time basis working a minimum of ten hours per day and more frequently 12 or more hours per day. The technicians fed the calves, maintained the fluid therapy, administered the antibiotics and did most of the record keeping. The veterinarian evaluated the calves clinically, initiated the intravenous fluid therapy and monitored the clinical response. DISCUSSION
There was no clear indication that any treatment regime was superior. When all calves, regardless of the length of hospitalization, were considered, the differences in survival rates were slight and not significant. Of the calves which were hospitalized for three days or more the survival rate was highest in those fed milk and given nifuraldezone orally and chlora-mphenicol parenterally, but the difference was not significant. Those calves which responded quickly to the fluid therapy were discharged alive from the hospital on the first or second day and thus they were not fully subjected to an evaluation of starvation versus continued feeding or to the entire complement of antimicrobials. For this reason, the survival rates for all calves cannot be evaluated statistically. The calves which were hospitalized for three days or more were, however, subjected to a complete regime of starvation versus continued feeding as well as the antibacterial treatment and the data should stand up to statistical analysis. Whether calves affected with diarrhea should be starved from milk for 24 hours or fed milk throughout the treatment period could not be determined from this trial. Based on the high survival rate of calves in Group 4 it would appear that the combination of chloramphenicol, nifuraldezone and continuous milk feeding is desirable.
No. 5 5 4 3 2 2 2 2
Approximately 50% of the calves had diarrhea for one day or less before admission and 70% of the calves were classified clinically on admission as moderately to severely dehydrated. Thus, the single most important part of treatment of calves affected with acute neonatal diarrhea is the correction of the dehydration and acidosis (3, 24). The physiological and biochemical events which occur in calves with diarrhea have been studied intensively and the fluid and electrolyte losses must be restored (3, 32). The relationship between degree of dehydration and response to treatment was not examined but it is reasonable to expect a higher survival rate in calves which are just mildly dehydrated and owners must be educated to have their diarrheic calves treated as early as possible. Whether or not antimicrobials are indicated in calves affected with acute neonatal diarrhea cannot be determined clearly from this trial. The rationale for their use has been that enteropathogenic E.coli and Salmonella sp. proliferate in the intestines resulting in an enteritis and concurrently may penetrate the intestinal mucosa resulting in a bacteremia or septicemia (5, 7). There appears to be little scientific information available to show that antimicrobials by the oral route are necessary in neonatal diarrhea in calves. In fact, the effect which orally administered antimicrobials has on the intestinal microflora of calves is not known. When one considers the complexity of the intestinal microflora, it is difficult to explain how antimicrobials would have a beneficial effect. The relationship between the serum immune globulin levels in the calves and their death or survival was not studied in this trial. Many observations have been made which show that the mortality rate from diarrhea is significantly higher in newborn calves with low levels of serum immune globulins (8, 9, 13). If a rapid method of determining the serum level
222
NEONATAL DIARRHEA
of immune globulins were available it might be possible to provide a reasonably accurate prognosis when presented with a calf affected with acute neonatal diarrhea. In the experience of this clinic, calves with gamma globulin levels below 1 g/100 ml are difficult to treat successfully and commonly relapse after an initial response; those with levels below 0.5 g/100 ml will probably die in spite of exhaustive therapy. Calves with serum immune globulin levels over 1.5 g/100 ml usually respond quickly, completely and do not relapse, and seem to require only minimum treatment. The use of preparations containing bovine gamma globulins to correct the hypogammaglobulinemia seems to be the logical approach but thus far the results have been equivocal. Many different lesions were present in the calves which died. Many calves had multiple lesions in addition to the common pathological findings associated with neonatal diarrhea such as dehydration and emaciation. Most of the complicating lesions were infectious in origin which justifies the use of parenteral antimicrobials, but in spite of their use, lesions were still present, which suggests that the organisms were drug resistant or the drugs were inaccessible to the lesions. The non-enteric lesions such as peritonitis, pneumonia, arthritis, and even meningitis were frequently not recognized clinically probably because all calves were presented with a history and clinical findings of diarrhea from which logically follows a diagnosis of neonatal diarrhea. The failure to detect the presence of these complicating lesions emphasizes the necessity for detailed clinical examination on admission and careful clinical monitoring during hospitalization. However, it is probable that during times of peak clinic loads animals often do not receive the intensive care which is necessary to detect all abnormalities which are present. The rather high incidence of salmonellosis was unexpected and illustrates the problems associated with the clinical diagnosis of the disease and the potential difficulties which can be encountered with control and prevention of the disease under a clinic situation. It is extremely difficult to break the chain of Salmonella infection in a clinic and depopulation of the clinic, the handling of as many patients as possible as outpatients and the isolation of all known carriers must be instituted immediately along with a general clean up and disinfection. The findings in this trial provide some clues for future meaningful investigations. Follow-up information on treated calves after they are discharged alive from the clinic is essential 223
before the different treatments can be evaluated, both biologically and economically. Reliable data on the prevalence of the disease on individual farms are not available. The range of prevalence of the disease in herds and also the percentage of diarrheic calves which are treated successfully on the farm by the owner and the percentage of calves which do not respond to treatment on the farm and therefore are brought to the clinic for intensive care should be determined. It is possible that those calves which are brought to the clinic are "poor risk" calves affected with one or more complications and which are uneconomical to treat and the veterinarians' efforts would be more profitable on the farm, assisting the farmer in minimizing the disease. This study also pointed out the limitations of studying a common disease such as neonatal diarrhea in calves in a clinic situation without a parallel examination of the epidemiology of the disease on the farm. The amount of vital information which can be generated for use in the economical control and prevention of the disease at farm level is limited. Morris and Blood (22) have pointed out the need for the collection of disease data on the farm so that the economical impact of each disease can be assessed using the whole farm approach and control strategies selected based on the relative importance of each disease. CONCLUSIONS
AND
RECOMMENDATIONS
From the results of this trial and the reported experiences from elsewhere, some conclusions and recommendations can be made to help to reduce the mortality in calves affected with acute neonatal diarrhea. 1. Owners must be educated to appreciate the serious nature of diarrhea in newborn calves and to institute oral fluid and electrolyte therapy promptly to minimize the severity of acidosis and dehydration. Seventy percent of the calves in this trial were moderately to severely dehydrated when admitted to the clinic. Larouche and Black (17) found a relationship between the severity of clinical signs on arrival and subsequent survival; the survival rate was 77% in calves admitted with mild systemic signs and only 37% in calves with severe systemic signs such as severe dehydration and prostration.
2. Veterinarians should instruct their clients on the importance of early treatment of calves affected with neonatal diarrhea. Af-
CANADIAN VETRNARY JOURNAL
fected calves should be isolated from the remainder of the herd and treated with oral fluids and electrolytes to minimize acidosis and dehydration. 3. Calves which do not respond to therapy on the farm and continue to have a profuse watery diarrhea should be brought to the clinic for parenteral fluid therapy. Many owners will continue to treat calves until they are severely dehydrated and weak, then seek assistance.
4. Antimicrobial agents used orally and/or parenterally should be discontinued after three days. The ideal situation would be to use antimicrobial agents only when there is clinical evidence of bacteremia and/or septicemia but it is usually impossible to know that either one or both do not exist in a particular calf without laboratory assistance. An examination of a hemogram may
reveal evidence of the fection.
presence
of
an
in-
5. The relationship and the mechanism between the serum levels of immune globulins and mortality from diarrhea in calves must be examined closely to determine if indeed calves with low levels of immune globulins cannot be saved even with intensive therapy. Is it possible that the deficits which exist in some calves can be corrected with purified preparations of bovine gamma globulins? To minimize the incidence of hypogammaglobulinemia in calves, Kruse (15) has calculated that a 35 kg calf should receive at least 2 kg of colostrum within the first five hours after birth. It appears from the literature that an adequate serum level of immune globulins will prevent death from diarrhea but perhaps the administration of large quantities of gamma globulin in an attempt to correct the deficit in hypogammaglobulinemic calves is not curative. 6. For the veterinarian the ideal situation for the most effective intensive fluid and electrolyte therapy of calves with diarrhea would be to monitor the total input (intravenous and oral fluid and electrolytes) and output (urinary output) and the serum electrolyte profile and to correct the deficits accordingly. Until such a system is economically feasible, veterinarians will have to use balanced electrolyte solutions and monitor the condition of the calf clini-
cally. 224
7. No evidence was obtained from this trial or is available to recommend that calves with diarrhea should be starved from milk or fed milk during the diarrheic stage of the disease. One study found a beneficial effect from feeding milk replacer to scouring calves (19). It appears logical to recommend starvation or at least partial starvation until there is clinical evidence that the diarrhea has stopped at which time presumably the digestive function of the abomasum and intestines has returned to normal. Certainly calves with persistent profuse diarrhea should be starved and other methods of alimentation attempted if economics permit. There is a need to assess the usefulness of parenteral alimentation which is used in infants with malabsorption syndromes. Mixtures of emulsified lipids, hypertonic solutions of carbohydrates, amino acids and vitamins and minerals are infused intravenously for several days until gastrointestinal function returns to normal (14).
8. The use of Lactobacillus acidophilus organisms or acidophilus milk for diarrheic calves should be re-examined. Their rationale is that LactobaciUus sp. competitively reduce the numbers of enteropathogenic bacteria in the intestinal microflora (26). If effective, they would provide a useful alternative to the widespread indiscriminate use of antimicrobial agents which may not be serving any useful function and may actually unnecessarily contribute to the development of drug resistant enteropathogens. 9. More accurate methods of determining the etiology of acute neonatal diarrhea of calves must be developed. Most calves with acute diarrhea are similar clinically and it is usually impossible for the veterinarian to make a definitive etiological diagnosis without the assistance of sophisticated microbiological techniques for the isolation and characterization of enteropathogenic bacteria, viruses and chlamydia. Thus the veterinarian usually assumes that the diarrhea is infectious in origin. Still further he assumes that if it is bacterial in origin that antimicrobials are indicated and if it is viral in origin that the calf will overcome the infection with its natural body defenses providing the physiological effects of the diarrhea can be treated successfully. Williams-Smith (29) reported that most cases of calf diarrhea were noninfectious in origin and he pos-
NEONATAL DIRRHEA
tulated that the cause was related to modem calf management techniques. There are probably many outbreaks of calf diarrhea which are viral in origin but the diagnostic work necessary to isolate the viral agents has not been done. The control of viral enteritis in calves will still depend on ensuring that newborn calves are not infected immediately after birth - the same principle as for the control of diarrhea caused by E.coli. 10. The large number of different complicating lesions which was present in the calves in this trial emphasizes the need for more careful clinical examination and that postmortem examinations are necessary to determine those which are not detectable clinically.
nifuraldezone 44, 70%; 4) continuous feeding chloramphenicol - nifuraldezone 45, 84%; 5) starvation - no antibacterial therapy 48, 60% and 6) continuous feeding - no antibacterial therapy 34, 76%. There was no statistical difference in survival rates between these six groups. If only the calves that were hospitalized for more than 48 hours were considered, there was still no significant difference in survival rates.
Post-mortem examination revealed many different pathological diagnoses, many of which were not detected clinically and emphasized the importance of a detailed clinical examination. In addition, the need for strict sanitation and isolation facilities was noted when treating diarrrheal calves on an in-clinic basis. The problems associated with treatment of neonatal diarrhea in calves are also reviewed and discussed briefly.
11. Almost nothing is known about the efficacy of anticholinergics for the treatment of acute neonatal diarrhea of calves. There RESuME is a need to determine if abnormal gastrointestinal motility plays a role in the pathoCette etude consistait en une experience genesis of neonatal diarrhea in calves and clnique d'une duree de 60 jours, impliquant whether the use of anticholinergic drugs 254 veaux souffrant de diarrh6e neo-natale are indicated in treatment. Benzetimide has aigue et non sp6cifique. Tous ces veaux recurent been used for the treatment of diarrhea in la meme fluidotherapie afin de corriger leur newborn calves and adult cattle (31). deshydratation et de maintenir leur hydratation. 12. Intestinal protectants such as kaolin, pectin, On priva de lait la moitie de ces veaux, and bismuth salts are commonly incorpo- pendant 24 heures apres leur admission "a la rated in calf diarrhea preparations but there clinique et on leur donna ensuite du lait de is no conclusive clinical evidence to show vache. Les autres veaux s'aliment'erent des that they are useful. qu'ils purent et voulurent t6ter. On partagea plus tard chacun de ces deux groupes en trois autres groupes que l'on traita de facon difSUMMARY f6rente. Le premier re,ut de l'ampicilline par A clinical trial involving 254 calves affected la voie buccale et le second, du chloramph6niwith acute undifferentiated neonatal diarrhea col en injection intra-veineuse et du nifuralwas conducted over a period of 60 days. All dezone par la voie buccale; le troisieme ne calves were given the same type of fluid re,ut aucune antibioth6rapie. Le nombre de therapy to correct dehydration and maintain veaux composant chacun des six groupes et le hydration. pourcentage de ceux qui survecurent sont les One-half of the calves were starved from suivants: 1) je'une et ampicilline: 45 et -73%; milk for a period of 24 hours after admission 2) alimentation continuelle et ampicilline: 38 and then fed cows milk. The other half were et 63%; 3) je'une et traitement au chloramphefed milk as soon as they were able and willing nicol et au nifuraldezone: 44 et 70%; 4) alito suck. -Each group was further subdivided mentation continuelle et traitement au chloraminto three treatment groups. The first received ph6nicol et au nifuraldezone: 45 et 84%; 5) ampicillin orally, the second a combination je'une sans antibiotherapie: 48 et 60%; 6) aliof chloramphenicol intravenously and nifural- mentation continuelle sans antibiotherapie: 34 dezone orally, and the third received no anti- et 76%. On ne releva aucune diff6rence statismicrobial therapy. The number of calves in tique concernant le taux de survie au sein des each of the six groups and percentage survival six groupes. En ne considerant que les veaux rates were as follows: 1) starvation - ampicillin hospitalises pour plus de 48 heures, on ne 45, 73%; 2) continuous feeding - ampicillin decela pas non plus de difference relative au 38, 63%; 3) starvation - chloramphenicol - taux de survie. 225
CANADIAN VETERINARY JOURNAL
La necropsie revela une vari6t6 de conditions pathologiques dont plusieurs ne furent pas d6cel6es cliniquement; cette observation fait ressortir l'importance d'un examen cinique d6taille. On nota 6galement le besoin de conditions hygieniques strictes et de facilit6s d'isolement, lorsqu'on traite dans une clinique des veaux souffrant de diarrhee neo-natale. Les auteurs passent en revue et commentent brievement les problemes inh6rents au traitement de la diarrhee neo-natale des veaux. ACKNOWLEDGMENTS The authors thank Dr. Dan Mascaluk for his work in compiling and correlating the data from the individual records and Mr. E. B. Edwards for his assistance with the statistical analysis. The long hours worked by the veterinary technician is gratefully acknowledged. Thanks are also due to Mrs. Donna Knights who tped the manuscript. REFERENCES
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Benzetimide in the treatment of diarrhea in newborn calves and adult cattle. Vet. Rec. 94: 180-183. 1974.
32. TENNANT, B., D. HARROLD and M. R REINA-
BOOK REVIEW Advances in Cardiology - Comparative Pathology of the Heart. Edited by F. Homburger and I. Lucas. Published by S. Karger AG, Basel, Switzerland. 1974. 379 pages. Price $95.00. This book contains the papers presented at a symposium on Comparative Patology of the Heart in Boston, September 1973. This book contains 379 pages and at the price of $95.00 U.S. dollars, the prospective purchaser will want information and new knowledge not available from other sources. One cannot say that the book does not cover what its title proposes, Comparative Pathology of the Heart. In fact, the book covers a wide variety of subjects relating to the heart. However, the individual interested in specifics or only one area, will find little information or knowledge, that is not already available. In the introductory chapter, an after dinner speech is included entitled: The Patient's Insight - Its Role in the Evolution of Cardiology by S. J. Reiser of Boston. This is a good historical review of a general medical practitioner in England, Sir James Mackenzie. Interesting, but no contribution to new knowledge which is the reason for books like this. The next article by Robert W. Wissler of the University of Chicago entitled: Atherosclerosis - Its Pathogenesis in Perspective, is an excellent review of all of the concepts believed to be involved in the pathogenesis of atherosclerosis. The placement of this excellent article in this section rather than in section III on Atheromatosis, is questionable. There are numerous good papers presented in this book, unfortunately some of them are much too brief. For example a paper by Had-
low from the Rocky Mountain Laboratories in Hamilton, Montana entitled: Myopathies of Animals - A Brief View, is just that. Hardly a help to anyone seeking new knowledge. A veterinarian who might refer to this book in a search for knowledge concerning such things as spontaneous cardiovascular lesions in dogs and cats, cardiomyopathies in animals or the pathological and genetic studies of congenital heart disease in the dog, would not find any of the articles rewarding. The gross lesions, the functional pathology and the clinical signs, information that the veterinarian would be seeking are not well defined in any paper in this book. Additionally, most of the material has been published in journals comprising the veterinary literature. Again the error in the book is the very broad area that the authors are attempting to cover. The most unusual presentation which the author makes in the introductory remarks should be sufficient warning to the reader. Dr. Homburger mentions that the concept of the symposium was first rejected by the American College of Cardiology in 1971 and the National Foundation in 1972. As well that year, the Nuffield Foundation, the World Health Organization and the Wellcome Trust also rejected this symposium. The symposium application submitted to the Na-
tional Institutes of Health in 1972 was approved but not funded for six months. Additionally, some 18 major drug houses in chemical manufacturers turned down the requests for support. We must congratulate Dr. Homburger and his colleagues for their persistence, however as a contribution to the literature, such persistence is not rewarding. H. C. Rowsell.
227
THE CANADIAN VETERINARY JOURNAL LA REVUE VETERINAIRE CANADIENNE August-aout 1975
No. 8
A CLINICAL EVALUATION OF ANTIMICROBIAL AGENTS AND TEMPORARY STARVATION IN THE TREATMENT OF ACUTE UNDIFFERENTIATED DIARRHEA IN NEWBORN CALVES 0. M. Radostits, C. S. Rhodes, M. E. Mitchell, T. P. Spotswood and M. S. Wenkoff* INTRODUCTION
NEONATAL DIARRHEA is a major cause of economic loss in raising calves (23). The morbidity in some herds may reach 75% and the mortality rate can vary from 10 to 25% of all calves born (12, 30). In Western Canada the mortality rate of affected calves which
of fluids and electrolytes (3, 4, 9, 32). At least two aspects of treatment of calves with diarrhea for which there is little or no information available are 1) the rationale for the use of antimicrobial agents orally and parenterally and 2) the rationale for starvation from milk or continued feeding of milk during the diarrheic period. Veterinarians have usually assumed that diarrheic calves have an infectious enteritis and the potential to develop bacteremia and/or septicemia and thus the widespread use of calf scour preparations containing antimicrobial agents for oral administration. But what is the evidence that the calf affected with acute neonatal diarrhea needs an antibiotic orally? Is it not possible that the antibiotic might alter the intestinal microflora and actually make things worse? There may be some justification for the parenteral use of antibiotics to combat the effects of bacteremia and to prevent localization in meninges, joints and eyes. One recent report by Boyd et al (2) showed that severely affected calves which were unable to stand had a leucocytosis suggestive of an infectious process. Whether or not calves with diarrhea should be starved from milk or be fed continuously (in the case of beef calves, taken off the cow or left with the cow) has been controversial. Blaxter (1) has shown that the digestibility of nutrients in diarrheic calves is reduced considerably and used the term "physiological starvation" to describe the negative nutrient balance which existed in the calves. Continued feeding of milk to diarrheic calves could aggravate the diarrhea by providing excessive substrate to the intestinal microflora and therefore they should be starved until they return to normal. Conversely it might be argued that diarrheic calves should be fed some milk (even though a reduced amount) because they are use
are
treated for diarrhea in veterinary clinics varies from 30 to 50% (0. M. Radostits, unpublished information). Even with the considerable effort which veterinarians put into the treatment of "scouring calves", the overall survival rate of calves submitted to large animal clinics is only about 70% and there is general agreement that of the calves which are discharged from the clinic alive a further 10 to 15% relapse and die on the farm. Both the treatment and control of neonatal diarrhea in calves are difficult, frustrating, and unrewarding because often the cause of the diarrhea cannot be determined quickly and accurately. The causes of acute neonatal diarrhea in calves include enteropathogenic Escherichia coli and Salmonellae (7, 11, 27), Reo and Corona-like viruses (10, 20), Chlamydia sp. (6), possibly the viruses of infectious bovine rhinotracheitis and bovine virus diarrhea (16, 21, 25, 33), adenovirus (18) and nutritional causes such as milk replacers containing heat denatured whey proteins (28). There are probably other causes which have not yet been determined. The biochemical events which occur in newborn calves affected with acute diarrhea are known and considerable progress has been made in the last ten years in treating the physiological effects of the disease through the *Department of Veterinary Clinical Studies, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO.
)19
CAN. VET. JOUR., vol. 16, no. 8, August, 1975
CANADIN VETINARY JOURNAL
TABLE I CONDITIONS AND DESIGN OF TREATMENTS USED IN TREATING CALVES WITH
Feeding regime
DIARRHEA
Milk-starved for 24 hours and given oral electrolytes during period of starvation
Antibacterial Ampicillin orally No. 1 (45)a Nifuraldezone No. 3 (44) orally and chloramphenicol parenterally No antibacterial No. 5 (48) "No. of calves in each treatment group.
in a state of negative nutrient balance and starvation. The objectives of this clinical trial were to compare the survival rates of calves affected with acute undifferentiated neonatal diarrhea and treated with two different antimicrobial treatments and no antimicrobial agents. Also, the effect of continued feeding of cows' whole milk to diarrheic calves was compared with starvation for a 24 hour period.
Cows' whole milk given when willing to suck from nipple bottle No. 2 (38) No. 4 (45)
No. 6 (34)
TABLE II ORAL ELECTROLYTE FORMULA Sodium chloride Potassium chloride Sodium bicarbonate Potassium phosphate
117.0 g 150.0 g 168. 0 g
(K2HPO4)
135.0 g Total 570. 0 g For 1000 ml of solution add 5.7 g of powder to which may also be added 50 g of glucose. For 4000 ml of solution add 23 g of powder to which may be added 200 g of glucose. The above final solution is offered to calves by nipple bottle or given by stomach tube at a rate of 150 ml per kg body weight per 24 hours in three divided doses.
MATERIALS AND METHODS During April and May of 1973 (for a 60 day period) each calf which was admitted to the large animal clinic of the Western College of Veterinary Medicine for the treatment of acute neonatal diarrhea was assigned to one of six different randomized treatment groups. Each calf was examined clinically on admission, placed in an individual pen and fluid travenously. Nifuraldezone was administered therapy begun and continued as necessary. at the dose rate of 2 gm initially, followed by The fluids and electrolytes used consisted of 1 gm every 12 hours for up to six treatments. equal mixtures of isotonic saline (0.85%) and Chloramphenicol was given at a dose rate of isotonic sodium bicarbonate (1.3%). Rehydra- 20 mgm per kg body weight every 12 hours tion therapy at 100 ml per kg body weight for a total of six treatments. No antimicrobial usually required from four to six hours and therapy was given to calves in Groups 5 and 6. maintenance therapy at 150 ml per kg body Calv'es in Groups 1, 3 and 5 were starved weight was continued for 20 hours or more from milk for the first 24 hours but did receive (3) using indwelling intravenous catheters fluids and oral electrolytes orally during this (34). period (Table II). Following starvation, The experimental design of the clinical trial were fed milk by stomach tube if they calves were is shown in Table I. Calves in Groups 1 and 2 unwilling to drink voluntarily. Cows' whole received ampicillin1 orally at approximately milk was obtained daily from the University 400 mg per 34 kg body weight every 12 hours of Saskatchewan dairy herd and fed in nippled for up to five days. Groups 3 and 4 received bottles at the rate of 8% body weight equivanifuraldezone2 orally and chloramphenicol3 in- lent divided into two feedings. When the calves appeared clinically normal, 1Penbritin, Ayerst Laboratories, Montreal, Quedrank voluntarily and had passed formed feces, bec. 2Entefur, Eaton Laboratories, Norwich, New they were discharged and considered a surYork. vival statistic. No follow-up information was 3Veticol, Clark-Cote, Calgary, Alberta. obtained after discharge from the clinic. 220
NEONATAL DIARRHEA
TABLE III PERCENTAGE SURVIVAL RATE OF CALVES IN EACH GROUP (a) Includes all calves regardless of length of hospital stay. (b) Includes only calves hospitalized for three or more days. Feeding regime
Antibacterial
Ampicillin orally Nifuraldezone orally and chloramphenicol parenterally No antibacterial
Milk-starved for 24 hours and given oral electrolytes during period of starvation
Cows' whole milk given when willing to suck from nipple bottle
a
b
a
b
73 70
60 53
63 84
50 90
60
61
76
60
RESULTS A total of 254 calves were included in the
trial. The survival rates were analyzed statistically: 1) for all calves regardless of the length of hospitalization and 2) for only those calves which were hospitalized for three days or more. When all calves were considered (Table III) the survival rates in Groups 1, 4 and 6 were greater than in Groups 2, 3 and 5, but the differences were not significant (P < .05). Of the calves which were hospitalized for three days or more (Table III) the survival rate was highest in Group 4 (nitrofuraldezone orally, chloramphenicol parenterally and continued milk feeding) but not significantly (P < .05) higher than the survival rates in the other groups. The degree of clinical dehydration of the calves on admission to the clinic is shown in Table IV. Calves affected with mild dehydration (4 to 6% of total body weight) were able to stand, those affected with moderate dehydration (6 to 8% of total body weight) were unable to stand without assistance and were in sternal recumbency, while those with severe dehydration (8 to 10% of total body weight) were in lateral recumbency and usually comatose. The duration of diarrhea in days prior to admission to the clinic is shown in Table V. Length of hospitalization in days is shown in Table VI. The pathological findings of calves which died are shown in Table VII. The professional and technical man hours which were necessary to conduct the trial were enormous. The trial extended over a 60 day period and required one veterinarian and two 221
TABLE IV CLINICAL EVALUATION OF DEHYDRATION OF CALVES ON ADMISSION
Degree of dehydration Mild 4-6% of body weight Moderate 6-8% of body weight Severe 8-10%
No. of calves
Percent
70
28
76
31
of body weight
101
41
TABLE V DURATION OF DIARRHEA BEFORE CALVES ADMITTED TO THE CLINIC
No. of days Less than one 1 2
3 4 More than four
No. of calves
Percent
52 62 33 29 15 36
23 27 15 13 7 16
TABLE VI NUMBER OF DAYS CALvEs HOSPITALIZED DURING TREATMENT FOR DIARRHEA
No. of days 1 2 3
4-5 6-7 More than seven
No. of calves
Percent
94 67 41 24 15 13
37 26 16 9 6 5
CANADUIN VETERINARY JOURNAL
TABLE VII FREQUENCY OF LESIONS FOUND AT NECROPSY OF 75 CALVES WHICH DIED Lesion or pathological diagnosis Enteritis Salmonellosis Bronchopneumonia Arthritis Pulmonary edema Peritonitis Omphaphlebitis Serouis atrophy
Lesion or pathological diagnosis Nephritis Abomasitis Intestinal obstruction Meningitis Hydronephrosis Cystitis Aspiration pneumonia Hepatic degeneration
No. 48 28 16 11 9 7 7 5
animal technicians on a full-time basis working a minimum of ten hours per day and more frequently 12 or more hours per day. The technicians fed the calves, maintained the fluid therapy, administered the antibiotics and did most of the record keeping. The veterinarian evaluated the calves clinically, initiated the intravenous fluid therapy and monitored the clinical response. DISCUSSION
There was no clear indication that any treatment regime was superior. When all calves, regardless of the length of hospitalization, were considered, the differences in survival rates were slight and not significant. Of the calves which were hospitalized for three days or more the survival rate was highest in those fed milk and given nifuraldezone orally and chlora-mphenicol parenterally, but the difference was not significant. Those calves which responded quickly to the fluid therapy were discharged alive from the hospital on the first or second day and thus they were not fully subjected to an evaluation of starvation versus continued feeding or to the entire complement of antimicrobials. For this reason, the survival rates for all calves cannot be evaluated statistically. The calves which were hospitalized for three days or more were, however, subjected to a complete regime of starvation versus continued feeding as well as the antibacterial treatment and the data should stand up to statistical analysis. Whether calves affected with diarrhea should be starved from milk for 24 hours or fed milk throughout the treatment period could not be determined from this trial. Based on the high survival rate of calves in Group 4 it would appear that the combination of chloramphenicol, nifuraldezone and continuous milk feeding is desirable.
No. 5 5 4 3 2 2 2 2
Approximately 50% of the calves had diarrhea for one day or less before admission and 70% of the calves were classified clinically on admission as moderately to severely dehydrated. Thus, the single most important part of treatment of calves affected with acute neonatal diarrhea is the correction of the dehydration and acidosis (3, 24). The physiological and biochemical events which occur in calves with diarrhea have been studied intensively and the fluid and electrolyte losses must be restored (3, 32). The relationship between degree of dehydration and response to treatment was not examined but it is reasonable to expect a higher survival rate in calves which are just mildly dehydrated and owners must be educated to have their diarrheic calves treated as early as possible. Whether or not antimicrobials are indicated in calves affected with acute neonatal diarrhea cannot be determined clearly from this trial. The rationale for their use has been that enteropathogenic E.coli and Salmonella sp. proliferate in the intestines resulting in an enteritis and concurrently may penetrate the intestinal mucosa resulting in a bacteremia or septicemia (5, 7). There appears to be little scientific information available to show that antimicrobials by the oral route are necessary in neonatal diarrhea in calves. In fact, the effect which orally administered antimicrobials has on the intestinal microflora of calves is not known. When one considers the complexity of the intestinal microflora, it is difficult to explain how antimicrobials would have a beneficial effect. The relationship between the serum immune globulin levels in the calves and their death or survival was not studied in this trial. Many observations have been made which show that the mortality rate from diarrhea is significantly higher in newborn calves with low levels of serum immune globulins (8, 9, 13). If a rapid method of determining the serum level
222
NEONATAL DIARRHEA
of immune globulins were available it might be possible to provide a reasonably accurate prognosis when presented with a calf affected with acute neonatal diarrhea. In the experience of this clinic, calves with gamma globulin levels below 1 g/100 ml are difficult to treat successfully and commonly relapse after an initial response; those with levels below 0.5 g/100 ml will probably die in spite of exhaustive therapy. Calves with serum immune globulin levels over 1.5 g/100 ml usually respond quickly, completely and do not relapse, and seem to require only minimum treatment. The use of preparations containing bovine gamma globulins to correct the hypogammaglobulinemia seems to be the logical approach but thus far the results have been equivocal. Many different lesions were present in the calves which died. Many calves had multiple lesions in addition to the common pathological findings associated with neonatal diarrhea such as dehydration and emaciation. Most of the complicating lesions were infectious in origin which justifies the use of parenteral antimicrobials, but in spite of their use, lesions were still present, which suggests that the organisms were drug resistant or the drugs were inaccessible to the lesions. The non-enteric lesions such as peritonitis, pneumonia, arthritis, and even meningitis were frequently not recognized clinically probably because all calves were presented with a history and clinical findings of diarrhea from which logically follows a diagnosis of neonatal diarrhea. The failure to detect the presence of these complicating lesions emphasizes the necessity for detailed clinical examination on admission and careful clinical monitoring during hospitalization. However, it is probable that during times of peak clinic loads animals often do not receive the intensive care which is necessary to detect all abnormalities which are present. The rather high incidence of salmonellosis was unexpected and illustrates the problems associated with the clinical diagnosis of the disease and the potential difficulties which can be encountered with control and prevention of the disease under a clinic situation. It is extremely difficult to break the chain of Salmonella infection in a clinic and depopulation of the clinic, the handling of as many patients as possible as outpatients and the isolation of all known carriers must be instituted immediately along with a general clean up and disinfection. The findings in this trial provide some clues for future meaningful investigations. Follow-up information on treated calves after they are discharged alive from the clinic is essential 223
before the different treatments can be evaluated, both biologically and economically. Reliable data on the prevalence of the disease on individual farms are not available. The range of prevalence of the disease in herds and also the percentage of diarrheic calves which are treated successfully on the farm by the owner and the percentage of calves which do not respond to treatment on the farm and therefore are brought to the clinic for intensive care should be determined. It is possible that those calves which are brought to the clinic are "poor risk" calves affected with one or more complications and which are uneconomical to treat and the veterinarians' efforts would be more profitable on the farm, assisting the farmer in minimizing the disease. This study also pointed out the limitations of studying a common disease such as neonatal diarrhea in calves in a clinic situation without a parallel examination of the epidemiology of the disease on the farm. The amount of vital information which can be generated for use in the economical control and prevention of the disease at farm level is limited. Morris and Blood (22) have pointed out the need for the collection of disease data on the farm so that the economical impact of each disease can be assessed using the whole farm approach and control strategies selected based on the relative importance of each disease. CONCLUSIONS
AND
RECOMMENDATIONS
From the results of this trial and the reported experiences from elsewhere, some conclusions and recommendations can be made to help to reduce the mortality in calves affected with acute neonatal diarrhea. 1. Owners must be educated to appreciate the serious nature of diarrhea in newborn calves and to institute oral fluid and electrolyte therapy promptly to minimize the severity of acidosis and dehydration. Seventy percent of the calves in this trial were moderately to severely dehydrated when admitted to the clinic. Larouche and Black (17) found a relationship between the severity of clinical signs on arrival and subsequent survival; the survival rate was 77% in calves admitted with mild systemic signs and only 37% in calves with severe systemic signs such as severe dehydration and prostration.
2. Veterinarians should instruct their clients on the importance of early treatment of calves affected with neonatal diarrhea. Af-
CANADIAN VETRNARY JOURNAL
fected calves should be isolated from the remainder of the herd and treated with oral fluids and electrolytes to minimize acidosis and dehydration. 3. Calves which do not respond to therapy on the farm and continue to have a profuse watery diarrhea should be brought to the clinic for parenteral fluid therapy. Many owners will continue to treat calves until they are severely dehydrated and weak, then seek assistance.
4. Antimicrobial agents used orally and/or parenterally should be discontinued after three days. The ideal situation would be to use antimicrobial agents only when there is clinical evidence of bacteremia and/or septicemia but it is usually impossible to know that either one or both do not exist in a particular calf without laboratory assistance. An examination of a hemogram may
reveal evidence of the fection.
presence
of
an
in-
5. The relationship and the mechanism between the serum levels of immune globulins and mortality from diarrhea in calves must be examined closely to determine if indeed calves with low levels of immune globulins cannot be saved even with intensive therapy. Is it possible that the deficits which exist in some calves can be corrected with purified preparations of bovine gamma globulins? To minimize the incidence of hypogammaglobulinemia in calves, Kruse (15) has calculated that a 35 kg calf should receive at least 2 kg of colostrum within the first five hours after birth. It appears from the literature that an adequate serum level of immune globulins will prevent death from diarrhea but perhaps the administration of large quantities of gamma globulin in an attempt to correct the deficit in hypogammaglobulinemic calves is not curative. 6. For the veterinarian the ideal situation for the most effective intensive fluid and electrolyte therapy of calves with diarrhea would be to monitor the total input (intravenous and oral fluid and electrolytes) and output (urinary output) and the serum electrolyte profile and to correct the deficits accordingly. Until such a system is economically feasible, veterinarians will have to use balanced electrolyte solutions and monitor the condition of the calf clini-
cally. 224
7. No evidence was obtained from this trial or is available to recommend that calves with diarrhea should be starved from milk or fed milk during the diarrheic stage of the disease. One study found a beneficial effect from feeding milk replacer to scouring calves (19). It appears logical to recommend starvation or at least partial starvation until there is clinical evidence that the diarrhea has stopped at which time presumably the digestive function of the abomasum and intestines has returned to normal. Certainly calves with persistent profuse diarrhea should be starved and other methods of alimentation attempted if economics permit. There is a need to assess the usefulness of parenteral alimentation which is used in infants with malabsorption syndromes. Mixtures of emulsified lipids, hypertonic solutions of carbohydrates, amino acids and vitamins and minerals are infused intravenously for several days until gastrointestinal function returns to normal (14).
8. The use of Lactobacillus acidophilus organisms or acidophilus milk for diarrheic calves should be re-examined. Their rationale is that LactobaciUus sp. competitively reduce the numbers of enteropathogenic bacteria in the intestinal microflora (26). If effective, they would provide a useful alternative to the widespread indiscriminate use of antimicrobial agents which may not be serving any useful function and may actually unnecessarily contribute to the development of drug resistant enteropathogens. 9. More accurate methods of determining the etiology of acute neonatal diarrhea of calves must be developed. Most calves with acute diarrhea are similar clinically and it is usually impossible for the veterinarian to make a definitive etiological diagnosis without the assistance of sophisticated microbiological techniques for the isolation and characterization of enteropathogenic bacteria, viruses and chlamydia. Thus the veterinarian usually assumes that the diarrhea is infectious in origin. Still further he assumes that if it is bacterial in origin that antimicrobials are indicated and if it is viral in origin that the calf will overcome the infection with its natural body defenses providing the physiological effects of the diarrhea can be treated successfully. Williams-Smith (29) reported that most cases of calf diarrhea were noninfectious in origin and he pos-
NEONATAL DIRRHEA
tulated that the cause was related to modem calf management techniques. There are probably many outbreaks of calf diarrhea which are viral in origin but the diagnostic work necessary to isolate the viral agents has not been done. The control of viral enteritis in calves will still depend on ensuring that newborn calves are not infected immediately after birth - the same principle as for the control of diarrhea caused by E.coli. 10. The large number of different complicating lesions which was present in the calves in this trial emphasizes the need for more careful clinical examination and that postmortem examinations are necessary to determine those which are not detectable clinically.
nifuraldezone 44, 70%; 4) continuous feeding chloramphenicol - nifuraldezone 45, 84%; 5) starvation - no antibacterial therapy 48, 60% and 6) continuous feeding - no antibacterial therapy 34, 76%. There was no statistical difference in survival rates between these six groups. If only the calves that were hospitalized for more than 48 hours were considered, there was still no significant difference in survival rates.
Post-mortem examination revealed many different pathological diagnoses, many of which were not detected clinically and emphasized the importance of a detailed clinical examination. In addition, the need for strict sanitation and isolation facilities was noted when treating diarrrheal calves on an in-clinic basis. The problems associated with treatment of neonatal diarrhea in calves are also reviewed and discussed briefly.
11. Almost nothing is known about the efficacy of anticholinergics for the treatment of acute neonatal diarrhea of calves. There RESuME is a need to determine if abnormal gastrointestinal motility plays a role in the pathoCette etude consistait en une experience genesis of neonatal diarrhea in calves and clnique d'une duree de 60 jours, impliquant whether the use of anticholinergic drugs 254 veaux souffrant de diarrh6e neo-natale are indicated in treatment. Benzetimide has aigue et non sp6cifique. Tous ces veaux recurent been used for the treatment of diarrhea in la meme fluidotherapie afin de corriger leur newborn calves and adult cattle (31). deshydratation et de maintenir leur hydratation. 12. Intestinal protectants such as kaolin, pectin, On priva de lait la moitie de ces veaux, and bismuth salts are commonly incorpo- pendant 24 heures apres leur admission "a la rated in calf diarrhea preparations but there clinique et on leur donna ensuite du lait de is no conclusive clinical evidence to show vache. Les autres veaux s'aliment'erent des that they are useful. qu'ils purent et voulurent t6ter. On partagea plus tard chacun de ces deux groupes en trois autres groupes que l'on traita de facon difSUMMARY f6rente. Le premier re,ut de l'ampicilline par A clinical trial involving 254 calves affected la voie buccale et le second, du chloramph6niwith acute undifferentiated neonatal diarrhea col en injection intra-veineuse et du nifuralwas conducted over a period of 60 days. All dezone par la voie buccale; le troisieme ne calves were given the same type of fluid re,ut aucune antibioth6rapie. Le nombre de therapy to correct dehydration and maintain veaux composant chacun des six groupes et le hydration. pourcentage de ceux qui survecurent sont les One-half of the calves were starved from suivants: 1) je'une et ampicilline: 45 et -73%; milk for a period of 24 hours after admission 2) alimentation continuelle et ampicilline: 38 and then fed cows milk. The other half were et 63%; 3) je'une et traitement au chloramphefed milk as soon as they were able and willing nicol et au nifuraldezone: 44 et 70%; 4) alito suck. -Each group was further subdivided mentation continuelle et traitement au chloraminto three treatment groups. The first received ph6nicol et au nifuraldezone: 45 et 84%; 5) ampicillin orally, the second a combination je'une sans antibiotherapie: 48 et 60%; 6) aliof chloramphenicol intravenously and nifural- mentation continuelle sans antibiotherapie: 34 dezone orally, and the third received no anti- et 76%. On ne releva aucune diff6rence statismicrobial therapy. The number of calves in tique concernant le taux de survie au sein des each of the six groups and percentage survival six groupes. En ne considerant que les veaux rates were as follows: 1) starvation - ampicillin hospitalises pour plus de 48 heures, on ne 45, 73%; 2) continuous feeding - ampicillin decela pas non plus de difference relative au 38, 63%; 3) starvation - chloramphenicol - taux de survie. 225
CANADIAN VETERINARY JOURNAL
La necropsie revela une vari6t6 de conditions pathologiques dont plusieurs ne furent pas d6cel6es cliniquement; cette observation fait ressortir l'importance d'un examen cinique d6taille. On nota 6galement le besoin de conditions hygieniques strictes et de facilit6s d'isolement, lorsqu'on traite dans une clinique des veaux souffrant de diarrhee neo-natale. Les auteurs passent en revue et commentent brievement les problemes inh6rents au traitement de la diarrhee neo-natale des veaux. ACKNOWLEDGMENTS The authors thank Dr. Dan Mascaluk for his work in compiling and correlating the data from the individual records and Mr. E. B. Edwards for his assistance with the statistical analysis. The long hours worked by the veterinary technician is gratefully acknowledged. Thanks are also due to Mrs. Donna Knights who tped the manuscript. REFERENCES
11. GAY, C. C. Escherichia coli and neonatal disease of calves. Bact. Rev. 29: 75-101.
1965. 12. HARTMAN, D. A., R. W. EVERETT, S. T. SLACK and R. G. WARNER. Calf mortality. J. Dairy Sci. 57: 576-578. 1974. 13. HURVELL, B. and H. FEY. Comparative studies on the gamma globulin level in sera of market calves in relation to their health. Acta. vet. scand. 11: 341-360. 1970. 14. HYMAN, C. J., J. REITER, J. RODNAN and A. DRASH. Parenteral and oral alimentation in
the treatment of the non-specific protracted diarrheal syndrome of infancy. J. Pediatrics 78: 17-29. 1971. 15. KRUSE, V. Yield of colostrum and immunoglobulin in cattle at the first milling after parturition. Anim. Prod. 12: 619-626. 1970.
16. LAMBERT, G. and F. L. FERNELIUS. Bovine
viral diarrhea virus and Escherichia coli in neonatal calf enteritis. Can. J. comp. Med. 32: 440-446. 1968. 17. LAROUCHE, Y. and W. D. BLACK. A survey of calves treated for calf diarrhea at the Ontario Veterinary College 1966-1971. Can. vet. J. 14: 307-310. 1973. 18. MATTSON, D. E. Naturally occurring infection of calves with a bovine adenovirus. Am. J. vet. Res. 34: 623-629. 1974. 19. MCLEAN, D. M. and L. F. BAILEY The effectiveness of three treatments for scouring in calves. Aust. vet. J. 48: 336-338. 1972.
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32. TENNANT, B., D. HARROLD and M. R REINA-
BOOK REVIEW Advances in Cardiology - Comparative Pathology of the Heart. Edited by F. Homburger and I. Lucas. Published by S. Karger AG, Basel, Switzerland. 1974. 379 pages. Price $95.00. This book contains the papers presented at a symposium on Comparative Patology of the Heart in Boston, September 1973. This book contains 379 pages and at the price of $95.00 U.S. dollars, the prospective purchaser will want information and new knowledge not available from other sources. One cannot say that the book does not cover what its title proposes, Comparative Pathology of the Heart. In fact, the book covers a wide variety of subjects relating to the heart. However, the individual interested in specifics or only one area, will find little information or knowledge, that is not already available. In the introductory chapter, an after dinner speech is included entitled: The Patient's Insight - Its Role in the Evolution of Cardiology by S. J. Reiser of Boston. This is a good historical review of a general medical practitioner in England, Sir James Mackenzie. Interesting, but no contribution to new knowledge which is the reason for books like this. The next article by Robert W. Wissler of the University of Chicago entitled: Atherosclerosis - Its Pathogenesis in Perspective, is an excellent review of all of the concepts believed to be involved in the pathogenesis of atherosclerosis. The placement of this excellent article in this section rather than in section III on Atheromatosis, is questionable. There are numerous good papers presented in this book, unfortunately some of them are much too brief. For example a paper by Had-
low from the Rocky Mountain Laboratories in Hamilton, Montana entitled: Myopathies of Animals - A Brief View, is just that. Hardly a help to anyone seeking new knowledge. A veterinarian who might refer to this book in a search for knowledge concerning such things as spontaneous cardiovascular lesions in dogs and cats, cardiomyopathies in animals or the pathological and genetic studies of congenital heart disease in the dog, would not find any of the articles rewarding. The gross lesions, the functional pathology and the clinical signs, information that the veterinarian would be seeking are not well defined in any paper in this book. Additionally, most of the material has been published in journals comprising the veterinary literature. Again the error in the book is the very broad area that the authors are attempting to cover. The most unusual presentation which the author makes in the introductory remarks should be sufficient warning to the reader. Dr. Homburger mentions that the concept of the symposium was first rejected by the American College of Cardiology in 1971 and the National Foundation in 1972. As well that year, the Nuffield Foundation, the World Health Organization and the Wellcome Trust also rejected this symposium. The symposium application submitted to the Na-
tional Institutes of Health in 1972 was approved but not funded for six months. Additionally, some 18 major drug houses in chemical manufacturers turned down the requests for support. We must congratulate Dr. Homburger and his colleagues for their persistence, however as a contribution to the literature, such persistence is not rewarding. H. C. Rowsell.
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