Farm animal problem solving (Proceedings)

The majority of food animal veterinarians do their best to make the most appropriate decisions for their clients' livestock. But there are times when we simply don't know what the best decision is. Likewise, there are times when a "new" procedure or "new" product is suggested by the client or one of our colleagues that we are unaware of or have not tried. Problem solving requires the use of multiple sources to educate oneself about the particular problem. Ultimately, we would like to have scientific studies that document the solution. When scientific studies have not been done or have not solved the current dilemma, other resources should be investigated. These resources include: veterinary textbooks, medical textbooks, known experts in the field and known experts within our immediate work environment, on-line veterinary resources such as VIN (Veterinary Information Network), Cornell Consultant (good for differentials of diseases but also good because it lists references), list-serves such as AABP and AASRP (American Association of Small Ruminant Practitioners) can be especially helpful. The world-wide web has put information at our fingertips and various documents (extension publications and association publications) and information is readily available. Probably the least reliable resources are personal testimonials regarding methods or products, but sometimes this is all we get. No resource is infallible. Scientific studies can be misleading. Veterinary textbooks can and are wrong at times. What follows are real "problems" or issues that arose via treating/managing individual farm animal cases, via on-farm recommendations or calls from clients or other veterinarians.

Question 1. Is Mastoblast® H.P. efficacious for mastitis treatment or lowering SCC?

Short answer: Other than testimonials, no evidence of the product's efficaciousness could be found. No scientific studies published in peer-reviewed literature and no published studies that showed evidence for the product being effective in treating mastitis or lowering SCC could be found.

To answer this question:

1. Google (or your preferred search engine) to find out about the product. I find out that it is a homeopathic formula for the treatment of mastitis in cows. It contains bryonia alba, carbo vegetabilis, Echinacea, laccaninum, lachesis, phytolacca decandra, ruta graveolens, silicea, sulphur, alcohol and distilled water. This of course leads to a whole bunch of organic items that I don't know anything about. The product is to be administered orally (or sprayed on the nose) @ 2 ml per head morning and evening for 10 days (although the directions vary somewhat depending on the site).....so cows are to be treated for 10 days, hmmm. Many clinical mastitis cases are clinically cured by 10 days with or without treatment (Roberson et al., 2004). Another website lists under warning: "for external use only". So being open-minded try to find scientific data.

2. Try Pubmed for scientific studies (others to try are NLM Gateway, ISI web of knowledge). No studies of Mastoblast come up.

3. Go back to Google and type in Mastoblast study: I can find testimonials easily. I can find literature from the company that mentions all the clinical trials and studies that have been performed. Although obtaining these articles was more trouble than I would expect most people to go through, our librarian was able to get a couple of proceedings papers (there were no published clinical trials or studies). One only says that "The incidence of mastitis cases have been reduced by using Arnica both orally and topically for bovine teat injuries" (Sheaffer, 1996a). Nothing else...no references or data. The other proceedings article contained an anecdotal account of how Mastoblast reduced the SCC in dairy herds (Sheaffer, 1996b). I found a patent document that actually included a 24-cow subclinical mastitis study on Mastoblast that was conducted at the University of Connecticut (SureChem, 2009). No actual data was presented. Results showed a significant effect for IgG1 only, yet the conclusion was that the actual incidence of mastitis in animals not receiving the homeopathic medication was much higher than those who received the homeopathic medication. This was a 60 day study and there were only 24 cows tota…. so I don't know what "much higher" really means.

4. Called the company to see where I could get their clinical trials. The company veterinarian was not in. I'm still waiting to be called back.

Question 2. Is frequent milk-out (FMO) an effective treatment for cases of clinical mastitis?

Short answer: No, there is little to no evidence that FMO is an effective treatment for mastitis. It might be just as ineffective as some other treatments though.

Discussion: Most of the major food animal veterinary textbooks published prior to the year 2000 in the US encourage FMO. The 2nd edition of Smith's Large Animal Internal Medicine states "The flushing effect of milkings is a notable mechanism for shortening the clinical course of coliform mastitis", "Repeated milkings throughout acute coliform mastitis events can be useful in removing inflammatory mediators that may be harmful if allowed to persist for extended periods", and "Frequent milkings (i.e., q2h) to eliminate toxins, inflammatory mediators, and bacteria are one of the most important considerations in the treatment of coliform mastitis" (Cullor and Tyler, 1996). Although there is little doubt that FMO will help eliminate some inflammatory mediators, toxins, and bacteria, no references were given that could provide evidence as to whether this procedure actually results in a better outcome for the cow with clinical mastitis. In "Diseases of Dairy Cattle", FMO of the affected quarter is considered the most valuable nursing procedure for cows with acute clinical mastitis (Rebhun, 1995). Frequent milk-out at 4-6 hour intervals was also recommended for cows with chronic mastitis. No references were given for either of these statements. Another popular food animal text states "Even though many dairy workers abhor the chore, nursing care, particularly frequent stripping of affected quarters, is a first step to recovery" (Timoney and Erickson, 1999). No reference was given for the aforementioned statement which was made in reference to streptococcal mastitis. Frequent milk-out may actually be detrimental for clinical cases of streptococcal mastitis in that the clinical phase of the disease may last longer (Roberson et al., 2004). Another section of the Howard text states "Oxytocin alone or in conjunction with other therapies has been shown to have positive clinical effects by improving udder drainage during infection, decreasing the buildup of inflammatory mediators, and helping flush out the causative organism" (Archbald LF. 1999). This statement was referenced. The reference states "Oxytocin and frequent milking at 1-2 hour intervals are recommended to remove toxic material from the udder and to maintain milk duct patency" (Ziv, 1980). The Ziv article was not a specific study but the statement provided by Ziv was referenced. The aforementioned reference was quoted verbatim from a report of the panel of the colloquium on bovine mastitis (1977). The statement by the panel was not referenced. Thus, FMO had become a very important method of treating clinical mastitis based on a recommendation without any quoted scientific evidence. To date, I have been unable to find a single scientific study in which the study results support FMO as an effective therapy for clinical mastitis. Despite the lack of scientific evidence as to the efficacy of FMO, it remains a commonly recommended method for managing cases of clinical mastitis (Faull et al., 1997; Neubauer, 2001). Frequent milk-out had become firmly established because on the surface it made sense. In theory, FMO of the affected quarter(s) helps remove the infectious agent and toxic products of the infection but complete milk-out is not possible and the process removes good inflammatory mediators (neutrophils, complement, antibodies etc.). Recently, the new editions of some food animal textbooks note that FMO may not be efficacious or don't mention it at all (Morin, 2009; Wagner and Erskine, 2009). Yet, FMO is still a recommendation for treatment of coliform mastitis in a couple of recent food animal textbooks (Barrington, 2008; Radostits et al., 2007). No references or direct evidence of efficacy was supplied.

Question 3. Is ryegrass staggers an important disease for alpacas in the United States? A client wanted to know if problems would occur from putting alpacas on ryegrass in Tennessee.

Short answer: No published scientific studies were found that actually answered this question. Experiences reported from Ohio, Oregon and New Zealand (where much more ryegrass is utilized) via the American Association of Small Ruminant Practitioners listserve (AASRP-l) suggests that the disease does occur but tends to be intermittent and sporadic with cases varying considerably from year to year (may go years without a case). So...important? Maybe. Maybe not. Best solution is to not graze alpacas on ryegrass.

Discussion: A search of Pubmed revealed 4 case reports in countries other than the US. This then brought into question whether ryegrass staggers was ever a problem in the US. The question was put out (AASRP-l). AASRP respondents reported cases in Ohio where quite a bit was seen and in Oregon where it was reported to be a very occasional problem. Perennial rye grass staggers is a neurological condition that is caused by the ingestion of an endophyte fungus (Neotyphodium lolii) located in the leaf sheaths, flower stalks and seed of perennial ryegrass. The neurotoxins responsible are lolitrems, primarily lolitrem B (Aldrich-Markham et al., 2007). Many domestic species may be affected. The main clinical signs are tremors of the head and neck that can progress to complete recumbency. If the affected stock are removed from the endophyte, the majority recover. Clinical improvement should be evident within 1-2 days of removal from the source. Improvement after removal from the source and confirmation of lolitrem in the ryegrass should be sufficient evident for a diagnosis (Dr. Morrie Craig @ Oregon State developed an assay for lolitrem B). The client had already seeded the pasture with ryegrass prior to the phone call. Because the disease does appear to be relatively rare, the pasture could be used and the alpacas watched closely for any evidence of neurologic dysfunction at which point they should be removed. In addition, the ryegrass ration could be diluted out with other feedstuffs making ingestion of a toxic dose less likely. Alternatively, the pasture could be grazed during the spring and summer because cases have been reported more frequently in the fall (although Ohio reports cases in the spring). It was also noted that the individual toxic dose varies and may affect only 1 alpaca out of 100.

Question 4. Does injectable flunixin meglumine reach therapeutic levels when given orally in cattle?

Short answer: Yes.

Discussion: The veterinary information network (VIN) was used to answer this question. Dr. Lisle George, a long time VIN consultant and respected UC Davis clinician, noted that cattle get excellent absorption and achieve therapeutic blood concentrations when the drug is administered orally at a dose of 2.0 mg/kg body weight. There is also scientific documentation. A 1996 study concluded that flunixin granules may be an alternative to parenteral use of flunixin in bovine practice (Odensvik and Magnusson, 1996). In the aforementioned study, flunixin administered orally prior to experimentally-induced endotoxemia exerted an effect equal to that of IV administration. It should be noted that flunixin meglumine is only label for IV use in cattle. Oral administration of flunixin meglumine was also found to be equivalent to IV or IM administration in dairy goats (Königsson et al., 2003).

Question 5: Is there scientific evidence of the efficacy of domperidone in improving postpartum milk production in camelids?

Short answer: No scientific evidence could be found.

Discussion: Neither PubMed, NLM Gateway, nor ISI Web of Knowledge listed any studies conducted on the effect of domperidone on camelids (llama or alpaca). A search on Google did not identify any studies either. Domperidone has been recommended and is used to help bring camelids into milk. Domperidone does help with mares experiencing fescue toxicosis but studies of its efficacy in other species are limited. However one study of beef heifers showed that domperidone was efficacious in alleviating the effects of fescue toxicosis (improved weight gains and decreased rectal temperature over non-treated controls) but milk production was not studied (Jones et al., 2008). So should it be used in camelids? It is something to try and reports of serious side-effects are rare but it is fairly expensive.

Question 6: What is the pathogenesis of nervous coccidiosis?

Short answer: Still not known. No published studies were found that confirmed a definitive pathogenesis.

Discussion: Various hypotheses have been proposed for the pathogenesis of the neurological signs associated with bovine enteric coccidiosis. One theory proposed that this problem is not due to coccidia per se but to a combination of stressors, including the damage by the coccidia to the GI tract, which results in tissue Mg and serum Ca depletion and the production of the neurological syndrome observed (Fanelli, 1983). To support this theory, advocates point out that treatment of affected animals with IV and SQ Ca, Mg and dextrose solution, balanced electrolyte solutions, oral MgO and sulfamethazine has been relatively successful when given early, while the animal is still able to stand and appears normal until disturbed. In the latter stages, treatment has been disappointing. The most recent studies of the pathogenesis were from Isler and coworkers (1987a) who disputed the role of Na, K, Ca, P, Mg, vitamin A, thiaminase, severity of coccidial infection and GI flora alterations. Isler and others (1987b) discovered a neurotoxin in the serum of calves with nervous coccidiosis that was not found in the serum of normal calves or calves with just enteric coccidiosis. No studies of this neurotoxin have been published since 1987.

Question 7: Why do some pigs with Salmonella infections develop rectal strictures?

Short answer: Salmonella can cause an ulcerative proctitis that heals by fibrosis and due to a limited blood flow to the rectum results in strictures.

Discussion: When infection was experimentally-induced with Salmonella typhimurium a severe enterocolitis with ulcerative proctitis resulted (Wilcock and Olander, 1977). Healed lesions were annular cicatricial ulcers in the rectal area. The same type lesion was reproduced by injecting chlorpromazine into the cranial hemorrhoidal artery of pigs. When injected with dye, if the pigs were treated with chlorpromazine or had naturally occurring strictures, it would be stopped at the cranial margin of the transverse mucosal lesion whereas the dye perfused the entire rectum of normal pigs. The arterial blood supply to the rectum in pigs is normally precarious which renders the rectum unusually susceptible to ischemic injury and decreases in reparative capacity.

References

Aldrich-Markham S, Pirelli G, Craig AM. Endophyte toxins in grass seed fields and straw: Effects on livestock. Oregon State University Extension Service 2007, EM 8598-E.

Archbald LF. Bovine mastitis. Howard & Smith Current Veterinary Medicine 4: Food Animal Practice, 4th edition, W.B. Saunders Company, Philadelphia, PA, 1999, pg 563-568.

Barrington G. 2008. Mastitis: Coliform. Blackwell's Five-minute Veterinary Consultant: Ruminant, 1st edition, Wiley-Blackwell, Ames, IA, pg 524-525.

Cullor J, Tyler J. Mammary gland health and disorders. Bradford P. Smith Large Animal Internal Medicine, 2nd edition, Mosby, Philadelphia, PA, 1996, pg 1177-1193.

Faull WB, JW Hughes, et al. 6th Edition A Mastitis Handbook for the Dairy Practitioner, Liverpool University Press 1997.

Fanelli HH. Observations on nervous coccidiosis in calves. Bov Pract 1983, 18:50-53.

Isler CM, Bellamy JEC, Wobeser GA. Pathogenesis of neurological signs associated with bovine enteric coccidiosis - A prospective study and review. Canadian J Vet Res 1987a, 51:261-270.

Isler CM, Bellamy JEC, Wobeser GA. Labile neurotoxin in serum of calves with nervous coccidiosis. Canadian J Vet Res 1987b, 51:253-260.

Jones KL, Schulze JL, Strickland JR et al. Evaluation of domperidone dosages and delivery methods for the treatment of fescue toxicosis in beef heifers. The Professional Anim Scientist 2008, 24:342-348.

Königsson K, Törneke K, Engeland IV et al. Pharmacokinetics and pharmacodynamic effects of flunixin after intravenous, intramuscular and oral administration to dairy goats. Acta Vet Scand 2003, 44:153-159.

Morin D. Mammary gland health and disorders. Bradford P. Smith Large Animal Internal Medicine, 4nd edition, Mosby, Philadelphia, PA, 2009, pg 1112-1143.

Neubauer G. 2001. Mastitis treatment strategies: "Old myths and new facts". In Proc Milk Quality Conference, April 9-10, Madison, WI. pp 55-59.

Odensvik K, Magnusson U. Effect of oral administration of flunixin meglumine on the inflammatory response to endotoxin in heifers. Am J Vet Res 1996, 57:201-204.

Radostits OM, Gay CC, Hinchcliff KW, Constable PD. Diseases of the mammary gland. 10th Edition Veterinary Medicine, Saunders Ltd, Philadelphia, 2007 pp 673-762.

Rebhun WC. 1995. Diseases of the teats and udder. Diseases of Dairy Cattle, Williams and Wilkins, Media, PA pp 253-308.

Report of the panel of the colloquium on bovine mastitis. 1977. J Am Vet Med Assoc 170(10):1119-1123.

Roberson JR, Warnick L, Moore G. Mild to moderate clinical mastitis: efficacy of intramammary amoxicillin, frequent milk-out, intramammary amoxicillin and frequent milk-out compared to no treatment. J Dairy Sci 2004, 87:583-592.

Sheaffer CE. Introduction to veterinary homeopathy. Proceedings Am Vet Holistic Vet Med Assoc Annual Conf 1996a, pg. 9-11.

Sheaffer CE. The use of homeopathic medicine in herds of livestock. Proceedings Am Vet Holistic Vet Med Assoc Annual Conf 1996b, pg. 112-114.

SureChem. 2009. http://www.surechem.org/index.php?Action=document&docId=1307715&db=WOPCT&tab=desc&lang=&db_query=0%3A%3A0%3A%3A0%3A&markupType=all

Timoney J, Erickson ED. Streptococcal disease. Howard & Smith Current Veterinary Medicine 4: Food Animal Practice, 4th edition, W.B. Saunders Company, Philadelphia, PA, 1999, pg 390-391.

Wagner SA, Erskine RJ. 2009. Decision making in mastitis therapy. Current Veterinary Medicine: Food Animal Practice, 5th edition, W.B. Saunders Company, Philadelphia, PA, 2009, pg 502-509.

Wilcock P, Olander HJ. The pathogenesis of porcine rectal stricture, II. Experimental salmonellosis and ischemic proctitis. Vet Pathol 1977, 14:43-55.

Ziv G. Drug selection and use in mastitis: Systemic vs local therapy. J Am Vet Med Assoc 1980, 176:1109-1115.