Monensin toxicosis in a dairy herd

Abstract

An acute onset of illness was reported in a lactating dairy herd in Canada in which monensin had been incorporated in error in its ration at almost 10 times the prescribed level. All of the lactating cows became lethargic, were inappetant, developed diarrhea, and had decreased milk production from 28 kg/cow/day, the day before exposure, to 23 kg/cow/day, 3 d later. Within 9 d, all animals recovered from the incident and milk production returned to previous levels.

The owner of a 64-head Holstein-Friesian dairy herd reported an acute onset of illness. The lactating cows were on pasture, supplemented with silage, hay, and commercially produced pelleted feed that contained 50 ppm (50 mg/kg feed) of monensin (Rumensin; Elanco Animal Health, Guelph, Ontario) in the tie-stall. Each cow was fed 6 kg/d of the pelleted feed divided in 2 rations, regardless of the milk production, intended to deliver approximately 300 mg monensin/animal/d (0.5 mg/kg body weight [BW]/d).

On August 1 (day-1), a new batch of pelleted feed was delivered to the farm and the cows were fed the new concentrate in the morning of the next day (day 0). During the evening feeding on day 0, the farmers noticed that the cows consumed the pellets more slowly than usual. On day 1, all of the lactating cows became lethargic, were inappetant, and had loose to watery feces, while some of them walked with a stiff-legged or “funny” gait, as described by the farmers. The farmers reported that some cows were reluctant to enter the barn. The close association between the onset of clinical signs and the introduction of the new feed prompted the farmers to contact the feed company. The feed manufacturer confirmed that a mixing error had occurred with the batch of pellets, resulting in the addition of 500 ppm of monensin instead of 50 ppm. That afternoon, a monensin-free pelleted feed was offered to the lactating cows. No changes in roughage ration were made. By late afternoon, although many cows were reported to prefer staying in sternal recumbency, all of them were able to rise and go to pasture.

Case description

On the afternoon of day 2, the Farm Service of the Atlantic Veterinary College (AVC), University of Prince Edward Island was called to the farm for a herd evaluation. On arrival, most cows were standing and eating hay. Approximately 50% of the cows appeared dull. Physical examination of the 8 dullest cows did not detect significant abnormalities other than the presence of profuse diarrhea, which was also evident in all the other lactating herdmates. According to the farmer, some of the cows had started to pass more normal feces that day. Some animals were salivating and only a few were ruminating. No treatment was administered.

Blood samples were taken from all of the lactating cows. The samples of the 6 cows that seemed to be most dull were submitted for hematologic analysis and determination of liver, muscle, and kidney enzymes; serum proteins; selenium; magnesium; calcium; phosphorus; and other electrolytes. Cardiac troponin I (cTnI) levels were also determined with a microparticle enzyme immunoassay (Abbott AXSYM system, Troponin-I; Abbot Laboratories Diagnostics Division, Abbott Park, Illinois, USA). The hematologic and biochemical results results were all within reference ranges. Concentrations of cTnI were all < 0.1 ng/mL. A sample of the suspect pelleted feed was collected and submitted (Animal Health Laboratory, University of Guelph, Guelph, Ontario) for determination of the monensin concentration; it was found to contain 479 ppm of the ionophore monensin, as determined by high performance liquid chromatography, using post-column derivatization.

On day 3, the cows had improved clinically. However, some animals were still eating less than expected, and the milk production had decreased. At the time of the incident, the 64 lactating cows were, on average, 194 d in milk (DIM). Milk production changes are documented in Figure 1. Bulk tank milk was collected every 2 d. Milk collection occurred on the morning of day 0. The daily production for the prior 2 d was 28.0 kg/cow/d, which was relatively stable over the previous 2-week period. Production in the first 2-day period after exposure decreased to 24.6 kg/cow/d and declined further to 22.8 kg/cow/d on the 2nd pickup (days 3 and 4 post-exposure). This value was the lowest recorded during the year. Bulk tank milk fat and protein levels were evaluated weekly. There were no apparent changes in the percent fat or percent protein during or immediately after the exposure period (data not shown).

Figure 1.

Kilograms of milk shipped per cow per day based on every other day bulk milk receipts from a Prince Edward Island dairy herd experiencing an acute mononsin toxicosis.

On day 4, 5 cows were dried off, as previously planned (~ 60 d before the expected calving date). Between day -1 and day 10, no cows calved; no changes occurred in feeds, other than the changes in pellet; and no meaningful environmental changes took place. Milk production rapidly returned to pre-exposure levels, and on day 10, with 59 cows milking an average of 197 DIM, milk production was on average 28.8 kg milk/cow/d. These values, together with the return of the cows to their expected food intake, suggested a complete recovery of the lactating herd from the intoxication.

Discussion

Monensin is a monovalent carboxylic polyether ionophore antibiotic produced by the fungus Streptomyces cinnamonensis (1,2). Monensin is safe and effective in target species, when used at recommended dosages (3,4). Ionophores have been used widely in the beef and poultry industry for improved feed efficiency and control of coccidiosis (1). However, intoxication may come after mixing errors that result in their inclusion in the diets of nontarget species or in excessive concentrations in the diets of target species (1,5–7). The toxicity of monensin for cattle and other species is well documented and is known to be dose dependent (4,5). Due to their interference with membrane cation transport, polyether antibiotics can cause cell death by perturbing the intracellular ionic homeostasis and destabilizing biological membranes (6). Monensin toxicity is particularly evident in cardiac and skeletal muscle cells (8). There is no antidote or specific treatment for toxicoses induced by ionophores (6). Consistent lesions associated with monensin toxicosis in cattle are cardiac and skeletal muscle degeneration and necrosis, with secondary lesions from acute cardiac failure or chronic cardiovascular insufficiency (8).

In Canada, the label warning prohibiting the use of monensin premix in lactating dairy cattle was removed in June 1996; since then, the use of monensin as an aid in the prevention of subclinical ketosis has become a common practice in lactating dairy cattle (3).

To our knowledge, this is the first report of monensin toxicosis in monensin-supplemented lactating dairy cattle and in lactating dairy cows in North America. In 1981, Wentink and Vente (11) reported a case of monensin intoxication in dairy cattle where monensin had accidentally been added to the herd’s ration and there had been no previous exposure to lesser concentrations.

In cattle, the clinical signs of acute monensin toxicity are anorexia (24 to 36 h post ingestion), diarrhea, dullness, weakness, ataxia, dyspnea, prostration, and death within 3 to 14 d of the ingestion of the incriminated feed (1,2,6–8). The clinical signs seen in the outbreak described here started within 24 h of initial exposure to the monensin containing feed. Diarrhea, lethargy, and reduced feed intake of all the lactating cows were the most noticeable signs, which alerted the farmers that something was wrong. In this case, the rapid association of the clinical signs that the herd showed with the introduction of the new concentrate, followed by the prompt removal of the concentrate, may have allowed the farmer to avoid more severe consequences and losses.

The monensin LD50 for cattle was estimated to range from 21.9 to 80 mg/kg BW, LD₁₀ 11.2 mg/kg BW, and the LD1 5.5 mg/kg BW (1,4,5). According to this, LD₁ can be estimated as being 3300 mg for a 600 kg bovine animal (4). It is apparent that, in cattle, a large safety range exists between the daily dose usually given and the single dose necessary to cause death (8). In this case, the average 600-kg dairy cow ingesting 3 kg of concentrate for a total of 3 feedings (24-h period) would have received a dose of 4.8 mg monensin/kg BW/d (2874 mg/head/d) and a total dose of 7.2 mg monensin/kg BW (4300 mg/head) in 36 h. This dose could have been sufficient to produce some deaths and was enough to produce evident clinical signs within 24 h of exposure and to decrease milk production. One possible explanation for this herd not presenting more severe symptoms is that it had been supplemented with monensin daily, prior to the toxic exposure and, therefore, that the rumen microflora had already adapted to the ionophore. Van Vleet et al (8) found an apparent lack of enhancement of toxicosis in calves that were given 2 doses of 40 mg of monensin/kg BW at a 7-day interval, rather than 1 dose, indicating that the calves may have developed tolerance. Potter et al (4) supported this observation and concluded that the greatest risk of intoxication occurs when cattle receive a feed containing monensin for the first time.

Clinicopathologic changes induced by monensin are consistent with dehydration, electrolyte disturbances, and muscle damage. However, these changes have been shown to be dose dependent and nonspecific, with abnormalities reflecting generalized organ failure (2). Increased aspartate amino-transferase, creatine kinase, serum protein, blood urea nitrogen, creatinine, total bilirubin, urine protein, and decreased serum potassium, serum sodium, serum calcium and leukocytosis have been reported with monensin toxicosis (5). Cardiac troponin I has proven to be a highly specific and sensitive marker for myocardial cellular damage in many mammalian species (10). Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and the elevation persists for up to 8 d (10). Normal ranges for cTnI plasma concentrations have been established in horses, dogs, and cats, but not in cattle. In this case, the cTnI concentrations in the sampled cows were < 0.1 ng/mL, compared with < 0.1 and 0.9 ng/mL in 2 normal cows from the AVC herd used as controls. Because cTnI appears to be highly conserved among mammalian species and because the normal plasma cTnI concentration in peripheral blood of dogs, cats, and horses is similar to that of humans (0.0 to 0.4 ng/mL) (9,10), it is reasonable to assume that the human assay used for this report detected a human cTnI-like compound that was bovine cTnI and that the values obtained could be considered as within normal limits. The near absence of clinicopathologic manifestations may have reflected the relatively low dosage of monensin received by the cows, the short duration of exposure, and the post exposure sampling interval.

The most important clinical signs in this case were the profuse diarrhea, dullness, and the reduced feed intake. At the time of our visit, the farmer and the feed company had already suspected that a monensin toxicosis had occurred. However, a blood sample was collected from all the lactating cows in case monensin toxicosis could not be confirmed and further diagnostic testing was required. The most important differential diagnoses for the profuse diarrhea would be bovine viral diarrhea; winter dysentery; salmonellosis (Dublin and Typhimurium); malignant catarrhal fever; ruminal acidosis; parasitic infections, such as ostertagiosis; and Fusarium intoxication. Because the signs occurred in all lactating animals at the same time, and the young stock and dry cows were not affected, a point source affecting only the lactating cows was likely. This made infectious causes, such as bovine viral diarrhea, malignant catarrhal fever, and parasitic infections, unlikely. Additionally, the time of the year did not suggest winter dysentery as a cause. No attempts were made to rule out these differential diagnoses, because the monensin toxicosis had already been confirmed.

The herd’s milk production required approximately 6 d to return to previous levels, providing evidence that in dairy cattle the ingestion of toxic levels of monensin, even over a short period of time, can have economic consequences.

Cattle that recover from acute ionophore toxicosis may also suffer unexpected acute cardiac failure, especially if exercised or stressed (2), and deaths can occur for extended periods after exposure has stopped (5). In the 6 mo after this incident, no deaths occurred in this herd. CVJ