Ionophore Use and Toxicosis in Cattle.

Ionophores are a commonly used feed additive for animals and when used properly are safe. When feed mis-mixing occurs and an elevated dose of ionophore is given, a toxicosis can develop. Myocardial and skeletal muscles are the targets of a toxicosis. In many species there is a delay from the time of ingestion of a toxic dose in feed to when clinical signs occur. This makes it difficult to collect the feed in question that was at an elevated concentration. Cardiac troponins in serum can be used to make a diagnosis of an ionophore toxicosis.

Acute and long-term cardiomyopathy and delayed neurotoxicity after accidental lasalocid poisoning in horses.

BACKGROUND: Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity. OBJECTIVES: To describe accidental lasalocid poisoning on a farm in Belgium. ANIMALS: Eighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27. METHODS: The most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin I (cTnI) at admission and during follow-up. On day 57-70, cardiac examination, cTnI determination or both were undertaken on 72 remaining horses. RESULTS: Short-term effects of lasalocid intoxication included inappetance, lethargy, sweating, and muscular weakness. All 7 horses admitted to the clinic demonstrated signs of myocardial degeneration such as increased cTnI, dysrhythmia and reduced myocardial contractility. Four horses developed ataxia on day 40-50. Five horses died or were euthanized on day 30-370, 2 horses recovered fully and returned to previous athletic use. None of the 72 remaining horses exhibited clinical signs between day 57-70, but 34 had dysrhythmia and 13 had increased cTnI concentrations. After a period of rest, all horses returned to their previous work. Lasalocid was detected in hepatic tissue of 2 necropsied horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Lasalocid intoxication induced myocardial and neurological damage. Although uncommon, this should be included as differential diagnosis for unexplained inappetance, signs of depression, cardiomyopathy, and ataxia in horses.

Long-term assessment of horses and ponies post exposure to monensin sodium in commercial feed.

REASONS FOR PERFORMING STUDY: Acute monensin intoxication in equids is well described; however, the long-term effects of sublethal intoxication and ability to return to previous use are less well understood. Long-term observations may allow improved estimation of prognosis in cases of sublethal intoxication. OBJECTIVES: To assess horses and ponies exposed to sublethal amounts of monensin for evidence of chronic sequelae and ability to return to prior/intended use. METHODS: Twenty-nine horses and 8 ponies were assessed utilising serum biochemistry, treadmill exercise stress testing, electrocardiography, and pre- and post exercise echocardiography > or = 6 weeks after ingestion of monensin-contaminated feed. Animals with evidence of monensin-induced cardiomyopathy were re-examined after a period of rest of > or = 11 months. Follow-up information was obtained by owner telephone interview > or = 52 months after exposure. RESULTS: During resting echocardiography, 11 animals had reduced/low-normal left ventricular fractional shortening (FS); an increase in FS in 8 of these animals was measured > or = 11 months later. Six animals had reduced or low-normal FS during post exercise echocardiography. Two horses had ventricular premature depolarisations during exercise. Follow-up information was available for 35 animals: 21 returned to athletic/reproductive use, 13 were retired immediately and one died. Mean FS increased significantly (P < 0.001) between initial and second examination in 15 animals that underwent resting echocardiography on 2 occasions. CONCLUSIONS: Some equids exposed to sublethal doses of monensin may not develop permanent myocardial disease and a return to athletic/reproductive use is possible. POTENTIAL RELEVANCE: Exercise stress testing, echocardiography and electrocardiography may be useful for detection and monitoring of cardiac dysfunction in equids exposed to monensin and determining whether a return to athletic/reproductive use is possible.

Monensin toxicosis in water buffaloes (Bubalus bubalis).

The consumption of monensin-containing feed resulted in deaths of water buffaloes from a feedlot in which cattle and buffaloes were kept together. The monensin formulation was recommended only for use in cattle. Anorexia, muscular weakness, dyspnea, and recumbency were the major clinical findings. The most significant gross lesions were focal pale areas in semitendinosus and semimembranosus muscles, in which segmental necrosis of myofibers was seen microscopically. To compare susceptibilities of species to monensin, 3 bovine calves and 3 buffalo calves were orally dosed. At 5, 7.5, and 10 mg/kg of monensin, only the buffaloes became ill and died. Clinical signs initiated 18-20 h postdosing and were comparable to those from field cases. Gross changes consisted of ascites, hydrothorax, hydropericardium, hepatomegaly, and focal pale areas in the myocardium and to a lesser degree in semitendinosus and semimembranosus muscles. Histopathological changes also resembled those from the field cases, but were especially pronounced in the myocardial cells. The hypothesis that buffaloes could have a lower tolerance to monensin than cattle has been supported by experimental cases.

An unaddressed issue of agricultural terrorism: a case study on feed security.

In the late winter of 2003, a number of livestock animals in the Midwest were poisoned due the accidental contamination of a popular commercial feed with a lethal additive. Although all the evidence indicates this incident had no malicious or terrorist intent, it is informative as a case study highlighting potential security implications with respect to a terrorist event directed at U.S. agriculture.

Rapid forensic selected reaction monitoring liquid chromatography/mass spectrometry determination of ionophore antibiotics found at toxic levels in animal feeds.

A rapid, accurate, and selective method was developed for the forensic determination of ionophore antibiotics in animal feeds. A simple extraction procedure and liquid chromatography/tandem mass spectrometry (LC/MS/MS) in the selected reaction monitoring (SRM) mode were used for rapid identification and confirmation of monensin and lasalocid in feed samples and for quantitation of monensin. Extracts from a homogenous portion of ground feeds were prepared using liquid-solid extraction and liquid-liquid extraction techniques. Feed extracts were further purified by a simple defatting and solvent wash step and then concentrated to dryness. Feed extract residues were reconstituted in 1 mL LC mobile phase and a 2 microL aliquot injected into the SRM LC/MS system. The latter system used a C18, 100 x 2.0 mm, LC column coupled to a PE-Sciex API 2000 tandem triple quadrupole mass spectrometer equipped with a TurbolonSpray LC/MS interface. Feed samples were extracted and analyzed for the determination of monensin and lasalocid within a couple of hours. Control feed samples fortified with monensin at concentrations from 50 ppb to 5 ppm provided a linear response and calibration curve across this range with a correlation coefficient of 0.996.

Accidental monensin toxicosis in horses in Mozambique.

Horses on several farms in Mozambique were inadvertently fed with a concentrate containing 69 ppm monensin. The horses developed acute signs of toxicity and several died. The animals were depressed, anorectic and paretic before death. Epistaxis was observed in 1 case. Petechial haemorrhages were present in the muscles, heart, lungs, gastrointestinal tract and spleen in 3 horses necropsied. No significant histopathological cardiac and skeletal muscle lesions were seen, except in 1 case, in which there was focal loss of myofibrils.

Toxic feed constituents in the horse.

Poisoning cases in horses associated with dietary exposures can encompass a wide variety of etiologies that can be caused by natural or man-made components. Feed mixing errors and ingestion of feed formulated for other species are the most common means by which poisonings from man-made materials occur. Ionophore feed additives and antibacterial agents are especially toxogenic to horses. Effects of ionophores in horses include clinical, clinicopathologic, and pathologic changes associated with cardiac, muscular, and neurologic tissues involvement. The acute effects of ionophores, however, can result in long-term cardiac dysfunction. Antibacterial effects are associated with changed microbial populations in the digestive tract that results in bacterial toxin liberation. These bacterial toxins damage the mucosa, and they result in systemic effects. For either type of feed-associated poisoning, it is critical that samples be analyzed for an accurate diagnosis.

Ionophore use and toxicosis in cattle.

Ionophores comprise a rapidly expanding class of antibiotics produced by filamentous branching bacteria of the order Actinomycetales. The use of ionophores as coccidiostats and growth promotants has resulted in the occurrence of toxicoses in target and nontarget species. Clinical and pathologic effects of ionophore poisoning are caused by bioactivity and damage to excitable tissues such as cardiac muscle, skeletal muscle, smooth muscle, and the nervous system. Ionophore toxicoses are often related to errors in feed mixing, so the practitioner should give primary importance to the removal of suspect feeds and testing to confirm excessive exposure.

Monensin poisoning in Brazilian horses.

Three outbreaks of monensin poisoning caused 12 deaths in 16 horses. The illnesses were associated with the ingestion of the same batch of a commercial ration labeled for feeder calves which contained 180 +/- 20 ppm sodium monensin. The morbidity rate was 100% and lethality was 60%, 75%, and 100%. Clinical signs were tachycardia and cardiac arrythmia, groaning, incoordination, sudoresis, recumbency, and paddling movements with the limbs before death. Two horses had dark discolored urine (myoglobinuria). Serum levels of creatine phosphokinase activity were increased. Main necropsy findings were in the skeletal muscles and myocardium.

Salinomycin-induced polyneuropathy in cats: morphologic and epidemiologic data.

In April 1996, an outbreak of toxic polyneuropathy in cats occurred in the Netherlands. All cats had been fed one of two brands of dry cat food from one manufacturer. Chemical analyses of these foods, stomach contents, and liver and kidney of affected cats revealed contamination with the ionophor salinomycin. Epidemiologic and clinical data were collected from 823 cats, or about 1% of the cats at risk. In 21 affected cats, postmortem examination was performed. The affected cats had acute onset of lameness and paralysis of the hindlimbs followed by the forelimbs. Clinical and pathologic examination indicated a distal polyneuropathy involving both the sensory and motor nerves.

Monensin toxicity in a flock of ostriches.

A total of 42 birds from a flock of 104 farmed ostriches showed signs of toxicity after the accidental inclusion of monensin in their concentrate ration. The initial clinical signs were muscle weakness and ataxia which progressed to recumbency, dyspnoea and death, despite intensive supportive therapy. The serum activity of the enzymes creatine kinase, aspartate aminotransferase and lactate dehydrogenase was high in the affected birds, indicating significant muscle pathology. Few gross lesions were identifiable postmortem, but widespread lesions of degenerative myopathy were present at the histopathological level. However, these degenerative changes were restricted to the skeletal muscle and there was no evidence of cardiomyopathy in any of the birds examined. The birds were fed a ration which contained 215 to 224 ppm monensin for 13 days. New clinical cases ceased to occur shortly after the withdrawal of the source of monensin, but all the individuals which showed clinical signs of toxicity died or were euthanased on humane grounds.

Acute maduramicin toxicity in calves.

A herd of 277 beef-breed calves in three age groups was mistakenly given the poultry coccidiostat maduramicin in a total mixed ration. It caused an acute toxicosis in which sudden death was the sole clinical finding in most cases. One group of 212 calves aged five to eight months suffered a mortality of 51 per cent in eight days and a total mortality of 56 per cent during the 40 days in which mortality was recorded. Mortality of only 3 per cent was recorded in two other groups of calves aged nine to 16 months in eight days and a total mortality of 11 per cent over the 40-day period.

A chronic cardiomyopathy in feedlot cattle attributed to toxic levels of salinomycin in the feed.

The clinical signs and pathology in an outbreak of toxicity in feedlot cattle attributed to the ingestion of toxic levels of the ionophore antibiotic salinomycin over an extended period of 11 weeks are described. Thirty-nine out of 380 cattle developed signs consistent with cardiac failure and 8 of these died. Clinical signs included dyspnoea, tachypnoea, tachycardia and exercise intolerance. Two cattle were necropsied and in one there were macroscopic lesions suggestive of congestive heart failure, namely pulmonary oedema, hydrothorax and hepatomegaly. Histopathology revealed a chronic cardiomyopathy characterised principally by extensive myocardial fibre atrophy with multifocal hypertrophy and interstitial and replacement fibrosis. Hepatic and pulmonary lesions were consistent with those of congestive cardiac failure. The myocardial lesions in this outbreak were similar to those encountered in cases of a chronic toxicity associated with the ingestion of litter derived from poultry rations containing ionophores (ionophore-associated poultry litter toxicity). Hence, the clinical and pathological findings in this outbreak indicate that in cattle, the prolonged ingestion of ionophores over several weeks may result in the development of chronic myocardial lesions comparable to those of IAPLT but significantly different from those encountered in the more traditional acute outbreaks of ionophore toxicity as described in the literature.

Cardiomyopathy of ruminants induced by the litter of poultry fed on rations containing the ionophore antibiotic, maduramicin. II. Macropathology and histopathology.

This report contains an account of the gross and histopathological lesions of 20 cattle and four sheep in 15 field outbreaks of poultry litter toxicity, one steer fed ad lib. and six sheep dosed with toxic poultry litter, and ten sheep fed experimental rations containing c 2,5 ppm and 5 ppm maduramicin. The principle macroscopic lesions in most cattle that died in field outbreaks were indicative of congestive heart failure. The lesions in sheep were similar, but generally milder. Cardiac dilatation was observed in both sheep and cattle. Microscopically, the cardiac lesions were more pronounced in cattle and comprised varying degrees of atrophy, hypertrophy, degeneration, necrosis of myocardial fibres, and interstitial fibrosis. Skeletal muscle lesions were usually more severe in sheep, particularly in the muscles of the hindquarters which appeared pale, oedematous and mottled. One of the sheep in the poultry litter dosing trial developed signs of congestive heart failure and the hearts of two others were dilated. Extensive hypertrophy and atrophy of myocardial fibres were evident in the steer fed ad lib. with this material. As in field cases, the myocardial lesions of the sheep were less severe than those of the steer. Mild cardiac dilatation was present in four of the seven sheep in the maduramicin feeding trial. Diffuse hypertrophy of myocardial nuclei was present in all seven cases, myocardial fibre atrophy in six, multifocal fibrosis and necrosis in six and two cases, respectively, and focal endocardial thickening in two. The skeletal muscles revealed granular degeneration and foci of necrosis and regeneration. The cardiac and skeletal lesions in the field outbreaks, poultry litter feeding trials and maduramicin feeding trials, were highly comparable. This suggests that this form of poultry litter intoxication is a chronic form of ionophore toxicity the pathology of which is characterized by a dilated cardiomyopathy with congestive heart failure and mild (cattle) to severe (sheep) skeletal muscle lesions.

Ionophore antibiotic (narasin) poisoning in rabbits.

Outbreaks of narasin poisoning in rabbits from several commercial rabbit-raising farms in the state of Parana, Brazil, are reported. Approximately 5,000/35,000 rabbits died after having consumed a pelleted ration to which poultry ration premix had been added. Clinical signs included apathy, anorexia, muscle weakness, impaired walking, diarrhea, respiratory distress, and opistothonus. Gross findings were not remarkable, but varying degrees of degeneration, necrosis and regeneration of skeletal muscles were consistent histopathological features in affected rabbits. Myocardial changes were mild or absent. Thirty ppm of narasin were detected in the ration fed the rabbits. The disease was experimentally reproduced by feeding the suspected ration and by administering narasin po to rabbits.

An outbreak of narasin poisoning in swine.

An outbreak of narasin poisoning in swine is described. Forty nine out of 108 lactating sows died over a period of one month after being fed a ration accidentally contaminated with narasin. Clinical signs included anorexia, respiratory distress, lethargy and posterior paresis, progressing to lateral recumbency and death. Necropsy examination in 3 pigs revealed extensive myocardial and skeletal muscle damage. Analysis of the feed confirmed the presence of high concentrations of narasin.

The veterinary importance of the toxic syndrome induced by ionophores.

Monensin, lasalocid, salinomycin, narasin and maduramicin are carboxylic ionophores intended for use as anticoccidial drugs for poultry and as growth promotants for ruminants. Generally, ionophores have been found safe and effective in the target animals receiving recommended dosage levels. However, toxic syndromes can result from overdosage and misuse situations. More information and reports of adverse reactions are available for monensin than the other ionophores because of monensin's longstanding and widespread use in the poultry and livestock industries. Care must be exercised in the diagnosis of ionophore toxicoses since clinical signs and lesions are not pathognomic. However, a feed-related problem characterized clinically by anorexia, diarrhea, dyspnea, ataxia, depression, recumbency and death, and pathologically by focal degenerative cardiomyopathy, skeletal muscle necrosis, and congestive heart failure may warrant a presumptive diagnosis of ionophore toxicity. Confirmatory diagnosis will require considerations of differential diagnoses and laboratory assays to determine the specific ionophore involved. Presently, there is no antidote or treatment for toxicoses induced by the ionophores. Judicious use, avoidance of overdosing, and adherence to species recommendation will help prevent the occurrence of adverse effects associated with this class of compounds.