Intoxication of cattle by Ricinus communis in northwestern Argentina

Abstract

Here we describe 2 outbreaks of intoxication by Ricinus communis in cattle in Argentina. In outbreak 1, in 2010, 180 heifers were introduced to a paddock heavily invaded by R. communis. Thirty-two animals developed watery diarrhea, and 6 of them were drooling, and had constant chewing motions, blindness, incoordination, depression, and prostration. Four affected animals died 12–14 h after the onset of clinical signs; another died 4 d later. The surviving 27 animals were removed from the paddock and recovered. At autopsy, several organs were congested and hemorrhagic, and abundant pericarps, leaves, and seeds of R. communis were found in the rumen content. The main microscopic lesion was acute, diffuse, superficial necrotizing gastroenteritis, and intestinal congestion and hemorrhage. In outbreak 2, in 2013, severe neurologic signs were observed in 12 of 300 cows after being introduced into a corn paddock without grain production that had been severely invaded by R. communis. Affected animals were excited and had tremors, drooling, incoordination, and prostration. The herd was immediately transferred to another paddock, and all affected cows recovered without treatment. In outbreak 1, the clinical signs and lesions were characteristic of simultaneous poisoning by R. communis fruits, which contain ricin and cause mainly digestive signs and lesions, and by leaves and pericarps, which contain ricinine and cause nervous signs. In outbreak 2, clinical signs and the recovery of the animals suggest that the intoxication was caused by ricinine, which is present in the leaves of R. communis.

Ricinus communis is a plant in the Euphorbiaceae family; it is known in Argentina as tártago or ricino, in Brazil as mamona or carrapateira, and in English-speaking countries as castor bean. The plant has 2 toxic principles: 1) ricin, also called toxalbumin, which causes digestive signs and lesions, and 2) ricinine, which causes nervous signs without significant gross or microscopic lesions. ¹⁷

Ricin is present in the seeds of R. communis. The chemical structure of ricin allows it to bind to galactoside components on the cell surface, facilitating its endocytosis and subsequent inhibition of protein synthesis.^4,5 Other mechanisms of tissue damage induced by ricin include apoptosis, structural and functional alteration of the cell membrane, and release of inflammatory cytokines. ⁴ Ricin consists of a toxic A chain and a cell-binding B chain. Chain A acts by depurating rRNA, which specifically cleaves the 28S rRNA and inactivates 1,500 ribosomes/min. ¹⁶ The B chain is a galactose-specific lectin that binds via lectin receptors to cell-surface glycolipids and glycoproteins found on all vertebrate cells.

Ricinine is a piperidine alkaloid present in all parts of the plant, including leaves and pericarp. In mice, ricinine causes hyperactivity, seizures, and subsequent death due to respiratory arrest. ¹⁸

Natural intoxication by R. communis has been described in horses, ¹⁴ pigs, chickens, ¹⁷ humans, ¹⁸ cattle, ² sheep, ³ goats,^7,12 and dogs. ¹⁵ Experimental intoxication with seeds of the plant has been performed in goats, horses, pigs, rabbits, chickens, ducks, ¹⁷ and cattle.^13,17 There is only one report of spontaneous intoxication of cattle by consumption of R. communis, ² but in that report, no nervous signs are described despite the high consumption of whole plants. We describe here the pathologic and epidemiologic aspects of 2 outbreaks of spontaneous intoxication of cattle by R. communis in Argentina.

Both outbreaks occurred on a farm located in the department of Güemes, Salta province, northwestern Argentina. One of the authors of our paper (Raúl E. Marin) visited the farm during both outbreaks and inspected the paddocks, collected epidemiologic information, examined sick animals, and performed autopsies on animals on site. The farm had ~1,200 head of cattle of different breeds and categories grazing on ~1,150 ha of Cenchrus ciliaris (buffel grass) pasture. Another 150 ha were used for corn production.

Outbreak 1 occurred in February 2010 (summer in the Southern Hemisphere). One hundred eighty, 12–14-mo-old heifers, weighing an average of 210 kg, were moved to an 8-ha paddock with an overgrazed natural pasture. Most of the surface of the paddock (~80%) was covered by R. communis plants, and most were laden with green fruits. Most of the R. communis plants had signs of consumption ( Fig. 1 ). No other toxic plants were found. Watery diarrhea was observed in 32 heifers 24 h after they were introduced to this paddock; 6 also had anorexia, colic, drooling, constant chewing motions, depression, and incoordination of the hindquarters. Four animals progressed to prostration and death after a clinical course of 12–24 h, and another animal died 4 d later. An additional animal developed nervous signs, consisting of circling, central blindness, depression, constant chewing movements, drooling, and production of pasty feces; these clinical signs improved progressively over 10 d, until the animal recovered completely. All of the surviving animals were removed from the paddock when the first clinical signs were noticed, and all of them recovered after 4 d. No treatment was instituted. Morbidity and mortality were 17.7% and 18.7%, respectively.

Figures 1–4.

Ricinus communis–invaded pasture and gross lesions of intoxication in cattle.

Figure 1. R. communis–invaded pasture with signs of consumption in the grazed paddock.

Figure 2. Epicardial and large vessel adventitial hemorrhages.

Figure 3. Severe congestion and hemorrhages of the abomasal mucosa.

Figure 4. Severe congestion and hemorrhage of the small intestinal mucosa.

In autopsies on 3 animals that died 12–14 h after the onset of clinical signs, petechiae and ecchymoses were observed in the subcutaneous and mesenteric fat, epicardium, endocardium, and adventitia of large vessels ( Fig. 2 ). There were areas of pallor in the myocardium and moderate-to-severe congestion, hemorrhages, and edema of the mucosae of the forestomachs, abomasum, small and large intestine, and rectum. These lesions were most severe in the abomasum and duodenum (Figs. 3, 4). The content of the abomasum and small and large intestine was liquid and dark. The liver was congested and had a diffuse enhanced acinar pattern. Numerous R. communis seeds, leaves, and pericarp remains were observed in the ruminal content.

Samples of abomasum, small intestine, cecum, liver, kidney, and heart were fixed by immersion in 10% neutral-buffered formalin, and routinely processed for the production of 4-µm-thick H&E-stained sections. Microscopically, severe congestion and hemorrhage were observed in the mucosa and submucosa of the abomasum, with abundant intracellular deposits of dark-brown pigment in the perivascular tissue. Severe centrilobular hydropic degeneration, portal and sinusoidal congestion, and disorganization of hepatic cords were observed in the liver. In the duodenum, acute diffuse superficial mucosal necrosis, many ulcers, hemorrhage, lymphoplasmacytic inflammatory infiltrates, congestion of the mucosa and submucosa, submucosal edema, and lymphangiectasia were observed (Figs. 5, 6). The kidneys had acute tubular degeneration. In the heart, congestion and endocardial and epicardial hemorrhage with focal coagulative necrosis of the myocardium were observed. Some animals had nervous clinical signs; unfortunately, the CNS was not examined at autopsy, and samples were not collected.

Figures 5, 6.

Microscopic lesions of intoxication by Ricinus communis in cattle. H&E.

Figure 5. Acute diffuse superficial duodenal necrosis and hemorrhage.

Figure 6. Higher magnification of Fig. 5, highlighting the loss of epithelium.

Outbreak 2 occurred in September 2013 (spring in the Southern hemisphere) on the same farm. Severe neurologic signs were observed in 12 of 300 (4%) pregnant cows, after being introduced into a 100-ha corn paddock, with no grain production due to severe drought but with heavy invasion by R. communis. Most of the castor bean plants were fruitless, although a few specimens had small fruits. Large quantities of leaves and stems were consumed by the animals, which developed excitement, tremors, drooling, incoordination, and prostration 3 d after entering the paddock. No animals died. After the first clinical signs, the herd was immediately transferred to a new paddock, and the affected cows recovered without treatment.

In outbreak 1, the diagnosis of intoxication by R. communis was based on the clinical history of R. communis consumption, clinical signs, gross and microscopic findings, and the abundant pericarps and seeds of R. communis in the rumen. In this outbreak, morbidity (17.7%) and mortality (18.7%) were lower than in previous reports of natural intoxication by R. communis.^2,3 This was probably due to the removal of animals from the problem paddock as soon as clinical signs were observed. Infectious and parasitic diseases with gastrointestinal clinical signs were excluded, based on epidemiologic, clinical, and pathology evidence. Other toxic plants that produce similar clinical signs and/or lesions are Baccharis spp. (gastrointestinal disease), and Senna spp. and Nerium oleander (myocardial necrosis).

In outbreak 2, the diagnosis of intoxication by R. communis was based on clinical history, including access to a paddock heavily infested by R. communis, and clinical nervous signs. Recovery after the animals were removed from the paddock supported the diagnosis. The nervous clinical signs caused by ricinine poisoning are associated with the ingestion of the leaves, which, in this case, was compatible with the animals consuming only leaves and stems, as very few and small seeds were available in the paddock. The regression of the clinical signs after the withdrawal of the herd from the paddock also supports this hypothesis. In this outbreak, the 4% incidence was lower than that in outbreak 1, and all animals recovered, probably because of the rapid removal of the animals from the paddock.

In an outbreak caused by the ingestion of leaves of R. communis in goats, all 22 animals that ingested leaves from pruned branches of the plant developed clinical signs, and 4 died after a clinical course of ~24 h. No significant lesions were observed in the CNS. ⁷ Most seeds can pass through the digestive system intact, but mastication and rumination can significantly enhance the release of ricin from plant seeds.^1,10 Ricin is present at 1–5% of the weight of R. communis seeds, and it has particular avidity for reticuloendothelial cells, causing apoptosis.^1,5,6 Experimentally, apoptosis of endothelial and lymphoid cells in various tissues has been confirmed by activated caspase-3 immunohistochemistry. ¹³ In cattle, the lethal dose of ground seeds is 2 g/kg for adults and 0.5 g/kg for calves, whereas the lethal dose of leaves for adult cattle is nearly 20 g/kg.^8,17, Additionally, the lethal dose of seeds can vary depending on the age and sensitivity of the animals, even among individuals of the same species,^17,18 and the lesions are dose dependent. ¹³ In both outbreaks, similar to previous reports,^2,12 the main predisposing factor for the intoxication appears to be the introduction of naive animals into paddocks invaded by R. communis. Additionally, the low availability of forage in the paddocks could have been important in the occurrence of the poisoning. The introduction of animals in areas invaded by the plant,^2,12 or the access of animals to plants cut or pruned and placed within their reach,^3,7 are the main factors that trigger poisoning.

Another form of poisoning occurs when castor bean cake, a byproduct of the production of oil from the seeds of this plant, which is used as a fertilizer, is mistakenly used to feed livestock, as occurred with horses in Brazil. ¹⁴ In the case of poisoning by the plant’s fruits, animals that have previously ingested the plant and not been poisoned may develop immunity to ricin. The induction of immunity to ricin administered by different routes, including the oral route, has been demonstrated experimentally.^11,17 However, the epidemiologic significance of this resistance in spontaneous poisonings has not been investigated.

In outbreak 1, the clinical signs were consistent with simultaneous poisoning by R. communis leaves and pericarps, which contain ricinine and cause nervous signs, and by fruits, which contain ricin and cause digestive signs. The gastroenteric lesions observed are characteristic of fruit poisoning (ricin) as described in cattle, ² goats, ¹² and sheep. ³ Nervous and digestive clinical signs, and lesions of the digestive tract, occur in intoxication by both seeds (ricin) and leaves (ricinine). In contrast, the exclusively nervous clinical signs (caused by ricinine) and the recovery of all animals in outbreak 2 clearly show that the presentation of R. communis poisoning depends on the part of the plant ingested.

Despite the wide distribution of R. communis in northwestern Argentina, ⁹ we found no case reports of natural intoxication of cattle by R. communis in a search of Google, PubMed, CAB Direct, Web of Science, and Scopus using the search terms “Ricinus communis”, “intoxication”, “poisoning”, “cattle”, “Argentina”, suggesting that this condition has not been reported previously in this species in this country. The low frequency of intoxication is probably due to the lack of epidemiologic conditions necessary for its occurrence; the introduction of animals, probably naive, into areas invaded by the plant; or the access of animals to R. communis cuttings. Poisoning may also be underdiagnosed, mainly due to the variation in its clinical signs and the similarity with other diseases of the digestive system and/or nervous system.

R. communis is a highly invasive weed in disturbed and fertilized soils, and spreads easily in temperate, subtropical, and tropical climates, making control measures costly. Anecdotal reports of producers observing adult cattle eating R. communis with impunity are common, which may be related to possible individual immunity, or simply consumption of insufficient toxic doses. The main preventive measure is to avoid the access of animals to paddocks densely invaded by R. communis; this is particularly important for naive animals.