Cyanobacteria, formerly known as blue-green algae, are ancient photosynthetic freshwater, brackish water, marine and soil-dwelling prokaryotes with a worldwide distribution. Omnipresent in freshwater systems, they are critical to the ecology of lakes and ponds. Proliferation of toxigenic cyanobacteria have been termed freshwater harmful algal blooms (FHABs) when they affect local ecosystems and animal health via oxygen depletion and/or toxin production. FHABs are a global problem, impacting water security in parts of the world where freshwater is scarce. Cyanobacteria are known to produce hundreds of bioactive compounds, and many of these compounds can negatively affect humans, companion animals, and wildlife. There are 40 known genera of cyanobacteria with toxic potential.
FHABs have been increasing worldwide and appear to be increasingly toxigenic due to anthropogenic changes to ecosystems. Contributing factors to the increased incidence of FHABs include climate change, water temperatures > 20°C, and pollution, particularly eutrophication (nutrient loading) of bodies of water from inputs of phosphorus and nitrogen. Climate change increases stratification of the water column, resulting in areas of anoxia and release of nutrients from sediments. Warmer and more nutrient-rich water bodies produces earlier, longer lasting, and more expansive FHABs. The ability of some cyanobacteria to move within the water column gives them an advantage when competing with phytoplankton, including eukaryotic algae, for light and nutrients. A large-scale FHAB event occurred in 2014 in Toledo, Ohio, where the city water supply became contaminated with the cyanotoxin microcystin.
Most toxicoses associated with FHABs are caused by direct ingestion of cyanotoxins either in the producing organisms or free in the water after cell lysis. There is evidence that microcystins, saxitoxins, and other cyanotoxins can accumulate in shellfish and other organisms in the food chain. Domestic animal exposures to FHABs can cause acute or chronic effects with varying degrees of severity depending upon the species of animal, the cyanotoxin(s) present, and the levels of exposure. Because there are a number of cyanobacterial toxins and exposure scenarios, clinical signs and findings are variable and the onset of illness may begin within minutes to days of initial exposure.
Morbidity and mortality in domestic animals have been reportedly caused by microcystins, anatoxin-a, and guanitoxin [formerly called anatoxin-a(s)], saxitoxins, and cylindrospermopsins.
Microcystins are the most common hepatotoxins and they often cause hepatocellular necrosis, which can present as acute liver failure.
Cylindrospermopsins are cyanotoxins produced byCylindrospermopsis raciborskii and other organisms and are known to bioaccumulate in freshwater mussels, snails, crayfish, and finfish. Cylindrospermopsins comprise the second most-reported group of cyanotoxins associated with FHABs worldwide, after microcystins. Cylindrospermopsins inhibit protein synthesis, reduce glutathione synthesis, cause oxidative stress and damage to DNA. Ingestion causes early gastroenteritis, followed by hepatic and renal necrosis and hemorrhage.
Anatoxins are neurotoxic and can present with nicotinic signs (muscle stimulation, tremors, seizures, and terminal respiratory paralysis.
Guanitoxin inhibits peripheral but not brain cholinesterase and thus it causes nicotinic as well as muscarinic signs (salivation, lacrimation, increased urination, diarrhea, and vomiting).
Saxitoxins can occur at lethal concentrations from FHABs, but they are better known as the cause of paralytic shellfish poisoning after ingestion of marine bivalves and sometimes other seafoods. Saxitoxins block voltage-gated sodium channels.
The emerging cyanotoxin beta-N-methylamino-L-alanine (BMAA) has been implicated in chronic neurologic damage, but its importance in that regard is disputed.
Recently, aetokthonotoxin, an unusual pentabrominated biindole alkaloid, has been reported to produce vacuolar myelinopathy, which has been most often seen in coots and bald eagles that prey on affected loons and other plant-eating waterbirds. The toxin is produced by cyanobacteria that grow on exotic invasive Hydrilla verticillata in southern lakes and reservoirs in the United States. Turtles and tadpoles that feed on the contaminated Hydrilla have experienced similar neurologic damage and it has been reproduced experimentally in turtles.
Lyngbyatoxins and aplysiatoxins, often found in coastal marine and estuarine waters, sometimes in FHABs, may cause ocular, respiratory and severe skin irritation in humans as well as dermatitis in dogs. Dermatologic and allergic responses are reported with a variety of cyanobacteria, and some cyanobacteria can also produce lipopolysaccharides.
Etiology, Epidemiology, and Pathogenesis of Algal Poisoning of Animals
Cyanobacteria are microscopic organisms and can appear as blue-green, green, brown, red, or white scum on the water surface. They are not visibly filamentous and may be found at the surface, on the shore, as crusts in recently flooded areas where the water has receded; as well as in the water column, associated with symbiotic plants, or in sediments. Cyanobacterial blooms generally occur when increased nutrient concentrations are present in the water column. Phosphorus and nitrogen pollution contribute to FHABs. Blooms typically occur when the water temperature is greater than 15°C and there is ample sunlight. Stagnant water bodies are often affected. Blooms are sometimes visible on surfaces of lakes or ponds, where they can accumulate downwind, but they may not be visible because many of the toxigenic species contain gas vesicles that control buoyancy, so they can be at any level of the water column.
Not all species of cyanobacteria are toxigenic, and some toxigenic species can produce more than one cyanotoxin. Additionally, strains of cyanobacteria that are toxigenic do not always produce cyanotoxins. There is seasonal variation to the genera causing FHABs, and blooms may be composed of a single dominant species or co-occurring species, sometimes with mixed assemblages of toxigenic and nontoxigenic species. Blooms that produce multiple toxins may lead to cyanotoxin interactions.
Important cyanobacterial toxins include:
Microcystins are the most common cause of poisoning associated with FHABs, are a group of approximately 250 cyclic heptapeptides that vary greatly in toxicity. Microcystin-LR is the most studied congener, one of the most commonly encountered, and among the most toxic members of this group. Microcystins are produced by a number of cyanobacteria, including Microcystis spp, Dolichospermum (formerly Anabaena) spp, Planktothrix spp, and Oscillatoria spp. Microcystins are toxic to mammals, reptiles, amphibians, invertebrates, and plants. Microcystins are suspected tumor promoters, and the WHO recommended upper limit for microcystin in recreational water is 1 mcg microcystin-LR/L. Ingested microcystin is transported to the liver via the portal circulation, where it is taken up by a bile acid carrier and accumulates within hepatocytes. Microcystin irreversibly inhibits protein phosphatases 1 and 2A, which are needed for cytoskeletal integrity and multiple cellular functions. With high level exposures, microscopically, there is loss of hepatic structure and blood pools in the damaged liver, which can cause hemorrhagic shock.
Nodularins, are structurally similar cyclic pentapeptide hepatotoxins, that are produced by Nodularia spumigena in brackish water. There are 10 known congeners of nodularin. The mechanism of action and effects of nodularins are similar to those described for microcystins.
Anatoxin-a and structurally related anatoxins can be produced by species of many genera of cyanobacteria, including Dolichospermum (formerlyAnabaena), Planktothrix, Aphanizomenon , Arthrospira, Cuspidothrix, Tychonema, Blennothrix, Chrysosporum, Phormidium, Microcoleus, and Cylindrospermum. Unlike microcystin, anatoxin-a is unstable in the environment. Deaths from anatoxin-a exposure have been reported in dogs, cattle, bats, flamingos, waterfowl, and carp. Anatoxin-a appears to be rapidly absorbed because clinical signs are almost immediate. Anatoxin-a acts as an agonist at nicotinic receptors, causing continuous stimulation at neuromuscular junctions, which can result in depolarizing neuromuscular blockade with terminal respiratory paralysis.
Guanitoxin [formerly Anatoxin-a(s)] is produced by Dolichospermum (formerly Anabaena) spp. Poisonings have been reported in swine, dogs, and birds. Guanitoxin is a naturally occurring acetylcholinesterase inhibitor, so the presentation is similar to animals exposed to organophosphorus insecticides. Guanitoxin blocks the enzyme that degrades acetylcholine, leading to a buildup of acetylcholine at receptors, including nicotinic and muscarinic receptors present in the peripheral nervous system, including receptors at pre- and postganglionic neurons, neuromuscular junctions, and exocrine glands. There are acetylcholine receptors in the CNS, but unlike acetylcholine-inhibiting insecticides, guanitoxin does not cross the blood-brain barrier. Because its chemical structure and toxic effects are different from those of anatoxin-a, the name was recently changed from anatoxin-a(s) to guanitoxin.
Though less well known, cyanotoxins also need to be considered. Cylindrospermopsins are tricyclic alkaloid toxins that have several mechanisms of action, which include: inhibiting protein synthesis, damaging DNA, causing oxidative damage, and altering biochemical cascades that are central to normal cell physiology and replication. They can affect the GI system, liver, kidneys, and other organs.
The amino acid toxin beta-N-Methylamino-L-alanine (BMAA) is produced by some cyanobacteria and increased synthesis has been associated with nitrogen deprivation. BMAA can bioaccumulate in mollusks, fish, mammals, and plants and has been implicated in some reports on amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders in people. BMAA has also been implicated in the pathogenesis of beta-amyloid plaques in the brains of vervet monkeys and stranded dolphins. The mechanism of action of BMAA has yet to be fully elucidated, but it appears to stimulate glutamate receptors. Recent reports have called into question the methods used to identify BMAA and the doses used in experimental studies, thus the role of BMAA as a cause of neurodegenerative diseases is a matter of debate.
Saxitoxins in freshwater systems are produced by Dolichospermum (formerlyAnabaena) spp., Aphanizomenon spp, Cylindrospermopsis spp, Planktothrix spp, and other genera of cyanobacteria. They are better known because of their production by marine dinoflagellates and associated paralytic shellfish poisonings. Saxitoxins act by blocking voltage-gated sodium channels.
The chemical structure of aetokthonotoxin, the cyanotoxin that causes vacuolar myelinopathy (VM), was recently elucidated.The syndrome was first termed avian vacuolar myelinopathy (AVM) when it was reported in American coots and other waterfowl, as well as predatory birds such as bald eagles and great horned owls that consume affected waterfowl. This disease has been associated with the freshwater plant Hydrilla verticillata, which is an invasive exotic in North America t when it has been colonized by the epiphytic cyanobacterium, Aetothonos hydrillicola. Experimentally, VM has been reproduced in carp, domestic chickens, mallards, red-tailed hawks, painted turtles, and tadpoles. The lesions of VM are characterized by multifocal myelin edema in the CNS.
Clinical Findings and Lesions of Algal Poisoning of Animals
Onset, severity, and type of clinical signs and lesions due to cyanotoxin poisoning are dependent on the species of exposed animal(s), the cyanotoxins involved, and the level of exposure. Although oral exposure is the most commonly recognized form of cyanotoxin poisoning in domestic animals, dermal and pulmonary exposures have been reported in humans. Skin irritation as well as symptoms associated with inhalation of cyanobacteria can include coughing, throat irritation, and nasal exudate. Occasionally, dietary supplements containing cyanobacteria have been associated with adverse effects, most likely due to quality control failure and misidentification of the organisms in the supplement. For example, after repeated exposure to dietary supplements containing microcystins, a dog experienced liver failure, but ultimately survived in response to vigorous supportive care, while a horse died from liver damage after developing clinical signs consistent with hepatoencephalopathy.
Microcystin exposure can lead to onset of clinical signs within minutes to days of ingestion. Affected animals can present peracutely with signs of shock including pale mucous membranes, or show signs of acute hepatotoxicosis such as diarrhea, vomiting, and weakness. Intrahepatic hemorrhage due to profound liver damage can occur acutely, or generalized hemorrhage secondary to coagulopathy can occur as the clinical signs progress. Survivors of acute clinical signs can develop icterus, and herbivores may have secondary photosensitization. Results of serum biochemical analysis in animals with early microcystin toxicosis include increased alanine transaminase, alkaline phosphatase, and creatine kinase activities; and increased total bilirubin concentration, with hypoglycemia, hyperphosphatemia, hyperkalemia Hyperkalemia in Ruminants Hyperkalemia (plasma potassium concentration >5.5 mmol/L) is common in animals with inadequate urine excretion, particularly when they are also acidemic (blood pH 7.2). Affected animals are... read more , and increased coagulation times. Later in microcystin toxicosis, increased total bilirubin concentration and hypoalbuminemia are seen. Postmortem findings include icterus, hemorrhage, acute diffuse hepatic necrosis, and renal tubular necrosis. Clinical signs and lesions due to nodularin exposure are similar to those for microcystin toxicosis.
Anatoxin-a is a nicotinic receptor agonist, causing continuous neuromuscular junction stimulation. Affected animals present with muscle fasciculations, tremors, generalized muscle rigidity, and eventual paralysis and respiratory failure. Because the constant stimulation does not allow repolarization of the axonal membrane, animals progress to paralysis from depolarizing blockade and can die of respiratory failure within minutes. No consistent changes in the results of serum biochemical clinical analysis or a CBC are typical, and no characteristic lesions are expected on postmortem examination.
Guanitoxin [formerly anatoxin-a(s)] produces clinical signs similar to those due to insecticides that inhibit acetylcholinesterase. Signs occur rapidly and include salivation, lacrimation, urination, diarrhea, and vomiting, as well as nicotinic signs, as seen with anatoxin-a, which could include depolarizing blockade and subsequent respiratory paralysis. No consistent changes in serum biochemical analysis or CBCs are expected, and no specific lesions are expected on postmortem examination.
Diagnosis of Algal Poisoning of Animals
Based on clinical signs and a history of exposure
A tentative clinical diagnosis of cyanotoxin poisoning is often based on appropriate clinical signs, necropsy findings, and a history of exposure to a potentially contaminated freshwater or brackish water source. The source is usually a pond, lake, reservoir, or slow-moving stream, but cyanobacteria can also grow in containers such as open water tanks and buckets. Aside from clinical findings and lesions, the following can support a diagnosis of cyanotoxin poisoning:
Microscopic examination of the water for identification of toxigenic cyanobacteria, although organism identification does not confirm the presence of toxins.
Use of ELISA for microcystin and anatoxin-a.
Reduced blood acetylcholinesterase activity support a diagnosis of guanitoxin poisoning in animals with known exposure and appropriate clinical signs. Brain acetylcholinesterase is not suppressed by guanitoxin.
Definitive cyanotoxin analyses:
Specialized testing and quantitation of cyanotoxins in water samples, including liquid chromatography and tandem mass spectroscopy for microcystin, nodularin, cylindrospermopsins, anatoxin A, guanitoxin, and saxitoxins are available from some veterinary and environmental laboratories. It is important to sample the water that was ingested and include the bloom itself.
Quantitative tests can also be used for biologic samples: anatoxin-a has been detected in canine urine, microcystins have been detected in canine stomach contents and liver, nodularin has been detected in canine liver and kidney, and microcystin and nodularin have been detected in dolphin liver.
Treatment of Algal Poisoning of Animals
Although ingestion is considered the major type of exposure for domestic animals, immediate dermal decontamination of animals with exposure to water contaminated with cyanobacteria is critical to prevent ingestion through grooming behaviors. Early decontamination is the best defense for all types of FHAB exposures:
Removal of the animal from the source of the FHAB
Removal of FHAB material from the haircoat via copious lavage with uncontaminated fresh water
GI decontamination for ingested material
Targeted treatment measures based on the specific cyanotoxin suspected include:
Activated charcoal can be of value in binding microcystins, but cholestyramine is preferred. Symptomatic and supportive care is focused on hepatoprotectants and fluid therapy. S-Adenosyl methionine and N-acetylcysteine have been used as hepatoprotectants. Although the prognosis is often poor, some dogs have survived with intensive management.
Anatoxin-a treatment is similar to that for other nicotinic receptor agonists. Supportive care includes tremor and seizure control using muscle relaxants, benzodiazepines, and barbiturates as needed. Propofol is contraindicated if there is respiratory or cardiac compromise. Longterm artificial respiration is likely to be required if gut absorption continues, but detoxification of the GI may enable a much faster recovery Maintenance of body temperature, hydration, and electrolytes is critical. The prognosis is often poor at best, but recovery may be complete in survivors.
Treatment for guanitoxin poisoning is primarily decontamination, along with symptomatic and supportive care. Because it is an acetylcholinesterase inhibitor, atropine or preferably glycopyrrolate can be administered with caution to reverse life-threatening cholinergic signs. Pralidoxime is not beneficial. Although most animals exposed to guanitoxin die rapidly, recovery in survivors is complete.
Prevention of Algal Poisoning of Animals
Because animals exposed to cyanotoxins have a guarded to poor prognosis, prevention is key. Provision of fresh, clean water regularly maintained in tanks, pools, and containers for domestic animals is important. Small, plastic "kiddie pools" for water-loving dog breeds are recommended. Physical barriers are often used to prevent domestic animals and livestock from accessing standing water with the potential for FHABs. Direct control of cyanobacteria in water is one possible way to diminish exposure.
Minimizing nitrogen and phosphorus pollution is a longterm objective for controlling blooms. Control measures can include mixing the water column with pumps to destratify the blooms and increase the flow rate of water. Concerns regarding the sensitivity of beneficial plankton and other fauna to copper, as well as the potential for increasing dissolved cyanotoxin concentrations in the water precludes the application of copper sulfate to control cyanobacteria. Other algaecides may also be toxic to aquatic organisms: glyphosate can be a source of phosphorus, and diquat dibromide may be a source of bromine used by cyanobacteria in the synthesis of aetokthonotoxin. Controlling bromine contamination from coal-fired powerplants and use in drinking water disinfection may also have value in decreasing cyanobacterial synthesis of that toxin. Some cyanotoxins remain in the water for several weeks after cyanobacteria are killed. Algaecides are not selective herbicides and may kill other types of phytoplankton and aquatic flora, thus decreasing competition for cyanobacteria and possibly increasing the likelihood of future blooms. Newer ways to control ongoing blooms include binding phosphorus or reducing sunlight, for example, by shading blooms with dyes or other material are likely to be more effective at killing cyanobacteria without exterminating competing phytoplankton and aquatic flora.
Overgrowth of microscopic cyanobacteria overgrowth results in FHAB. Climate change and eutrophication are contributing factors to increased reporting of FHABs.
FHABs can look blue, green, or brown, and may appear like pea soup, spilled paint, or striations in the water, or they may be invisible.
Some species of cyanobacteria have the potential to become freshwater harmful algal blooms and may produce cyanotoxins.
The cyanotoxins of major veterinary importance are the hepatotoxins microcystin and nodularin, the hepatotoxic and nephrotoxin cylindrospermopsins, and the neurotoxins anatoxin-a, guanitoxin, saxitoxins, and aetokthonotoxin.
Treatment is based on immediate decontamination accompanied by symptomatic and supportive care.
Because the prognosis is guarded at best, prevention is of critical importance.
For More Information
Anderson-Abbs B, Howard M, Teberski K, et al. California Freshwater Harmful Algal Blooms Assessment and Support Strategy, SWAMP-SP-SB-2016-0001. 2018.
Puschner B, Roegner A. Cyanobacteria (blue-green algae) toxins. In: Gupta R, ed. Veterinary Toxicology basic and Clinical Principles. 3rd ed. Waltham, MA: Elsevier Inc.; 2018:763-773.
Sebbag L, Smee N, van der Merwe D, et al. Liver failure in a dog following suspected ingestion of blue-green algae (Microcystis spp.): a case report and review of the toxin. J Am Anim Hosp Assoc 2013;49:342-326.
Stewart I, Seawright AA, Shaw GR. Cyanobacterial poisoning in livestock, wild mammals and birds--an overview. Adv Exp Med Biol 2008;619:613–37.
World Health Organization. Algae and Cyanobacteria in Fresh Water. In: WHO | Guidelines for safe recreational water environments. Malta: World Health Organization; 2003:136.