Blue-green algae are actually bacteria, known as cyanobacteria, and are found in fresh, brackish (slightly salty) and marine water bodies (Figure 1). Although they often have a blue-green colour they can also be red, brown and black. Chlorophyll within their cells contributes to their blue-green colour and also makes them capable of photosynthesis. Cyanobacteria grow as single cells, cell clumps or filaments as floating (planktonic) blooms or bottom-dwelling (benthic) mats in water bodies (Gunn, 1992; Gunn et al, 1992; Faassen et al, 2012). These cyanobacterial blooms occur worldwide (Massey et al, 2020), and it has been recognised for over a century that they are responsible for deaths in livestock, birds, fish, wildlife and dogs (Stewart et al, 2008; Nolen, 2018; Smith and Daniels, 2018).
Circumstances of exposure
Cyanobacteria occur in both freshwater and marine environments. Under certain environmental conditions cyanobacteria can quickly form extensive and often visible growths or blooms. These most commonly occur in warm weather and affect the colour, odour and taste of the water (Wood, 2016). If there is a strong wind or if the water is disturbed, cells can lose their ability to regulate their own buoyancy and may sink to the bottom or float to the top and cause surface scums (Figure 2). Often the bloom is found on the downwind (leeward) shore of a body of water having been blown over the surface by wind. These blooms are then concentrated and close to shore making them more accessible to animals (Gunn et al, 1992). In temperate regions blooms occur during late summer and early autumn and last 2–4 months, but in subtropical environments the bloom can occur earlier and last longer. In dry years in tropical or subtropical areas blooms may occur throughout the year (Van Apeldoorn et al, 2007). A bloom is not necessarily toxic; analysis of blooms in Europe and North America found that 40% were toxic (Tyagi et al, 1999).
In most cases the toxins (cyanotoxins) are released after cell death, which generally occurs at the end of the bloom period (Bischoff et al, 2001). High cell growth from eutrophication (an enrichment of water by nutrients) results in nutrient limitation, which ultimately causes the death of cells and release of their toxins — this also occurs if poor growth conditions occur. Often treatment of water bodies to kill cyanobacteria can increase the risk of poisoning by causing release of toxins on death. It is essential in these cases to prevent access to the water for at least 3 days to allow the toxins to decompose (Bischoff et al, 2001).
Dogs are commonly affected by cyanotoxins, however, many other species develop toxicosis if a sufficient dose is ingested (Wood, 2016). Dogs have been reported to die after licking (including grooming) or eating algal material or swimming in affected water (Codd et al, 1992; Hamill, 2001; Hoff et al, 2007; Faassen et al, 2012; van Overbeeke, 2012; Backer et al, 2013). Cyanobacterial scum may also be ingested after washing up on the shore (Lürling and Faassen, 2013). Although cases involving dogs usually involve a few animals, mass mortality events are described in livestock and wildlife (Stewart et al, 2008; Wood, 2016). It also seems that some animals may actually seek out and eat algal mats or crusts, even when clear water is accessible; the reasons for this behaviour are unknown (Codd et al, 1992).
It is also worth noting that canine deaths have been reported after ingestion of cyanobacteria that were not associated with a bloom but were growing in detached clumps of water plants floating near the lakeside (Fastner et al, 2018). In addition, administration of blue-green algae dietary supplements obtained from natural sources is also a risk and poisoning has been reported in a dog (Bautista et al, 2015) and a horse (Mittelman et al, 2016) given blue-green algae dietary supplements.
Mechanism of toxicity
Many cyanobacteria contain or produce a variety of toxic substances (cyanotoxins). Only a few of the 250 species have been shown to be toxic and many produce more than one type of toxin (Tyagi et al, 1999). The toxins produced by the cyanobacteria have a high acute toxicity and exposures frequently result in fatality, which usually occurs very rapidly.
The mechanisms of toxicity vary. The two main types of toxin are neurotoxins and hepatotoxins.
Neurotoxins
Neurotoxic compounds are produced by Anabaena, Oscillatoria, Aphanizomenon and Trichodesmium species of cyanobacteria (Tyagi et al, 1999). Anabaena and Oscillatoria species produce anatoxin-a (previously called very fast death factor (VFDF)), which mimics acetylcholine and binds to acetylcholine receptors but is not degraded by acetylcholinesterases (Tyagi et al, 1999). These cyanobacteria and Aphanizomenon also produce an unstable cholinesterase inhibitor, with an organophosphate structure (Cook et al, 1989), named anatoxin-as, where the s stands for salivation. Homoanatoxin is another neurotoxin and is related to anatoxin-a.
Aphanizomenon species produce two similar neurotoxins, saxitoxin and neosaxitoxin, as well as three related compounds of similar structure. Saxitoxin and neosaxitoxin are fast-acting sodium channel blockers and are better known from marine dinoflagellates (singled celled organisms, an important component of plankton). Saxitoxin is the cause of paralytic shellfish poisoning (Turner et al, 2018).
Hepatotoxins (liver toxins)
Hepatotoxic compounds are the most commonly encountered toxin in cases of poisoning with cyanobacteria (Carmichael, 1992; Tyagi et al, 1999). Common cyanobacteria that produce hepatotoxins are Microcystis, Anabaena, Nodularia, Oscillatoria and Nostoc spp. (Carmichael, 1992). These hepatotoxins disrupt the normal structure of cells (Falconer and Yeung, 1992; Dawson, 1998). This leads to rounding of the hepatocytes (liver cells), disruption of their structure, separation and hepatic necrosis and failure. Hepatic haemorrhage also occurs. Depletion of coagulation factors and nephritis have also been reported. Fatalities resulting from exposure to this type of toxin normally occur as a result of hepatic necrosis, haemorrhage and hypovolaemic shock (McDermott et al, 1998). Some hepatotoxins are also potent tumour promoters, which may have implications for animals that survive the exposure (Carmichael, 1992), although the significance of this remains unknown. The most common toxins are nodularins, produced by Nodularia species, and microcystins, produced by Microcystis species which have been well studied and characterised. The toxins are released on cell death. Microcystins may also cause oxidative stress via release of reactive oxygen species that may cause serious cellular damage (Ding and Nam Ong, 2003).
Cylindrospermopsin produced by Cylindospermopsis species and many other cyanobacteria (Kinnear, 2010) causes necrotic injury to the liver (also to kidney, spleen, lungs and intestine). It is a protein synthesis inhibitor and is also genotoxic through DNA fragmentation (Bazin et al, 2012). Bioaccumulation of cylindrospermopsin occurs because of its extracellular deposition (Kinnear, 2010). Cylindrospermopsis species are usually found in tropical to subtropical climates; however, increased monitoring is starting to show evidence elsewhere, although this may be attributable to changes in global weather and temperatures (Kinnear, 2010).
Other toxic compounds
In addition to neurotoxins and hepatotoxins, the cell walls of many cyanobacteria contain endotoxins, which are irritant to mucous membranes and skin. It is thought that some of the gastrointestinal clinical effects in animals that eat cyanobacteria may be in part a result of the irritant nature of these endotoxins (Bláha et al, 2009).
These compounds are toxic to the skin and include lyngbyatoxin, aplysiatoxin and debromoaplysiatoxin. They can cause pruritus, erythema and blisters (Kuiper-Goodman et al, 1999).
Clinical signs
The clinical signs, onset and duration of effects from bluegreen algae exposure will depend on the type of cyanobacteria involved and the toxin ingested, and it is possible that more than one type of cyanobacteria or toxin could be involved in the same incident, although there is usually a dominant type.
Irritant effects
Gastrointestinal effects are often the presenting sign after cyanobacteria exposure. Common gastrointestinal features are acute salivation, vomiting, haematemesis, abdominal tenderness and, more rarely, diarrhoea which may be haemorrhagic (Corkill et al, 1989; Elford et al, 2012).
Dermatitis is possible and although reported in humans is rare in dogs, possibly because their hair provides some degree of protection from direct skin contact. In a published case severe pruritus and urticaria occurred in a dog within 24 hours of swimming in a lake containing a visible algal bloom and debromoaplysiatoxin was found in samples of lake water (Puschner et al, 2017).
Neurotoxins
Signs of neurotoxin exposure can occur as early as 5–15 minutes after ingestion but may take up to 1 hour (Puschner et al, 2010). Death is also rapid, often within 10–30 minutes of the onset of clinical effects (Edwards et al, 1992; Gunn et al, 1992, see Case report 1), but may be several hours later. In some cases, death occurs so rapidly that animals are found dead at the water's edge (Mahmood et al, 1988).
Signs of anatoxin-a exposure include mild salivation, muscle rigidity and tremors, ataxia, paralysis, cyanosis and respiratory failure. Anatoxin-as causes hypersalivation, lacrimation, diarrhoea, urination, bradycardia, tremors, respiratory distress, convulsions and collapse. Clinical signs of these two toxins may be difficult to distinguish.
Hepatotoxins
Dogs are most commonly exposed to hepatotoxic cyanotoxins and increases in the activities of liver enzymes usually occurs within 24 hours of exposure (Harding et al, 1995). Death can occur within a few hours to a few days after exposure (Tyagi et al, 1999, see Case report 2).
Initial signs of hepatotoxic cyanotoxin ingestion are non-specific with vomiting, diarrhoea, anorexia and lethargy. This is followed by weakness, pale mucous membranes, evidence of haemorrhage, hypotension or hypovolaemic shock and jaundice. Nephritis and liver failure may develop with coagulopathy, low fibrinogen and protein concentrations in blood, marked elevation of liver enzymes, bile acids, creatinine and urea. Anuria and decreased renal perfusion are also present in some cases (Simola et al, 2012). Death is as a result of hypovolaemic shock with hepatic haemorrhage or hepatic insufficiency.
Diagnosis
Diagnosis of cyanotoxin poisoning is usually based on clinical signs and a history of swimming in or drinking from an affected water body. See Table 1 for a list of differential diagnoses for cyanobacteria poisoning in dogs.
Table 1. Differential diagnosis for cyanobacteria (bluegreen algae) poisoning in dogs
| Liver toxicity | Neurotoxicity |
|---|---|
|
|
Identification of cyanobacteria species cannot be performed by eye or by the general appearance of the bloom and confirmation of exposure is not routine in most cases. In addition, different strains of the same species can be toxic or non-toxic. In a review of 368 suspected or confirmed canine cases, cyanobacterial poisoning was only biochemically confirmed in 30 cases (8%) (Backer et al, 2013). Cyanobacteria or cyanotoxins may be identified in water samples or scum from the coat, vomitus (Carlson et al, 2006), stomach contents (Gunn et al, 1992; Carlson et al, 2006; Hoff et al, 2007; Puschner et al, 2008; Puschner et al, 2010; Faassen et al, 2012; Fastner et al, 2018), faeces (Rankin et al, 2013), bile or urine (Puschner et al, 2010), and can be used to confirm exposure. More recently it has become possible to analyse cyanotoxins in tissue samples. Microcystins were identified in vomitus and liver samples in a dog euthanased after drinking from a lake (van der Merwe et al, 2012, Case report 2). Nodularin was detected in liver and kidney samples in a dog euthanased after developing hepatic failure and anuria after exposure to sea water containing an algae bloom (Simola et al, 2013). Depressed blood cholinesterase activity has been reported in animals with anatoxin-as poisoning (Cook et al, 1989). Anatoxinas does not depress brain cholinesterase activity as (unlike organophosphate insecticides) it does not cross the blood brain barrier (Cook et al, 1989).
In some countries environment authorities regularly test water bodies such as reservoirs for the presence of algae and toxins, and post warning signs if necessary. This testing, however, will not necessarily include ponds in parks and farmland. Suspected blue-green algae exposure may be a reportable incident and animals, and dogs in particular, often act as a sign of water body safety (van Overbeeke, 2012; Backer et al, 2013). In the UK blue-green algae incidents should be reported to the Environment Agency which has a 24-hour Incident Hotline (telephone 0800 80 70 60, website https://www.gov.uk/government/organisations/environment-agency). If identification is required, then contact the local or government authority for advice. Samples should be refrigerated not frozen.
Prognosis
Exposure to cyanotoxins generally carries a poor prognosis. In an analysis of canine cases reported in the US in media, state and federal agency reports and scientific literature from the late 1920s to August 2012, 115 events involving 260 dogs were identified. Of these 215 dogs (83%) died and 45 (17%) became ill but survived (Backer et al, 2013). In many cases of neurotoxic cyanotoxin exposure death occurs before treatment can be instituted. With hepatotoxins, death usually occurs soon after admission, but there are occasional reports of successful treatment. A dog that developed hepatic failure after microcystin exposure survived with aggressive therapy including fluids, whole blood and fresh frozen plasma transfusions, vitamin K, vitamin B complex, S-adenosyl-L-methionine and silibinin (Sebbag et al, 2013). Another dog with hepatopathy and severe coagulopathy after confirmed microcystin exposure survived after treatment with gut protectants, fluids, vitamins, antibiotics, S-adenosyl-L-methionine and colestyramine during 8 days of hospitalisation (Rankin et al, 2013).
In contrast, for dogs with only dermatological signs prognosis is good (Bautista and Puschner, 2016).
Treatment
Treatment of cyanobacteria exposure is aggressive and supportive, as there are no specific antidotes. Speed is essential in the management of cyanobacteria poisoning. As it is not possible to confirm exposure within a clinically relevant time frame, all exposures are initially considered toxic and the animal should be decontaminated. In addition, it will not be possible immediately to determine whether a dog has been exposed to a hepatotoxin or a neurotoxin and there is the possibility that both types of toxin could be involved.
Decontamination
Emesis can be induced but only if ingestion was very recent (<1 hour) and the dog is asymptomatic. Adsorbents (activated charcoal) should be given if practicable, depending on the clinical condition of the dog. For suspected or confirmed hepatotoxic cyanotoxins the use of colestyramine (1–2 g/dog orally every 12 hours for 7 days or discharge) instead of activated charcoal has been advocated and was used in a dog that survived microcystin poisoning (Rankin et al, 2013). Colestyramine may still be useful several days after exposure (it was started on day 5 in the case reported by Rankin et al, 2013). The rationale for colestyramine is based on in vivo and in vitro studies showing binding of microcystin to colestyramine. In a rat study the degree of liver damage was less in those receiving colestyramine after microcystin administration compared with controls (Dahlem et al, 1989).
Thorough dermal decontamination is essential to prevent or reduce exposure to material on the coat in animals that have been swimming in an affected water body. In critically ill animals, the dog should be stabilised first and then washed and a collar applied. It is important to wear protective clothing (e.g. gloves, apron) during decontamination procedures as there is a risk of dermatitis (Bautista and Puschner, 2016). If appropriate, samples of algal material on the coat or vomitus can be collected and stored for identification or analysis.
Observation
Animals with suspected cyanobacteria exposure will require aggressive treatment. All asymptomatic animals should be observed for at least 6 hours post-exposure to assess for possible exposure to a neurotoxic cyanotoxin. The vital signs, particularly heart rate, respiration and mentation should be monitored. If there is no evidence of neurotoxicity within 6 hours, it is reasonable to assume this is no longer a risk. Any further treatment of a symptomatic animal should be aimed at monitoring and management of potential liver toxicity.
Supportive care
In symptomatic animals it is essential to monitor liver function, clotting parameters, renal function and vital signs. Other treatment is mainly supportive with intravenous fluids and an antiemetic if required, to ensure hydration. Gut protectants and nutritional supplements have also been used. The placement of a peripheral catheter may be required in symptomatic animals to allow repeated blood sampling and administration of drugs.
Neurotoxin exposure
Assisted ventilation may be required for respiratory depression following neurotoxic cyanotoxin ingestion, but dogs rarely present in time for it to be instituted.
Diazepam can be given for control of severe muscle twitching or convulsant activity, although it is not always effective. In general, use of morphine, succinylcholine, barbiturates and phenothiazines should be avoided because their effects will be exacerbated in animals exposed to the cholinesterase inhibitor anatoxin-as. Propofol or isoflurane can be used but the animal will need to be closely monitored because of the risk of respiratory depression and cardiac effects. Sedated dogs should be turned regularly. Atropine may be considered if the animal is exhibiting cholinergic signs such as hypersalivation or bradycardia (Beasley et al, 1989).
Hepatotoxin exposure
Initial signs of hepatotoxic cyanotoxin ingestion are nonspecific, so dogs should be monitored for gastrointestinal signs and inappetence. Liver enzymes should be measured to establish a baseline when an animal with suspected cyanobacteria exposure is brought into the veterinary practice, even if asymptomatic. If abnormal or the animal is symptomatic the liver enzymes should be measured again at 24 and 48 hours. If liver enzymes are normal after 48 hours, it is unlikely the animal is at risk of hepatotoxicity. If liver enzymes are raised monitoring should continue until signs start to resolve. Liver enzymes may be elevated for several weeks in animals with poisoning from cyanobacteria.
If there is evidence of haemorrhage a clotting profile should be checked and vitamin K1 given if coagulopathy is present. Blood transfusions and correction of electrolyte imbalance is recommended (Stewart et al, 2008). Dogs with signs of haemorrhage should be handled with care.
Liver protectants such as acetylcysteine (same regimen as for paracetamol poisoning) and/or S-adenosyl-L-methionine (SAMe; 20 mg/kg orally every 24 hours for 7 days) could be considered in dogs with suspected hepatotoxic cyanobacteria exposure. The efficacy of these drugs in dogs with hepatotoxicosis from cyanotoxins has not been investigated but liver protectants were used with other interventions in two dogs that survived hepatotoxin cyanotoxin exposure (Rankin et al, 2013; Sebbag et al, 2013). Silymarin is another liver protectant (sometimes called silibinin) (Mereish and Solow, 1990; Rankin et al, 2013) and has been effective in treating experimental animals with microcystin exposure when given by intraperitoneal injection (Mereish et al, 1991), but was ineffective when given as a single oral dose. There is no information on its effect on other algal toxins, but silymarin administration could be considered in combination with either SAMe or acetylcysteine; it is well tolerated and high doses can be given.
Case report 1: neurotoxin exposure (anatoxin-a)
Several dogs died after drinking from or swimming in a Scottish loch. Two dogs developed convulsions and coma and died within 10 minutes after walking along the shoreline. Four days later a dog died 30 minutes after drinking from the loch. Signs in this case were cyanosis, rigors, twitching and salivation. A year later a dog died 15 minutes after swimming in the loch. A month after that, one of two spaniels retrieving sticks from the loch became unwell with hyperaesthesia, bradycardia and salivation but recovered with treatment. There were no obvious blooms in the loch, but benthic cyanobacteria (Oscillatoria species) had accumulated along the shoreline. Anatoxin-a was found in the stomach contents of dogs and samples of cyanobacterial scum. Filaments of Oscillatoria were also found in the stomach contents (Edwards et al, 1992; Gunn et al, 1992).
Case report 2: hepatotoxin exposure (microcystins)
A 6-year-old Briard dog (35.5 kg) presented a day after drinking water from a lake. That evening she lost her appetite, vomited green-coloured fluid and had diarrhoea. She continued to have gastrointestinal signs the next morning and became recumbent. On examination approximately 24 hours after exposure she had haemorrhagic diarrhoea and melaena with abdominal discomfort. Blood tests showed low glucose concentration, coagulopathy, elevated pack cell volume and haemoglobin, elevated liver enzymes and icteric plasma. She received intravenous fluids, dextrose, vitamin K1, antiemetics, acetylcysteine and fresh frozen plasma. A urinary catheter was also placed, and the urine was found to be dark and positive for haem and protein. She continued to have gastrointestinal signs and 4 hours after placement of the catheter no further urine was produced. She continued to decline and was euthanased 13.5 hours after presentation. Post-mortem examination revealed diffuse, acute massive hepatic necrosis and haemorrhage. The cyanobacteria Microcystis aeruginosa was found in the vomitus (which had been collected by the owner on the second vomiting episode). Microcystin was found in the lake water, vomitus and liver (van der Merwe et al, 2012).
Conclusions
Poisoning from cyanobacteria (blue-green algae) is typically associated with an algae bloom but not all blooms are toxic. Cyanotoxins produced by cyanobacteria are usually neurotoxic or hepatotoxic. Neurotoxic effects typically manifest rapidly and death can occur within minutes to hours. Signs of liver damage from hepatotoxins generally occur within 24 hours and death may occur within hours to days. There is no specific treatment for poisoning with cyanotoxins and treatment is supportive with decontamination, monitoring and liver protectants (if appropriate). Prognosis is generally poor for dogs with significant signs after exposure to cyanotoxins. Survival is rare but has been reported after hepatotoxin exposure managed with aggressive treatment.
KEY POINTS
- Dogs are at risk of poisoning from swimming in or drinking from a water source containing cyanobacteria (blue-green algae).
- Not all blooms contain toxic species and it is not possible to tell from the appearance of the bloom or identification of the species present.
- There are a number of cyanotoxins but the most commonly encountered are either neurotoxic or hepatotoxic.
- Death can occur within a few minutes to within 24 hours from neurotoxic cyanotoxins, and within a few hours or after a few days with hepatotoxic cyanotoxins.
- Treatment of cyanobacteria poisoning is supportive, but prognosis is generally poor.