Protecting animals and people from lethal cyanotoxins
R. Scott Nolen
March 28, 2018
Updated April 20, 2018
Cyanobacteria were ancient when our ancestors were taking their first tentative steps millions of years ago. Over 2 billion years ago, cyanobacteria oxygenated the earth's atmosphere, creating an environment that enabled the evolution of animal life. Moreover, through endosymbiosis, cyanobacteria became chloroplasts that plants have relied on ever since for photosynthesis. Free-living cyanobacteria, also known as blue-green algae, remain important today, fertilizing soils, capturing nutrients, and releasing oxygen in bodies of water, from the hot springs of Yellowstone to lakes, streams, catfish ponds, open oceans, and frigid seawater beneath polar ice caps.
Another unique characteristic of cyanobacteria is that they've been killing and injuring people and animals for as long as anyone can remember. When environmental conditions are right—often meaning the presence of warm, nutrient-rich, stagnant water—cyanobacteria can grow prolifically, forming colonies of tremendous size.
Depending on the cyanobacterial species and strain and the growing conditions, these accumulations will range from harmless to toxic. The latter are referred to as harmful algal blooms, and their toxins are called blue-green algal toxins, cyanobacterial toxins, or simply cyanotoxins.
The first scientific report on a harmful cyanobacterial bloom was a letter by George Francis published in the journal Nature in 1878. Francis described the deaths of horses, sheep, pigs, and dogs within hours after the animals drank from a lake in South Australia where a bloom was observed. Numerous accounts of animal and human poisonings have since been attributed to cyanobacteria exposure.
Ingestion of intact toxigenic cyanobacterial cells or toxins released into the water as the cyanobacteria die can lead to clinical poisoning and often death within minutes, hours, or days. People have also experienced less serious illnesses as a result of inhalation and skin contact. One or many animals or humans can be affected.
Microcystins, a group of hepatotoxins found in freshwater blooms, killed 75 patients at a human kidney dialysis center in Brazil in 1995 when the patients were dialyzed with water from a reservoir that contained the toxins. Dogs have died after drinking contaminated water as well as after licking the cyanobacterial cells from their fur. A yet-to-be identified cyanotoxin has killed coots as well as bald eagles that ate the poisoned coots. In that case, the cyanobacteria had colonized exotic, invasive hydrilla plants that the coots ingested.
Concerns like these, along with the likelihood that HABs are growing in frequency and distribution, have galvanized a global community of veterinarians and other scientists who interact with like-minded experts in government agencies in a one-health approach to better understand toxigenic cyanobacteria, the seriousness of the threats they pose, and how to prevent HABs.
Why so lethal?
Of the thousands of cyanobacterial species, roughly 200 are known to be toxigenic, according to Greg Boyer, PhD, director of the Great Lakes Research Consortium and a professor of biochemistry at State University of New York. Those toxigenic species also happen to be among the most common. "Even though it's a small number," Dr. Boyer said, "chances are good they're present in your water body."
You may think of cyanobacteria as a primitive organism, but I think of them as an organism that's had 3 billion years to figure out how to get it right. They're very advanced.
Greg Boyer, PhD, director, Great Lakes Research Consortium, and professor of biochemistry, State University of New York
Dr. Boyer has studied cyanobacteria for the past 40 years, specifically those that produce poisons. The list of cyanotoxins identified so far is large and includes hepatotoxins, neurotoxins, endotoxins, and cytotoxins (toxins that harm cells)—and Dr. Boyer believes more will be discovered. Why these ancient microorganisms synthesize such potent toxins is a question that is yet to be fully understood.
"You may think of cyanobacteria as primitive organisms, but I think of them as organisms that have had 3 billion years to figure out how to get it right. They're very advanced," Dr. Boyer observed. Dr. Boyer's lab assays specimens for a wide array of cyanotoxins.
Efforts to protect humans from exposures via drinking water and recreational waters
There's good reason to worry that cyanotoxins could wind up in a community's drinking water. For three days in 2014, the water in Toledo, Ohio, was shut down when microcystins from a massive algal bloom in Lake Erie were discovered in the city water supply. The following year, the Environmental Protection Agency issued health advisories for microcystins and cylindrospermopsin—another cyanotoxin—to guide municipalities' cyanotoxin test and response procedures for drinking water. Also in 2016, the EPA issued a draft advisory for microcystins and cylindrospermopsin for recreational waters used by swimmers. A number of states have similar advisories.
Problems in domestic and wild animals
"Monitoring drinking water and setting standards for recreational waters are important to protect people," Dr. Val Beasley said, "but we can't forget about outdoor dogs, livestock, and terrestrial wildlife that may drink from surface waters; coastal marine mammals in areas where cyanobacteria from nutrient-rich water bodies are washed downstream into the ocean; or salmon that are exposed in coastal net-pen aquaculture systems."
Dr. Beasley, a professor of veterinary, wildlife, and ecological toxicology at Pennsylvania State University, has investigated cases of cyanobacterial toxicosis since 1983, when he encountered swine in Illinois dying after drinking from a contaminated farm pond. He has published extensively on research into the pathophysiology, lesions, diagnosis, and management of cyanotoxin poisonings in animals.
He explained, "More veterinarians in practice will need to be watching for cyanotoxin problems, and more should specialize in toxicology. These and other poisoning problems are national and global concerns—and our training provides a needed foundation in basic biology, pathology, toxicology, diagnostics, epidemiology, and preventive medicine."
Dr. Deanna Grad-Vosslar, a practitioner at Rugby Veterinary Services in Rugby, North Dakota, has witnessed the lethality of cyanotoxins up close. In June 2017, she was called to a ranch where the owner had returned in the evening to find four of his cows dead, two calves close to death, and several other cows ill.
"When I arrived, there were about 27 head of cattle acting abnormally," Dr. Grad-Vosslar recalled. "They were slow-moving, not aggressive. Many were lying down, and if they did walk, it seemed like they were sore or stiff. They staggered some and had a dull attitude. If you tried doing too much with them, some would go down, like you stressed them too much and they might die.
"The owner had rural water as the main source of water for these cattle. He told me it was shut off for a few hours earlier in the day because a break in the line had to be repaired. So, the cattle most likely had gone down to the lake to drink during that time."
In the end, seven cows and two calves died, and the surviving cattle recovered. Testing of water samples and necropsies revealed the presence of two cyanobacterial neurotoxins: anatoxin-a and homoanatoxin-a. Dr. Grad-Vosslar wasn't surprised by the results. "Many of the signs we saw were consistent with what the toxicology textbooks describe for blue-green algae," she said.
Dr. Melissa Miller, a veterinary pathologist with the California Department of Fish and Game, says she graduated from veterinary college thinking she'd never see a case of cyanotoxicosis. "I thought of it as a kind of zebra, something exotic you only see once in a blue moon, if ever," Dr. Miller said.
Then in 2010, Dr. Miller was the lead author on a report that for the first time linked a freshwater cyanotoxin to the deaths of a marine mammal species. Twenty-one southern sea otters that were recovered from along the California coast had died of microcystin intoxication after eating clams, mussels, and oysters in which high concentrations of the toxin were found. The source of the cyanotoxins was traced to a freshwater lake about a mile inland. Tributaries carried the toxins to the coast, dumping them into the bay where the otters feed.
"Harmful algal blooms are a huge issue in California now. It's something we deal with every week," Dr. Miller said.
Don't feed the bacteria, and don't constrain the streams
Wayne Carmichael, PhD, is an emeritus professor of Wright State University and an international expert on toxigenic cyanobacteria. He started studying them in 1970 when little else besides their lethality was known. Within a few years, Dr. Carmichael would identify the first cyanotoxin—anatoxin-a—and subsequently discover that cyanobacteria produce multiple types of toxins. He's traveled the world lecturing on cyanobacteria, to Australia, South Africa, Brazil, and Panama. He's authored reports for the World Health Organization and advised numerous federal and state agencies.
Cyanobacteria, he says, are an essential component of our ecosystem. They are rugged organisms, capable of surviving in extreme habitats, including desert soil and at high altitudes. Cultures in Africa and China have cultivated cyanobacteria as a food source for millennia, and their pharmacologic potential is currently being investigated. "Think of cyanobacteria as colonizer organisms," Dr. Carmichael explained.
Algal blooms occur in eutrophic environments, that is, water containing high concentrations of nitrogen or phosphorus, which the cyanobacteria rely on to multiply. The primary sources for such nutrients are human and animal waste as well as fertilizers. Additional commonly cited drivers of bloom events are climate change, drought, and anthropocentric manipulations of watersheds.
Harmful algal blooms have been around for ages, but the rise in bloom events raises the question of whether the trend is attributable to better detection methods or an actual increase in number. Dr. Carmichael said it's both. "Our identification methods are improving, but there's no question blooms are increasing," he explained.
"They're found more and more in water supplies where blooms didn't occur so much before. Maybe they occurred every five or 10 years, and now they're every year. And if you expand the growing season with warmer springs and warmer falls, you might have blooms going six to eight months a year instead of one to two months. The more stagnant, polluted, nutrient-rich waters we produce, the more cyanobacteria cyanotoxins we'll have."
Dr. Beasley explained, "Nutrients have built up in soils, and they will be leaching them for a long time to come. Poisonings of animals and humans from ingestions of cyanobacterial toxins will continue to be a growing concern until societies take actions that reduce free nutrient concentrations in water and more streams are flowing freely.
"Needed actions include conservation of water, precision application of fertilizers, that is, only where and when needed, widespread use of cover crops, and restoring wetlands and native plant communities that surround water bodies. Natural resource managers and agricultural producers are working on aspects of this, but more is needed, including efforts by smaller-scale animal producers and those who are responsible for urban and suburban lawns, golf courses, and large- and small-scale sewage systems."
See something, say something
While most states have a reporting system for harmful algal blooms, reporting is not mandatory. Moreover, cyanotoxicosis in humans and other animals may not be recognized and, therefore, may go unreported. A study published by the Centers for Disease Control and Prevention in November 2017 described the results of a pilot surveillance system for cyanobacteria HAB–associated illness implemented in 16 New York counties between June and September 2015. Fifty-one human and canine HAB-associated illnesses were reported, including 35 that met the CDC case definition, i.e., skin reaction, eye and ear irritation, liver damage, and gastrointestinal, respiratory, and neurologic signs and symptoms. Of those, 32 were in humans and three in dogs.
In previous years, New York never had more than 10 such illnesses reported statewide. "The pilot surveillance results … suggest that HAB-associated illnesses might be more common than previously thought," the study concluded.
"My experience," Dr. Miller said, "is these exposures are underreported for a variety of reasons. We lack an infrastructure that makes reporting compulsory, easy, and simple. There's a lot still unknown about these toxins, so recognizing a case can be tricky. I'm aware of anecdotal events from people I know who got sick after being in the water during a bloom event. Their symptoms weren't bad enough to report."
In 2016, the CDC launched the One Health Harmful Algal Bloom System as part of its National Outbreak Reporting System. OHHABS is unique with the agency in allowing states to report animal cases in addition to human illnesses. After five years, the CDC plans to publish a report summarizing the data.
"That will allow us to understand, going forward, if we are seeing an increase in the number of human health effects from these events," said Lorraine Backer, PhD, a senior epidemiologist with the CDC who researches the public health impacts of harmful algal blooms.
Dr. Karyn Bischoff, a veterinary toxicologist and a senior extension veterinarian at Cornell University College of Veterinary Medicine as well as chair of the AVMA Committee on Environmental Issues, says veterinarians, and the AVMA itself, are uniquely positioned to help mitigate the impacts of harmful blooms on animals.
"When there is a cyanobacterial bloom event, veterinarians are on the front lines, taking care of sick animals. Veterinarians are also behind the scenes in the lab running diagnostics. We can take a stronger role in educating the community about this serious issue," Dr. Bischoff said.
Additionally, the AVMA has convened a multientity HABs working group that is studying how the Association can most effectively participate in this one-health issue. Dr. Bischoff envisions a national harmful algal bloom database that veterinarians can access for up-to-date information about bloom events in their area.
"Knowing this kind of information is mission-critical when taking care of a patient that may have ingested a cyanotoxin," she said.
Clarification: In an earlier version of this article, two photos were not characteristic of harmful algal blooms caused by cyanobacteria. Rather, they appeared to be green filamentous algae, which can pose an indirect threat to aquatic animals by rendering water hypoxic, especially at night or when the organisms die. It is important to the protection of human and animal health to be able to recognize the gross appearance of cyanobacteria. The first two photos here are of HABs caused by cyanobacteria at lakes in Minnesota and New York. The blue color of cyanobacterial blooms, which is often most evident at the shoreline, develops as the organisms degenerate. Microscopic examinations of cyanobacterial cells and cyanobacterial toxin analyses by individuals with expertise in this area are also of great value.