CCF-BLUE GREEN ALGAE

http://www.epi.state.nc.us/epi/hab/bluegreen.html

Blue-Green Algae and Human Health

Prepared by Thomas Morris, M.D., M.P.H.
Medical Epidemiologist
N.C. Harmful Algal Blooms Program
Occupational and Environmental Epidemiology Branch
December 2000

Executive Summary:

Cyanobacteria (blue-green algae) are ubiquitous around the world. Blooms of blue-green algae seem to be commonplace in North Carolina. The toxins produced by selected species of cyanobacteria are secondary metabolites of the algae and fall into three general categories: neurotoxic, hepatotoxic and non-specific (mostly cytotoxic effects). Cyanobacteria also have lipopolysaccharides (LPS, similar to compounds found in the cell walls of Gram-negative bacteria such as Escherichia coli) which are potent mediators in the mammalian immune system. Mortality from cyanobacteria is mostly confined to veterinary reports in pets and livestock that have drunk water densely packed with algae. Adverse human health effects associated with cyanobacteria are rare in the medical literature: these are mostly anecdotal case reports and are often circumstantial (e.g., no other cause was found for these effects); in some instances neither the algae nor the toxin(s) are identified. No human deaths from cyanobacteria have been reported in the United States. Ingestion and immersion are the primary routes of ill-health effects from toxic metabolites of cyanobacteria. Exposure to airborne components of algae can result in irritant and allergic symptoms and are likely mediated by non-toxic cellular components of the algae. The mouse bioassay is the established method to determine presence of toxic substrates in algae, and there are numerous laboratory methods for elucidating chemical structures from algae-tainted water. Field testing kits for toxins are not yet available.

Ecology of Cyanobacteria:

Cyanobacteria are found worldwide in both marine and freshwater habitats. (It should be noted that not all cyanobacteria are blue-green in color-some in these genera can range from green to red to brown. In this memorandum, cyanobacteria and 'blue-green' are considered interchangeable terms.) There are more than 50 genera of freshwater blue-green algae, and about one-third of them have been identified with toxin production. Blue-green algae in small numbers are a natural part of the water system. In large numbers, the algae spoil the water because of malodor and form thick scum on the water (increasing the viscosity and composition), and as a result cause the water to be distasteful. Decaying algae consume oxygen in the water, so fish may die as a result of oxygen deprivation. Also, a dense algal bloom floating on the surface may potentially alter the benthic community underneath by shading it from the sun and altering the community's ecological system.

While eutrophication of surface water from industrial and agricultural activities has been cited as the stimuli for blooms, the causes are more complex. Nutrient loading in the water is not the sole reason for blooms to occur. Although much is still to be learned about the ecology of cyanobacteria and their interaction with the aquatic environment, known factors in excessive algal blooms include:

• Runoff into waterways with nutrients (nitrogen and phosphorus) from sewage, agriculture fertilizers, industrial effluent, etc

• Poor water flow-blooms generally do not occur in steadily moving water.

• Alteration of lake and river ecosystems through land clearing, agriculture and settlement, and water management systems (locks, dams, etc.).

Adverse events, toxins, and other problems:

For this discussion, 'toxic' refers to a systemic effect that is non-discriminatory; 'irritant' is a local physical effect (such as skin inflammation after contact; any reference to 'allergy' emphasizes the interaction of host (humans) and environmental stimulus (in this document, algae and their constituent products). Some people are hypersensitive (have an exaggerated immune response) to such stimuli while others are not. Asthma, also referred in the medical literature as 'reactive airway disease,' is an example.

Not all cyanobacteria produce toxins, and even those known to produce toxins are not always producing the compounds shown to be toxic. Common genera of cyanobacteria associated with toxic metabolites include Microcystis, Anabaena, Aphanizomenon, and Oscillatoria; others to consider are Cylindrospermopsis and Lyngbya. The toxic chemical compounds are considered secondary metabolites, e.g., they are not essential for the cell to live. In addition, the 'toxicity' must be carefully defined: is the organism toxic to other aquatic bacteria, to fish, to birds and mammals, and/or to humans? Toxicity for other aquatic life forms, such as fish or bacteria, is not a good predictor of human health risk (many different fish, for example, are tolerant of cyanobacterial toxins). A fish kill does not necessarily point to toxic algal activity. Algal blooms may deplete dissolved oxygen in the water, resulting in fish kills. The algae also increase the viscosity of water, which may impede water flow over a fish's gills, hindering gas exchange and causing suffocation.

Various toxins have different effects on different organisms. The known cyanobacterial toxins are listed in the general categories of hepatotoxins, neurotoxins and non-specific toxins. A fourth category is not really a secondary metabolite but a component of the algal cell wall; the component is called lipopolysaccharide (LPS) and is similar to the LPS identified in Gram-negative bacteria such as Escherichia coli and Salmonella sp. Hepatotoxins can cause liver failure. Neurotoxins disrupt electrical transmissions vital to nerve and brain function. The toxin of Cylindrospermopsis is considered a cytotoxin (poisonous to most cells); its sites of action are non-specific. Most of the knowledge about the toxicity of these compounds, including dose-response interactions, comes from animal experiments. Because of the rarity of proven human exposure and resulting toxicity from direct algal exposure, there is no dose-response data or even experimental data in humans. In fact, most of the studies in which an algal bloom was blamed for toxic effects typically did not identify the algae present or the toxin(s) implicated, or both. The evidence was circumstantial, as investigations sought but did not find other established causes. The compounds implicated in taste and odor problems associated with cyanobacteria, such as geosmin, in and of themselves are not thought to pose a health risk to humans. It is important to note that cyanobacteria do not actively excrete the toxic compounds but that the toxins are released into the aquatic environment as a result of cell lysis (breaking apart of the cell and its death). This has particular ramifications for management of a bloom in that applying an algacidal agent such as copper sulfate may worsen water quality for consumption and use, since the toxins are released into the water as the algal cells die. There are data to suggest that neurotoxins degrade rapidly in the environment, but the hepatotoxic microcystins may persist for an indeterminate time.

Health effects in humans are seldom seen from blue-green algae, although reports of illness in animals are slightly more frequent. Medical literature concerning direct contact with algae is sparse and located mostly in non-U.S. medical publications. In countries around the world and in some parts of the U.S., deaths have been reported in animals (particularly pets and cattle) that drank water containing high levels of cyanobacteria, particularly in drought conditions when stagnant, contaminated water was the animals' only water source.

The toxins of freshwater cyanobacteria do not appear to bioaccumulate in fish and other edible freshwater aquatic life, as they do in marine (e.g., saltwater) organisms. This is not to say it does not occur, but unlike in seafood and shellfish harvested from brackish and saltwater habitats, toxic events from consumption of freshwater animals have not been documented or proven. By far the most prevalent adverse human health events related to algae are poisonings from consuming tainted seafood such as marine clams, oysters, and predatory fish, which can concentrate these algal toxins from many sources through bioaccumulation. The marine life itself throughout the food chain can be unaffected by the toxic byproducts of algae, such as the brevetoxin (a neurotoxin) associated with Gymnodinium breve, the red-tide marine alga.

Cyanobacteria toxins and human health:

There have been no confirmed reports in North Carolina of human illnesses or deaths attributable to blue-green algae, and less than a handful of possible animal deaths associated with blue-green algae in this state (only two events involving animals have been documented since the N.C. Division of Water Quality began investigating algal blooms in 1984). Human and animal exposures to toxic metabolites occur from direct contact with algal bloom-encrusted water or its downstream effluent. The routes of exposure are ingestion and/or immersion in affected water.

Cyanobacteria are thought to cause a wide range of symptoms in humans. Probably the most notable symptom and sign is abdominal pain with nausea, vomiting and diarrhea (epidemic gastroenteritis). Dermatologic problems (e.g., rash) and eye irritations can also occur, but there is nothing characteristic about the eruption and the literature does not discuss whether the cause is a mechanical irritation or an allergic reaction to toxic metabolites or algal components. Contact dermatitis from algae may likely appear similar to contact with poison ivy; the skin reaction may be more an exaggerated immune response to irritant properties of algal components and not necessarily indicative of its toxic potential. There is some evidence and case reports of adverse human health effects from the aerosolization of algal products. Intact algae have been identified and cultured in house dust and may be a factor in respiratory allergy. However, it should be noted that this phenomenon is not necessarily evidence that the algae are actually producing toxins; instead algal products may trigger a reaction in persons hypersensitive to environmental stimuli. There have been comparative studies of skin testing in patients with allergic (hayfever-like) symptoms and raised serum IgE levels. Algae, like many other environmental allergens such as dust, mold, and animal dander, may trigger severe allergic symptoms in people with allergies.

In a 1999 report by Ahluwalia, Microcystis aeruginosa was a causative agent for rhinosporidiosis (polyps in the nasal cavity). To date, this is the only example of invasive disease by a cyanobacterium. The transmitting agent is considered a nanocyte that free-floats in ostensibly clean water. In the paper, however, nothing was said about whether exposure came from outdoor swimming or contact with an algal bloom. In another instance, from a 1990 report by Turner, et al., two military recruits participated in canoeing exercises that implied immersion in water (water was swallowed) in which a mass of Microcystis aeruginosa was present. They subsequently had sore throats, abdominal pain with diarrhea, dry cough, blistering around the mouth, and malaise. All symptoms resolved within one week. In the investigation, it was noted that the water had unsuitably high counts of E. coli, but did not contain detectable levels of enteroviridae (a cause of hand, foot, and mouth disease which may have mimicked the mouth blisters).

The most dramatic documented event of human fatality from cyanobacterial toxins occurred in February 1996. Sixty patients with kidney failure died and 66 others were rendered ill in a hemodialysis clinic in Caruaru, Brazil, when untreated turbid water contaminated with an unspecified type of cyanobacteria was used for dialysis during a water shortage. The causative toxic agent was microcystin, a hepatotoxin. The morbidity and mortality occurred from the use of partially treated water in the dialysis procedure, which resulted in each patient's bloodstream being directly exposed to approximately 125 L of contaminated water. This breakdown in the system occurred because untreated water from the water source was trucked in, bypassing the local water treatment facility. A nearby hemodialysis clinic that was still on treated water from the same water source was unaffected. The predominant algae were never identified, and interestingly, there were no reports of similar human illness or animal effects from other exposures to the same water source. This is a unique circumstance in that this was not an environmental exposure. This is also the only instance where toxin exposure with human health effects was considered causal rather than circumstantial, as microcystins were detected in the source water, dialysate and the patients.

In some investigations the algae are implicated by circumstance, when 'the usual suspects,' e.g., bacteria, viruses and/or parasites, are not found. To illustrate: a large epidemic in Brazil involving human deaths occurred in 1988-over 2,000 residents suffered from gastroenteritis over an 8-week period, with 88 deaths. An epidemiologic investigation implicated drinking water from a reservoir, even water that had been boiled before use. Infectious agents, metals or toxins were not found; however, the cyanobacterium genera Anabaena and Microcystis were found in great quantities in untreated water from the reservoir. Algal toxins were not assayed, but the circumstantial evidence strongly implicated the cyanobacteria as the cause.

In addition to the direct effects of exposure to microcystins, there is some observational evidence that microcystins may also be promoters of carcinogenesis. At present the data are weak with strong confounders (for example, aflatoxins and hepatitis B virus have carcinogenic potential) and no human cases have been found; however, this may be of long-term concern.

It should be noted that the cyanobacterial genus Spirulina is sold as a dietary supplement in U.S. markets, ostensibly as a diet aid. While Spirulina has not been implicated as a toxin-producing blue-green alga, the full understanding of if, how and when cyanobacteria are able to produce toxic compounds is far from complete. Of more compelling concern is that there is no standard for the harvesting of blue-green algae, and Spirulina may be confused for or contaminated with a known toxin-producing cyanobacterium. In 2000, the Oregon State Department of Health surveyed 87 commercially available products of blue-green algae and found 85 of them (98%) contaminated with microcystin compounds. Dietary supplements are exempt by law from Food and Drug Administration (FDA) regulation.

Means of detection:

Blooms are not always caused by only one species of algae, but may consist of several species. Cyanobacteria can be identified, using light microscopy, by a botanist or microbiologist or other personnel trained to analyze microorganisms. Microscopy cannot determine whether the algae under examination are producing toxic compounds.

Laboratory tests of water samples can confirm whether or not a bloom is toxic. The best established method for toxicity is the mouse bioassay, in which algal components are injected into the mice's abdomens and the mice observed for effects. The LD50 (lethal dose, enough to kill 50% of the observed group) is determined by this method. This method is not suitable for field testing. Other methods to elucidate compounds of interest include liquid and gas chromatography, mass spectrometry, and ELISA (enzyme link immunosorbant assay), which can establish the presence or absence of characterized compounds known to be toxic, such as microcystins. These laboratory methods, particularly the mouse bioassay, are not readily available and are typically done by research institutions. The University of North Carolina at Wilmington conducts research on algae and their toxins, and utilizes most, if not all, of the above methods. Several forms of microcystins have been characterized, but Microcystin-LR is considered the most potent. An important caveat is that many of these toxic compounds are congeners. That is, the side-chains (or attachments) to the compounds' base chemical structure can alter the potency of the toxin. This may have implications in testing for compounds in that screening for one well-characterized toxin such as microcystin-LR may be negative while other forms of the base molecule are indeed present but not detected by the assay. The sensitivity, specificity and predictive value of these tests are not yet defined.

At present, field testing kits for toxin detection are not widely available.

Precautions to take around blooms of blue-green algae:

The likelihood of people being affected by a blue-green algae bloom is very low. Those with a predisposition to environmental allergies may have an increased risk mostly from exposure to aerosolized blue-green algae. Risk appears to be related to intensity and duration of contact, as well as route of exposure. The primary risk of exposure to toxic metabolites is from ingestion or immersion in water in direct proximity to a bloom.

During a cyanobacterial bloom, water looks and smells bad, and the inclination is to avoid such water. Older children or adults would not voluntarily drink, get close to, or swim in the water. However, younger children and animals might get in it or drink it, and so would be at higher risk from a bloom.

Therefore, to minimize the risk of direct contact one should:

• Limit exposure to water where blue-green algae are readily visible. Boating is less risky than swimming or wading; walking on the shore or fishing from a dock is less risky than being out on the water.

• Do not wade or swim in water containing visible blooms. Avoid contacting dense mats of algae unless precautions are taken to prevent direct contact.

• Do not drink the water or let children, livestock or pets get into or drink the water.

• Do not drink untreated water from water bodies regardless of whether noticeable blooms are present nearby. In addition to possible health risks from algal blooms, other gastrointestinal illnesses can also be contracted by drinking untreated water, such as giardiasis, cryptosporidiosis, hepatitis A viral infection or E. coli-related diseases.

• People who are prone to hay fever and asthma from environmental triggers should avoid algal bloom areas.

• Because of the potential for local irritation from direct skin contact, it is recommended that water-resistant gloves be used in handling and removing unwanted algae that may build up or wash up on shores and surfaces. If contact is made, clean water should be used to dilute and remove algal residues.

• Contact the county health department and (or) the regional office of the N.C. Division of Water Quality about investigating the bloom and identifying the predominant species.

• Wild animals, birds and even pets may drink and become ill from drinking algae-tainted water. If unusual numbers of dead animals are seen around a lake, that fact should be reported to the county Health Department and/or the county Animal Control section.

Conclusions:

Around the world and in the United States, researchers and public health officials are looking into blue-green algae's effect on water quality, both for drinking and recreational uses. Blue-green algae blooms are an increasing problem worldwide, clogging waterways, polluting ponds, and threatening drinking water supplies. A cyanobacteria bloom indicates that the local ecosystem is out of balance. Because of continuing eutrophication and other negative impacts on aquatic ecology, this problem will undoubtedly become worse.

Cyanobacteria and their constituents can be unsightly and unpleasant to be around. Some cyanobacteria are potentially toxic, but these effects have been more problematic in other countries, notably Australia and Canada, and primarily with respect to animals rather than humans. These two countries have large programs investigating water quality issues and causes of freshwater blooms because of the growing impact on drinking water sources. While many toxins have been described, reports of actual ill-effects from direct exposure to algae are exceedingly rare in the human medical literature and are mostly associated with the marine algae. The greatest risk for severe disease from any algae is from ingestion of contaminated water and/or contaminated shellfish, which concentrate the toxins. Adverse health effects from being in proximity to an algal bloom (other than reacting to the smell) are difficult to prove and likely depend on the individual, as some people are sensitized to environmental allergens like mold, grass, pollen, and perhaps certain algae. While there are a number of treatments for symptoms, the best method is prevention, that is, simply avoiding direct exposure.

Bibliography:

1. Ahluwalia KB. Culture of the Organism that Causes Rhinosporidiosis. J Laryng Otol 113:523-528, 1999.
2. Elder GH, Hunter PR, Codd GA. Hazardous Freshwater Cyanobacteria (Blue-Green Algae). Lancet 341:1519-20, 1993.
3. Gilroy DJ, Kauffman KW, et. al. Assessing Potential Health Risks from Microcystin Toxins in Blue-Green Algae Dietary Supplements. Environmental Health Perspectives 108(5), 435-39, 2000.
4. Jochimsen EM, Carmichael WW, et. al. Liver Failure and Death after Exposure to Microcystins at a Hemodialysis Center in Brazil. NEJM 338(13):873-878, 1998.
5. Kuiper-Goodman T, Falconer I, Fitzgerald J. "Human Health Aspects". In: Toxic Cyanobacteria in Water: A Guide to their Public Health Consequences, Monitoring and Management. Chorus, I and Bartram J (ed.), London: E &FN Spon, 1999.
6. Pouria S, de Andrade A, et. al. Fatal Microcystin Intoxication in Haemodialysis Unit in Caruaru, Brazil. Lancet 352:21-26, 1998.
7. Ressom R, Soong FS, Fitzgerald J, et. al. Health Effects of Toxic Cyanobacteria (Blue-Green Algae). National Health and Medical Research Council, Commonwealth of Australia, 1994.
8. Turner PC, Gammie AJ, et al. Pneumonia Associated with Contact with Cyanobacteria. Brit Med J 300:1440-1, 1990.

If you liked this article please let us know by signing our guestbook.