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BLUE-GREEN ALGAE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) There are numerous genera of freshwater blue-green algae. One or more species may be present during an algae "bloom". This "bloom" may range from harmless to deadly.
    B) There are several types of toxins (eg, anatoxins, microcystins, nodularins and cylindrospermopsin) involved, they are released when the algae cell dies.
    C) Cyanobacterial toxins are categorized based on the organ system involved and include: neurotoxins, hepatotoxins, cytotoxins and irritants and gastrointestinal toxins. Gastrointestinal illness is the most common organ system affected.

Specific Substances

    A) CYANOBACTERIAL SPECIES/GENERA ASSOCIATED WITH BLUE-GREEN ALGAE BLOOMS
    1) Anabaena
    2) Anabena spp.
    3) Anabaena flos-aquae
    4) Anabaena lemmermannii
    5) Anabaena torulosa
    6) Anabaena variabilis
    7) Anabaenopsis spp.
    8) Aphanocapsa spp.
    9) Aphanizomenon
    10) Aphanizomenon flos-aquae
    11) Arthrospira spp.
    12) Caelosphaerium keutzingianum
    13) Cylindrospermopsis
    14) Cylindrospermposis raciborskii
    15) Gloerichia echinulata
    16) Hapalosiphon spp.
    17) Lyngbya birgei
    18) Lyngbya majuscula
    19) Lyngbya wollei
    20) Microleus lyngbyaceus
    21) Fireweed (common name for Microleus lyngbyaceus)
    22) Blanketweed (common name for Microleus lyngbyaceus)
    23) Mermaid's hair (common name for Microleus lyngbyaceus)
    24) Seaweed itch (outbreak of Microleus lyngbyaceus)
    25) Seaweed dermatitis
    26) Stinging dermatitis
    27) Microcystis
    28) Microcystis aeruginosa
    29) Microcystis flos-aquae
    30) Microcystis incerta
    31) Microcystis viridis
    32) Microcystis wesenbergii
    33) Phormidium
    34) Planktothrix
    35) Planktothrix spp.
    36) Nodularin spp.
    37) Nolularia spumigena
    38) Nostoc spp.
    39) Nostoc rivulare
    40) Oscillatoria
    41) Oscillatoria spp.
    42) Raphidiopsis raciborskii
    43) Rhaphidiopsis
    44) Schizothrix calciola
    45) Snowella spp.
    46) Synechococcus sp
    47) Umizakia natans
    48) Woronichinia spp.
    GENERAL SYNONYMS BLUE-GREEN ALGAE
    1) Cyanobacteria
    2) Algae, blue green
    3) Blue-green Algae
    4) Cyanophytes
    5) Cyanophyceae
    6) Cyanophyta
    7) 2-acetyl-9-azabicyclo(4.2.1)non-2,3-ene
    TOXINS-ASSOCIATED WITH BLUE-GREEN ALGAE BLOOMS
    1) Anatoxins
    2) Anatoxin-a
    3) Aplysiatoxins
    4) Homoanatoxin-a
    5) Anatoxin-a(s)
    6) Lyngbyatoxin-a
    7) Microcystin
    8) Microcystins
    9) Nodularins
    10) Cylindrospermospsin
    11) CYN
    12) Debromoaplysiatoxin
    13) DAT
    14) Lyngbyatoxin A
    15) Lipopolysacharide endotoxins
    16) Very Fast Death Factor (VFDF) (term related to Anatoxin)

Available Forms Sources

    A) SOURCES
    1) DRINKING WATER - Cyanobacterial toxins have been found in drinking water supplies following cyanobacterial blooms in source waters. Cyanobacteria can inhabit fresh-, brackish, and marine waters. Cyanobacterial species are likely present in all aquatic systems. The amount species will vary depending on the nutrients (ie, agricultural fertilizer use, urban run-off and sewage discharge) and light available. Dried scum that appears on the surface of the water can appear blue-green or red through liberation of phycocyanin pigment, which leads to the familiar "blue-green algae". The blooms proliferate in warm weather and extensive blooms can appear in late summer (Dittmann & Wiegand, 2006; Falconer & Humpage, 2005).
    2) It is presumed that the increase in global temperatures will produce an increase in the proliferation of cyanobacteria. Currently, it is not uncommon to find permanent blooms of toxic cyanobacteria in drinking water reservoirs. Persistent heavy blooms of Cylindrospermopsis racibrorskii have occurred in the main reservoirs of Brisbane, Australia (Griffiths & Saker, 2003), and heavy blooms of Microcystis aeruginosa are found in in the drinking water reservoirs of Sao Paulo in Brazil. Although paralytic shellfish poisoning is more commonly reported in Mexico, cyanobacterial toxin poisoning (ie, microcystins) has been reported on the coasts of Mexico (Hernandez-Becerril et al, 2007).
    a) Livestock have been exposed to cyanobacterial toxins because of limited water sources such as ponds or small lakes found on ranches or farms. However, human exposure to contaminated drinking water containing cyanobacterial toxins have produced illness (Falconer & Humpage, 2005). In general, the risk of human intoxication increases with bloom density and as cell lysis occurs (Dittmann & Wiegand, 2006).
    3) The largest known human poisoning by cyanobacterial toxins (in particular microcystins and cylindrospermopsins) occurred in renal dialysis patients in Brazil. Poisoning occurred from direct exposure to the toxins through renal dialysis (ie, perfusion) due to contaminated filters. Multiple deaths were reported (Falconer & Humpage, 2005).
    B) USES
    1) FOOD SUPPLEMENTS - Supplements containing blue-green algae are available. These products may be combined with a wide variety of nutrients, minerals and vitamins. Most of these products are derived from the Spirulina species or Aphanizomenon flos aquae cultures. They can purportedly improve memory, increase energy, relieve exhaustion, depression and premenstrual syndrome. Contamination of these products by toxin-producing strains of algae has led to the detection of microcystins in some products (Dittmann & Wiegand, 2006).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdcd.gov.
    b) ACUTE SYMPTOMS
    1) GENERAL - Ingestion of concentrations high enough to cause serious toxicity is uncommon. Gastrointestinal effects following ingestion and dermatitis following contact are the most common effects. Pneumonia (uncommon), sore throat, fever, vomiting, diarrhea, lassitude, rhinitis, conjunctivitis, perioral blisters, dermatitis, mild liver enzyme elevations, and electrolyte imbalance have been reported. Symptoms are generally mild, but may be severe.
    2) Microcystin - Clinical evidence of hepatotoxicity (ie, elevated liver enzymes), vomiting, diarrhea, abdominal pain, malaise and rash.
    3) Nodularin - Hepatotoxicity, renal damage and skin and eye irritation with dermal contact.
    4) Lyngbyatoxin - Very few documented exposures: dermal irritation, blistering following marine exposure; freshwater exposures are rare. Other dermatologic symptoms may include: acute lesions, itching, burning and/or red skin, blisters, sore eyes. Respiratory: Asthma-like symptoms; GI: Upper GI inflammation upon ingestion. Other: Headache.
    c) CHRONIC SYMPTOMS
    1) At the time of this review, limited data available.
    2) Microcystin - Liver failure
    d) FATALITY RATE
    1) At the time of this review, limited data available.
    2) Microcystin contamination of water used in hemodialysis was associated with a 76% fatality rate.
    e) TIME TO ONSET OF SYMPTOMS
    1) GENERAL - GASTROINTESTINAL effects usually occur within 3 to 5 hours with abdominal cramping, diarrhea, nausea and vomiting.
    2) Anatoxin-a or Anatoxin-a(s) - Minutes to hours
    3) Microcystin - contamination of hemodialysis: less than 24 hours; other type of exposures: Unknown
    4) Lyngbyatoxin - Less than 24 hours
    5) Nodularin - Unknown
    f) DURATION
    1) Usually 1 to 2 days.
    g) CAUSATIVE ORGANISM
    1) Anatoxin-a - Anabaena spp., Aphanizomenon spp., Planktothrix spp.; Phormidium, Rhaphidiopsis, and Oscillatoria spp.
    2) Anatoxin-a(s) - Anabaena flos-aquae
    3) Microcystin - Microcystis aeruginosa, M. virdis, M. wesenbergii, Anabena spp., Anabaenopsis spp., Aphanocapsa spp., Arthrospira spp., Hapalosiphon spp., Oscillatoria spp., Nostoc spp., Planktothrix spp., Snowella spp., Woronichinia spp., Synechococcus sp.
    4) Nodularin - Nodularia spumigena, Nodularin spp.
    5) Lyngbya majuscula (marine species), other Lyngya spp.
    h) TOXINS
    1) Anatoxin-a - Anatoxin-a (alkaloid neurotoxin); Very Fast Death Factor (VFDF) (as seen in experiments with laboratory mice); CAS 64285-06-9
    2) Anatoxin-a(s) - Anatoxin-a(s); CAS 103170-78-1
    3) Nodularin - Nodularin (peptides with 9 amino acids); CAS 118399-22-7
    4) Microcystins (series of cyclic peptides with 7 amino acids; CAS 77238-39-2
    5) Lyngbya species (dermatoxins) are thought to produce a number of toxins in varying quantities although toxin production is not always found. Known dermatoxins produced are indole alkaloids called Lyngbyatoxin-a and aplysiatoxins (specifically debromoaplysiatoxin); Lyngbya wollei has also been shown to produce neosaxitoxins.
    i) ROUTE OF EXPOSURE
    1) Anatoxin-a or Anatoxin-a(s) - Ingesting contaminated water. In dogs, intoxication may occur after coming in contact with contaminated water.
    2) Microcystin - Ingesting contaminated water, using contaminated water for hemodialysis. Other sources are theoretical; no documented human poisonings: fish and shellfish (eg, Tilapia, fish and shellfish (Brazil)); lettuce contaminated by irrigation, blue-green algae dietary supplement; aerosols.
    3) Nodularin - Unknown
    4) Lyngbyatoxin - Skin contact with contaminated water.
    j) VECTOR
    1) Anatoxin-a or Anatoxin-a(s) - Contaminated water.
    2) Lyngbyatoxin is only found in marine waters.
    3) Microcystin - Contaminated water. Other possible sources are theoretical no documented human poisoning: fish and shellfish (eg, Tilapia, fish and shellfish (Brazil)); lettuce contaminated by irrigation, blue-green algae dietary supplement; aerosols.
    4) Nodularin - Fresh and brackish water
    k) DOSE
    1) Anatoxin-a - Mouse: LD50 (IP) - 250 to 375 mcg/kg
    2) Anatoxin-a(s) - Mouse: LD50 - 20 to 40 mcg/kg
    3) Microcystin - Mouse: LD50 - 45 to 1000 mcg/kg
    4) Nodularin - Mouse: LD50 - 30 to 50 mcg/kg
    l) MECHANISM
    1) Anatoxin-a - Blocks post-synaptic depolarization, mimics acetylcholine
    2) Anatoxin-a(s) - Naturally occurring organophosphate, anticholinesterase
    3) Microcystin - Alterations of actin micorfilaments, destruction of parenchymal cells, lethal hemorrhage, or hepatic insufficiency. Inhibition of protein phosphatases. Possible skin irritant; tumor promoter.
    4) Nodularin - Inhibition of protein phosphatases; tumor promoter
    5) Lyngbyatoxin - Dermatotoxic alkaloid; potent tumor promoter; highly inflammatory response
    m) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Anatoxin-a or Anatoxin-a(s) - Fresh waters
    2) Microcystin - Fresh water found worldwide; brackish water
    3) Lyngbyatoxin - Tropical, subtropical and temperate climates
    4) Nodularin - Unknown
    n) DIFFERENTIAL DIAGNOSIS
    1) Anatoxin-a or Anatoxin-a(s) - Pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, or other aquatic toxin poisonings
    2) Microcystin poisoning: Rule out nodularin poisoning.
    3) Nodularin poisoning: Rule out microcystin poisoning.
    4) Lyngbyatoxin poisoning: Possible chemical burn; exposure to another dermatologic irritant, possible brevetoxin skin poisoning.
    o) DIAGNOSIS
    1) History of swimming in bloom waters; head immersion and/or accidental swallowing of bloom water. Demonstration of algal cells in feces; toxin demonstrated in blood (other tissues and body fluids at autopsy such as liver and vitreous fluid). Absence of other types of algal toxin and cells.
    2) Microcystin - Evidence of hepatic dysfunction and history of exposure.
    3) Nodularin - Unknown
    p) SUSPECT CASE
    1) GENERAL - Exposure to water with a cyanobacteria water bloom and onset of weakness and or difficulty breathing.
    2) Microcystin - Gastrointestinal or dermal symptoms and ingestion or contact with contaminated water with a cyanobacteria water bloom. Development of jaundice, visual disturbances, abdominal pain, nausea, vomiting, bad taste in mouth, and routine dialysis with contaminated water source.
    3) Nodularin - A possible case, acute symptoms and exposure to waters suspected to contain nodularin.
    4) Lyngbyatoxin - Exposure to a cyanobloom and onset of dermal symptoms within 24 hours.
    q) CONFIRMED CASE
    1) Anatoxin-a or Anatoxin-a(s) or Microcystin - Suspect case and confirmation of one of the toxins found in clinical specimen or water.
    2) Lyngbyatoxin - Suspect case and confirmation of lyngbyatoxins in environmental samples or clinical specimens; the threshold for exposure is not know, but presumed to be a concentrated or relevant amount, not just presence or absence.
    r) ANIMAL SENTINEL DATA
    1) Anatoxin-a or Anatoxin-a(s) - Domestic animals (in particular dogs) may be the first victims of a toxin-producing bloom. Birds may also become ill.
    2) Microcystin - Evidence of acute liver failure in domestic or wild animals; often fatal
    3) Lyngbyatoxin - none known
    s) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Fever has been reported following exposure to water contaminated with cyanobacteria.
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Human effects include conjunctivitis, earache, swollen lips, and headache.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Atypical pneumonia and a hay-fever like syndrome have been reported.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Headache and malaise have occurred in humans. Partial paralysis and respiratory paralysis has been reported in animals and birds.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Human reports include nausea, vomiting and diarrhea. Cases may appear as enteritis or amebic dysentery. Onset is 3 to 5 hours post ingestions, with recovery in 1 to 2 days.
    0.2.9) HEPATIC
    A) WITH POISONING/EXPOSURE
    1) Elevated liver enzymes were documented in residents who drank from a contaminated reservoir.
    2) Hepatic failure occurred in dialysis patients from microcystin contaminated water.
    0.2.10) GENITOURINARY
    A) WITH POISONING/EXPOSURE
    1) Glycosuria, proteinuria, and occasionally hematuria have been reported.
    0.2.15) MUSCULOSKELETAL
    A) WITH POISONING/EXPOSURE
    1) Humans have reported muscle weakness and pain in the limbs and joints.
    0.2.17) METABOLISM
    A) Anatoxin A is known to have anticholinesterase activity, based on effects in animals.

Laboratory Monitoring

    A) Methods of identifying cyanobacteria from stool and vomitus, and for differentiating cyanobacteria-like bodies from cyanobacteria, are available. However, diagnosis is based on characteristic symptoms in most cases, along with testing the suspected contaminated seafood to support the diagnosis.
    B) To aid in diagnosis, feces and stomach contents may be examined for the presence of cyanobacterial cells.
    C) Monitor fluid and serum electrolytes in patients who experience severe vomiting or diarrhea or prolonged symptoms.
    D) Monitor liver enzymes in patients with persistent symptoms.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Gastroenteritis symptoms are likely to occur following a significant exposure. Replace fluids and electrolytes as needed.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Serious complications are NOT anticipated following exposure. Hepatotoxicity has been reported infrequently. Monitor liver enzymes in patients with persistent symptoms. Rare reports of toxicity occurred following exposure to contaminated dialysate fluid. Inhalation or aspiration of contaminated water has resulted in rare cases of atypical pneumonia and respiratory symptoms. Monitor respiratory function in symptomatic patients; obtain a chest radiograph and provide supportive care.
    C) DECONTAMINATION
    1) PREHOSPITAL: DERMAL EXPOSURE: Symptoms are usually limited to the 'bathing suit' area, and may include intense burning and eruptions on the skin. Prompt showering/washing after swimming in potentially contaminated water may help to avoid or minimize symptoms. ORAL EXPOSURE: Treatment is not indicated.
    2) HOSPITAL: Gastric decontamination is unlikely to be necessary. Many of the toxins appear to be quickly absorbed and spread throughout the water ingested. Vomiting and diarrhea are common symptoms associated with possible ingestion of contaminated water.
    D) AIRWAY MANAGEMENT
    1) Although not reported in humans, respiratory failure is a primary cause of death in animals. Assess airway; support airway as indicated.
    E) PATIENT DISPOSITION
    1) HOME MANAGEMENT: Mild symptoms can likely be treated at home. Laboratory confirmation may be necessary in cases of a suspected outbreak of cyanobacteria.
    2) OBSERVATION MANAGEMENT: Patients with severe gastrointestinal symptoms may require IV fluid replacement and to be observed for several hours until able to tolerate liquids.
    3) ADMISSION CRITERIA: Unlikely to be necessary; patients with alterations in respiratory function or evidence of hepatotoxicity made need to be admitted.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) TOXIC DOSE: A toxic dose for humans has not been established. There are numerous toxic substances involved with various toxic doses. The toxin(s) concentration may vary from day to day during any particular bloom.
    B) ANIMAL DATA: Animal minimum lethal doses range from 10 to 40 mg/kg.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdcd.gov.
    b) ACUTE SYMPTOMS
    1) GENERAL - Ingestion of concentrations high enough to cause serious toxicity is uncommon. Gastrointestinal effects following ingestion and dermatitis following contact are the most common effects. Pneumonia (uncommon), sore throat, fever, vomiting, diarrhea, lassitude, rhinitis, conjunctivitis, perioral blisters, dermatitis, mild liver enzyme elevations, and electrolyte imbalance have been reported. Symptoms are generally mild, but may be severe.
    2) Microcystin - Clinical evidence of hepatotoxicity (ie, elevated liver enzymes), vomiting, diarrhea, abdominal pain, malaise and rash.
    3) Nodularin - Hepatotoxicity, renal damage and skin and eye irritation with dermal contact.
    4) Lyngbyatoxin - Very few documented exposures: dermal irritation, blistering following marine exposure; freshwater exposures are rare. Other dermatologic symptoms may include: acute lesions, itching, burning and/or red skin, blisters, sore eyes. Respiratory: Asthma-like symptoms; GI: Upper GI inflammation upon ingestion. Other: Headache.
    c) CHRONIC SYMPTOMS
    1) At the time of this review, limited data available.
    2) Microcystin - Liver failure
    d) FATALITY RATE
    1) At the time of this review, limited data available.
    2) Microcystin contamination of water used in hemodialysis was associated with a 76% fatality rate.
    e) TIME TO ONSET OF SYMPTOMS
    1) GENERAL - GASTROINTESTINAL effects usually occur within 3 to 5 hours with abdominal cramping, diarrhea, nausea and vomiting.
    2) Anatoxin-a or Anatoxin-a(s) - Minutes to hours
    3) Microcystin - contamination of hemodialysis: less than 24 hours; other type of exposures: Unknown
    4) Lyngbyatoxin - Less than 24 hours
    5) Nodularin - Unknown
    f) DURATION
    1) Usually 1 to 2 days.
    g) CAUSATIVE ORGANISM
    1) Anatoxin-a - Anabaena spp., Aphanizomenon spp., Planktothrix spp.; Phormidium, Rhaphidiopsis, and Oscillatoria spp.
    2) Anatoxin-a(s) - Anabaena flos-aquae
    3) Microcystin - Microcystis aeruginosa, M. virdis, M. wesenbergii, Anabena spp., Anabaenopsis spp., Aphanocapsa spp., Arthrospira spp., Hapalosiphon spp., Oscillatoria spp., Nostoc spp., Planktothrix spp., Snowella spp., Woronichinia spp., Synechococcus sp.
    4) Nodularin - Nodularia spumigena, Nodularin spp.
    5) Lyngbya majuscula (marine species), other Lyngya spp.
    h) TOXINS
    1) Anatoxin-a - Anatoxin-a (alkaloid neurotoxin); Very Fast Death Factor (VFDF) (as seen in experiments with laboratory mice); CAS 64285-06-9
    2) Anatoxin-a(s) - Anatoxin-a(s); CAS 103170-78-1
    3) Nodularin - Nodularin (peptides with 9 amino acids); CAS 118399-22-7
    4) Microcystins (series of cyclic peptides with 7 amino acids; CAS 77238-39-2
    5) Lyngbya species (dermatoxins) are thought to produce a number of toxins in varying quantities although toxin production is not always found. Known dermatoxins produced are indole alkaloids called Lyngbyatoxin-a and aplysiatoxins (specifically debromoaplysiatoxin); Lyngbya wollei has also been shown to produce neosaxitoxins.
    i) ROUTE OF EXPOSURE
    1) Anatoxin-a or Anatoxin-a(s) - Ingesting contaminated water. In dogs, intoxication may occur after coming in contact with contaminated water.
    2) Microcystin - Ingesting contaminated water, using contaminated water for hemodialysis. Other sources are theoretical; no documented human poisonings: fish and shellfish (eg, Tilapia, fish and shellfish (Brazil)); lettuce contaminated by irrigation, blue-green algae dietary supplement; aerosols.
    3) Nodularin - Unknown
    4) Lyngbyatoxin - Skin contact with contaminated water.
    j) VECTOR
    1) Anatoxin-a or Anatoxin-a(s) - Contaminated water.
    2) Lyngbyatoxin is only found in marine waters.
    3) Microcystin - Contaminated water. Other possible sources are theoretical no documented human poisoning: fish and shellfish (eg, Tilapia, fish and shellfish (Brazil)); lettuce contaminated by irrigation, blue-green algae dietary supplement; aerosols.
    4) Nodularin - Fresh and brackish water
    k) DOSE
    1) Anatoxin-a - Mouse: LD50 (IP) - 250 to 375 mcg/kg
    2) Anatoxin-a(s) - Mouse: LD50 - 20 to 40 mcg/kg
    3) Microcystin - Mouse: LD50 - 45 to 1000 mcg/kg
    4) Nodularin - Mouse: LD50 - 30 to 50 mcg/kg
    l) MECHANISM
    1) Anatoxin-a - Blocks post-synaptic depolarization, mimics acetylcholine
    2) Anatoxin-a(s) - Naturally occurring organophosphate, anticholinesterase
    3) Microcystin - Alterations of actin micorfilaments, destruction of parenchymal cells, lethal hemorrhage, or hepatic insufficiency. Inhibition of protein phosphatases. Possible skin irritant; tumor promoter.
    4) Nodularin - Inhibition of protein phosphatases; tumor promoter
    5) Lyngbyatoxin - Dermatotoxic alkaloid; potent tumor promoter; highly inflammatory response
    m) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Anatoxin-a or Anatoxin-a(s) - Fresh waters
    2) Microcystin - Fresh water found worldwide; brackish water
    3) Lyngbyatoxin - Tropical, subtropical and temperate climates
    4) Nodularin - Unknown
    n) DIFFERENTIAL DIAGNOSIS
    1) Anatoxin-a or Anatoxin-a(s) - Pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, or other aquatic toxin poisonings
    2) Microcystin poisoning: Rule out nodularin poisoning.
    3) Nodularin poisoning: Rule out microcystin poisoning.
    4) Lyngbyatoxin poisoning: Possible chemical burn; exposure to another dermatologic irritant, possible brevetoxin skin poisoning.
    o) DIAGNOSIS
    1) History of swimming in bloom waters; head immersion and/or accidental swallowing of bloom water. Demonstration of algal cells in feces; toxin demonstrated in blood (other tissues and body fluids at autopsy such as liver and vitreous fluid). Absence of other types of algal toxin and cells.
    2) Microcystin - Evidence of hepatic dysfunction and history of exposure.
    3) Nodularin - Unknown
    p) SUSPECT CASE
    1) GENERAL - Exposure to water with a cyanobacteria water bloom and onset of weakness and or difficulty breathing.
    2) Microcystin - Gastrointestinal or dermal symptoms and ingestion or contact with contaminated water with a cyanobacteria water bloom. Development of jaundice, visual disturbances, abdominal pain, nausea, vomiting, bad taste in mouth, and routine dialysis with contaminated water source.
    3) Nodularin - A possible case, acute symptoms and exposure to waters suspected to contain nodularin.
    4) Lyngbyatoxin - Exposure to a cyanobloom and onset of dermal symptoms within 24 hours.
    q) CONFIRMED CASE
    1) Anatoxin-a or Anatoxin-a(s) or Microcystin - Suspect case and confirmation of one of the toxins found in clinical specimen or water.
    2) Lyngbyatoxin - Suspect case and confirmation of lyngbyatoxins in environmental samples or clinical specimens; the threshold for exposure is not know, but presumed to be a concentrated or relevant amount, not just presence or absence.
    r) ANIMAL SENTINEL DATA
    1) Anatoxin-a or Anatoxin-a(s) - Domestic animals (in particular dogs) may be the first victims of a toxin-producing bloom. Birds may also become ill.
    2) Microcystin - Evidence of acute liver failure in domestic or wild animals; often fatal
    3) Lyngbyatoxin - none known
    s) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Fever has been reported following exposure to water contaminated with cyanobacteria.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) FEVER: Pyrogenic reactions have been reported in patients on hemodialysis using water contaminated with lipopolysaccharides, possibly from cyanobacteria in the local water supply (Hindman et al, 1975). Testing of the public water supply for total microbes and cyanobacterial speciation were not performed; gram negative microbes may also have been a source of endotoxin.
    a) Fever has occurred following ingestion of contaminated water (Giannuzzi et al, 2011; Codd et al, 2005; Dillenberg & Dehnel, 1960; Hayman, 1992).
    2) HYPOTHERMIA: Subnormal temperatures were reported in poisoned animals (Deem & Thorp, 1939).

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Human effects include conjunctivitis, earache, swollen lips, and headache.
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CONJUNCTIVITIS: Contact conjunctivitis has occurred in humans (Bourke & Hawes, 1983; El Saadi & Cameron, 1993).
    2) Visual disturbances have been reported following human cases of cyanobacterial exposure (Codd et al, 2005)
    3) CASE SERIES: In a series of 131 patients with dialysis dependent renal failure who received hemodialysis with water contaminated with cyanotoxins (microcystins and cylindrospermopsin) 116 (89%) developed visual disturbances (Carmichael et al, 2001).
    3.4.4) EARS
    A) WITH POISONING/EXPOSURE
    1) EARACHE, contact conjunctivitis, and swollen lips occurred in humans after swimming in a lake contaminated with Anabaena species (Bourke & Hawes, 1983).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) RHINITIS can occur (Elder et al, 1993).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) SORE THROAT has occurred in humans who swallowed cyanobacteria-contaminated water (Codd et al, 2005). It has been reported in individuals following canoeing exercises (Turner et al, 1990).

Cardiovascular

    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEMORRHAGE
    a) Petechial hemorrhages of the heart are a consistent autopsy finding in animals (Senior, 1960).

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Atypical pneumonia and a hay-fever like syndrome have been reported.
    3.6.2) CLINICAL EFFECTS
    A) PNEUMONIA
    1) WITH POISONING/EXPOSURE
    a) Atypical pneumonia has been reported (Elder et al, 1993). Microcystin intoxication has reportedly produced pneumonia (Dittmann & Wiegand, 2006).
    b) ROUTE OF EXPOSURE: Pulmonary exposure either by inhalation or aspiration may occur following exposure to contaminated water, aerosols, water spray during recreation, work and showering (Codd et al, 2005).
    c) CASE SERIES: Pneumonia developed in 2 individuals 4 to 5 days after canoeing exercises in a reservoir contaminated with cyanobacteria (Turner et al, 1990). Ingestion of the water was suspected.
    d) CASE REPORT: A 19-year-old man, who was practicing watersports in Salto Grande dam, Argentina, experienced nausea, vomiting, and muscle weakness 4 hours after being immersed in the water for 2 hours. The patient's condition progessively worsened over the next 72 hours post-exposure, presenting to the hospital with dyspnea, hypoxemia (PO2 40 mmHg), nausea, abdominal pain, and fever, leading to a diagnosis of atypical pneumonia. A chest x-ray and lung CT scan revealed bilateral interstitial infiltrates in the lower lobes. In addition, he also developed hepatotoxicity and acute renal failure. With supportive therapy, the patient gradually recovered and was discharged without sequelae. Analysis of water samples at the Salto Grande dam revealed the presence of cyanobacterial blooms with high levels of Microcystin-LR (48.6 +/-15 mcg/L) (Giannuzzi et al, 2011).
    B) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) A hay-fever-like syndrome was reported by Bourke and Hawes (1983) (Bourke & Hawes, 1983).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PARALYSIS
    a) Anatoxin-a (very fast death factor found in Anabaena) is an alkaloid which causes pre- and post-synaptic neuromuscular blockage which is not reversed by edrophonium or neostigmine.
    b) It causes respiratory paralysis in mammals and seizures in fowl (Beasley et al, 1983; Mahmood et al, 1988).
    2) THROMBOSIS PULMONARY
    a) The pentapeptide found in M. aeruginosa caused pulmonary thrombosis in injected mice (Slatkin et al, 1983).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Headache and malaise have occurred in humans. Partial paralysis and respiratory paralysis has been reported in animals and birds.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache has been reported following ingestion (Dillenberg & Dehnel, 1960; Hayman, 1992) and canoeing exercises which may have resulted in ingestion of contaminated water (Turner et al, 1990).
    B) MALAISE
    1) WITH POISONING/EXPOSURE
    a) Malaise can occur (Hayman, 1992).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PARALYSIS
    a) Partial paralysis occurs in both animals and birds (Deem & Thorp, 1935). Aphanizomenon species contain a potent nerve and muscle blocking agent (Sawyer et al, 1968). Anatoxin-A (very fast death factor found in Anabaena) is an alkaloid which causes pre and postsynaptic neuromuscular blockage which is not reversed by edrophonium or neostigmine.
    b) Respiratory paralysis has been reported in mammals and seizures in fowl (Beasley et al, 1983; Mahmood et al, 1988).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Human reports include nausea, vomiting and diarrhea. Cases may appear as enteritis or amebic dysentery. Onset is 3 to 5 hours post ingestions, with recovery in 1 to 2 days.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting and diarrhea occur following human exposure to these toxins (Giannuzzi et al, 2011; Dittmann & Wiegand, 2006; Codd et al, 2005; Bourke & Hawes, 1983; Spoerke & Rumack, 1985; Turner et al, 1990; Elder et al, 1993; El Saadi et al, 1995).
    b) Seasonal outbreaks of microcystin cases have been reported in the US (along the Ohio River) during summer months following inadequate drinking water purification (Dittmann & Wiegand, 2006).
    c) ROUTE OF EXPOSURE: Oral exposure may occur via the following: drinking water, recreational water, food (eg, shellfish, fin fish) if toxin accumulation has occurred during production; plant food (ie, lettuce) irrigated with water containing cyanobacterial toxins or dietary supplements (pills or capsules) that may contain dried cyanobacterial cells with toxins (Codd et al, 2005).
    d) Cases may appear as amebic dysentery. Onset is 3 to 5 hours, with recovery in 1 to 2 days (Dillenberg & Dehnel, 1960; Libby & Erb, 1976).
    e) These organisms or cyanobacteria-like bodies have been found in the stools of affected persons (Suave et al, 1986; (Hart et al, 1990; Long et al, 1990).
    f) CASE SERIES: In a series of 131 patients with dialysis dependent renal failure who received hemodialysis with water contaminated with cyanotoxins (microcystins and cylindrospermopsin) 116 (89%) developed nausea and vomiting (Carmichael et al, 2001).
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain has been reported (Giannuzzi et al, 2011; Codd et al, 2005; Turner et al, 1990).
    C) BLISTER
    1) WITH POISONING/EXPOSURE
    a) Blistering around the mouth has occurred in humans exposed to algal bloom of Microcystis aeruginosa (Turner et al, 1990; Edney, 1990) and contact with water contaminated with Anabaena circinalis and other cyanobacteria (El Saadi & Cameron, 1993; El Saadi et al, 1995).
    b) MICROCOLEUS LYNGBYACEUS ("Stinging Seaweed"): Intense burning of the lips, tongue, and mouth were reported in an adult after chewing on Microcoleus lyngbyaceus thought to be another type of seaweed. The patient immediately spit out the seaweed, but the symptoms were described as an excruciating burning sensation. Symptomatic treatment including local application of viscous lidocaine did not provide any pain relief; only ice temporarily relieved symptoms. Twenty four hours after exposure the patient was reexamined and the mucous membranes appeared scalded, with several erosive lesions. The patient was free of pain approximately 3 days after exposure, and within 2 weeks the area was completely healed (Sims & ZandeevanRilland, 1981). Its suggested that an actual ingestion of this seaweed would produce severe oropharyngeal, esophageal and gastric toxicity.
    D) LOSS OF APPETITE
    1) WITH POISONING/EXPOSURE
    a) Anorexia may occur (Hayman, 1992).

Hepatic

    3.9.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Elevated liver enzymes were documented in residents who drank from a contaminated reservoir.
    2) Hepatic failure occurred in dialysis patients from microcystin contaminated water.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Elevated liver enzymes (gamma-glutamyl-transpeptidase and alanine aminotransferase) have been documented in residents who drank from a contaminated reservoir. Enzyme levels were normal before and after the cyanobacteria's bloom period (Falconer et al, 1983; Hawkins et al, 1985).
    b) CASE REPORT: A 19-year-old man, who was practicing watersports in Salto Grande dam, Argentina, developed hepatotoxicity approximately 3 days after having been immersed in the water for 2 hours. Five days post-admission, his maximum liver enzyme levels were as follows: ALT 427 international units/L (10 fold higher than normal), AST 330 international units/L (9 fold higher than normal), gamma-glutamyltransferase 343 international units/L (6 fold higher than normal). In addition, he also developed respiratory distress and acute renal failure. With supportive therapy, the patient gradually recovered and was discharged without sequelae. Analysis of water samples at the Salto Grande dam revealed the presence of cyanobacterial blooms with high levels of Microcystin-LR (48.6 +/-15 mcg/L) (Giannuzzi et al, 2011).
    B) LARGE LIVER
    1) WITH POISONING/EXPOSURE
    a) Cylindrospermopsin is a known hepatotoxin, however the bioavailability of the toxin to humans following consumption of contaminated fish or shellfish is unknown (Griffiths & Saker, 2003).
    b) Tender hepatomegaly was present after Cylindrospermopsis raciborskii ingestion (Hayman, 1993).
    C) HEPATIC FAILURE
    1) WITH POISONING/EXPOSURE
    a) At a Brazil dialysis center in 1996, 131 patients developed abdominal pain, nausea, vomiting dizziness, lethargy, myalgia, and in severe cases, visual disturbances and grand mal seizures, associated with hemodialysis. One hundred patients developed liver failure. One month later, 25 patients had died. Within 7 months, approximately 60 patients had died either from direct hepatotoxic effects or indirectly from complications, such as sepsis, gastrointestinal bleeding, and cardiovascular disturbances.
    1) It was determined, by enzyme-linked immunoabsorbent assay (ELISA), that the water used at the dialysis center came from a reservoir contaminated with microcystins and cylindrospermiopsin produced by cyanobacteria. Serum and liver samples taken before and after death confirmed the presence of microcystins (Carmichael et al, 2001; Jochimsen et al, 1998; Pouria et al, 1998).
    b) ROUTE OF EXPOSURE: Water used for hemodialysis containing cyanobacterial toxins (Codd et al, 2005).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Elevated liver enzymes have been documented in animals that drank from a contaminated reservoir. These elevated enzymes were not associated with illness (Falconer et al, 1983).
    b) Hepatoenteritis and toxic liver injury is common with M. aeruginosa (Bourke & Hawes, 1983; Jackson et al, 1984; Galey et al, 1987). A distinct hemorrhagic necrosis of the liver has occurred in animals (Carmichael et al, 1985) Yu et al, 1990).
    c) Lesions shown by electron microscope were aggregation of endoplasmic reticulum with displacement of subcellular organelles, toward the edges of the hepatocyte and vacuolation of the contents of severely affected cells (Jackson et al, 1984).

Genitourinary

    3.10.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Glycosuria, proteinuria, and occasionally hematuria have been reported.
    3.10.2) CLINICAL EFFECTS
    A) ALBUMINURIA
    1) WITH POISONING/EXPOSURE
    a) Patients with "Palm Island Mystery Disease", believed to be from drinking water contaminated with Cyclindrospermopsis raciborskii, developed glycosuria, proteinuria, ketonuria, and occasionally hematuria (Byth, 1980; Hayman, 1992). Copper poisoning may have contributed to these effects (Prociv, 1987).
    B) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 19-year-old man, who was practicing watersports in Salto Grande dam, Argentina, developed acute renal failure approximately 3 days after having been immersed in the water for 2 hours. His serum creatinine and BUN concentrations peaked at 2.4 mg/dL and 128 mg/dL, respectively. In addition, he also developed respiratory distress and elevated liver enzyme levels. With supportive therapy, the patient gradually recovered and was discharged without sequelae. Analysis of water samples at the Salto Grande dam revealed the presence of cyanobacterial blooms with high levels of Microcystin-LR (48.6 +/-15 mcg/L) (Giannuzzi et al, 2011).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) THROMBOCYTOPENIA
    a) The pentapeptide found in M. aeroginosa caused thrombocytopenia and pulmonary thrombi when injected into mice (Slatkin et al, 1983).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) SEAWEED DERMATITIS OR SWIMMER'S ITCH: Rashes, itching and/or blistering have been reported in persons who had contact with water which had confirmed or suspected cyanobacteria (ie, microcoleus lyngbyaceus) contamination (Osborne et al, 2001; Soong et al, 1992; El Saadi & Cameron, 1993; El Saadi et al, 1995; Izumi & Moore, 1987). The pattern of exposure usually occurs after swimming in water that has seaweed filaments for minutes to hours followed by the continual wearing of a swim suit without immediate showering (GRAUER & ARNOLD, 1961).
    b) ONSET: Visible dermatitis with redness can begin after 3 to 8 hours. This is typically followed by blisters and deep desquamation which can be painful. Characteristically, eruptions occur in areas covered by a bathing suit. The duration of exposure correlates with the extent of symptoms (GRAUER & ARNOLD, 1961).
    c) CASE REPORT: A human developed allergic erythematous papulovesicular dermatitis after swimming in contaminated water (Bourke & Hawes, 1983).
    B) ERYTHEMA
    1) WITH POISONING/EXPOSURE
    a) Outbreaks of dermatitis in swimmers have been reported following exposure to cyanobacteria L. majuscula (also known as Microcoleus lyngbyaceus). Initial symptoms usually begin several hours after exposure and usually include erythema and a burning sensation. Blister formation and deep desquamation can follow. In several studies, patch testing has confirmed that L. majuscula can produce acute toxic dermatitis (GRAUER & ARNOLD, 1961).
    b) ONSET: Gradual itching and burning within a few minutes to a few hours after swimming and visible dermatitis with redness usually occurs 3 to 8 hours after exposure (GRAUER & ARNOLD, 1961).
    c) SYMPTOMS: Individuals may experience all of the following: itching, rash, burning, blisters, deep desquamation, and pain. Areas most likely affected are the genitals, eyes and lips (GRAUER & ARNOLD, 1961).
    d) TOXINS: Debromoaplysiatoxin and aplysiatoxins are dermatoxic alkaloids that can produce an inflammatory response (Katircioglu et al, 2004).

Musculoskeletal

    3.15.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Humans have reported muscle weakness and pain in the limbs and joints.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Humans have reported muscle weakness and pain (Giannuzzi et al, 2011; Dillenberg & Dehnel, 1960).
    B) JOINT PAIN
    1) WITH POISONING/EXPOSURE
    a) Pain in the limbs and joints have occurred in exposed humans (Dillenberg & Dehnel, 1960).
    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PARALYSIS
    a) Animals have developed progressive muscle weakness, progressing to paralysis (McLeod & Bondar, 1952).

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNE SYSTEM DISORDER
    a) Intraperitoneal injection of cyanobacteria cells caused suppression of the number of plaque-forming cells in mice at high doses (0.4 mg/mouse) and lower concentrations (0.2 mg/mouse) caused immunostimulation (Mundt et al, 1991).
    2) IN-VITRO STUDIES
    a) Cyanobacterial extracts inhibited (3)H-thymidine incorporation into mitogen-stimulated human lymphocytes (Mundt et al, 1991).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) A study in Serbia revealed that statistically significant differences in the incidence of 10 cancer types (brain cancer; heart, mediastinum and pleura cancer; ovarian cancer; testicular cancer; gastric cancer; colorectal cancer; retroperitoneum and peritoneum cancer; leukemia; malignant melanoma of the skin; and primary liver cancer) could be correlated with cyanobacterial blooms in drinking water reservoirs (Svircev et al, 2014).
    B) CARCINOMA
    1) In a study conducted in China, exposure to cyanobacteria in drinking water was associated with an increased risk of hepatocellular carcinoma (Falconer, 1999).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) In an animal study, microcystins were potent tumor promoters (Nishiwaki-Matsuchima & Ohta, 1992).

Genotoxicity

    A) Microcystis aeruginosa extracts fed to rats caused mutagenesis, and a cyanobacterial bloom was associated with a high human birth defect rate (Bourke & Hawes, 1983).

Laboratory Monitoring

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Methods of identifying cyanobacteria from stool and vomitus (Elder et al, 1993), and for differentiating cyanobacteria-like bodies from cyanobacteria, are available (Long et al, 1991; McIntyre & Lyons, 1992; Gascon et al, 1993).
    2) ELISA - Sera samples from hemodialysis patients were used to confirm the presence of microcystin following a cyanobacterial bloom which contained Microcystis and Anabaena toxins that contaminated a drinking water supply in Brazil. Serum microcystin concentrations ranged from less than 0.16 to 0.96 ng/mL during the 2 month sampling period (Soares et al, 2006).
    3) The toxic heptapeptides from Microcystis aeruginosa can be identified and purified by HPLC (Runnegar et al, 1986). ODS-silica gel cartridge and high performance liquid chromatography with ODS-gel is an effective method (Watanabe et al, 1988; Krishnamurthy et al, 1986).
    4) Anatoxin A is frequently degraded quickly in toxic blooms and is difficult to find. Smith and Lewis (1987) detailed a method of isolating dihydro-anatoxin A, which is a metabolite.
    5) A variety of methods are available for the detection of microcystin in water (Lam et al, 2000).
    a) The mouse bioassay is easy to interpret and technically simple but expensive and labor intensive.
    b) HPLC allows for accurate detection and quantification of different toxins, but has relatively low sensitivity and often requires preconcentration and pretreatment.
    c) ELISA methods can detect different structural variants of toxins (however, a wide spectrum of antibodies may be required) and commercial kits are available for semiquantitative detection.
    1) ELISA testing (using a commercial ELISA plate kit from Envirologix Inc, Portalnd, ME, ) was used to analyze water samples containing microcystins following a cyanobacterial bloom outbreak in Brazil which contaminated the drinking water supply (Soares et al, 2006).
    d) Cytotoxicity assays are highly sensitive if primary liver cells are used (but their production is labor intensive); there are established cell lines that provide for routine testing, but they are generally less sensitive.
    e) A radiometric protein phosphate inhibition assay is specific for inhibitors of serine/threonine protein phosphatases type 1 and 2A and is highly sensitive, but it is not specific for various structural variants, and requires freshly prepared radiolabelled substrate and subsequently the disposal of radioactive waste.
    f) A colorimetric protein phosphate inhibition assay is rapid and simple, highly sensitive and has high throughput, but is not specific for various structural variants of microcystins and requires a pure preparation of serine/threonine protein phosphatases type 1 or 2A.
    6) Bioassays for cyanobacterial toxins have been developed using a protozoan (Spirostomum ambiguum), crustaceans (Thamnocephalus platurus) and cladoceran (Daphnia magna) (Tarczynska et al, 2001).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Methods of identifying cyanobacteria from stool and vomitus, and for differentiating cyanobacteria-like bodies from cyanobacteria, are available. However, diagnosis is based on characteristic symptoms in most cases, along with testing the suspected contaminated seafood to support the diagnosis.
    B) To aid in diagnosis, feces and stomach contents may be examined for the presence of cyanobacterial cells.
    C) Monitor fluid and serum electrolytes in patients who experience severe vomiting or diarrhea or prolonged symptoms.
    D) Monitor liver enzymes in patients with persistent symptoms.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Serum levels are not useful except for identification. No serological test for exposure exists, but one is being worked on by Chester Public Health Laboratory of the UK (Elder et al, 1993).
    2) Monitor liver enzymes should be monitored. Monitor fluid and electrolytes if vomiting and/or diarrhea are severe or prolonged.
    4.1.3) URINE
    A) URINALYSIS
    1) Obtain urinalysis for detection of protein, glucose, ketone, and blood.
    4.1.4) OTHER
    A) OTHER
    1) To aid in diagnosis, feces and stomach contents may be examined for the presence of cyanobacterial cells (Elder et al, 1993).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Unlikely to be necessary; patients with alterations in respiratory function or evidence of hepatotoxicity made need to be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Mild symptoms can likely be treated at home. Laboratory confirmation may be necessary in cases of a suspected outbreak of cyanobacteria.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with severe gastrointestinal symptoms may require IV fluid replacement and to be observed for several hours until able to tolerate liquids.

Monitoring

    A) Methods of identifying cyanobacteria from stool and vomitus, and for differentiating cyanobacteria-like bodies from cyanobacteria, are available. However, diagnosis is based on characteristic symptoms in most cases, along with testing the suspected contaminated seafood to support the diagnosis.
    B) To aid in diagnosis, feces and stomach contents may be examined for the presence of cyanobacterial cells.
    C) Monitor fluid and serum electrolytes in patients who experience severe vomiting or diarrhea or prolonged symptoms.
    D) Monitor liver enzymes in patients with persistent symptoms.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Prehospital gastrointestinal decontamination is unlikely to be necessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) No information was found regarding the use of charcoal in cyanobacteria ingestions (Cooney, 1995). Charcoal use is at the physician's discretion.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) AIRWAY MANAGEMENT
    1) Although not reported in humans, respiratory failure is a primary cause of death in animals. Support respiratory function. Anticholinergics and oximes have not been tried in cases of Anatoxin-a poisoning.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Monitor fluid and electrolytes and treat with intravenous or oral hydration as indicated. Prolonged periods of vomiting and/or diarrhea may result in loss of fluids and essential electrolytes.
    C) MONITORING OF PATIENT
    1) Monitor liver enzymes. Although changes in liver enzymes have been reported in humans, the extent and result of these changes have yet to be determined. Liver failure has been reported in limited cases following systemic exposure during dialysis after using water containing cyanobacterial toxins.
    D) GENERAL TREATMENT
    1) Treatment in humans is symptomatic and supportive and is likely related to gastroenteritis symptoms.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) DERMATITIS
    1) Microcoleus Lyngbyaceus or "stinging seaweed" a finely filamentous blue-green algal organism, can form intense burning and eruptions on the skin following contact. In most cases, symptoms include a pruritic eruption which can last from a few hours to a few days. Symptoms are usually limited to the 'bathing suit' area. Prompt showering/washing after exposure in potentially contaminated water is usually beneficial to avoid or minimize skin irritation(GRAUER & ARNOLD, 1961).
    2) POTENTIAL FOR INFECTION: In some individuals lymphadenopathy, pustular folliculitis and local infection have been reported following Microcoleus Lyngbyaceus exposure. It has been noted that the bacterium Vibrio alginolyticus has been cultured from these specimens and was sensitive to chloramphenicol, gentamicin, tetracycline, sulfadiazine, and trimethoprim/sulfamethoazole (Sims et al, 1993).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) TOXIC DOSE: A toxic dose for humans has not been established. There are numerous toxic substances involved with various toxic doses. The toxin(s) concentration may vary from day to day during any particular bloom.
    B) ANIMAL DATA: Animal minimum lethal doses range from 10 to 40 mg/kg.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) TOXIC DOSE: A toxic dose for humans has not been established; there are several toxic substances involved, with various toxic doses. The toxin(s) concentration may vary from day to day during any particular bloom.
    2) PROVISIONAL GUIDELINE: The WHO established a provisional guideline value of 1.0 mcg microcystins/g in drinking water based on acute toxicity testing in animals (mice and swine) (Dittmann & Wiegand, 2006).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) CYANOBACTERIAL TOXINS
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) Microcystin-LR - 50 mcg/kg (Dittmann & Wiegand, 2006)
    b) Microcystin-YR - 70 mcg/kg (Dittmann & Wiegand, 2006)
    c) Microcystin-RR - 600 mcg/kg (Dittmann & Wiegand, 2006)
    d) Anatoxin-a - 200-250 mcg/kg (Dittmann & Wiegand, 2006)
    e) Anatoxin-a(s) - 20 mcg/kg (Dittmann & Wiegand, 2006)
    f) Nodularin - 50 mcg/kg (Dittmann & Wiegand, 2006)
    g) Cylindrospermopsin as a cell-free extracts - 0.2 mg/kg (estimated) (Griffiths & Saker, 2003)

Pharmacology Toxicology

Toxicologic Mechanism

    A) TOXINS - SITE OF ACTION
    1) There are two main types of toxins in these cyanobacteria. The first are neurotoxic alkaloids (anatoxins) and the second are hepatotoxic peptides also called fast-death factor, microcystine, cyanoginosin, cyanoviridin, and cyanogenosin (Anon, 1988; Kungsuwan et al, 1988).
    2) Lipopolysaccharides (endotoxins) are also present and are believed to cause the skin rashes, dermal and eye irritation following contact with cyanobacteria-contaminated water (Baxter, 1991).
    B) TOXIN TYPES - Toxins included in these algae include alkaloids, polypeptides, pteridines and lipopolysaccharides (endotoxins).
    C) TOXINS - COMPOSITION
    1) Botes et al (1982a-b; 1984) found four different toxins in M. aeruginosa, all thought to be pentapeptide. Each contained three common pairs and a unique pair of amino acids. The pairs were combinations of leucine and arginine, tyrosine and arginine, leucine and alanine, or tyrosine and alanine (Botes et al, 1982b).
    2) The hepatotoxin in M. aeruginosa is a pentapeptide or a double pentapeptide (Bourke & Hawes, 1983).
    D) TOXINS - SPECIFIC
    1) ANATOXIN-A (ANTX-A) is manufactured by Anabaena flos-aquae. It is a potent depolarizing neuromuscular blocking agent active at both the nicotinic and muscarinic receptors (Dittmann & Wiegand, 2006; Mahmood & Carmichael, 1986; Mahmood et al, 1988). Intoxication may produce seizure activity and tetany (Dittmann & Wiegand, 2006).
    2) ANATOXIN-A(S), also from Anabaena flos-aquae has a different mechanism of action, producing intense salivation.
    a) It is thought to be a peripheral-acting organophosphorus anticholinesterase agent (Mahmood & Carmichael, 1986). A. flos-aquae is also known to contain hepatotoxic peptides (Krishnamurthy et al, 1986).
    b) In animals, anatoxin-(s) most frequently is seen with pigs, dogs, and waterfowl. Ruminants are more resistant (Beasley, 1990).
    c) Anatoxin-a(s) inhibits cholinesterases in blood, lung, and muscle. Retinal and brain cholinesterases are not affected (Beasley, 1990).
    3) APHANTOXIN - The toxin found in Aphanizomenon flos-aquae is very similar to both saxitoxin (paralytic shellfish poisoning) and tetrodotoxin (Adelman et al, 1982; Jackim & Gentile, 1968).
    a) Data obtained from axon testing of the giant squid demonstrated that aphantoxin is a potent and specific inhibitor of the voltage-dependant sodium ion channel (Adelman et al, 1982).
    4) MICROCYSTIN - is a hepatotoxic algaltoxin. Microcystin is a cyclic peptide consisting of 7 amino acids (Dittmann & Wiegand, 2006). Experiments have shown that cell injury was not due to extracellular but due to intracellular calcium flux (Bunner & Morris, 1990). Microcystins can also produce oxidative stress.
    a) Microcystis toxins are called microcystins and undergo different rates of decomposition. In one in vitro experiment microcystin YR was found to decompose faster than microcystin LR (Watanabe et al, 1992).
    b) Microcystin LR (a cyclic heptapeptide) is a hepatotoxin. When tested in rodents, the lowest consistent lethal dose was 160 mcg/kg in rats and 100 mcg/kg in mice (Hooser et al, 1989).
    1) Hepatic lesions have been seen as soon as 10 minutes after inspection of rats injected with microcystin LR. Centrilobular necrotic cells were noted within 60 minutes (Hooser et al, 1990).
    c) Microcystins bind and inhibit protein phosphatase 1 and 2A in the hepatocyte, disrupting maintenance of cell structure and function (Gilroy et al, 2000).
    5) CYLINDROSPERMOPSIN (CYN) is a hepatotoxin. It is an alkaloid that contains a cyclic guanidine group. Based on bioassay studies using chlorinated derivatives of cylindrospermopsin, the pyrimidine ring is essential for toxicity (Griffiths & Saker, 2003).
    a) In animal studies, intraperitoneal injection of cylindrospermopsin-containing cell extracts caused centrilobular to massive hepatocyte necrosis, along with damage to the kidneys, adrenal glands, lungs and intestines. Pure CYN produced only liver damage in mice, with no other systemic injury (Griffiths & Saker, 2003).

Physicochemical

Physical Characteristics

    A) The Microcystis aeruginosa liver toxin is non-volatile, relatively heat stable.

Molecular Weight

    A) Not applicable

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) PARALYSIS - Partial paralysis has been seen in birds (Deem & Thorp, 1935). Anatoxin-A (very fast death factor found in Anabaena) is an alkaloid which causes pre and postsynaptic neuromuscular blockage which is not reversed by edrophonium or neostigmine. It causes seizures in fowl (Beasley et al, 1983).
    B) QUAIL - When microcystin RR is administered to quail, the spleen, not the liver becomes enlarged (Takahashi & Kaya, 1993).
    11.1.2) BOVINE/CATTLE
    A) Spoerke et al (1985) reported 11 cattle who died after drinking water contaminated with A. flos-aquae, Microcystis aeruginosa and Aphanizomenon flos-aquae. Two of the animals were found dead in the water, 4 within 5 yards, and the remainder within 100 yards.
    B) Smith & Lewis (1987) reported the rapid deaths of 16 cows who drank from an algae covered lake. The samples taken contained anatoxin A and dihydro anatoxin.
    C) Staggering, profuse salivation, ataxia, muscle tremors and bloody diarrhea was reported in Holstein cows who were exposed to pond water containing Microcystis aeruginosa (Kerr et al, 1987).
    11.1.3) CANINE/DOG
    A) Two groups of dogs were poisoned at Richmond Lake, SD. The suspected agents were Anabaena flos-aquae (90%), Aphanizomenon-flos-aquae (5-7%) and Microcystis Aeruginosa (3-5%).
    1) The first group had signs of liver necrosis, non-specific fecal hyperemia and were found near the lake shore. Group 2 had severe diarrhea, vomiting and loss of motor coordination by 1 hour post ingestion.
    2) The dominant algal species was variable during the exposure times (Mahmood et al, 1988).
    B) The bottom-dwelling species Oscillatoria (containing anatoxin-a) caused seizures, cyanosis, limb-twitching, rigors, and hypersalivation within one hour of drinking water from a contaminated site.
    1) Death in these dogs ensued between 10 and 30 minutes of the initial symptom presentation (Gunn et al, 1991; Gunn et al, 1992).
    C) Gross pathology found in one exposure was widespread petechial hemorrhages that were conspicuous on the intestinal serosae, and liver congestion. Histology was hemorrhagic lesions of the liver, kidney, stomach and small intestine (Kelly & Pontefract, 1990).
    11.1.7) ICHTHYOID/FISH
    A) Northern pike, bullhead fish & carp were found dead in a lake contaminated with Anabaena flos-aquae (Mahmood et al, 1988).
    11.1.9) OVINE/SHEEP
    A) Autopsy of poisoned sheep showed hepatic lesions with coagulative necrosis and hemorrhage. Examination of the kidney showed mild tubular nephrosis (Done & Bain, 1993).
    11.1.10) PORCINE/SWINE
    A) Chengappa et al (1989) reported the death of 7 of 26 hogs over a 24 hour period after drinking water containing Anabaena spiroides.
    1) Symptoms included vomiting, dull appearances, lethargy, anorexia, muscle tremors, difficulty in breathing, bloody diarrhea, sneezing, coughing and frothing at the mouth.
    2) Necropsy showed congested lungs, mild disorganization of hepatic cords and mild hepatocyte necrosis. Although the pigs were moved after the 7 died, and no further exposure allowed, 13 more died.
    3) Respiratory paralysis may be seen (Beasley et al, 1983; Chengappa et al, 1989).
    11.1.12) RODENT
    A) M. aeruginosa extracts fed to rats has caused mutagenesis (Bourke & Hawes, 1983).
    B) THROMBOCYTOPENIA - The pentapeptide found in M. aeroginosa has caused thrombocytopenia and pulmonary thrombi when injected into mice (Slatkin et al, 1983).
    11.1.13) OTHER
    A) OTHER
    1) Most of the serious poisonings have been in animals. Many cases show such rapid onset that animals die before leaving the water from which they are drinking. Others die in 6 to 24 hours after ingestion (Brandenburg & Shigley, 1974).
    a) Animals do not like to drink the contaminated water, but will if sufficiently thirsty (Stewart et al, 1950).
    2) A characteristic animal death caused by one of these blue-green algae (Aphanizomenon) includes symptoms of irregular respirations, spastic twitching, loss of coordination, violent tremors, gaping mouth, and death by respiratory failure.
    a) The toxin is a potent nerve and muscle blocking agent which alters conduction without affecting transmembrane potential (Sawyer et al, 1968). Microcystis aeruginosa is potentially hepatotoxic (Galey et al, 1987).
    3) The effects seem to be much more serious in animals; whether this is due to higher ingested doses (as above) or an actual difference in reaction to the toxin is known.
    4) PARALYSIS - Partial paralysis has been seen in both animals and birds (Deem & Thorp, 1935). Anatoxin-A causes pre and postsynaptic neuromuscular blockage which is not reversed by edrophonium or neostigmine.
    a) Anatoxin-A causes respiratory paralysis in mammals and seizures in fowl (Beasley et al, 1983).
    5) LIVER INJURY - Elevated liver enzymes have been documented in populations who drank from a contaminated reservoir. These elevated enzymes could not be associated with increases in any illness (Falconer et al, 1983).
    a) Hepatoenteritis and toxic liver injury is commonly seen with M. aeruginosa (Bourke & Hawe, 1983; (Jackson et al, 1984; Galey et al, 1987).
    1) Lesions shown by electron microscope were aggregation of endoplasmic reticulum with displacement of subcellular organelles, toward the edges of the hepatocyte and vaculation of the contents of severely affected cells (Jackson et al, 1984).
    6) HEMORRHAGE - Petechial hemorrhages of the heart are a consistent autopsy finding in animals (Senior, 1960).

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) GENERAL
    1) Two-thirds of the cyanobacterial scums examined at 91 UK sites were found to be toxic in one 1989 study (Lawton & Codd, 1991) Natl River Author, 1990).
    B) SHEEP
    1) When sheep were inoculated with Microcystis aeruginosa "bloom", death occurred within 18 to 48 hours, primarily due to liver damage (Jackson et al, 1984).

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