Marine Toxins & Intoxications Brian J Ward

JD MacLean Centre for Tropical Diseases

Colloque Blue 2012

Overview of talk ◗  Toxins

• fish (eg: ciguatera scromboid) • shellfish (eg: domoic acid) • phyto/zooplankton

◗  Stings/envenomations • vertebrates (eg: rays, lionfish) • invertebrates (eg: jellys, cones,corals) • phyto/zooplankton

You Never Really Know Who You’ll be Sharing the Water With ...

travel.webshots.com/photo

Toxins & Intoxications

◗  Fish • ciguatera • scromboid • puffer fish

◗  Shellfish • PSP, DSP, ASP, etc

◗  Phyto/zooplankton • Pfisteria spp

◗  Amnesic Shellfish Poisoning (ASP) ◗  Paralytic Shellfish Poisoning (PSP) ◗  Neurotoxic Shellfish Poisoning (PSP) ◗  Ciguatera Fish Poisoning (CFP) ◗  Diarrhetic Shellfish Poisoning (DSP) ◗  Pfiesteria Intoxication

Human Illnesses Associated with Marine & Estuarine Plankton

Ciguatera Intoxication

◗  Ingestion of bioaccumulated dinoflagellate toxins in tropical reef fish (snapper, barracuda….)

◗  Dinoflagellate species (various) •  Gambierdiscus toxicus, Prorocentrum spp.,

Amphidinium.spp. ◗  Major Toxins

•  Ciguatoxin --opens voltage dependent Na channels

•  Maitotoxin --Calcium channel activator

Ciguatera

Plankton - Dinoflagellates

Reef Fish - Snapper http://www.missbonita2.com/

www.botany.ut.ee

Ciguatera Incidence/Prevalence Reported Incidence and Prevalence of CFP

Geographic Region Incidence/10,000/year Data time period Reference Reunion Island 0.78 1986–1994 Quod 1996 [25] Queensland, Australia 3 1965–1984 Gillespie 1986 [4] Hawaii 0.3 1975–1981 Anderson 1983 [96] US Virgin Islands 7.6 1982 Morris 1982 [97] Guadeloupe 30 1984 Czernichow 1984 [98] South Pacific Region 970 1973–1983 Lewis 1986 [99] Marshall Islands 2,820 1982–1983 Lewis 1986 [99] French Polynesia 5,850 1979–1983 Lewis 1986 [99] Dade County, FL 5 1974–1976 Lawrence 1980 Culebra, Puerto Rico 73.6–169.5 2005–2006 Luber, In prep [100]

Geographic Region Prevalence (%) Time range Citation US Virgin Islands 4.4 Annual (1980) McMillan 1980 [101] Puerto Rico 7 Lifetime Holt 1984 [102] Tahiti 8.45 Annual (1966) Bagnis 1979 [16] Hao (Tuamotos) 43 Annual (1978) Lewis 1986 [99] Polynesian Islands 70 Lifetime Lewis 1986 [99]

Mar Drugs. 2008 September; 6(3): 456–479.

Ciguarera - Clinical Presentation

◗  Constellation of neurologic, GI, and cardiovascular symptoms •  nausea, vomiting, diarrhea •  paresthesias, headache, numbness, weakness •  (paralysis and coma may ensue) •  arrhythmias, hypotension, brady/tachycardia

◗  Neurologic Sx: median duration 2-3 weeks, but chronic or relapsing syndromes can occur for years

Reef Russian Roulette

www.photographersdirect.com

Eat me … you lose

www.informaction.org

Treatment ◗  IV mannitol (0.5-1 g/kg over 30-45 minutes)

•  Little convincing evidence of benefit •  Little risk •  Very little evidence of effect >72 hours

◗  Avoidance of certain foods (idiosyncratic) including fish, alcohol, nuts, caffeine, pork … ◗  Supportive

Mar Drugs. 2008 September; 6(3): 456–479.

Mattei C et al. Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells. PLoS One. 2008;3(10):e3448. Epub 2008 Oct 20.

Department of Fisheries and Oceans, the Canadian Food Inspection Agency and Environment Canada

Executive Summary Consumer Awareness and Perceptions of Shellfish Consumption and Recreational Harvesting: Findings from the Baseline Survey Prepared for Canadian Food Inspection Agency December 15, 2006

• Telephone survey 1400 (390 coastal): 37% of non-coastal visited coast(s)

• 27% had eaten shellfish harvested by themselves: 9% in last 12 months

• 10% had bought shellfish from the back of a truck and 10% from fisherman

• 70% thought all shellfish sold in Canada is safe

• 16% thought shellfish caught by themselves or friends might be unsafe

• Most thought that ‘pollution was the main risk (23% said mercury)

• 54% didn’t think that eating any shellfish was a serious risk for healthy adults

• 70% believe shellfish are safe after cooking

Canadian Shellfish Sanitation Program (CSSP)

Paralytic Shellfish Poisoning

◗  Ingestion of bioaccumulated dinoflagellate toxins in shellfish (mussels, clams, oysters….)

◗  Dinoflagellate species •  Alexandrium spp •  Gonyaulax spp

◗  Major Toxins: •  Saxitoxins: Voltage dependent •  Na channel blockade (extremely potent toxins)

www.chemgapedia.de

PSP - clinical presentation

◗  Predominantly neurologic syndrome: tingling, burning, numbness, drowsiness, dysarthria, and paralysis: can be life-threatening.

◗  Signs & symptoms usually appear within ~one hour of eating contaminated shellfish

◗  Residual sequelae uncommon ◗  Prevention through shellfish monitoring

Red Tide

pathtosustainable.wordpress.com

Eutrophication ◗  an increase in chemical

nutrients in an ecosystem to an extent that increases the primary productivity of the ecosystem.

Neurotoxic Shellfish Poisoning ◗  Ingestion of bioaccumulated dinoflagellate toxins

in shellfish (bivalves). Rarely, aerosol exposure to toxins

◗  Dinoflagellate: Karenia breve (Gymnodinium) ◗  Toxin:

•  brevetoxins: linear polycyclic ethers •  (similar structure to ciguatoxins) •  Voltage dependent Na channel activation

NSP - Clinical presentation ◗  Clinical symptoms include both neurologic

and gastrointestinal effects: •  circumoral paresthesias, dizziness, ataxia •  nausea, abdominal pain, vomiting, diarrhea •  respiratory symptoms with aerosol exposure

◗  Clinical onset within minutes to hours; recovery usually complete.

◗  Prevention: monitoring G. breve counts Errera RM et al. Variation in brevetoxin and brevenal content among clonal cultures of Karenia brevis may influence bloom toxicity. Toxicon. 2010 Feb-Mar;55(2-3):195-203

Bivalves - Natures Filters

Filter-concentration of up to 40 GALLONS of water per day

• Plankton toxins • Hepatitis A • Polio (?) • Other viruses (?) • Cholera • Cryptosporidium

Diarrhetic Shellfish Poisoning

◗  Ingestion of bioaccumulated dinoflagellate toxin in shellfish (mussels, scallops, clams.)

◗  (Japan, Europe. Not reported in U.S.) ◗  Dinophysis fortii, D. acuminata ◗  Toxin: okadaic acid

•  polycyclic ether compound •  protein phosphatase 1 & 2A inhibitor

DSP - Clinical presentation

◗  DSP produces gastrointestinal symptoms, usually within 30 minutes of consumption of contaminated shellfish.

◗  Diarrhea (may be incapacitating), nausea, vomiting, abdominal cramps, chills.

◗  Recovery within 2-3 days, with or without treatment. No sequelae identified

Amnestic Shellfish Poisoning ◗  Ingestion of bioaccumulated diatom toxins in

shellfish (mussels, clams, oysters..) ◗  Nitzschia pungens & Pseudo-nitzchia sp ◗  Recognized outbreaks: Maritime Canada, U.S.

northern Atlantic & Pacific coasts ◗  Toxin: domoic acid (water soluble)

•  structurally related to the excitatory amino acid neurotransmitter glutamic acid

www.orhab.org/education/Pseudo_nitzschia_sp.htm

ASP - Clinical presentation

◗  Life-threatening disorder with both gastrointestinal and neurologic symptoms

◗  GI: nausea, vomiting, diarrhea, cramps ◗  Neurological: dizziness, headache, seizures,

diorientation, short-term memory loss, coma •  information encoding, generally intact •  delayed recall significantly impaired •  hippocampal & amygdaloid nucleus necosis

ASP - Clinical presentation II

◗  Disease most severe in the elderly and those with renal impairment.

◗  Among survivors, sequelae may include significant memory deficits and motor neuropathy

◗  Prevention through water and shellfish monitoring (diatom counts, toxin assays)

Pfiesteria piscicida ◗  1988 - cause of fish deaths in aquaria at North

Carolina University Veterinary School ◗  1991 - cause of natural habitat fish kills in the

estuarine system of North Carolina. ◗  Since then, repeatedly identified as a cause of fish

kills in North Carolina (106-109 fish)

http://www.uncwil.edu/riverrun/river_tutorial/12pfiesteria.jpg www.whoi.edu/.../pfiesteriafishsores.html

‘Ambush’ or ‘Predator’ Dinoflagellates

◗  Dinoflagellate species which are induced, upon chemical detection of prey, to: •  undergo stage transformations •  ‘swarm’ or multiply •  (for Pfiesteria)... produce toxin (s) •  exploit nutritional source •  then, re-encyst, or disperse

Trophic controls of Pfiesteria

◗  Heterotrophic with cleptochloroplasts ◗  Benthic forms (amoebae, cysts) predominant ◗  Factors influencing Pfiesteria toxin production

(and stage transformation) not fully known, but include: •  presence of live fish •  abundance of algal prey species •  water nutrient levels (phospates, nitrates)

Pfiesteria Toxins ◗  Several toxins have been isolated, and

partially characterized ◗  Lipid soluble toxins (fractions)

•  one kills fish rapidly; is difficult to isolate •  one peels skin off fish (takes time)

◗  Water soluble toxin •  appears to be unique (i.e. not one of the above) •  icthyotoxic, cytotoxic in cell culture

http://blog.mlive.com/chronicle/2008/04/07deadfish.jpg

Pfiesteria - Clinical presentation

◗  ‘Cardinal Signs & Symptoms’ •  Memory Loss, OR •  Confusion, OR •  Skin ‘burning’ on contact with water, OR

◗  ‘Secondary Signs & Symptoms’ •  3 or more of the following:

•  headache skin rash •  eye irritation upper respiratory irritation •  muscle cramps gastrointestinal complaints

http://news.bbc.co.uk/olmedia /images/_20403_human.jpg

www.flickr.com/photos/38832546@N00/3848358627/

www.unep.org/dewa/vitalwater/article177.html

Why is this happening?

Why is this happening - II?

geology.com/news/2006/01/global-warming-graph

Scromboid

◗  Commonest poisoning worldwide ◗  Dark-fleshed, fatty fish

• Common - tuna, bonito, mackerel, barracuda • Rare - sardines, anchovies, salmon, herring

◗  ‘Histamine’ poisoning (?? unclear) ◗  Biogenic amines (histamine, putrescine,

cadaverine, and tyramine) ◗  ? bacterial metabolism of histidine ◗  ? histamine-spiked fish - minimal toxicity

Scromboid - Clinical presentation

◗  Non-specific symptoms ◗  Tingling of lips/mouth/tongue ◗  Flushing, sweating, bright red rash ◗  Swelling of face/tongue swelling, wheezing ◗  GI distress: nausea, vomiting, diarrhea ◗  Tachycardia --> cardiovascular collapse

Other Toxins

◗  Puffer fish (tetrodotoxin) •  50 deaths/year in Japan •  ? Bacterial (Vibrio spp) toxin concentrated in fish

◗  Red Whelk (tetramine) •  Curare-like effects

◗  Cyanobacteria (microcystins, nodularin, anatoxins) ◗  Mussels (azaspiracid)

Other agents •  Jellyfish of all sizes & shapes •  Corals (eg: fire coral) •  Sea urchin spines •  Fish spines (eg: lion fish, sting ray, catfish) •  Conidiae •  Sea snakes

thestashbox.wordpress.com

life-sea.blogspot.com

firstaid.about.com

Jellyfish Stings

lifestyle.ca.msn.com

diveinstead.com

Urine Acidification

Diabetes

Diarrhea

Dehydration

Acidosis

Starvation

Meat eater

Treatment?

Other agents - Corals

Fire Coral

Various Corals

www.bluezooaquatics.com

www.usdivetravel.com

Other agents - Corals

Fire Coral Stings www.scubaboard.com

Other agents - Sea Urchin (& Other) Spines

Black Sea Urchin

Crown-of-Thorns Starfish

bcrc.bio.umass.edu

spressivo.com/isa/coralreef/animals.htm

Other agents - Stonefish

Masters of ...

… Disguise jaysdaysaway.blogspot.com

aquaviews.net

Other agents - Fish Spines

Lionfish/Zebrafish

Triggerfish

Ray - Tail barb

www.amnh.org

www.beachhunter.netps3029.k12.sd.us/State/trigger%20fish.jpg

Other agents - Cones

home.comcast.net/

www-tc.pbs.org

Other agents - Seasnakes

Green Seasnake

Yellow Seasnake

• >80% of bites envenomed • potent myotoxins & (less) neurotoxins

fieldherpforum.com

divehappy.com

Other agents

Octopus Seaworms exxxplorer.files.wordpress.com

greennature.com

The marine environment isn’t always ‘safe’ … but there are benefits too.

Doucette GJ, etal. Endangered North Atlantic right whales (Eubalaena glacialis) experience repeated, concurrent exposure to multiple environmental neurotoxins produced by marine algae. Environ Res. 2012 Jan;112:67-76.

Right Whale poop for exposure to • paralytic shellfish toxins (PSTs) • domoic acid (DA)

140 Fecal Samples studied • 70-80% + PSTs • 25-30% + domoic acid

It’s Not Just Us …