Ciguatera Fish Poisoning Stephanie Perez Mallery Quetawki Sara Jones.

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1 Ciguatera Fish Poisoning Stephanie Perez Mallery Quetawki Sara Jones

2 Introduction Gambierdiscus toxicus Importance of study Macroalgae in coral reefs Ciguatoxins Reef Fish Mechanism Ciguatera Fish Poisoning (CFP) Epidemiology Symptoms, treatment & prognosis Prevention

3 Introduction cont… Fun Facts Discussion Summary Extra info

4 Importance of Study G. Toxicus leads to Ciguatera Fish Poisoning in humans. Sea food diners and consumers need to be educated on risks for exposure to Ciguatoxins Disruption of environment, both natural and man- caused, can lead to adverse effects on animals and humans.

5 Gambierdiscus toxicus Photosynthetic benthic dynoflagellates that grow predominately in association with microalgae in coral reefs in tropical and subtropical climates

6 Gambierdiscus toxicus Found in the Pacific Ocean, Red Sea, Indian Ocean, and Caribbean Seas from 35°N to 35°S

7 Gambierdiscus toxicus Bio accumulated ciguatoxins in the viscera of fish becomes progressively concentrated upwards along the food chain Gambierdiscus Small carnivorous Larger Fish Humans Toxicus fish Ciguatoxin concentration from G.Toxicus consumption

8 Cycle of Toxin Destruction of coral reef ecosystem, due to human activities or natural events, cause recolonization of microalgae on damaged surfaces. This sparks an outbreak of ciguatera in the damaged regions. The freshly grown algae is then consumed by smaller fish where the toxin accumulates in the liver, eggs and skin. It is suggested that there maybe chemical alterations of the toxin as it is metabolized inside these fish as well as the next carnivorous fish that eats them. This process thus causes accumulation and an increase in lethality as it goes up the food chain.

9 Tropical/Subtropical Fish Moray eel Barracuda Grouper Kingfish Jacks Snapper Surgeonfish Parrot Fish Hogfish Coral trout Flowery cod Red emperor Wrasses Spanish Mackerel All carriers of ciguatoxins in their viscera

10 Grouper Snapper Moray EelSpanish Mackerel Flowery Cod Barracuda

11 Ciguatoxin: Info & Mechanism Heat stable and are not destroyed by cooking, freezing, or acid Tasteless & Odorless Some of the most potent biological toxins known Poses a health risk at concentrations as low as 0.08 to 0.1 μg/kg Start to exert their effects with a level of detection at ~0.1 parts per billion. Potent heat stable, non- protein, lipophilic sodium channel activator toxin The poison binds to voltage- dependent sodium channels in muscle and nerve cells, so that they remain open. Rest remains unknown however, other studies suggest the following: Can lead to sensitization to ciguatoxins in CFP patients the poison inhibits the action of cholinesterase

12 Ciguatoxin Type-2 Backbone

13 Ciguatoxin Type-1 Backbone

14 Ciguatera Fish Poisoning (CFP) Epidemiology occurs in 10-50,00 people per year incidence rates may be as high as 50 to 500 per 10,000 population per year in the South Pacific region Mortality is low (0.1 to 4%) Seasonal differences in occurrence of toxin in ecosystems Under-reporting occurs in part because individuals with CFP often do not seek medical attention Ciguatera poisoning currently poses the largest single constraint on fisheries development in the eastern Caribbean

15 Clinical Signs of Ciguatera Poisoning Symptoms begin 6-12 hours after ingestion of fish Occur in 3 major organ systems: GI, Neurologic, and Cardiovascular First reported symptoms are usually GI symptoms which last for a few days after ingestion. Within the first 3 hours, Neurological symptoms can be present and are commonly moderate to severe. Cardiovascular symptoms are reported last and are generally severe.

16 Clinical Signs Numbness and Tingling in the mouth. Abdominal pain, nausea, vomiting, and diarrhea. Dehydration from GI symptoms Dental pain, pruritus, arhralgias, myalgia, ataxia, vertigo, and respiratory paralysis may also be observed. Lingual and circumoral paresthesis, painful paresthesias of the extremities, and paradoxical temperature reversal (reversal of hot and cold sensation). Coma, bradycardia, and hypotension can be seen in extremely severe cases.

17 Diagnosis Although Ciguatera Fish Poisoning is the most commonly reported seafood illness in the world, doctors do not have a human biomarker to confirm Ciguarta fish posioning. All diagnosis are based on clincal signs and observation of the patient. (Friedman, M.A. et al 2008) A proper diagnosis is made by looking at the time line of the symptoms and type of fish consumed. Must rule out other illnesses (mostly shellfish poisonings or multiple sclerosis) which exhibit similar symptoms.

18 Diagnosis Current research is looking into detecting the presence of ciguatoxin in human blood or serum which could be a future diagnostic tool. This research is looking into using ELISA bioassays for use of detection. The most accurate diagnosis is made after the timeline of symptoms has been checked and verified with symptoms seen with ciguatera fish poisoning. If a sample is present, testing the viscera of the fish for the ciguatoxin will give the most accurate diagnosis.

19 Treatment Due to the absence of a concrete method of diagnosing an actual case of CFP, it is hard to research new drug treatments. The lack of accurate diagnosis paired with the sporadic cases makes clinical research for therapeutic drugs very difficult. Currently, Mannitol is the main drug used for Ciguatoxin cases as it is the most widely studied. However, it is the only drug therapy that has shown promise in clinical studies.

20 Treatment The main course of treatment is to treat the symptoms. Treatment varies on the symptoms as the poisoning presents different signs in different patients. Charcoal can help with GI decontamination. It only works if it is administered within 3-4 hours of the initial ingestion. Antiemetics may control nausea and vomiting. Cold showers and antihistamines can help with pain from pruritus.

21 Medications There are six different kinds of medicines that are most affective in treating CFP. They are: neurologic agents, serotonin- norepinephrine reuptake inhibitors, antihistamines, analgesics, antipyretics, and anti-inflammatories

22 Medications A NTIHISTAMINES Mainly used to relieve pruritus (itching) Diphenhydramine (Benadryl) It is the main treatment for pruritus as it blocks histamine release. Hydroxyzine (Atarax) Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. It is another pruritus treatment. Cyproheptadine used to treat pruritus. Unknown mechanism

23 Medications S EROTONIN / NOREPINE PHRINE REUPTAKE INHIBITORS The inhibitors block the active reuptake of norepinephirne and serotonin. Have central and peripheral anticholingeric and sedative effects. Amitriptyline is commonly used to relieve pruritus and dysesthesias. It is most effective for chronic neurologic symptoms. Blocks Na+ channels that were activated by the ciguatoxinn

24 Medications A NALGESICS Used for pain relief Acetaminophen and Paracetamol are most commonly used. Indomethacin (Indocin) used to relieve myalgias and arthralgias. D IURETICS, O SMOTICS These medications treat neurological signs. They have been proven to relieve neurological symptoms within 2 days (Mitchell, G. et al. 2005). Mannitol is the main osmotic diuretic used for treatment of neurological symptoms.

25 Mannitol Previously, Mannitol was only used for acute neurological symptoms. Recent studies have shown that Mannitol has beneficial effects on mild to moderate cases as well. (Mitchell, G. 2005) Mannitol is primarily used to lessen the severity of acute cases and to prevent the onset of chronic neurologic symptoms. Mannitol is administered through IV and should be administered within 2-3 days after ingestion of toxic fish. Precautions must be taken when administering Mannitol as it can cause further dehydration in patients suffering from severe vomiting and diarrhea.

26 Mannitol The exact mechanism is unknown, but it is thought to be mediated by the osmotic reduction of neuronal edema caused by the increase of sodium and ultimate depolarization of the nerve cell. Mannitol may inhibit the reaction of the ciguatoxin at the sodium and potassium channels thus deactivating the voltage gated sodium channels in the cell membranes.

27 Prognosis In almost all cases, the patient will make a full recovery. Ciguatera poisoning has extremely low mortality rates ~ 0.1% Most deaths are attributed to severe cases and are caused by severe dehydration, cardiovascular shock, or respiratory paralysis. The patient will feel weak and lethargic for a period of a week up to a month after infection. In some cases, chronic neurologic symptoms may remain for months and in some cases, years. These cases have not been studied at length. Future studies will focus on this topic.

28 Prognosis Increased sensitivity to the toxin has been noted in some cases. Patients who had a past bout of CFP experienced a reoccurrence of ciguatera poisoning after eating a ciguateraic fish when other people who ate it showed no symptoms. Ingestion of fish, shellfish, alcohol, nuts, Opiates, and Barbiturates have been reported to intensify the symptoms among patients who are recovering from CFP. These same products can also cause a reoccurrence of neurological symptoms years later. The exact reason for this is unknown

29 Prevention Home products are available and are able to test if ciguatoxin is present in fish that are cooked. However, there is insufficient data available to show if these products are effective or not. If you think you may have ciguatera poisoning, report your symptoms and what fish you ate to your doctor, local emergency room, or health department. If possible, save meal remnants.

30 Prevention Knowledge is your best prevention. The next best preventative measure is to stop or reduce destruction of coral reefs which lead to G. Toxicus accumulation. Educate yourself about seafood fish posioning. Know what types of fish are vectors for the ciguatoxin and be sure you know where it came from if you are planning on consuming reef fish. Florida has an aquatic toxins program to teach their residents about the dangers of seafood poisoning. http://www.myfloridaeh.com/med icine/aquatic/index.html http://www.myfloridaeh.com/med icine/aquatic/index.html

31 Fun Facts: Folk Science If no flies on fish= +CFP Feed fish to cat and the cat vomits= +CFP

32 Discussion There is a need for protection of aquatic habitats so that G. toxicus does not disperse. There is further research needed to find how ciguatoxins effect animal and human physiology. Greater knowledge about this will lead to better diagnostic techniques, drug therapies, and treatment plans. Further studies should focus on how and why toxin is produced during disturbance of coral reef.

33 Discussion Questions remain: If other toxins can be used in a variety of other ways, is it true to say that G. toxicus can be used for other things such as pesticides, cosmetics or everyday housecleaning agents? What is the exact mechanism that the toxin undergoes in the fish to cause it to accumulate in the tissues? What other health effects does it have on humans? Will we ever find a proper method for testing for and preventing spread of ciguatoxins? Does ciguatoxin have any biomedical uses? How can fish avoid eating the toxic algae? Do fish feel the same symptoms as humans?

34 Discussion Is this toxin produced as a defense mechanism for G. toxicus although a majority of the fish do not seem to exhibit side effects from exposure? Could fish use this toxin, if not harmed by it, for use against predation? At what costs are the toxin made? Even disruption from natural disasters causes accumulation of toxin in damaged areas of reef. Better dispersal method since natural disturbances are common?

35 Summary G. toxicus emerges from disrupted ocean beds and reefs, concluding that oceanic ecosystem destruction causes harm to animals and humans via dispersal of toxin. When herbivore fish ingest G. toxicus they accumulate in organs and tissues as well as in the next predator fish that consumes them. Humans are ailed with Ciguatera Fish Poisoning upon ingestion of infected fish. Symptoms of illness varies across individuals. Mannitol is best treatment available. Prevention is key Know where your fish are coming from and reduce oceanic ecosystem destruction. Further study must be done to understand bioaccumulation of toxin as well as its mechanism in humans.

36 Videos Watch interviews on CFP encounters/symptoms. (8mins) YouTube - Ciguatera Interviews Other video on CFP testing if interested (10mins): http://www.youtube.com/watch?v=rbdEBUiXKV0

37 References Arnold, T. Toxicity, Ciguatera: Treatment & Medication. eMedicine 2007. http://emedicine.medscape.com/article/813869-treatment http://emedicine.medscape.com/article/813869-treatment Babinchak, J., Jollow, D.J., Voegtline, M.S. and Higerd, T.B. Toxin produced by Gambierdiscus toxicus isolated from the Florida Keys. Marine Fisheries Review, 1986; 48: 53-56. CDC/Emerging Infectious Diseases website: http://www.cdc.gov/ncidod/eid/vol11no12/05-0393-G.htmhttp://www.cdc.gov/ncidod/eid/vol11no12/05-0393-G.htm Empey, C.C. et al. Detection of ciguatoxin in fish tissue using sandwich ELISA and neuroblastoma cell bioassay. Journal of Clinical Laboratory Analysis 11 July 2008. Vol 22, Issue 4. Pp: 246-25 Friedman, M.A., Fleming, L.E., Fernandez, M., Bienfang, P., Schrank, K., Dickey, R., Bottein, M-Y., Backer, L., Ayyar, R., Weisman, R., Watkins, S., Granade, R. and Reich, A. Ciguatera fish poisoning: Treatment, prevention and management. Marine Drugs, 2008; 6: 456-479. Inoue, M., et al. Use of monoclonal antibodies as an effective strategy for treatment of ciguatera poisoning. Toxicon DOI 10.1016. Available Online 2/28/09. Kipping, R., Eastcott, H. and Sarangi, J. Tropical fish poisoning in temperate climates: food poisoning from ciguatera toxin presenting in Avonmouth. Journal of Public Health, 2006; 28: 343-346. Li, K-M. Ciguatera Fish Poison: A cholinesterase inhibitor. Science, 1965; 147: 1580-1581. Mitchell, G. Treatment of a mild chronic case of ciguatera fish poisoning with intravenous mannitol, a case study. Pac Health Dialog. 2005 Mar Vol. 12, Issue 1. Pp: 155-157. Morrison, K.E., Prieto, P.A. and Dominguez, A.C. An ecosystem approach to ciguatera fish poisoning in Cuba: Preliminary results. IEEE Xplore 2005. Pearn, J. Neurology of ciguatera. J. Neurol. Neurosurg. Psychiatry, 2001; 70: 4-8. Perez-Arenello, J-L. et al. Ciguatera Fish Poisoning, Canary Islands. CDC/Emerging Infectious Diseases, 2005; vol. 11, no. 12. Sobel, J. and Painter, J. Illnesses Caused by Marine Toxins. Food Safety, CID 2005: Vol41 (1 November) http://www.itg.be/itg/DistanceLearning/LectureNotesVandenEndenE/46_Marine_biotoxinsp2.htm U.S. Food and Drug Administration website. Ciguatera page. http://www.cfsan.fda.gov/~mow/chap36.htmlhttp://www.cfsan.fda.gov/~mow/chap36.html