DIAGNOSIS, TREATMENT, PREVENTION AND MANAGEMENT BY: PARESH GANDHI

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1 Ciguatera Fish Poisoning in Peel Region DIAGNOSIS, TREATMENT, PREVENTION AND MANAGEMENT BY: PARESH GANDHI

2 Ciguatera Fish Poisoning 1. Background 2. Diagnosis 3. Case study 4. Treatment 5. Prevention & Management

3 Ciguatera Fish Poisoning (CFP) is caused from the consumption of certain large tropical predatory reef fish that have bio-accumulated Ciguatoxin (CTX) [1] The main source of Ciguatoxin is the dinoflagellate Gambierdiscus toxicus, associated with seaweeds, sediments and dead coral. It is distributed around the tropics within the latitudes 32 o N and 32 o S and grows in shallow waters [2] Background Flower Garden Banks National Marine Sanctuary. source: NOAA, Nov 13, 2008,web, August 30, 2014

4 Ciguatoxin Fish are not affected by CTX [3] Fish do not appear spoiled or taste different [2] Toxin is heat stable, colourless and odourless [3] Highest concentration in viscera of fish [2] Affects the Na/K channels in humans [2] Sexually Transmitted and can pass to child through breast milk [2] Gambierdiscus toxicus Source: Florida Fish and Wildlife Conservation Commission (FWC)

5 Types of Ciguatoxin Source: Structures are by Fred Fry, Jr., Ph.D. Bad Bug Book 2 nd edition 0.01 mg/kg 0.1 mg/kg

6 Ciguatoxin Associated Fish Barracuda Amberjack Snapper Source: Grouper Surgeonfish

7 Distribution of Great Barracuda Reviewed Native Distribution Map for Sphyraena barracuda (modelled 2100 map based on IPCC A2 emissions scenario) (Great barracuda). version of Aug Web. Accessed 8 Sep

8 Background: Exposure Pathway

9 Background: Occurrence of CFP Globally 500,000 cases estimated annually [2] In Canada 22 cases reported over 14 year period [2] In U.S. 508 cases reported over 9 year period [2] In China 397 cases reported over a 4 year period [2]

10 Diagnosis of Ciguatera Fish Poisoning No reliable tests available for diagnosis in humans [5] Current standard method of diagnosis is matching the symptoms with fish consumption [5] Gold Standard [5] Confirmation of CTX in the consumed fish through laboratory testing Numerous individuals consuming the same fish showing signs and symptoms of CFP Incubation Period consistent with symptoms

11 Toxin Symptoms Incubation Time Neurotoxic Shellfish Poisoning (NSP) (brevetoxins) Reversal of hot and cold sensation, tingling; numbness of lips, tongue & throat; muscle aches, dizziness, diarrhea, vomiting. 25 min to 34 h Histamine (scombroid) Headache, dizziness, nausea, vomiting, peppery taste, burning of throat, facial swelling and flushing, stomach pain, itching of skin. Less than 1 h Paralytic Shellfish Poisoning (PSP) (saxitoxins) Tingling, burning, numbness, drowsiness, incoherent speech, respiratory paralysis. 0.5 to 2 h Ciguatera Toxin Tingling and numbness, gastroenteritis, dizziness, dry mouth, muscular aches, dilated pupils, blurred vision, paralysis, reversal of hot and cold sensation. 16 h Note. Adapted from Clinical Manifestations of Ciguatera, p , by N.A. Palafox and L.E. Buenconsejo-Lum

12 CFP Symptoms: Acute vs. Chronic ACUTE Gastrointestinal : Vomiting, Diarrhea, abdominal pain[5] Cardiovascular: hypotension, bradycardia, [5] CHRONIC Neurological: Paresthesia, temperature reversal*, ataxia, severe itching[5]

13 Standard Testing In vitro Assay[6] Ciguatoxin Testing in Fish Liquid Chromatography- Mass Spectrometry (LC- MS) [6] Source: Mar Drugs. 2010; 8(6): Jun 14, 2010,web accessed September 5, 2014

14 Investigation Timeline: Outbreak #1 August 7, 2013: complaint comes to Peel Health Environmental Contact Centre Etobicoke General contacts Peel Health 5 Patients, 3 in emergency Suspected Barracuda fish (Sheela in Tamil) Date of consumption: August 4, 2013 Incubation Period: 3 hours Symptoms: nausea, vomiting, abdominal cramps, tingling and numbness of fingers and toes. Still had symptoms

15 Investigation Timeline: Outbreak #1 3 are in hospital emergency 2 individuals seeing general physician Blood samples done. Infectious disease specialist is investigating Blood sampling did not reveal condition

16 Investigation Timeline August 7, 2013 The owner was contacted by phone and asked to fax shipping invoices so that trace back could be done. Visited store and put 10 barracuda on hold. The store owner indicated that one barracuda came in a box of Kingfish but it was different than other Barracuda they normally order.

17 Investigation Timeline: Inspection

18 Great Barracuda vs. King Fish State of New South Wales through Department of

19 August Investigation Timeline Barracuda taken from complainant s home Received shipping invoices via fax from shop owner

20 August Investigation Timeline August one Kingfish from display and two Barracuda fish from the box of 10 on hold, were taken for further analysis by CFIA CFIA still trying to determine if lab will be able to test the sample taken from the complainant s home CFIA to decide if they will test sample for Ciguatera toxin. Uncertain if trace-back could be done Frozen leftover sample which was taken from the complainant's home was provided to CFIA along with shipping invoices and one food history No other complaints received from the importer or distributor according to CFIA Surveying PHIs revealed no further fish related illness in Peel Peel received confirmation that complainants sample will be tested at the end of the day

21 Investigation Timeline: Outbreak # 2 August 28, 2013 August 29, 2013 Peel Health was waiting to hear back from CFIA regarding toxin analysis in Fish 2 nd case received by Peel Health through after hours Environmental Contact Centre DNA analysis revealed that fish was Great Barracuda that was sold to complainant

22 Investigation Timeline: Outbreak #2 Family of five ate the front half of the fish Date of consumption: August 19, 2013 Incubation time: 4 hours Cooked fish discarded No raw fish available for testing Fish purchased from shop on August 1, 2013 One case fainted due to hypotension, difficulty breathing, burning and tingling of tongue, joint pain in lower extremities, cool breeze creates burning sensation. Diarrhea, nausea, abdominal pain, vomiting

23 Investigation Timeline: Barracuda on Hold

24 Investigation Timeline August 30, 2013 August 31, 2013 The fish shop was visited again with CFIA inspector and 16 Barracuda put on hold as precaution Cases interviewed Cases asked to go see family doctor for symptoms Stool kits dropped off for 3 of the 5 clients who wanted to provide stool samples.

25 Investigation Timeline September 4, 2013 It was determined by CFIA that the Great Barracuda is not imported by the importer The supplier does not ship Great Barracuda either September 5, 2013 Names of suppliers were released to Peel Health The shipment originated in southern United States CFIA was informed of symptoms from 2 nd outbreak and that no food samples were available for testing

26 Investigation Timeline September 13, 2013 Family doctor of second set of cases follows up with Peel AMOH Dr. de Villa for assistance after patients symptoms persist Family doctor of first set of cases works at same clinic with the doctor with second set of cases and they realize the patients have the same conditions Both sets of cases were referred to tropical disease specialist in Toronto

27 Investigation Timeline: Result September 19, 2013 Analysis complete. No quantitative result available. Sample suspect positive of Caribbean Ciguatoxin

28 Investigation Timeline October 1 st, 2013 Ciguatera toxin testing is not common in Canada Few labs world wide that have the full capability to do testing including Canada, U.S. and Australia In order to do testing lab must have the purified version of actual toxin for instrument calibration The suspect positive Caribbean CTX was based on manual inputs of molecular weights of Caribbean CTX

29 Investigation Timeline October 1, 2013 U.S. FDA lab had Caribbean CTX but were not willing to provide it due to lack of availability and high cost Alabama lab had agreed to test the sample in their lab Lab affected by US federal government shutdown Oct 1-Oct 16, gm of Great Barracuda submitted.

30 Investigation Timeline January 21, 2014 Peel Health received confirmation from the CFIA National lab that the U.S. FDA lab was able to confirm their result of a positive Caribbean CTX finding Quantitative analysis not done due to cost and time constraints Materials used for testing cost $10,000 for 1 mg of substance

31 Summary of Testing Dates August 9, 2013: Sample provided to CFIA August 14, 2013: Sample shipped to Dartmouth, Nova Scotia lab August 22, 2013: Ciguatera toxin testing began after DNA ID analysis had been done. September 19, 2013 : Analysis complete. No quantitative result available. Suspect positive of Caribbean Ciguatoxin Jan 21, 2014: U.S. FDA lab confirms positive test result

32 Treatment: Supportive IV fluids and electrolyte re-balance [5] Mannitol within 72 hours of onset of symptoms has shown to be the most effective [5] Side effects include further loss of fluids if patient still has vomiting and diarrhea [5] Mannitol can adversely effect patients still suffering from bradycardia and hypotension [5] Atropine has been used effectively for bradycardia [5]

33 Prevention of CFP: Education Education [2] Recreational Fishermen Commercial Fishermen Travellers Travel Companies Local Fish shops Consumers need to know the risk Avoid head, viscera and roe of reef fish [2] 79% of cases in U.S. are from sport fishing [2] Cigua-Check TM [4] Source: health/aquatictoxins/ciguatera fish poisoning.html.accessed august 29,2014

34 Management of CFP In EU fishery products containing bio-toxins cannot be offered for sale [2] In U.S. FDA has proposed guidance levels of less than 0.1 μg/kg C-CTX-1 equivalents and less than 0.01 μg/kg P-CTX-1 equivalents [2] Globally, prohibition of the sale of high risk fish taken from areas where CTXs are known to be present [2] Bans on fish over a certain weight and complete ban on certain fish [2] Sale of Barracuda banned in Miami [2]

35 Challenges for Public Health No analytical standard in Canada for interpretation of results No human bio-markers for diagnostic purposes [5] No FDA approved commercial test kit which can be used on site to detect toxins [5] Purified CTX is very expensive and not widely available for instrument calibration and research [5] Medical staff need to recognize the signs and symptoms for improved diagnosis and treatment Climate change, increasing travel, increasing importation of fish [5]

36 Ciguatoxin Testing Video

37 References 1. De Fouw, J.C., Van Egmond, H.P., Speijers, G.J.A Ciguatera fish poisoning: a review. RIVM Report No H.P. Van Egmond, M.E. Van Apeldoorn and G.J.A. Speijers, et al, Marine Biotoxins, Food and Agriculture Organization of the United Nations Rome, Food and Drug Administration. Bad Bug Book, Foodborne Pathogenic Microorganisms and Natural Toxins. Second Edition. [Ciguatoxin, pp ] Palafox N.A, Buenconsejo lum L.E., Ciguatera Fish Poisoning:Review of clinical manifestations, J. Toxicol toxin reviews 20(2) , Friedmann M.A.,* Fleming L.E, Fernandez M, et al, Ciguatera Fish Poisoning: Treatment, Prevention and Management, Mar Drugs.; 6(3): , Sep Caillud A, Iglesia P, Darius HA, Update on Methodologies Available for Ciguatoxin Determination: Perspectives to Confront the Onset of Ciguatera Fish Poisoning in Europe,Mar Drugs. 8(6): , Pennotti R, Scallan E., Backer L., et al, Ciguatera and Scromboid Fish Poisoning in the United States, Foodborne Pathogens and Disease ;10(12) , Williams R.A, Zorn D.J, Hazard analysis and critical control point systems applied to public health risks: the example of seafood, Rev. sci. tech. off.int.epiz, 16 (2) , Todd E.C.D, Seafood associated diseases and control in Canada, Rev.Sci.tech.off.int.Epiz., 16 (2) , Juranovic LR, Park DL, Foodborne toxins in marine origin:ciguatera, Reviews of Environmental Contamination and toxicology,117:51 94, 1991.

38 Questions?

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