Summon Chomchai, MD, MPH Entomophagy associated histamine poisoning

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1 Summon Chomchai, MD, MPH Entomophagy associated histamine poisoning

2 Case A A 28-year-old female patient experienced a flushed face and generalized erythema 15 minutes after eating Thai drunken tuna spaghetti temperature was 36.7 C, blood pressure 104/44mmHg, faint pulse rate 136/minute and respiratory rate 30/minute. Generalized erythema, swollen eyelids and lips were noted

3 What is your diagnosis for case A?

4 What is your diagnosis for case A? a. Food allergy b. Food poisoning

5 What if.. A friend who dined with her at the same restaurant had tuna salad and developed similar symptoms at about the same time Would you change your diagnosis?

6 Scombroid (histamine) poisoning Ingestion of histamine (scombrotoxin), a heat-stable toxin De novo product from bacterial decarboxylation of histidine in fish meat Improperly preserved fish

7 News paper 25/07/ students with food poisoning on 24/07/2014 Nausea Vomiting Dizziness Itchy rashes Diarrhea Snacks after lunch: included fried insects Contamination of insecticides in insects!!!

8 News paper 25/07/ students with food poisoning on 24/07/2014 Nausea Vomiting Dizziness Itchy rashes!!! Diarrhea Snacks after lunch: included fried insects Contamination of insecticides in insects!!!

9 227 Secondary school students Aged years at the seminar 227 secondary school students 28 were sick Nausea, vomiting, abdominal pain, diarrhea, skin rashes, itch, dyspnea, chest tightness, headache, dizziness, numbness 18 presented to the hospital 2 were hospitalized

10 2 hospitalized cases Case 1: 14 y/o male, grade 9 Chief complaints: dyspnea, chest tightness 30 mins PTA Previously healthy, no allergy 1 hour: vomit x 2 (vomitus content= lunch) 30 mins: headache, progressive dyspnea On arrival: urticarial rashes on face, truck and upper extremities Case 2: 14 y/o male, grade 9 Chief complaints: dyspnea, chest tightness, skin rashes 30 mins PTA Previously healthy, no allergy 2 hours: itchy rashes face, chest and upper extremities 1 Hour: nausea, vomiting, diarrhea, abdominal pain 30 mins: dyspnea Lunch: 3 hours PTA One bag of approximately 10 fried silkworm pupae after lunch Lunch: 3.5 hours PTA One bag of approximately 10 fried silk worm pupae and 4-5 fried grasshoppers after lunch

11 At the Emergency Department, 16 more students with nausea, vomiting, diarrhea headache, dizziness, difficulty breathing pruritic skin rash

12 Is this an outbreak?

13 Outbreak Definition An increased in frequency of a disease above the usual rate (endemic rate) in a given: Time Place (or geographic area) Persons (or population) >2 patients have the same disease with at least one of the patients has relationship with others.

14 Materials and methods We contacted the Angthong Provincial Hospital Reviewed medical records of the sick children 227 respondents (100%) Outbreak investigations: retrospective cohort study: Symptoms, onset of symptoms Food and beverages ingested Health status, past medical history Medication history Allergic history Blood samples Food samples

15 Retrospective Cohort Study Best technique for analyzing an outbreak in a small, welldefined population To identify the source of the outbreak from this information, an item most likely to be the cause has: A high attack rate among those exposed and A low attack rate among those not exposed (so the difference or ratio between attack rates for the two exposure groups is high) In addition, most of the people who became ill should have consumed the item, so that the exposure could explain most, if not all, of the cases Relative risk can also be analyzed to evaluate the association between source food (exposure) and disease (outcome)

16 The Epidemic Curve Time components of an outbreak: histogram of the number of cases by their date of onset Shows: start, end, duration, peak, and outliers Helps to form hypotheses on route of transmission, probable exposure period, and incubation time

17 Case definitions: modified version of the 2011 criteria for scombroid toxin (histamine) published in the United States Center of Disease Control and Prevention s Guide to Confirming an Etiology in Foodborne Disease Outbreak

18 Number of cases Epidemic Curve: Consumption of Fried Insects/Pupae and onset of Illness Point (common) source pattern Common source pattern: single exposure, no secondary cases

19 Fried snacks

20 Result of Outbreak Investigation F1+F2 = people who ate fried grass hoppers or fried silkworm pupae or both both

21 Result of Outbreak Investigation

22 Our findings Serum tryptase: Case 1 (2 hours post-onset) <1.00 µg/l Case 2 (2.5 hours post onset) <1.00 µg/l Serum cholinesterase: within normal ranges Completely recovered overnight Chlorpheniramine Domperidone Nebulized salbutamol Histamine contents in food samples: Grasshoppers 9.73 mg/100g Silkworm pupae 7.66 mg/100g Common green frogs 0.58 mg/100 g Shrimps 1.22 mg/100g Reported cases in human 5 mg/100g Bartholomew BA, Berry PR, Rodhouse JC, et al. Epidemiol Infect. 1987;99:

23 (Mast cell) Tryptase Mediators in mast cells Released with histamine and leukotrienes Blood tryptase levels can indicate whether or not mast cells are activated When the body is not responding to environmental exposures the level of tryptase in the blood is very low Tryptase levels will be high Mast cell activation Increased mast cells in the body

24 Entomophagy: Insects as human food Good source of nutrients with high protein content. Protein (20-70 percent of raw protein) Fats (10-50 percent) Minerals and vitamins: phosphorus, potassium, iron, copper, zinc, manganese, sodium, vitamin B1 and B2 and niacin.

25 Edible Insects in Thailand At least 164 edible insect species are consumed in Thailand. Popular edible insects in Thailand are silkworm pupae, common house crickets, leaf-eating grasshoppers and bamboo carterpillars Insects sold on local markets in Thailand are Farmed domestically Imported from Cambodia, Myanmar, Lao PDR and China

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28 Silk spooling and pupae and the by-product

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36 Diagnostic features for fish histamine poisoning (Clin Rev Allergy Immunol Feb;50(1):64-9.) Suggestive symptoms Details in the history Details -Facial flushing, abdominal pain, diarrhea, headache, palpitations -Metallic, bitter, or peppery taste in the mouth -Symptoms occur within 20 min to 1 h of fish ingestion -What type of fish was ingested -No previous history of food allergies -Medications: isoniazid or monoamine oxidase inhibitors -Symptoms are self-limited and resolve within 6 8 h -Symptoms improve with antihistamines -Other patrons in the same location become ill with similar symptoms Laboratory data -Fish histamine level >50 mg/1kg -Skin prick testing (see text for details) -Normal tryptase level -Negative 5-HIAA, metanephrines, urinary PGD2

37 Our data A cluster of patients with a single source pattern Symptoms and signs similar to histamine poisoning Epidemiologically, fried grasshoppers and fried silkworm pupae as most likely causes of symptoms High histamine concentrations in fried grass hoppers and fried silkworm pupae samples Low tryptase concentrations: excluding endogenous histamine release Marinating sauce: soy sauce, fish sauce and sugar unlikely because it is used for all fried snacks at the vender

38 Histamine A biogenic amine Decarboxylation product of histidine All body tissues; esp. mast cells and basophil cytoplasmic granules and released quickly degranulation Ingested with food and beverages

39 Histamine metabolism

40 Food as sources of histamine exposure Dark meat fish Scombroidae and Scomberesocidae families, such as tuna, mackerel, skip-jack, and bonito Decarboxylating bacteria: Morganella, Krebsiella Temperature, time Products of microbial fermentation/ microbially spoiled food: Bacteria, yeast Aged chess, processed meat, sauerkraut, wine

41 Histamine fish (scombroid) poisoning Similar to type 1 hypersensitivity Typically occur within min of fish Duration 6 8 h Feelings of malaise can last for a day or more Treatment: similar to allergy Flushing Abdominal pain, Diarrhea, nausea, vomiting Headache, Dizziness Palpitations Urticaria, perioral itching Chest tightness, dyspnea Wheeze, hypotension Metallic, bitter, or peppery taste

42 Insect as sources of histamine Insect contains high level of histidine Silkworm pupa have been reported to cause an outbreak of histamine poisoning in Thailand J Health Sci. 2009;18: Anecdotal reports of anaphylaxis associated with silkworm pupa consumptions Allergy Oct;63(10): Prehosp Emerg Care Jul 19:1-3.

43 Sources of insects in this outbreak This street vender bought the insect from the market every 3-7 day Freezer at home Icebox on the sidecar vending Crickets: farms Bamboo borers: farms Silkworm pupae: Silk production Import Grasshoppers: catching, import Import whole sellers retailers

44 Postulated mechanisms Silkworm (Bombyx mori) pupae contains high histidine contents Int. J. Adv. Res. Biol. Sci. 2(9): (2015): Bacterial overgrowth bacterial decarboxylation of histidine change into histamine (a heat stable toxin) Proven by an experimental study Histamine production in preserved silkworm pupae Ingestion of histamine histamine poisoning

45 An experiment to study histamine production in fermented silkworm pupae Is histamine found naturally in silkworm pupae? Can histamine be produced in fermented silkworm pupae? Silk pupa: 270 Experimental temperatures: -20 o c, 10 o c, 25 o c Neogen Histamine Test Kit (competitive direct enzyme-linked immunosorbent assay (CD-ELISA)

46 Silk pupae preparation Silkworm pupae Extracted histamine Stored set at the temperature C, 10 0 C and 25 0 C. Incubated fort 24, 48, and 72 hr. Extracted Final extracted

47 Comparisons of histamine concentrations over 72 hours 70 Comparisons of histamine concentration changes over 72 hours Temp Comparisons p 30 Between groups < o C vs 10 o C < o C vs 25 o C < Time (hours) 10 o Cvs 25 o C <0.05

48 Prevention Food safety standard: Traceable and reliable sources of food Quality of refrigeration USFDA histamine content in fishery products 50 mg/kg

49 Further researches Human susceptibility to histamine poisoning from insects Histidine and histamine contents and histamine production in different kinds of edible insects What are safest way to use insects as a food source for human?

50 Special thanks Ms.Woranut Chantaworn, Angthong Provincial Health Office Mr. Sayan Kongchareon, Ban-it Subdistrict Health Clinic Dr. Darunee Ngamphoophan, Angthong Provincial Hospital Dr. Chanida Hansawasdi, Mahidol University International College Dr. Chulathida Chomchai, Mahidol University International College Pinsumon Chomchai, Shrewsbury International School, Bangkok

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