Foodborne Botulism or… Please don’t pass the olives! Unusual cases of food poisoning.

1. Foodborne Botulism or…Please don’t pass the olives! Unusualcases of food poisoning. Corinne Amar PhD Head of the foodborne pathogens reference services FPRS, Gastrointestinal Bacteria Reference Unit GBRU

2. Botulism • Rare but potentially fatal disease that causes paralysis • Caused by neurotoxins of Clostridium botulinum and by rare strains of C. baratiiand C. butyricum. • Botulism affect humans and other animals Foodborne botulism

3. A bit of history • Botulism first recorded in Europe in 1735 and that was suspected of being associated with a German sausage. It was named after the Latin word for sausage, ''botulus’’ • 1817: first publication of outbreak reports • In 1895, a botulism outbreak (34 cases) after a funeral dinner with smoked ham in the small Belgian village of Ellezelles led to the isolation of the pathogen Clostridium botulinumby Emile Pierre van Ermengem, bacteriologist at the University of Ghent. Johann von Autenrieth 1752-1832 Emile Pierre van Ermengem 1851 – 1922 or 1932 Foodborne botulism

4. The Hotel Loch Maree tragedy First recorded outbreak of botulism in the UK. • Summer 1922: a group of Londoners, staying at the hotel ordered their meal to be prepared in advance. • Potted duck had been on the menu all summer and on the 14th August, the last of the duck meat from the glass jar was scrapped to make sandwiches which were wrapped for a picnic. • All 8 people ate the sandwiches. • By following morning they were all ill. • 72h later, 6 people were dead and the • other 2 died within the next 5 days. • Bruce White from University of Bristol isolated • Clostridium ‘botulinus’ from remainder of one sandwich. Foodborne botulism

5. Clostridium botulinum • Organism exists in the natural environment as resistant spores in soil, sediment, mud, water. • Under the right conditions (anaerobic) spores germinate, multiply and produce toxin • Botulism Neurotoxin or BoNT can also be produced by rare strains of C. butyricumand C. baratii • Gram positive rod • Strictly anaerobe • Six antigenically distinct neurotoxins A to G • Types A, B, E and F associated with human disease, • Types C and D animal disease, G no disease Foodborne botulism

6. Four distinct groups of organisms by phenotypic characteristics and DNA homology – human disease groups I, II Foodborne botulism

7. Forms of botulism: • Foodborne botulism • Infant botulism • (main form of botulism at present in the UK) • Wound botulism • Accidental or deliberate release Foodborne botulism

8. Foodborne botulism • Intoxication • by ingestion of preformed toxin in food where the organism has grown Foodborne botulism

9. Infant botulism • Toxico infection • By ingestion of spores which germinate, multiply and • produce toxin in the gut: gut colonisation by the organism • Usually occurs in infants <1 year Foodborne botulism

10. Wound botulism • Wound infection where the bacterium multiplies under anaerobic conditions and produces toxin • Exclusive to illegal injection of drugs in the UK but reported in other patient groups elsewhere Foodborne botulism

11. Accidental/ deliberate release • Cosmetic or therapeutic • Bioterrorism – C. botulinum is a schedule 5 organism Foodborne botulism

12. Mechanism of action of the botulism neurotoxin Foodborne botulism

13. SymptomsA rapidly progressive descending symmetrical paralysis • Infant Botulism • Less specific: • Constipation, irritability followed by Lethargy • Poor feeding • Poor sucking • Drooling • Hypotonia • General weakness • Foodborne/ wound botulism • Possible D and V • Diplopia • dysphagia or dysarthria • dry mouth • Hypotension • Urinary retention, or constipation. • Respiratory failure, Cardiac arrest • Diminished or absent deep tendon reflexes notusually present: elevated blood pressure ; fever; altered mental state; altered sensation; Foodborne botulism

14. Myasthenia gravis: Tensilon test positive Differential diagnosis: Guillain-Barre syndrome: Ascending paralysis, CSF protein elevated Miller-Fisher Syndrome Descending paralysis Presence of anti-ganglioside antibodies: CSF protein elevated. Foodborne botulism

15. Laboratory confirmation of botulismBotulism is a Clinical Diagnosis Detection of the organism by: Detection of toxin Food, serum, faeces, rectal wash M.B.A. Culture and isolation of C. botulinum Food, faeces, rectal wash out, wound tissue, pus, environmental samples Detection of toxin genes A,B,E, F Food, faeces, rectal wash, pus, tissue Real time PCR Foodborne botulism

16. Specimens to send to the reference laboratory (Colindale) • Foodborne botulism: • Toxin detection by MBA: • Serum (2-10ml) NOT haemolysed – NOT plasma • Stool and others (vomitus, gastric contents, intestinal contents) • Food frozen except for tins and jars • Detection of the organism by toxin gene detection (PCR) and culture: • Stool in anaerobic broth (ex: CMB – Robinson – FAB) • Food • Others – vomitus, gastric contents…in anaerobic broth Foodborne botulism

17. Specimens to send to the reference laboratory (Colindale) • Infant botulism • Detection of the organism by toxin gene detection (PCR) and culture: • Stool or rectal wash out in anaerobic broth • Food (honey) • Dust and environment samples (water sediment – pet food) • Toxin detection: • Stool • Rarely: serum Foodborne botulism

18. Specimens to send to the reference laboratory (colindale) • Wound botulism • Toxin detection: • Serum (2-10ml) • Detection of the organism by toxin gene detection (PCR) and culture: • Pus, debrided tissue in anaerobic broth • Heroin Foodborne botulism

19. Timing of specimens is important • Serum: within 2 days of onset of symptoms • Neurotoxin detected in serum and faeces • >50% within 1 day of onset • <25% of cases after 3 days • Faeces: within a week of onset: • C. botulinumdetected in faeces • >70% within 2 days • 40% after 10 days Immunity to botulism does not develop, even with severe disease – repeated occurrence of botulism has been reported. Foodborne botulism

20. Foodborne botulism in the UK and Ireland 1922-1989 Foodborne botulism

21. Foodborne botulism in the UK and Ireland, 1998-2011 Foodborne botulism

22. Foodborne botulism July 2012 - Olives • 14th July: A 46 year old female Oxfordshire resident has a lunch/dinner party at friends. • 15th July: she developed mild symptoms of blurred vision, dry mouth. • 18th July: she goes to her GP who takes a blood specimen. • 19th July: Admitted to hospital, seen by neurologist on the 20th when the patient developed poor swallowing – the neurologist suggests botulism as diagnosis. • The patient is monitored – not ventilated • Cranial bilateral bulbar palsy • Proximal upper limb weakness • No sensory loss Foodborne botulism

23. Foodborne botulism July 2012 - Olives • 1 week after onset of symptoms… • 22nd July: Hospital contacts duty doctor in Colindale for obtaining antitoxins. • 23rd July: Reference laboratory contacted by duty doctor. • Follow a series of phone calls between Reference laboratory and the hospital – consultant micro, the ITU and Thames Valley HPU. Foodborne botulism

24. Foodborne botulism July 2012 - Olives • The patient ate at the party. She was the only one with symptoms and the only one to have eaten olives at the party. Another guest spat out an olive saying it did not taste right. • The olives were then put aside to be disposed of, but stay on a table at room temperature while the hosts went for a week abroad on holiday. • When the host came back, they learned their friend was ill, called the hospital and suggested the olives was the cause of illness. Foodborne botulism

25. Foodborne botulism July 2012 - Olives • 23rd July, at 17:20 • The olives arrived at Colindale. • The original jar with olives – pH 6.65 • A sterile container with olives (the original was leaking) • A CMB with a rectal swab DOC 22.07.12 – 7 days after onset of symptoms • Serum DOC 18.07.12 taken by GP – 3 days after onset of symptoms • Serum DOC 22.07.12 – pre-IG treatment – 7 days after onset of symptoms Foodborne botulism

26. Foodborne botulism July 2012 - Olives • 24th July, • The olives: • 10:30 - PCR results – POSITIVE for neurotoxin gene B • 11:30 – MBA results – POSITIVE for typical symptoms of botulism (neutralisation tests were performed the next day and detected neurotoxin B) • The clinical specimens: • Rectal swab - negative • Serum – negative FSA alerted National recall of olives and warming not to eat from this batch Foodborne botulism

27. Foodborne botulism July 2012 - Olives • 25th July, 10 days after onset of symptoms, a faecal specimen is collected from the patient, now at home. • 27th July, Friday: • A stool specimen arrived at Colindale. It can not be tested on receipt because it is not in a broth. • Broth inoculated with the stool specimen – incubated overnight • 30th July Monday: • PCR results – POSITIVE for neurotoxin gene B Foodborne botulism

28. Foodborne botulism - Scotland 2011 • 8th November: • A 5 year old child developed diplopia and dysphagia – taken to GP who sent the child back home. • During the night, child became very unwell, unable to swallow, drooling, taken to GP again then to hospital in Sterling. • Child had to be ventilated and was taken to Children’s Hospital PICU in Glasgow. • On same day in the afternoon, the 7 year old sister developed blurred vision. • 9th November: the 7 year old sister developed sore throat – admitted to Sterling Hospital and when deteriorating was taken to PICU in Glasgow and ventilated. NO D&V - no fever – CT scan and MRI normal – LP normal Neurology and immunology team: botulism as the most likely diagnosis Children received antitoxin and stabilised Colindale alerted Foodborne botulism

29. Foodborne botulism – Scotland 2011 • 10th November: first teleconference • Children received antitoxin and stabilised • The parents and the 3 year old sibling have no symptoms. • Food history: try to identify plausible foods eaten within 36h from onset of symptoms, by the children only. • Olives in jar (lots of discussion about olives because of recent • botulism outbreak in Helsinki and France) Foodborne botulism

30. Foodborne botulism – Scotland 2011 • Olives in jar • Carrots • Pitta bread • Humus • Curry sauce in jar with chicken: dad said ‘ smell funny’ but gave it to • the children • Hot dogs • Cheese • Chicken nuggets • Sun dried tomatoes in oil • Rice • Potatoes • Peppers • Vanilla yoghurt • Salad • Smoothies • biscuits • Cereal • Banana milkshake • Frozen raspberries • honey Foodborne botulism

31. Foodborne botulism – Scotland 2011 • IN OUT • Olives in jar Grilled chicken • Curry Sauce in jar Homemade biscuits • Yoghurt Carrots • Honey Raspberries • Pitta Bread Pasta, chicken, tomato sauce • Humusbroccoli • Sundried tomatoes Cereal • Banana Milkshake Foodborne botulism

32. Foodborne botulism – Scotland 2011 FSA issued National product recall Foodborne botulism

33. Foodborne botulism

34. Foodborne botulism – Scotland 2011 • 16th November: • 3rd sibling, a 3 year old girl, admitted to hospital after choking on food – gagged on food collapsed a few time and eyes were droopy. • Taken to A&E with ptosis – then discharged the next day ! • 17th November: • Choked on food again – antitoxin given • 23rd November: • Stool specimen for 3 year old PCR Positive for neurotoxin gene A Foodborne botulism

35. How to prevent foodborne botulism • C. botulinum has to grow to produce toxin. • The main limiting factors for growth of C. botulinum in foods are: • temperature, (optimum growth is 35°C or 25°C) • pH, below 4.6 • water activity, (min aw of ~0.94 is needed for growth) 10% NaCl • redox potential, presence of oxygen • food preservatives, (nitrite, sorbic acid, polyphosphates..) • competing microorganisms, lactic acid bacteria, intestinal microflora. • ‘Botulinum cook’: pressure cooker 121°C for 3 minutes Foodborne botulism

36. Who to speak to??? • Clinical diagnosis: • Consult neurologist and local ID Physician • Botulism duty doctor protocol (HPA website) • Microbiology confirmationand Guidelines and advice on specimens, availability and interpretation of results: • Reference laboratory Colindale • GBRU User Manual (LGP user manual HPA website) • Dr Corinne Amar or Dr Kathie Grant • Availability of antitoxin: • Duty doctor in Colindale • BabyBIG: Infant Botulism Treatment and Prevention Programme, California, USA. http://www.infantbotulism.org/ Foodborne botulism

37. Thank You, Foodborne botulism