Foodborne Botulism or Please dont pass the olives

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

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

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 botulinum by Emile Pierre van Ermengem, bacteriologist at the University of Ghent. Johann von Autenrieth 1752 -1832 3 Foodborne botulism Emile Pierre van Ermengem 1851 – 1922 or 1932

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 14 th 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. 72 h 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. 4 Foodborne botulism

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 Bo. NT can also be produced by rare strains of C. butyricum and 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 5 Foodborne botulism

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

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

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

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 9 Foodborne botulism

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 10 Foodborne botulism

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

Mechanism of action of the botulism neurotoxin 12 Foodborne botulism

Symptoms A rapidly progressive descending symmetrical paralysis 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 13 Foodborne botulism Infant Botulism Less specific: • Constipation, irritability followed by Lethargy • Poor feeding • Poor sucking • Drooling • Hypotonia • General weakness not usually present: elevated blood pressure ; fever; altered mental state; altered sensation;

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

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

Specimens to send to the reference laboratory (Colindale) Foodborne botulism: Toxin detection by MBA: • Serum (2 -10 ml) 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 16 Foodborne botulism

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 17 Foodborne botulism

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

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. botulinum detected 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. 19 Foodborne botulism

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

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

Foodborne botulism July 2012 - Olives 14 th July: A 46 year old female Oxfordshire resident has a lunch/dinner party at friends. 15 th July: she developed mild symptoms of blurred vision, dry mouth. 18 th July: she goes to her GP who takes a blood specimen. 19 th July: Admitted to hospital, seen by neurologist on the 20 th 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 22 Foodborne botulism

Foodborne botulism July 2012 - Olives 1 week after onset of symptoms… 22 nd July: Hospital contacts duty doctor in Colindale for obtaining antitoxins. 23 rd 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. 23 Foodborne botulism

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. 24 Foodborne botulism

Foodborne botulism July 2012 - Olives 23 rd July, at 17: 20 The olives arrived at Colindale. • • • 25 The original jar with olives – p. H 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

Foodborne botulism July 2012 - Olives 24 th 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 26 Foodborne botulism FSA alerted National recall of olives and warming not to eat from this batch

Foodborne botulism July 2012 - Olives 25 th July, 10 days after onset of symptoms, a faecal specimen is collected from the patient, now at home. 27 th 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 30 th July Monday: PCR results – POSITIVE for neurotoxin gene B 27 Foodborne botulism

Foodborne botulism Scotland 2011 8 th 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. 9 th 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 28 Foodborne botulism

Foodborne botulism – Scotland 2011 10 th 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 36 h 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) 29 Foodborne botulism

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 30 Foodborne botulism

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

Foodborne botulism – Scotland 2011 Food item Specimen information Toxin detection C. botulinum Comments on PCR by MBA detection by PCR results M&S wholemeal Pittas From rubbish bin Not detected C. botulinum A Spores only detected. Remnant of Korma sauce +Chicken From wheelie bin Toxin A detected C. botulinum A Vegetative cells and spores detected Lid from the consumed From rubbish wheelie bin Toxin A detected korma sauce jar C. botulinum A Vegetative cells and spores detected Empty jar of consumed korma sauce Vegetative cells and spores detected From recycling bin Toxin A detected C. botulinum A Opened but not consumed; From dry good cupboard Not detected Negative Empty container of olives From wheelie bin Not detected Negative Oil from sun-dried tomatoes From fridge Not detected Negative Houmous From fridge Not detected Negative Korma sauce jar FSA issued National product recall 32 Foodborne botulism

Patient specimen information Date of collection Toxin detection by MBA C. botulinum detection by PCR Boy Serum 08. 11 Not performed/ haemolysed NA boy Blood 09. 11 Not performed/ haemolysed NA Boy Blood 09. 11 Not performed/ EDTA treated NA Girl Serum 09. 11 NA Boy Serum 09. 11 Toxin detected - Classic symptoms of botulism observed, insufficient serum for confirmatory neutralisation test Girl Blood 10. 11 Not performed/ haemolysed NA Girl Blood 10. 11 Not performed/ EDTA treated NA 10. 11. 11 Not performed C. botulinum A Girl Boy 33 Rectal washout in Anaerobic broth NA Boy Rectal washout 10. 11 Not detected C. botulinum A Boy Gastric aspirate 10. 11. 11 Not detected Negative Girl Rectal washout 10. 11 Not detected Negative Foodborne botulism

Foodborne botulism – Scotland 2011 16 th November: 3 rd 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 ! 17 th November: Choked on food again – antitoxin given 23 rd November: Stool specimen for 3 year old PCR Positive for neurotoxin gene A 34 Foodborne botulism

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: 1. 2. 3. 4. 5. 6. temperature, (optimum growth is 35°C or 25°C) p. H, below 4. 6 water activity, (min aw of ~0. 94 is needed for growth) 10% Na. Cl redox potential, presence of oxygen food preservatives, (nitrite, sorbic acid, polyphosphates. . ) competing microorganisms, lactic acid bacteria, intestinal microflora. 7. ‘Botulinum cook’: pressure cooker 121°C for 3 minutes 35 Foodborne botulism

Who to speak to? ? ? Clinical diagnosis: • Consult neurologist and local ID Physician • Botulism duty doctor protocol (HPA website) Microbiology confirmation and 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 • Baby. BIG: Infant Botulism Treatment and Prevention Programme, California, USA. http: //www. infantbotulism. org/ 36 Foodborne botulism

Thank You, 37 Foodborne botulism