David Kirschke, MD Northeast Regional Office Epi Meeting 11/16/06 Botulism Associated with Commercial Carrot Juice --- Georgia and Florida, September 2006 David Kirschke, MD Northeast Regional Office Epi Meeting 11/16/06

Setting September 8: Georgia Division of Public Health notified of 3 suspected cases of foodborne botulism Three patients admitted to local hospital with cranial nerve palsies and progressive descending flaccid paralysis resulting in respiratory failure Patients had shared meals on September 7

Outbreak Three patients consumed juice from same 1-liter bottle of Bolthouse Farms carrot juice Bottle had "best if used by" date of September 18, 2006 Botulinum toxin type A was identified in serum and stool of all 3 patients Leftover carrot juice also tested positive for botulinum toxin type A

FDA Investigation Bolthouse Farms, Inc., manufacturing plant in Bakersfield, California Tested other bottles of implicated brand of carrot juice, including bottles from different lots All were negative for botulinum toxin

FDA Consumer Advisory Lapse in refrigeration during transport or storage was suspected September 17, FDA issued consumer advisory on importance of keeping carrot juice refrigerated “However, information obtained from patient interviews regarding storage and transport of the carrot juice did not confirm mishandling by the patients.”

Outbreak September 25: Florida Department of Health notified of patient hospitalized with respiratory failure and descending paralysis Botulinum toxin type A was identified in serum 450-mL bottle of Bolthouse Farms carrot juice was found by family member in hotel room where patient had been staying No refrigerator “Best if used by" date of September 19 and different lot number than Georgia cases Botulinum toxin type A was identified in carrot juice

Recall Bolthouse Farms Carrot Juice distributed in all 50 states, Mexico, Canada, and Hong Kong September 29, FDA warned consumers not to drink Bolthouse Farms carrot juice with "best if used by" dates of November 11, 2006 Bolthouse Farms issued a voluntary recall

Syndromes Foodborne botulism Wound botulism Infant botulism Ingestion of foods contaminated with toxin Wound botulism Wound colonization and toxin production Infant botulism Intestinal colonization and toxin production Adult intestinal toxemia botulism

Differential Diagnosis Includes Guillian-Barré Syndrome, myasthenia gravis, stroke, tick paralysis Outbreak setting diagnosis more evident

Toxin Effect Block neuro-transmitter (acetylcholine) Neuromuscular junction Blockade result in flaccid paralysis Most potent toxins known (lethal oral dose = 70µg)

Clinical Manifestations All cause same clinical syndrome Symmetric cranial nerve palsies Descending, symmetric flaccid paralysis Respiratory compromise Death Ptosis and facial paralysis

Foodborne botulism outbreaks, 1950-1996 Uncommon disease 9 foodborne outbreaks / yr with 2.5 cases / ob 23 cases / yr Caused by several types of Clostridium botulinum Type A (56%), B (21%), E (22%), F (1%)* Foodborne botulism outbreaks, 1950-1996

Toxin Production C botulinum forms heat-resistant spores Spores germinate and produce toxin: Anaerobic milieu Non-acidic pH Low salt / sugar Temperature 4°C-121°C

Geographic Distribution of Foodborne Botulism by Type, 1950-1996 Type B (59%) Type E (84%) Type A (59%)

Foodborne Botulism Named for association with home-made sausage (botulus in Latin) Associated with home-canned foods including green beans, asparagus, beets, and corn Toxin produced in food before consumption Toxin inactivated by heating to 85°C x 5 min Spores heat resistant and commonly ingested without causing illness

Risk Factors for Foodborne Botulism Home-canned foods (65%) Vegetables, fruits, meat products Commercially processed foods (7%) Pot pies, restaurant food Unknown source (28%)

Other Risk Factors Uneviscerated, Salt-Cured Fish Product Home-pickled eggs Home-canned bamboo shoots Black tar heroin (wound botulism) Fermented beaver Beached whale MMWRs

Infant Botulism Most common form (~80-100 cases / yr) Children aged <1 year Normal competing bowel flora not fully established C botulinum colonization of intestines with toxin production Honey a risk factor (≤ 20%) Newly licensed human-source antitoxin Avoid hypersensitivity to equine serum Efficacy of equine antitoxin not proven in infants With appropriate care survival ~100% (+/- antitoxin)

Wound Botulism Contamination of wounds with C botulinum Toxin produced in anaerobic wound Wound often unimpressive (boil) Associated with Western US and IVDU (skin-popping and black-tar heroin) Syndrome similar to foodborne

Other Syndromes Inhalational – intentional release of aerosolized toxin Iatrogenic – injection of toxin for cosmetic / therapeutic indications

Protocols for clinicians evaluating suspected cases of botulism For suspected foodborne botulism, wound botulism, or botulism of unknown source, health department should be contacted via 24-h emergency telephone number; If no response, CDC’s Emergency Operations Center should be contacted (770-488-7100) For suspected infant botulism occurring in any state, the California Department of Health Services, Infant Botulism Treatment and Prevention Program should be contacted (510-540-2646)

Laboratory Confirmation Demonstration of toxin in serum, gastric contents, stool, or food Bioassay (injected into mice) C botulinum in stool or wound for wound / infant botulism Clinical / public health management based on clinical diagnosis

Treatment Supportive intensive care Botulinum antitoxin Mortality rate decreased from 70% to 5% Botulinum antitoxin Neutralizes only unbound toxin Arrests but does not reverse paralysis

Thank You