Infantile Botulism (adapted from Medscape emedicine.medscape.

.com/article/961833-overview) Botulism is a potentially lethal illness that affects the neuromuscular junction by inhibiting the release of acetylcholine from presynaptic neurons, effectively deenervating the muscles triggered by the post synaptic receptor. It is caused by the botulinum toxin produced by the bacterium Clostridium botulinum, a gram positive, anaerobic, spore-forming rod in the same family as the pathogens causing tetanus (C. tetani), pseudomembranous colitis (C. difficile), and gangrene (C. perfringens). Botulinum toxin is the most potent naturally occurring toxin known to man, being lethal at the fentogram level (10-9 gram), making it approximately 15,000-100,000 times more lethal than sarin nerve gas. There is variance in the specific botulinum toxins produced by the bacterium, classified as types A-G, even though only types A, B, E, and F cause disease in humans. Among the varying etiologies of botulism (food borne, wound, infantile), infantile botulism is the most frequently occurring type in the United States, representing at least 1444 of 2310 (~63%) reported botulism cases from 1973-1996. While honey is classically taught as a vector for C.botulinum spores, currently only approximately 15% of infantile botulism cases are directly attributed to honey consumption, with the remainder originating from undetermined sources. The peak age of incidence is between the first 2-4 months of life. Infants who are breastfed appear to have some protection from lethal fulminant disease, however exclusively breastfed children are at greater risk. This may be due to a relatively underdeveloped or undiversified bowel flora that is more conducive to spore germination and toxin production. Following ingestion of the spores, incubation occurs over 2-4 weeks. Early signs and symptoms include constipation, suckling poorly, lethargy, and listlessness. Descending weakness and paralysis (the classic floppy baby syndrome) occur later as in food-borne disease. On physical examination infants will have signs of autonomic dysfunction, including dry mouth, blurred vision, orthostatic hypotension, ptosis, mydriasis, decreased ocular motility, as well as dysphagia, dysarthria, muscle weakness, or flaccid paralysis. The frequencies of the most common symptoms of infantile botulism are as follows:
Poor ability to suck - 96% Poor head control - 96% Hypotonia - 93% Weak crying - 84% Constipation - 83% Lethargy - 71% Facial weakness - 69% Irritability - 61% Hyporeflexia - 52% Sluggish pupils - 50% Respiratory difficulty - 43%

If one is familiar with the SLUDGE or DUMBBELSS mnemonics for symptoms of cholinergic excess in organophosphate/carbamate poisoning, you can think that the opposite effects would apply in a state of cholinergic deficiency such as botulism. You can also think of it in terms of rest and digest gone wild either depict the characteristic dysautonomia.

S L U D G E

Salivation Lacrimation Urination Defecation GI upset Emesis

D U M B B E L S S

Diarrhea Urination Miosis/muscle weakness Bradycardia Bronchorrhea Emesis Lacrimation Salivation Sweating

Work-up: Stool cultures positive in 60% of food-borne cases Mouse inoculation test serotyping of botulinum toxin from patient serum by inoculation of live mice vaccinated against individual serotypes of botulinum toxin (CDC Atlanta) Edrophonium test (r/o MG) EMG (r/o GB, but will not r/o LEMS) LP r/o GB Tx: Ventilator support Antitoxin most effective w/in first 24 hours Diet consider TPN if gut motility not preserved Consider stool softeners for constipation Abx contraindicated as may worsen toxin load. Also, AGs known for their ability to potentiate neuromuscular blockade (contraindicated in MG patients) Avoid sedatives/other CNS depressants

Antitoxin choices:
Class Summary These agents are used for food-borne and wound botulism. They are produced from horse serum stimulated with specific antibodies directed against C botulinum and provide passive immunity. Botulism immune globulin, human (BabyBIG) Solvent-detergenttreated and viral-screened immune globulin. Derived from pooled adult plasma from persons immunized with botulinum toxoid who developed high neutralizing antibody titers against botulinum neurotoxins type A and B. Indicated to treat infant botulism caused by type A or B C botulinum. Botulinum antitoxin, heptavalent (HBAT) Investigational antitoxin indicated for naturally occ urring noninfant botulism (But a vailable from CDC as treatment IND protocol for infantile botulism). Equine-derived antitoxin that elicits passive antibody (ie, immediate immunity) against Clostridium botulinum toxins A, B, C, D, E, F, and G. Available from CDC as treatment IND protocol. Replaces licensed bivalent botulinum antitoxin AB (BAT-AB) and investigational monovalent botulinum antitoxin E (BAT-E). To obtain, contact CDC Emergency Operations Center; telephone: (770) 488-7100.