Pediatric Botulism

Updated: Feb 28, 2019
  • Author: Muhammad Waseem, MBBS, MS, FAAP, FACEP, FAHA; Chief Editor: Russell W Steele, MD  more...
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Overview

Background

Botulism is a broad term encompassing 3 clinical entities caused by botulinum toxin. Propagation of this toxin under different circumstances can lead to food-borne, wound, or infant botulism.

Foodborne botulism was the first of the 3 entities to be described. Byzantine Emperor Leo VI documented cases of fatal food poisoning in the ninth century. In the 1820s, Justinus Kerner, a German physician, and romantic poet scrutinized a number of food-poisoning cases and found that most were caused by improperly prepared sausages. [1, 2] As a result, he named the disease botulism, after the Latin word for sausage, botulus. Kerner correctly deduced the presence of the culpable toxin in the sausages and extracted a compound he termed wurstgift (German for sausage poison). [3]

Kerner continued studying botulism. In an experiment that would surely cause controversy in any modern human investigations committee, Kerner injected himself with the wurstgift extract and demonstrated many of the signs and symptoms so convincingly that the causal relationship was proven. Lastly, Kerner presaged the therapeutic uses of this toxin in individuals with motor over-activity by some 150 years. Despite his contributions to the field, questions remained regarding how the toxin entered the sausages.

In 1897, the microbiologist Emile-Pierre van Ermengen identified a gram-positive, spore-forming, anaerobic bacterium in a ham that caused 23 cases of botulism in a Belgian nightclub. [4] He termed the bacterium Bacillus botulinus; it was later renamed Clostridium botulinum (see the image below).

This is a photomicrograph of Clostridium botulinum This is a photomicrograph of Clostridium botulinum stained with Gentian violet. The bacterium, C botulinum, produces a neurotoxin which causes the rare, but serious, paralytic illness, botulism.

Wound botulism was the next type to be described. C botulinum was cultured from the wounds of asymptomatic patients as early as 1942, but wound botulism was not described as it is known today until 1951. In 1973, Merson and Dowell reported the case of a girl who had open leg and ankle fractures. [5] The girl demonstrated clear clinical signs of botulism without any history of food-borne illness or symptomatic family members.

Infant botulism was described separately in 1976 by Midura and Arnon and by Pickett et al. [6, 7] Currently, the infant form is the most common presentation of botulism in the United States, with about 110 cases occurring annually. [8] Although frequently mentioned, raw honey is the apparent cause in only 15% of cases in the US and 58% of cases in Europe. It is more commonly seen in infants of immigrant families. [9, 10, 11] The origin of the spores is unknown in 85% of cases in the US, [12] but may be associated with soil and dust from nearby construction sites, nearby heavy traffic or from caretakers exposed to these risk factors. [13] Other possible sources of infant botulism, include corn syrup, powdered infant milk, infant cereal formulas, natural sweeteners, medicinal plants such as Matricaria chamomilla, and there is even one case report from Japan of infant botulism caused by spores in contaminated well water. [10]  There is also one case report of an infant who developed botulism after a wound, the infant was being treated for was treated with a honey dressing. The authors of this article caution about using honey dressings in infants. [14]

See 5 Cases of Food Poisoning: Can You Identify the Pathogen?, a Critical Images slideshow, to help identify various pathogens and symptoms related to foodborne disease.

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Pathophysiology

C botulinum is a gram-positive, spore-forming anaerobe that naturally inhabits soil, dust, and fresh and cooked agricultural products. Although classified as a single species, C botulinum is better described as a group of at least 3 (possibly 4) genetically unique organisms. All of the organisms share the ability to produce a type of botulinum toxin, although not all produce the same type. There are 7 serotypes of botulinum toxin: A through G. [8] Types A and B are by far the most common types. In the US, Type A is more common on the West Coast and Type B is more common on the East Coast. [10] Clostridium baratii and Clostridium butyricum also produce botulinum toxin. These organisms produce type E and F toxins. Whether Clostridium argentinense is a subgroup of C botulinum or a separate species is currently under debate.

Botulinum toxin is the most potent naturally occurring toxin known to humankind. Botulinum toxin is lethal at a dose of 10–9 g/kg, making botulinum toxin 15,000-100,000 times more potent than sarin gas.

Food-borne botulism is not seen after eating fresh foods. Some methods of food preparation, such as home canning, produce an anaerobic, low-acid (ie, pH >4.6), low-solute environment in which the toxin can be produced. A similar environment exists in wounds, thus providing an opportunity for wound botulism to develop. [15]

Infant botulism is unique. In persons older than 1 year, the spores are unable to germinate in the gut, and therefore food-borne disease is the result of ingesting a preformed toxin. C botulinum spores can germinate in the gut of infants younger than 1 year because of their relative lack of gastric acid, decreased levels of normal flora, and immature immune systems (ie, specifically lacking secretory immunoglobulin A). This environment is conducive to toxin production, and therefore, infant botulism can arise from eating the spores present in unprepared foods, such as honey. [16]

Once produced, several activating steps are required for the toxin to produce deleterious effects. The toxin precursor is produced as a 150-kd protein encoded by a single gene. The precursor is cleaved to a 100-kd heavy chain and a 50-kd light chain, joined by a disulfide bond. The bond is essential for membrane penetration, and reduction of the bond inactivates the toxicity of the polypeptides. The light chain is more toxic than the heavy chain, although both must be present to achieve the full toxic effect.

All botulinum toxins are zinc-metalloproteases that bind to different membrane proteins involved in fusion of the synaptic vesicle to the presynaptic membrane. This fusion allows the release of acetylcholine into the synaptic junction. The toxins are classified as types A through G, although only types A, B, E, and F cause human disease. Types A and E bind to synaptosomal-associated protein 25, type C binds to syntaxin, and types B, D, and F bind to the vesicle-associated membrane protein. Inhibition of the proteins effectively blocks acetylcholine transmission across the synapse and functionally denervates the muscle. This binding to presynaptic cholinergic receptors irreversibly prevents the release of acetylcholine (paper 4). The magnitude of the clinical effect depends on the proportion of synapses blocked and the effects can range from weakness to flaccid paralysis and atrophy. The toxin does not cross the blood-brain barrier, and that is why preservation of CNS and cognitive function is preserved unless complications such as hypoxic brain damage from hypoventilation occur. [8]

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Epidemiology

Frequency

United States

From 1973-1996, 724 cases of food-borne botulism, 103 cases of wound botulism, and 1444 cases of infant botulism were reported. As noted above infant botulism is the most common type of botulism in the US, with about 110 cases reported annually. [8] The type of botulism was undetermined in 39 cases. [17] Very rare causes of botulism, such as an Adult Enteric type seen in patients with Crohn’s Disease on chronic antibiotics, inhalation of spores nasally in laboratory workers, and overdose of injected toxic for cosmetic purposes, have recently been reported. [8]

Type A accounts for 50% of foodborne cases and the other 50% of cases are evenly split between types B and F. Wound botulism is caused by type A in 80% of cases and type B causes most of the remaining cases. In the 1990s, the US experienced a drastic increase in wound botulism, due to the injection subcutaneously of Heroin contaminated with C. botulinum spores, often referred to as Black Tar Heroin. [15] The cause of infant botulism is evenly split between types A and B. [17] Geographically, type A predominates west of the Mississippi River, whereas type B predominates east of the river. [18] A single case of type E infant botulism has been reported. [19]

International

In Europe, contaminated hams and sausages are the usual modes of transmission. Poland has the highest frequency by far, with 325 outbreaks and 448 cases in a 3-year period. China is a distant second with 39 outbreaks and 234 cases in a 25-year period. [20] Recently, case reports from Australia have appeared. [21] Five cases were recently reported in an 18-month period (2006-2008) in and around Toronto, Canada, [22] and recent epidemiology of foodborne botulism in Canada has been reported. [23] Many countries have recently reported cases of infant botulism, with the notable exception of countries in Africa, which have not yet reported a case of infant botulism, likely because of lack of recognition. [9] There are several excellent recent case reports and reviews of infant botulism from Great Britain and Canada. [16, 13, 8]

Mortality/Morbidity

Around the year 1900, the mortality rate associated with botulism was 70%. Today, the mortality rate approaches 15%.

Race

In Great Britain, infant botulism was found to be more common in immigrant families from Asia, probably due to the tradition of giving honey to infants. [9] In the Southwestern United States, there may be a greater risk of infant botulism among Hispanics, because of the greater use of honey pacifiers and herbals, such as chamomile, in this population. [11]

Botulism has no racial predilection, although foodborne botulism is endemic in Alaskan Natives. [24, 25]

Sex

Gender is not a factor in botulism infection.

Age

Infant botulism usually occurs in children aged 2-6 months, although it can occur in infants aged 3-382 days.

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