Continuing Education Activity

Infantile botulism is caused by Clostridium botulinum, which is an anaerobic spore-forming, gram-positive bacillus. It can be found in the soil, water, and air with a lethal toxin dosage as low as 1 mcg/kg. Botulism infection can occur in five different ways. This activity reviews the causes, pathophysiology, and presentation of infantile botulism and highlights the role of the interprofessional team in its management.

Objectives:

• Review the presentation of infantile botulism.
• Outline ways in which infantile botulism can be acquired.
• Summarize the treatment of infantile botulism.
• Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by infantile botulism.

Introduction

Infantile botulism is caused by Clostridium botulinum, which is an anaerobic spore-forming, gram-positive bacillus.[1][2][3][4] It can be found in the soil, water, and air with a lethal toxin dosage as low as 1 mcg/kg. Botulism infection can occur in five different ways:

• Foodborne botulism: When a person ingests the preformed toxin.
• Infant botulism: This has occurred in a small population of infants (children under the age of 1 year) who have C. botulinum colonization in their gastrointestinal tract.
• Wound botulism: When infected wounds contain C. botulinum, and they secrete the toxin.
• Iatrogenic botulism: This occurs when cosmetic or therapeutic procedures that use the C. botulinum toxin cause systemic intoxication.
• Intestinal colonization: When a person over the age of 1 year harbors the C. botulinum toxin within the gastrointestinal tract (infantile botulism in children and adults).

Even though there are multiple ways to contact botulism, only three main serotypes are responsible for all of these infections:

• Type A: Predominantly found west of the Mississippi River
• Type B: Predominantly found east of the Mississippi River
• Type E: Found in the Pacific Northwest with a preponderance in Alaska

In the USA, there are about 100 cases of infantile botulism reported each year. About 20% are linked to the consumption of raw honey. The infants affected are usually from immigrant families and the source of the spores in the majority of affected infants remains unknown. Experts suggest that the spores may be from contaminated soil and dust from nearby construction facilities. Other potential sources of botulism include the consumption of powdered milk, natural sweeteners, corn syrup, and medicinal herbs.

Etiology

Infantile botulism is the most common form of botulism infection and predominates 70% of all new cases of botulism annually. Infants will ingest contaminated milk or food, and the neurotoxin will colonize and replicate in the large intestine. Infantile botulism is caused equally by Type A and Type B serotypes. Foodborne botulism is rarely a childhood illness and is often seen in clusters.[5][6][7][8]

Epidemiology

Infantile botulism infection is responsible for approximately 70% of all new botulism cases a year. In the United States (US) alone, 1.9/100,000 live births yield approximately 77 new cases annually. There is an equal distribution of males and females. Risk factors for infantile botulism include higher birth weights, infants of mothers of advanced maternal age, and breastfed infants. Over 50% of the new cases of infantile botulism in the past 30 years have occurred in California.

The C. botulism toxin is the most implicated in infected food and dust particles. There is a strong association with foods that have been canned and preserved at home or with incorrect sterilization techniques or poor refrigeration. Approximately 20% of cases involve honey or corn syrup. How the spores are transported in these foods is still unclear. Also, living near construction sites with excessive dust particles and vacuum cleaner debris has also been implicated in infections.

Hispanics and Asian families have a higher incidence of infantile botulism because of their use of herbal medications and raw honey.

Pathophysiology

C. botulinum can produce several types of botulinum toxin. In fact, each subtype of clostridium can produce a different type of toxin. The botulinum toxin is potent and even at a dose of picomoles, it is more potent than mustard gas.

The active form of the C. botulinum spore produces a neurotoxin that causes descending paralysis. This active form is made of polypeptide chains connected with disulfide bonds. The toxin will enter the presynaptic nerve terminals where it prevents the release of acetylcholine by blocking calcium channels. The resulting action causes an overall decrease of acetylcholine at the neuromuscular junction and leads to flaccid paralysis. Traditionally, the toxin will first affect bulbar musculature than somatic musculature.

The key feature of infantile botulism is that it is only seen in children less than 12 months. The spores do not germinate in older children because of gastric acidity. Infants younger than 12 months have an immature immune system, a relative lack of gastric acidity, and diminished bacterial flora,- all factors that increase the risk of botulism.

Histopathology

Clostridium botulinum is a gram-positive anaerobic bacillus that is spore-forming. The inactive state is also heat-resistant.

History and Physical

The incubation period is 10-30 days, with the peak age of occurrence around 3-4 months. The initial symptoms are linked to the GI tract and include nausea, vomiting, and diarrhea.

Parents often describe their infant as having poor feeding, lethargy, a weak cry, and constipation. Babies can present with ptosis in the face and eyes, excessive drooling due to weak suck reflex, and shallow breathing due to respiratory suppression. The classic presentation is characterized by a “floppy baby.”

Progression of the infection shows advanced symptoms of toxin infestation including descending bilateral, symmetric paralysis and bulbar palsies (diplopia, dysarthria, dysphonia, and dysphagia). Many breastfed mothers notice breast engorgement due to their infant’s poor feeding and poor sucking ability. These symptoms can be subtle, especially since constipation, poor feeding, and drooling are all symptoms commonly brought up. The anal sphincter tone will be relaxed and decreased. Deep tendon reflexes can be either diminished or normal. Sensation will be intact but can be hard to distinguish due to weakened muscular tone. Usually, mental status will be preserved.

Some symptoms may not be obvious until neuromuscular fatigue sets in. Muscular fatigue tests include the following:

• Place the patient in a dark room and note the rapidity of the pupillary constriction with a light. Do this multiple times and note if there is sluggishness to the pupil constriction over two to three minutes.
• With a clean-gloved finger, note the infant’s suck reflex over time. If the patient is infected, the suck reflex will diminish over time.

The clues to the diagnosis include acquired hypotonia, constipation, weak sucking, hoarse crying, and symmetrical descending weakness. In addition, the infant will have marked head lag and diminished gag reflex. No time should be wasted with unnecessary testing as respiratory failure can occur suddenly.

Evaluation

The diagnosis should always be suspected with a clinically floppy infant or a history and physical with consistent findings. The reasoning is that routine lab tests are often normal. There may be secondary lab findings due to associated sequela from the botulism infection.[9][10][11]

To confirm the diagnosis, both a stool culture and direct toxin assay are required. The toxin assay can be obtained from the stool, serum, or gastric contents. A stool culture can be obtained with an enema but not glycerin suppositories. Stool samples can be put into a sterile urine container. Do not put stool samples in containers with preservatives. They can be stored in a refrigerator prior to being sent but should not be frozen. Results for the direct toxin specimen are often available the morning after the specimen has been received. Stool culture results can vary from one week to one month. Only 60% of stool cultures yield a positive result. The best test is the mouse inoculation test performed by the CDC. Today, polymerase chain reaction (PCR) is available to detect spores and the results are available within 24-72 hours. However, PCR is not readily available in all hospitals.

No imaging is required to make the diagnosis. Testing of the infected food can be done, however, results are often inconclusive and or delayed.

It is important to rule out meningitis by performing a lumbar puncture.

Treatment / Management

Until the diagnosis is confirmed, continue supportive care for the patient. With any patient, first assess and stabilize the airway, breathing, and circulation. Approximately 50% of infantile botulism cases will require intubation and an advanced airway regardless of whether they are treated with human botulism immune globulin intravenous (human BIG-IV); however, those who are not treated may require mechanical ventilation longer. As a result, a clinician should have a very low threshold to intubate a patient. This will require careful monitoring and admission to the intensive care unit.

If trying to decide if the patient requires an advanced airway, the best way to measure respiratory depression at the bedside is with the use of a continuous end-tidal carbon dioxide monitor. To help combat the respiratory distress, patients should be placed in Trendelenburg position at a 20-degree angle with a neck roll to stabilize the neck, cervical spine, and prevent sliding. If the patient has a decreased gag reflex, he or she is at increased risk for aspiration.

Human BIG-IV has shown to decrease the length of hospital stay and the length of mechanical ventilation. It is a single dose treatment that is infused intravenously over 30 minutes. The risk of anaphylactic shock is low but the cost of this IVIG is close to $50K.

There is antitoxin available and can rapidly reverse the course of symptoms, especially it is administered within 24 hours of symptoms.

There is no indication for the use of antibiotics in infantile botulism. Further supportive care involving ventilation, nutrition, and position are also essential in the patient’s care.

It is vital to avoid all aminoglycosides in the infant as they may potentiate the neuromuscular weakness. Penicillin G and metronidazole are recommended if the cause is a wound infection.

Differential Diagnosis

• Sepsis
• Electrolyte imbalance/dehydration (hypoglycemia, hyponatremia, hyperkalemia)
• Metabolic disorder and encephalopathy
• Congenital myopathy
• Leigh disease
• Myasthenia gravis
• Guillain-Barre syndrome

Prognosis

Prognosis is good with recognition and administration of human BIG-IV. After hospitalization, patients need to follow up with neurology and physical therapy. Most cases of infantile botulism result in complete recovery within several months to a year.

Compared to a century ago when the mortality was close to 90%, today the mortality is less than 15%.

Complications

• Respiratory failure
• Urinary retention
• Aspiration
• Apnea
• Death

Deterrence and Patient Education

Parents should be instructed to use safe methods of food handling and preparation, especially if canning foods is being done in the home. Parents should also be advised to avoid giving raw honey and corn syrup to infants. Once a patient has been treated for infantile botulism, family members should be instructed on the importance of strict handwashing and special handling of soiled diapers of these babies as they can continue to shed the toxin for weeks to months.

Pearls and Other Issues

• Following the resolution of the illness, all live-virus vaccinations should be delayed by 5 months.
• There have been no cases in which infected babies with resolved cases of infantile botulism have had a recurrence.
• If the baby was treated with human BIG-IV, they have a protective level of toxin-neutralizing antibody 6 months following administration.
• Any subsequent siblings of infected babies do not have an increased chance of contracting infantile botulism.
• Following discharge from the hospital, strict handwashing and special handling of soiled diapers of these babies should be practiced because they can continue to shed the toxin for weeks to months.

Enhancing Healthcare Team Outcomes

The diagnosis and management of infantile botulism are best done with an interprofessional team that consists of a pediatrician, nurse practitioner, primary care provider, anesthesiologist, and an infectious disease specialist. Until the diagnosis is confirmed, continue supportive care for the patient. With any patient, first assess and stabilize the airway, breathing, and circulation. Approximately 50% of infantile botulism cases will require intubation and an advanced airway regardless of whether they are treated with human BIG-IV; however, those who are not treated may require mechanical ventilation longer. As a result, a clinician should have a very low threshold to intubate a patient. This will require careful monitoring and admission to the intensive care unit. The pharmacist should make sure that the infant is on no medications that can potentiate the neuromuscular weakness

Human BIG-IV has shown to decrease the length of hospital stay and the length of mechanical ventilation. It is a single dose treatment that is infused intravenously over 30 minutes. With treatment, most infants do recover, but many may require physical therapy for months or even years. Fortunately, recurrence is very rare. Mothers should be educated on the importance of handwashing. Close communication between the clinicians is vital to avoid the high mortality of infantile botulism. [Level 5][12][13][14]