Case 

A 4 month-old ex-full term infant presents to the ED unresponsive. He is immediately brought to the trauma room and history is gathered from his mother. 

HPI: The mother began noticing that the child was less active over the past several days, had constipation, decreased PO intake, as well as nasal congestion and a cough. He has not had any fever, chills, shortness of breath, vomiting, diarrhea, or rashes. He was seen by his PCP two days ago, diagnosed with viral illness, and sent home with instructions for supportive care. This morning mother awoke to find him floppy and unresponsive. 

FSHx: The patient lives at home with his mother, father, and 2 year-old brother, all of whom are healthy. There is no concern that he may have accessed any medicines or household products. 

Vital signs: HR 140, BP 89/52, T 36.4 C, RR 53, SpO2 100% on NRB (80% on RA), blood glucose 120

Exam:

Gen: minimally responsive, grunting

HEENT: atraumatic, pupils equal and reactive

Cardiac: regular rate and rhythm, no murmurs

Pulm: poor inspiratory effort, clear lung sounds

Abd: soft, non-tender, non-distended

Extrem: moving extremities with poor effort

Neuro: minimally responsive, withdrawing from pain

Skin: no rashes

ED course: The child was emergently intubated for respiratory failure. A broad lab and imaging work up was obtained including cultures, chest x-ray, and head CT were obtained. His chest x-ray was suggestive of pneumonia so Ceftraixone was given and he was admitted to the PICU for further management. 

His head CT and blood cultures were negative. Additional workup, including a brain and spine MRI, lumbar puncture, and urine cultures were also negative. A viral panel was positive for rhino/enterovirus. He initially was diagnosed with flaccid paralysis secondary to Enterovirus. However, it was discovered that the patient’s father worked in construction and was frequently exposed to large amount of freshly dug up soil, which raised the suspicion for botulism, so he was started on anti-botulinum toxin and demonstrated improvement in his clinical status. On hospital day 9 his C. botulinum toxin study returned positive. He was extubated on hospital day 14 and continued to improve, until he was discharged on hospital day 19 with a normal neurological exam. He has followed up several times over the last few years and continued to do well.

Infantile Botulism

Background & Epidemiology: 

Botulism was first described in the 1820s in Germany in a case series of hundreds of patients who ingested contaminated sausage, thus giving the organism its name, stemming from the Latin word for sausage, botulus. The disease results from a potent neurotoxin produced by Clostridium botulinum, a group of spore-producing anaerobic gram positive rods. The toxin acts on the neuromuscular junction by blocking cholinergic signals, and it is also an inhibitor of multiple other neurotransmitters, such as serotonin, norepinephrine, dopamine, and GABA. Botulinum is the most potent bacterial toxin known, with a lethal dose of 0.0003mcg/kg in mouse models. It is estimated that a single gram of aerosolized botulinum could kill 1.5 million people, making it a concerning possible bioterrorism agent. Though it has never been used in an attack, it is believed that several countries have stockpiles intended for state-sponsored terrorism. 

Botulism can be introduced in several ways, including via wounds (puncture wounds, IV drug use), food, or iatrogenic use (Botox). Infantile botulism is most prevalent in the mid-Atlantic states, with a very high prevalence in Pennsylvania. In the US approximately 110 cases are reported each year, 75% of which are infantile. Since 1976 over 900 cases of infantile botulism have been reported in the US. The annual incidence of infantile botulism has remained stable for decades, however, the incidence of wound botulism has increased greatly over the last few decades. It has been theorized that a rise in IVDU has led to this. 

Infantile botulism occurs when a patient ingests the spores of the bacteria which then colonize the GI tract and release neurotoxin. In the US most cases occur as a result of exposure to soil or dust with spores in it. The classical teaching is that most infantile botulism occurs through raw honey, though we now know this is likely a very minor reservoir of the bacteria.

Clinical Manifestations:

The CDC has suggested the following key features of all patients with botulism (not just infantile):

• Absence of fever 

• Symmetric neurologic deficits

• Patient remains responsive 

• Normal vital signs 

• No sensory deficits 

Descending paralysis and cranial nerve involvement are also hallmarks of the disease. Imaging and CSF analysis are almost always completely unremarkable. Infantile botulism is most frequently seen between two and eight months of age. Presentation can be variable, but generally begins with constipation followed by decreased oral intake, hypotonia, drooling, and a weak cry.

Diagnosis and Treatment:

Botulism is a difficult diagnosis to make and is very frequently not identified until the child is well into their hospital stay. Stool assays can detect the toxin very reliably, but take days to result. Any suspected case of infantile botulism should be hospitalized in a highly monitored setting to monitor respiratory status. About half of all cases will require intubation and mechanical ventilation. 

Treatment is via a human derived anti-toxin IVIG (BabyBIG). It is a safe therapy that should be given when the disease is suspected without delaying for results of confirmatory testing. When compared to placebo this treatment reduced hospital length of stay (2.6 vs 5.7 weeks), ICU length of stay (1.8 vs 5 weeks), and ventilator time (1.8 vs 4.4 weeks). Average hospital charge was also $89,000 less in infants who received IVIG. 

Outside of IVIG, the treatment is entirely supportive, with the most important factor being close respiratory monitoring and early intubation. There is no role for antibiotics in the treatment of infantile botulism. For any infant with suspected botulism in any state it is recommended that the California DOH Infant Botulism Treatment and Prevention Program should be contacted for specific recommendations (www.infantbotulism.org or 510-231-7600).

Faculty Reviewer: Dr. Jane Preotle

References

1. American Academy of Pediatrics. Botulism and infant botulism. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.283.

2. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL (2006). Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006;354(5):462. 

3. Bodamer O, et al. (2019). Neuromuscular junction disorders in newborns and infants. https://www.uptodate.com/contents/neuromuscular-junction-disorders-in-newborns-and-infants?sectionName=INFANT%20BOTULISM&search=botulism&topicRef=5509&anchor=H14&source=see_link#H14

4. Centers for Disease Control and Prevention. National Botulism Surveillance. https://www.cdc.gov/botulism/ surveillance.html (Accessed on February 07, 2018).

5. Pegram S, et al (2019). Botulism. https://www.uptodate.com/contents/botulism?search=botulism& source=search_ result&selectedTitle=1~79&usage_type=default&display_rank=1

6. Yuan J, Inami G, Mohle-Boetani J, Vugia DJ. (2011) Recurrent wound botulism among injection drug users in California. Clin Infect Dis. 2011;52(7):862. 

7. Zilinskas RA (1997) Iraq’s biolgoical weapons. The past as future? JAMA. 1997;278(5):418.