Botulism: An Unusual Cause of Lethargy and Constipation in a 3-Month-Old

August 31, 2008

A 3-month-old boy was brought to the pediatrician with a 2-day history of "moaning," lethargy, and difficulty in latching on for breast-feeding. The infant had not had a wet diaper for the past 24 hours, and his last bowel movement was more than 48 hours ago.

 

A 3-month-old boy was brought to the pediatrician with a 2-day history of "moaning," lethargy, and difficulty in latching on for breast-feeding. The infant had not had a wet diaper for the past 24 hours, and his last bowel movement was more than 48 hours ago.

The initial physical examination was remarkable for overall pallor, weak cry, and decreased tone. Signs of severe dehydration were evident: cool extremities, thready peripheral pulses, poor skin turgor, and prolonged capillary refill.

The baby's past medical history was unremarkable. He was a fullterm infant, born without complication. Prenatal laboratory test results, including group B streptococcal status, were either normal or negative. The infant had been thriving, and his newborn screen showed normal results. There was no history of fever, vomiting, diarrhea, rash, sick contacts, recent travel, or pets in the home.

The patient was transferred to the emergency department (ED) via emergency medical services. He was afebrile (rectal temperature, 36.7°C [98.1°F]) and normotensive (blood pressure, 97/51 mm Hg), but tachypneic (54 breaths per minute). His pupils were equally round and reactive to light. Ptosis was not initially recognized or documented on physical examination. The oropharynx and tympanic membranes were clear. Clear lungs and normal heart sounds were auscultated, and there was no evidence of a murmur. The abdomen was soft, nontender, and nondistended, without masses or hepatosplenomegaly. The patient's skin appeared to be clear of any rashes or lesions. Neurological examination demonstrated poor tone and diminished gag reflex. His blood glucose level was 20 mg/dL. An intraosseous device was placed in the left tibia, and a dextrose 50% solution bolus followed by glucagon was infused.

In the ED, intravenous access was secured and a 40 mL/kg bolus of normal saline was infused. Blood glucose levels rose to 127 mg/dL. A complete blood cell count and arterial blood gas levels were normal. Levels of lactate, pyruvate, and ammonia, as well as toxicological screens of serum and urine were all within normal limits. A complete metabolic panel demonstrated a PCO2 pressure of 18 mm Hg and an anion gap of 16. Results of a lumbar puncture and urinalysis/urine culture and blood cultures were normal or negative.

Imaging studies, including CT scans of the head (to rule out intracranial pathology) and chest films (taken secondary to the patient's marked tachypnea) were unremarkable. The patient was transferred to the pediatric ICU (PICU) for further care. Although clinically stable, he remained lethargic with a markedly weak cry. The PICU staff ordered plain films of the abdomen to rule out intussusception. Images showed a relatively normal gas pattern, with air in the distal rectum. A considerable amount of stool correlated with the recent history of constipation. The infectious disease team was consulted, and a working diagnosis was established. The combination of lethargy, poor latch and tone, and constipation in the absence of any other symptoms or abnormal laboratory results was consistent with a diagnosis of infant botulism. The infant's weak gag reflex further supported the diagnosis. This diagnosis was officially confirmed weeks later (when the infant had regained his health) by a stool toxin assay that was positive for Clostridium botulinum toxin type B.

 

 

INFANT BOTULISM

Botulism is a rare but serious paralytic illness caused by a nerve toxin produced by the gram-positive anaerobic bacillus, C botulinum. The 3 main clinical presentations of this condition are food-borne, wound, and infant botulism. Botulinum toxin is considered a potential bioterrorism agent with associated clinical manifestations that cannot be distinguished from natural forms of the condition.

 

Infant botulism was first described in 1976. The condition occurs when ingested spores of C botulinum germinate and colonize the infant's intestinal tract. After colonization, botulinum toxin is synthesized and absorbed throughout the infant's gut. The toxin behaves as a protease, damaging an integral membrane protein of acetylcholinecontaining vesicles, which in turn, disrupts the release of acetylcholine into the synaptic cleft, thwarting the initiation of muscle contraction at the neuromuscular junction (Figure).1

 

Figure

 

The incidence of infant botulism in the United States is estimated to be approximately 100 cases annually.2 Half of the cases reported in 2001 through 2002 originated in California.2 Although there are 7 known antigenic variants of the toxin (A through G), most documented cases of infant botulism are caused by botulinum toxin types A and B and have been described in infants 6 months or younger.

Although ingestion of honey is a known risk factor, the principal route of exposure is believed to be ingestion of spores that are ubiquitously located in soil and dust. No history of honey ingestion could be elicited in our patient, and it is therefore believed that he was exposed to botulinus spores in the home environment. A fascinating recent publication lends further credence to this conjecture; using polymerase chain reaction testing, genetic similarity was demonstrated from both C botulinum isolates in an intestinally colonized infant and isolates from dust from the vacuum cleaner in the infant's home.3

Typically, the initial presenting symptom is constipation, followed by progressive weakness. Presenting symptoms may also include a weak cry, poor feeding, and dehydration. The infant with botulism becomes progressively weak, hypotonic, and hyporeflexic, showing bulbar and spinal nerve abnormalities. A "catastrophic" presentation of infant botulism has been documented in infants who initially demonstrated a paucity of signs and symptoms and whose death was attributed to sudden infant death syndrome.3 Physician awareness of infant botulism is therefore critical to early recognition and intervention, because the neuroparalytic disease unfolds in a sub-acute manner and may lead to devastating respiratory failure requiring mechanical ventilation.2

The differential diagnosis includes a variety of infectious, neurological, and metabolic conditions (Table). A retrospective study of 681 patients treated for presumed infant botulism revealed that spinal muscular atrophy, a metabolic disorder, or another infectious disease had been diagnosed in the approximately 5% of infants without a laboratory confirmed diagnosis.4

Table

Definitive diagnosis of infant botulism includes collection of feces through bacteriostatic saline enemas for direct toxin analysis as well as culture to isolate C botulinum. Infant botulism is a self-limited condition, because new nerve terminals are generated with time. However, once the diagnosis is presumed based on initial clinical presentation, treatment is initiated with Botulism Immune Globulin Intravenous (Human) (BIG-IV or BabyBIG) to hasten recovery and limit potential morbidities. BIG-IV was created and licensed in 1991 from pooled adult plasma of California Department of Health volunteers immunized with pentavalent botulinum toxoid. The preparation contains purified IgG from those with high titers against botulinum toxin types A and B.5 In a recent 5-year randomized clinical trial, BIG-IV markedly decreased average length of hospital stay and duration of mechanical ventilation by 3.1 weeks and 2.6 weeks, respectively.6

The potential use of botulinum toxin as a bioterrorism agent has recently raised great concern. The CDC has therefore designated C botulinum as a Category A bioterrorism threat.7 Although botulinum toxin could be isolated to contaminate food supplies, an aerosolized dissemination of the toxin is a plausible mechanism for a bioterrorism attack. Inhalational botulism cannot be clinically differentiated from any of the 3 naturally occurring forms of the disease. Health care professionals must remain attentive to indications of intentional release of a biologic agent that might include either an unusual geographical clustering of illness or a large number of cases of acute flaccid paralysis with prominent bulbar palsies.8

 

WRAP-UP

Lethargy in an infant is always an alarming clinical presentation. Fortunately, the patient in this case received BIG-IV within 2 days of presentation. He recovered rapidly and was discharged from the hospital within 4 weeks of treatment. The patient never required mechanical ventilation, although meticulous observation and frequent neurological examinations helped ensure airway patency. Nasojejunal tube feeds were initiated to reduce the risk of aspiration associated with a decreased gag reflex and dysphagia. The prognosis for this infant is excellent, and he is thriving and developing normally.

 

This case emphasizes the need for physicians to be aware of this rare but easily treatable disorder. Close attention must be paid to the concomitant warning signs of weak cry, poor feeding, and constipation. In addition, diligence is needed to recognize potential outbreaks of such clinical presentations as indication of possible bioterrorism.

 

References:

  • Cox N, Hinkle R. Infant botulism. Am Fam Physician. 2002;65:1388-1392.

  • Centers for Disease Control and Prevention. Infant botulism-New York City, 2001-2002. MMWR. 2003;52:21-24.

  • Nevas M, Lindström M, Virtanen A, et al. Infant botulism acquired from household dust presenting as sudden infant death syndrome. J Clin Microbiol. 2005;43:511-513.

  • Francisco AM, Arnon SS. Clinical mimics of infant botulism. Pediatrics. 2007;119:826-828.

  • Arnon SS. Creation and development of the public service orphan drug Human Botulism Immune Globulin. Pediatrics. 2007;119:785-789.

  • Arnon SS, Schechter R, Maslanka SE, et al. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006;354:462-471.

  • Darling RG, Catlett CL, Huebner KD, Jarrett DG. Threats in bioterrorism, I: CDC category A agents. Emerg Med Clin North Am. 2002;20:273-309.

  • Botulism. Centers for Disease Control and Prevention Web site. http://www.bt.cdc.gov/agent/ botulism. Accessed May 29, 2008.