Mary Anne Jackson, MD | Interim Dean - UMKC School of Medicine | Medical Editor, The Link Newsletter
The Texas Department of State Health Services issued a health alert on Nov. 16, 2018 after 10 reports (four confirmed cases) of infant botulism in the state of Texas, were received between August and the end of October. The cluster of cases raised concern for an outbreak from a common source; in the prior five years, 26 cases of infant botulism were reported in Texas (range 1-7/year).
All cases presented typically and after investigation, the cases were linked to pacifiers containing honey that were purchased in Mexico. Such pacifiers are also available in the U.S.
Infant botulism has a unique pathogenesis where Clostridium botulinum spores are ingested, toxin production in the intestine follows with the absorbed neurotoxin making its way to the circulation and to the neuromuscular junction, causing flaccid paralysis. Disease caused by C botulinum type A or B strains is most commonly reported, accounting for 99% of cases; 100-140 cases of infantile botulism are reported annually in the U.S. Type F botulism caused by C botulinum or neurotoxigenic C baratti accounts for <1% of cases and a very young infant onset (median age of onset 9 days), with rapid progression and severe paralysis is noted.
The age of onset is usually between 1 and 6 months (median age, 4 months). Presenting symptoms and signs in infant botulism mimic other common entities, often delaying diagnosis. New onset weakness, poor feeding, poor head control, ptosis (most notable when the infant’s head is held erect), disconjugate gaze, poor gag and suck reflex are most commonly encountered, with presentation evolving over several days. Constipation is an under-recognized symptom, but is common owing to the toxin effect on the intestine. Approximately half of infants will progress to respiratory failure.
An infectious diagnosis including bacterial and viral sepsis or meningitis, metabolic disorders, congenital myopathy, or spinal muscle atrophy are the diseases often considered in the differential diagnosis. In a decade-plus long study of infants treated for infantile botulism, 6.2% had an alternative diagnosis and spinal muscle atrophy was most frequently identified. An atypical so-called “catastrophic” presentation is also reported where infants present with rapid deterioration after presentation with poor feeding or poor suck. Coagulopathy, hyponatremia, hypoglycemia and/or acidosis are reported laboratory findings, suggesting an inborn error of metabolism initially, and delaying diagnosis (Mitchell WG and Tseng-Ong L Pediatrics 116(3) September 2005).
First recognized as a clinical entity in 1976, and nationally notifiable in the U.S. since 1983, a global survey found 524 cases reported between 1978-2006; cases were reported in all continents except Africa, with North and South America reporting more cases than other continents. Outside of the U.S., Argentina had the most cases identified, followed by Australia, Canada, Italy and Japan. Most cases were related to toxin A (83.4%) and honey ingestion was an identified preventable exposure. Other rarely implicated food sources in infant cases have included powdered infant formula (United Kingdom), herbal teas (Argentina) and medicinal herbs. Exposure to spores ingested from environmental sources is an important non-foodborne source, as in most countries including the U.S., the toxin types causing disease reflects the geographic distribution of C botulinum spores in the soil.
The diagnosis is confirmed by testing stool for toxin and culture. In some cases, obtaining stool requires use of enema to obtain the specimen in infants who have constipation (the specific procedure is available at http://www.infantbotulism.org/laboratorian/collection.php ); glycerin suppository should not be used. The specimens should be sent directly to the Infant Botulism Treatment and Prevention Program at the California Department of Public Health (clinical consultation is mandatory through the local public health department to access testing; California Department of Health 24-hour telephone: (510) 231-7600).
Supportive care that focuses on airway, nutrition and bowel and bladder management is required for all patients, and antibiotics should be avoided as they may increase the amount of botulinum neurotoxin that can be absorbed in the circulation. Practitioners should be alert for complications that range from atelectasis, vasomotor instability, seizures, electrolyte disturbance, and iatrogenic complications from hospitalization including aspiration, urinary tract infection, bacteremia and pneumonia. Infants have normal sensation and the central nervous system is intact, underscoring the importance of providing appropriate auditory and tactile support of the patient.
Botulinum antitoxin, marketed as BabyBIG®, is the only known treatment for infantile botulism. Safety and efficacy of human botulism immune globulin, was evaluated in a five-year, double-blind, placebo-controlled study involving 122 infants in California, and a subsequent national open trial over six years in 382 infants. The mean duration of ICU care, mechanical ventilation and tube feedings was reduced, hospital stay in treated patients was reduced from 5.7 to 2.6 weeks, and significant savings in hospital charges was demonstrated. (Arnon SS, Schechter R, Maslanka SE, et al. NEJM 2006; 354:462-71). BabyBIG® was licensed in 2003 and a post-licensure study that included cases treated over the next 12 years, showed the earlier the treatment was initiated in the infant’s course, the better the outcome. (Payne JR, Khouri JM, Jewell NP and Arnon SS; J Pediatr 2018; 193:172-7).
The recent report of infant botulism cases links to honey pacifiers acquired from Mexico; however, similar pacifiers are available from online retailers in the U.S. The recognition of the Texas cases allows for reinforcement of knowledge related to the epidemiology and clinical manifestations of disease allowing for faster diagnosis and treatment. It also underscores the importance of well-child guidance to avoid any honey products in children under one year of age.