Feb 8, 2006 (CIDRAP News) A human-derived antitoxin for babies with botulism shortened their hospital stays by an average of more than 3 weeks and reduced average hospital bills by about $88,000 in a randomized trial, according to a recent report.
Subsequent use of the drug to treat several hundred babies in an open-label study saved more than 20 patient-years of hospitalization and $34 million in hospital charges, according to the report in the Feb 2 New England Journal of Medicine. The study was authored by Stephen S. Arnon and colleagues, of the California Department of Health Services (CDHS), the Centers for Disease Control and Prevention, and the University of California, Berkeley.
Between 80 and 110 cases of infant botulism are reported each year in the United States, making it an orphan disease, the report says. The illness usually occurs when babies swallow Clostridium botulinum spores, which grow in the large intestine and produce botulinum toxin. The toxin enters the bloodstream and binds to nerves at neuromuscular junctions, leading to paralysis.
A botulism antitoxin derived from vaccinated horses is available for adults in the United States, but serious side effects deter its use in infants. To fill this gap, the California Department of Health Services developed the human-derived antitoxin, called Botulism Immune Globulin Intravenous (Human), or BIG-IV. The Food and Drug Administration licensed the drug as BabyBIG in 2003.
BIG-IV is made from blood plasma donated by CDHS laboratory workers and colleagues who were previously immunized with botulinum toxoid because they work with the toxin. The product contains antibodies against botulinum toxin types A and B, which cause almost all cases of infant botulism in the United States, according to the report.
The randomized trial included 122 infants who were hospitalized in California with botulism over a 5-year period from 1992 to 1997. (All infants hospitalized with suspected botulism were potential participants, but only those with laboratory-confirmed cases were included in the results.) Fifty-nine patients received BIG-IV; 63 received a placebo.
The treatment group had an average hospital stay of 2.6 weeks and average hospital charges of $74,800, versus 5.7 weeks and $163,400 for the placebo group (P<.001 for both results). The treatment group also required significantly shorter periods of intensive care, mechanical ventilation, and tube or intravenous feeding. The benefits were significant regardless of whether patients had type A or type B illness.
In the open-label study, BIG-IV was offered in cases of infant botulism, first in California and later in other states, between the end of the randomized trial and licensing of the drug in October 2003. For the 366 patients who were treated within 7 days of hospital admission, the mean hospital stay was 2.2 weeks and the average hospital bill was $57,900. The average hospital stay for patients treated within the first 3 days after admission was 2.0 weeks, significantly shorter than the 2.9 weeks for those treated between 4 and 7 days after admission.
The authors calculated that the open-label study saved a total of 20.3 years of hospitalization time and $34.2 million in hospital charges.
"We conclude that BIG-IV . . . is a safe and effective treatment for infant botulism type A and type B," the article states. "Treatment should be given as soon as possible after hospital admission and should not be delayed for confirmatory testing of feces or enema."
The authors write that because botulism is now classified as a category A biological weapon, a larger supply of human antitoxin than can be derived from blood plasma is needed, and a recombinant antitoxin is in development.
Arnon SS, Schechter R, Maslanka SE, et al. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med 2006;354(5):462-71 [Abstract]
See also:
California Department of Health Services' Infant Botulism Treatment and Prevention Program
http://infantbotulism.org/
