Infant botulism is the most common form of human botulism in the United States. In contrast to foodborne and wound botulism, infant botulism results from intra-intestinal production of botulinum toxin following ingestion and germination of Clostridium botulinum spores. In 1989 the California Department of Health Services (CDHS) undertook development of the orphan drug Human Botulism Immune Globulin (BIG-IV) for the treatment of infant botulism. In 1991 BIG-IV Lot 1 was made by plasmapheresis of CDHS staff and other volunteers previously immunized with botulinum toxoid. BIG-IV was evaluated in a statewide, randomized, placebo-controlled clinical trial (RCT) 1992-97 and in a subsequent national open-label study while licensure requirements were being met. RCT patients were enrolled within 72 hours of hospital admission based on clinical criteria; the placebo was identically-packaged, licensed normal human intravenous immune globulin (IGIV). Treatment consisted of a single intravenous infusion of 50 mg/kg of product. The primary efficacy outcome variable was reduction of length and associated cost of hospital stay. Safety was assessed by comparing adverse event rates.
Results 122 patients with eventual laboratory-confirmed infant botulism were enrolled during the 5-year statewide RCT (59 BIG-IV, 63 placebo). No adverse event occurred significantly more frequently in treated patients than in control patients, and no bronchospasm, anaphylaxis or deaths occurred in either group. Treatment with BIG-IV reduced mean per-patient hospital stay by 3.1 weeks, from 5.7 to 2.5 weeks (P≤0.0001) and reduced associated mean per-patient hospital costs by $84,600, from approximately $156,200 to approximately $71,600 (2004 dollars). Treatment with BIG-IV also significantly shortened length of ICU stay by ≥60% (P≤0.01), duration of mechanical ventilation by ≥70% (P≤0.001), duration of tube feedings by ≥60% (P=0.001) and mean adverse events by ≥40% (P=0.05). With nationwide open-label BIG-IV distribution since 1998, mean hospital stay of ≥430 patients was further reduced to 2.2 weeks. Aggregate avoided hospital stay for these ≥430 patients totaled 25.0 patient-years and aggregate avoided hospital costs totaled more than $39,500,000.
Conclusion BIG-IV is safe and effective treatment for infant botulism and in late 2003 was licensed by the U.S. FDA; CDHS is distributing it nationwide as a public service medicine.
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