International Experience with Human Botulism Immune Globulin for the Treatment of Infant Botulism

Abstract

Background:  Human Botulism Immune Globulin Intravenous (BIG-IV) was licensed in the United States in October 2003 for the treatment of the rare, life-threatening infectious disease, infant botulism (IB) due to botulinum toxin types A or B. International use of BIG-IV began in July 2005 on a case-by-case basis following approval by the respective countries’ medicines regulatory agencies authorizing its importation.  Since 2005, BIG-IV has been distributed to 16 countries on five continents.

Aims: To review the international utilization of BIG-IV for the treatment of IB over a 20-year period, describe the mechanisms by which BIG-IV is strategically stored and deployed domestically and internationally, and compare international and domestic patients according to  toxin type, demographic and clinical characteristics, transit time, time to diagnosis, time to BIG-IV infusion, and length of hospital stay (LOS).

Methods: Clinical, demographic, operational, and epidemiological data maintained in the California Department of Public Health’s Infant Botulism Treatment and Prevention Program comprehensive database were compiled and reviewed for BIG-IV-treated patients with laboratory confirmation of IB from July 1, 2005, through June 30, 2025.

Results:  Of the 2,792 treated IB patients between July 1, 2005, and June 30, 2025, 113 (4%) were outside of the U.S. and 2,679 (96%) were in the U.S. Toxin types differed for international vs U.S.-treated patients by region (p<0.001), in accordance with known geographic distribution of Clostridium botulinum. Infant feeding regimens were similar, but honey exposure was significantly lower in U.S. patients compared to international patients (p<0.001). Median BIG-IV transit time was 43.2 hours for international patients compared to 14.4 hours for U.S. patients (p<0.001). International patients were also diagnosed and treated later in hospitalization than U.S. patients (p-values <0.001) and had longer hospital LOS (p<0.001).

Conclusion: Treatment of international patients was more likely to be delayed until laboratory confirmation was obtained.  Longer time to BIG-IV infusion likely contributed to longer hospital LOS in international patients. Time to infusion differences could also be attributed to process delays in obtaining required approvals to import given BIG-IV is not licensed outside the U.S., transport challenges related to distance, and customs clearance delays.