Background We created the orphan drug Human Botulism ImmuneGlobulin Intravenous (BIG-IV), which neutralizes botulinum toxin,and evaluated its safety and efficacy in treating infant botulism,the intestinal-toxemia form of human botulism.
Methods We performed a five-year, randomized, double-blind,placebo-controlled trial statewide, in California, of BIG-IVin 122 infants with suspected (and subsequently laboratory-confirmed)infant botulism (75 caused by type A Clostridium botulinum toxin,and 47 by type B toxin); treatment was given within three daysafter hospital admission. We subsequently performed a 6-yearnationwide, open-label study of 382 laboratory-confirmed casesof infant botulism treated within 18 days after hospital admission.
Results As compared with the control group in the randomizedtrial, infants treated with BIG-IV had a reduction in the meanlength of the hospital stay, the primary efficacy outcome measure,from 5.7 weeks to 2.6 weeks (P<0.001). BIG-IV treatment alsoreduced the mean duration of intensive care by 3.2 weeks (P<0.001),the mean duration of mechanical ventilation by 2.6 weeks (P=0.01),the mean duration of tube or intravenous feeding by 6.4 weeks(P<0.001), and the mean hospital charges per patient by $88,600(in 2004 U.S. dollars; P<0.001). There were no serious adverseevents attributable to BIG-IV. In the open-label study, infantstreated with BIG-IV within seven days of admission had a meanlength of hospital stay of 2.2 weeks, and early treatment withBIG-IV shortened the mean length of stay significantly morethan did later treatment.
Conclusions Prompt treatment of infant botulism type A or typeB with BIG-IV was safe and effective in shortening the lengthand cost of the hospital stay and the severity of illness.
Source Information
From the Infant Botulism Treatment and Prevention Program (S.S.A., R.S.), California Department of Health Services, Richmond; the National Botulism Surveillance and Reference Laboratory, Centers for Disease Control and Prevention, Atlanta (S.E.M., C.L.H.); and the Division of Biostatistics, School of Public Health, University of California, Berkeley (N.P.J.). Dr. Hatheway is deceased.
Address reprint requests to Dr. Arnon at the California Department of Health Services, 850 Marina Bay Pkwy., Rm. E-361, Richmond, CA 94804, or at sarnon{at}dhs.ca.gov.
Grant, K. A., Nwarfor, I., Mpamugo, O., Mithani, V., Lister, P., Dixon, G., Nixon, G., Planche, T., Courtney, M., Morgan, J., McLauchlin, J.
(2009). Report of two unlinked cases of infant botulism in the UK in October 2007. J Med Microbiol
58: 1601-1606
[Abstract][Full Text]
Ibrahim, Y., Merritt, T. A., Barash, J. R., Arnon, S. S.
(2009). Index of Suspicion in the Nursery. NeoReviews
10: e36-e38
[Full Text]
Domingo, R. M., Haller, J. S., Gruenthal, M.
(2008). Infant Botulism: Two Recent Cases and Literature Review. J Child Neurol
23: 1336-1346
[Abstract]
Keller, J. E.
(2008). Characterization of New Formalin-Detoxified Botulinum Neurotoxin Toxoids. CVI
15: 1374-1379
[Abstract][Full Text]
Koepke, R., Sobel, J., Arnon, S. S.
(2008). Global Occurrence of Infant Botulism, 1976-2006. Pediatrics
122: e73-e82
[Abstract][Full Text]
Rathore, M. H.
(2008). BIG Babies Do Better with Infant Botulism. AAP Grand Rounds
19: 30-31
[Full Text]
Baldwin, M. R., Tepp, W. H., Przedpelski, A., Pier, C. L., Bradshaw, M., Johnson, E. A., Barbieri, J. T.
(2008). Subunit Vaccine against the Seven Serotypes of Botulism. Infect. Immun.
76: 1314-1318
[Abstract][Full Text]
Wenham, T., Cohen, A.
(2008). Botulism. Contin Educ Anaesth Crit Care Pain
8: 21-25
[Full Text]
Tseng-Ong, L., Mitchell, W. G.
(2007). Infant Botulism: 20 Years' Experience at a Single Institution. J Child Neurol
22: 1333-1337
[Abstract]
Underwood, K., Rubin, S., Deakers, T., Newth, C.
(2007). Infant Botulism: A 30-Year Experience Spanning the Introduction of Botulism Immune Globulin Intravenous in the Intensive Care Unit at Childrens Hospital Los Angeles. Pediatrics
120: e1380-e1385
[Abstract][Full Text]
Hirsch, N. P.
(2007). Neuromuscular junction in health and disease. Br J Anaesth
99: 132-138
[Abstract][Full Text]
Arnon, S. S.
(2007). Creation and Development of the Public Service Orphan Drug Human Botulism Immune Globulin. Pediatrics
119: 785-789
[Abstract][Full Text]
Francisco, A. M. O., Arnon, S. S.
(2007). Clinical Mimics of Infant Botulism. Pediatrics
119: 826-828
[Abstract][Full Text]
Eubanks, L. M., Hixon, M. S., Jin, W., Hong, S., Clancy, C. M., Tepp, W. H., Baldwin, M. R., Malizio, C. J., Goodnough, M. C., Barbieri, J. T., Johnson, E. A., Boger, D. L., Dickerson, T. J., Janda, K. D.
(2007). An in vitro and in vivo disconnect uncovered through high-throughput identification of botulinum neurotoxin A antagonists. Proc. Natl. Acad. Sci. USA
104: 2602-2607
[Abstract][Full Text]
Ravichandran, E., Gong, Y., Saleem, F. H. A., Ancharski, D. M., Joshi, S. G., Simpson, L. L.
(2006). An Initial Assessment of the Systemic Pharmacokinetics of Botulinum Toxin. J. Pharmacol. Exp. Ther.
318: 1343-1351
[Abstract][Full Text]
(2006). Orphan diseases and orphan drugs: infant botulism and BIG-IV. Arch. Dis. Child.
91: 611-611
[Full Text]
(2006). Botulism Immune Globulin as a Therapy for Infant Botulism. JWatch Neurology
2006: 3-3
[Full Text]
(2006). Other articles noted. Evid. Based Med.
11: 95-96
[Full Text]
Previous
