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Longer Treatment Window for Botulism?

By Amesh A. Adalja, MD, February 20, 2009

Optimal treatment of botulism requires administration of anti-toxin within 24 hours of symptom onset, which can occur as soon as 6 hours after ingestion of spores of Clostridium botulinum. Rapid treatment is necessary to ameliorate the paralysis associated with production of toxin and subsequent disruption of acetylcholine transmission at the synaptic junction.1 Results from a new study published in The Journal of Infectious Diseases demonstrate the persistence of botulinum toxin in the serum of patients up to 11 days after exposure. All were exposed through food. The prolonged persistence of toxin may allow for initiation of anti-toxin as long as 12 days after toxin ingestion with the expectation of efficacy.2

Toxin Identified at 11 Days Post-exposure in Alaskan Cases—Role for Toxinotype B?

The authors of the study reviewed records of botulism cases in Alaska from 1959-2007 and identified cases with a valid toxin ingestion date, serum collection date, and serum toxin assay result to include in the study. From a total of 180 cases, 64 met the inclusion criteria.2

Toxin assays performed at the Centers for Disease Control and Prevention (CDC) and the Alaska State Public Health Laboratory identified persistence of toxin in patient serum as long as 11 days after exposure. In all, 20% of specimens revealed the presence of toxin 10 days or more after exposure.2

Of 15 toxin-positive specimens that were collected after more than 3 days following exposure, 73% were type B, including those of the two patients with positivity at 11 days.2

Do Toxinotypes Matter?

In Alaska, of the 7 toxinotypes of C.botulinum, toxinotype B is responsible for only 14% of food-borne botulism cases, yet it was detected in 73% of patients with measurable toxin 3 days or more after exposure.2 Toxinotypes are geographically distributed, with type A more common in the U.S. and type B more common in Europe.1 The authors hypothesize that patients exposed to type B toxin may present for medical care later or have a longer time to diagnosis because of the milder clinical illness, longer incubation period, and lower case fatality rates (6.7% vs. 0% in cases occurring between 1990-96) associated with type B toxin.2,3

Is There a Longer Treatment Window?

The implications of this study are important because the results support the administration of antitoxin up to 12 days after food-borne exposure, as was done in a recent case in Florida.4

However, it is not clear if the results of this study will apply to inhalational botulism, which is believed to be the likely route of exposure in a bioterrorist event. Furthermore, delineation of the exact nature of the relationship between toxin dose and serum half-life is needed. As botulism is a class A bioweapon for which an effective countermeasure is available, defining the maximum time after exposure for which treatment may be effective is a key component of response planning.

References

  1. Sobel J. Botulism. Beyond Anthrax. Eds. Lutwick LI, Lutwick SM. New York: Humana Press, 2009. 85-106.

  2. Fagan RP, McLaughlin JB, Middaugh JP. Persistence of Botulinum Toxin in Patients’ Serum: Alaska, 1959-2007. J Infect Dis 2009; 199. http://www.journals.uchicago.edu/doi/abs/10.1086/597310. Accessed February 12, 2009.

  3. Centers for Disease Control and Prevention: Botulism in the United States, 1899-1996. Handbook for Epidemiologists, Clinicians, and Laboratory Workers. Atlanta: Centers for Disease Control and Prevention, 1998. http://www.cdc.gov/nczved/dfbmd/disease_listing/files/botulism.pdf. Accessed February 15, 2009.

  4. Centers for Disease Control and Prevention. Botulism associated with commercial carrot juice—Georgia and Florida, September 2006. MMWR Morb Mortal Wkly Rep 2006;55:1098–9. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5540a5.htm. Accessed February 12, 2009.