Morbidity and Mortality Weekly Report Recommendations and Reports / Vol. 70 / No. 2 May 7, 2021 Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 U.S. Department of Health and Human Services Centers for Disease Control and Prevention Recommendations and Reports CONTENTS Introduction ............................................................................................................1 Methods ....................................................................................................................3 Standards of Care: Conventional, Contingency, and Crisis ....................4 Diagnosis of Botulism ..........................................................................................5 Monitoring Illness Progression in Patients with Botulism ................... 15 Treatment Considerations ............................................................................... 17 Botulinum Antitoxin Treatment .................................................................... 17 Treatments Other than Botulinum Antitoxin ........................................... 22 Botulism, Antitoxin, and Breast Milk............................................................ 23 Critical Care: Considerations During Shortages ...................................... 24 Conclusion ............................................................................................................ 25 References ............................................................................................................. 25 The MMWR series of publications is published by the Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30329-4027. Suggested citation: [Author names; first three, then et al., if more than six.] [Title]. MMWR Recomm Rep 2021;70(No. RR-#):[inclusive page numbers]. Centers for Disease Control and Prevention Rochelle P. Walensky, MD, MPH, Director Anne Schuchat, MD, Principal Deputy Director Daniel B. Jernigan, MD, MPH, Acting Deputy Director for Public Health Science and Surveillance Rebecca Bunnell, PhD, MEd, Director, Office of Science Jennifer Layden, MD, PhD, Deputy Director, Office of Science Michael F. Iademarco, MD, MPH, Director, Center for Surveillance, Epidemiology, and Laboratory Services MMWR Editorial and Production Staff (Serials) Charlotte K. Kent, PhD, MPH, Editor in Chief Martha F. Boyd, Lead Visual Information Specialist Ian Branam, MA, Acting Lead Christine G. Casey, MD, Editor Alexander J. Gottardy, Maureen A. Leahy, Health Communication Specialist Mary Dott, MD, MPH, Online Editor Julia C. Martinroe, Stephen R. Spriggs, Tong Yang, Shelton Bartley, MPH, Terisa F. Rutledge, Managing Editor Visual Information Specialists Lowery Johnson, Amanda Ray, David C. Johnson, Lead Technical Writer-Editor Quang M. Doan, MBA, Phyllis H. King, Jacqueline N. Sanchez, MS, Cathy Lansdowne, Project Editor Terraye M. Starr, Moua Yang, Health Communication Specialists Information Technology Specialists Will Yang, MA, Visual Information Specialist MMWR Editorial Board Timothy F. Jones, MD, Chairman Matthew L. Boulton, MD, MPH William E. Halperin, MD, DrPH, MPH Patrick L. Remington, MD, MPH Carolyn Brooks, ScD, MA Christopher M. Jones, PharmD, DrPH, MPH Carlos Roig, MS, MA Jay C. Butler, MD Jewel Mullen, MD, MPH, MPA William Schaffner, MD Virginia A. Caine, MD Jeff Niederdeppe, PhD Nathaniel Smith, MD, MPH Jonathan E. Fielding, MD, MPH, MBA Celeste Philip, MD, MPH Morgan Bobb Swanson, BS David W. Fleming, MD Patricia Quinlisk, MD, MPH Recommendations and Reports Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 Agam K. Rao, MD1; Jeremy Sobel, MD1; Kevin Chatham-Stephens, MD1; Carolina Luquez, PhD1 1Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC Summary Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input. Introduction appropriate conditions and produce toxin, or intentionally, when toxin is added directly to foods. Foodborne botulism Background outbreaks usually affect few persons. However, because large These evidence-based guidelines provide health care personnel outbreaks are possible (“epidemic potential”), foodborne with recommended best practices for diagnosing, monitoring, and botulism is a public health emergency. Contamination of treating botulism in the settings of conventional, contingency, and wounds with Clostridium botulinum and subsequent in situ crisis standards of care. The following syndromes are described: botulinum toxin production is typically (in the United States) foodborne botulism (exposure to botulinum neurotoxin in caused by unsanitary injection of a particular type of heroin food), wound botulism (exposure to botulinum neurotoxin from (black tar heroin) subcutaneously or subdermally; although a wound colonized with the bacteria), inhalational botulism common-source heroin containing clostridial spores might (exposure to aerosolized botulinum neurotoxin, which could affect groups of injectors, wound botulism does not have be caused intentionally), and iatrogenic botulism (exposure the epidemic potential of foodborne botulism (1). Purified to botulinum neurotoxin by injection of high-concentration botulinum toxin, produced and weaponized by military botulinum toxin for cosmetic or therapeutic purposes). These biological warfare programs of various countries, could be guidelines do not address syndromes of botulism caused by dispersed as an aerosol and cause inhalational botulism. This intestinal colonization by botulinum-toxin–producing Clostridia form of botulism, which does not occur naturally and has species (i.e., infant botulism and adult colonization botulism), been reported once in a laboratory worker, could affect many which are inherently sporadic and have not occurred in outbreaks. persons (2). Therefore, throughout the text, terms such as “botulism” and Diagnosis of botulism depends on high clinical suspicion “patient with suspected botulism” refer to syndromes other than and a thorough neurologic examination. The timeliness of intestinal colonization. diagnosis is crucial to successful treatment because botulinum Contamination of foods with botulinum neurotoxin can antitoxin, the only specific therapy for botulism, must be occur unintentionally when botulinum spores germinate under administered to patients as quickly as possible. In the United States, botulinum antitoxin (to treat suspected botulism, other than infant botulism) is available emergently and free of charge Corresponding author: Jeremy Sobel, MD, Division of Foodborne, from the federal government. Health departments and CDC Waterborne, and Environmental Diseases, National Center for provide emergency clinical consultations 24 hours per day and Emerging and Zoonotic Infectious Diseases, CDC. Telephone: 404-639-7419; Email: [email protected]. facilitate rapid antitoxin delivery for treatment of suspected US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / May 7, 2021 / Vol. 70 / No. 2 1 Recommendations and Reports botulism, other than infant botulism. For suspected cases of neurotoxin enters the vascular circulation (through ingestion, infant botulism, the California Department of Public Health absorption from colonized wound or intestine, inhalation, or Infant Botulism Treatment and Prevention Program provides injection) and is transported to peripheral cholinergic nerve clinical consultation and access to the specific antitoxin licensed terminals, including neuromuscular junctions, postganglionic for treatment of infant botulism. parasympathetic nerve endings, and peripheral ganglia (12). All The recommendations in these guidelines address the toxin types produce a similar clinical syndrome of cranial nerve conventional standard of care, in which